HK1200186B - Systems and methods for multi-analysis - Google Patents

Description

System and method for multiplex analysis

Cross-referencing

The present application claims PCT application No. PCT/US2011/53188, filed on 25/9/2011; PCT application No. PCT/US2011/53189, filed on 9/25/2011; U.S. patent application Ser. No. 13/244,197 filed 9/26/2011; U.S. patent application Ser. No. 13/244,946, filed 9/26/2011; priority is granted to U.S. patent application No. 13/244,386, 9/26/2011, which is incorporated by reference herein in its entirety.

[ patent background ]

Most clinical decisions are based on laboratory and health monitoring data, but the methods and infrastructure used to collect such data severely limit the quality and utility of the data itself. In laboratory testing, almost all errors are associated with human or pre-analytical processing errors, and the testing process can take days to weeks to complete. Many times, by the time the medical practitioner obtains data to effectively treat the patient or to determine the most appropriate intervention, he or she has been forced to administer treatment to the patient empirically or prophylactically, typically because the data was not available at the time of visit or patient triage. Obtaining higher quality detection information earlier in the triage of patients enables earlier intervention and better management of disease progression, thereby improving efficacy and reducing medical costs.

Existing systems and methods for clinical testing suffer from significant drawbacks from the perspective of patients, healthcare professionals, taxpayers, and insurance companies. Consumers today can perform certain specialized tests in clinics or other specialized locations. If the physician ultimately depends on the results of the examination, the physical sample is transported to the site where the examination is to be performed. For example, these samples may include blood from a venous draw and typically collected from a subject at a dedicated location. The accessibility of these sites and the venipuncture procedure itself are major obstacles in the compliance and frequency of detection. The possibility of visiting blood sampling devices, the fear of needles, particularly in children and the elderly, for example, who often have rolling veins, and the difficulty associated with drawing large amounts of blood, drive people to be reluctant to test even when needed. Thus, conventional sampling and detection methods are tedious and require a significant amount of time to provide a detection result. Such methods are hampered not only by difficulties in the timing and/or limited accessibility of the harvester to provide the physical sample to the subject, but also by the associated turnaround time in sample batch processing in centralized laboratories and running laboratory tests. Thus, the total turnaround time involved in arriving at the harvester, obtaining the sample, transporting the sample, testing the sample, and reporting and delivering the results becomes unacceptable and severely limits the timely provision of best-known care by medical professionals. This often results in symptomatic treatment, rather than treatment of deep disease conditions or disease progression mechanisms.

Furthermore, conventional techniques are problematic for certain diagnoses. Some tests may be extremely time sensitive but take days or weeks to complete. Over such a period of time, the disease may progress beyond the point of treatment. In some cases, subsequent testing is required after the preliminary results, which requires additional time as the patient must return to a dedicated location. This impairs the ability of the medical professional to provide effective treatment. Furthermore, testing only in limited locations and/or infrequently reduces the likelihood that the patient's status can be monitored on a regular basis or that the patient can provide samples as often as possible quickly or on demand. For certain diagnoses or conditions, these deficiencies inevitably result in a lack of adequate medical response to constantly changing and deteriorating physiological conditions. Conventional systems and methods can also affect the integrity and quality of clinical testing due to sample degradation that often occurs when such samples are transported from the harvester to the site where the sample analysis is performed. For example, the decay of the analyte at a certain rate and the time delay of the analysis can lead to a loss of sample integrity. Different laboratories also work with different quality standards, which may lead to different degrees of error. In addition, manual preparation and analysis of samples in various sample collectors and laboratories has made possible the occurrence of prior human errors. These and other drawbacks inherent in conventional settings make longitudinal analysis difficult with high quality and reliability, particularly for chronic disease management.

Furthermore, such conventional analysis techniques are often not cost effective. Excessive time lag in obtaining test results leads to delays in diagnosis and treatment, which may have adverse effects on the patient's health; as the disease progresses further, the patient then requires additional treatment and ends up with some form of hospitalization that was unanticipated too frequently. Payers contributing to government health programs, such as health insurance companies and taxpayers, will eventually pay more for problems that treatment could otherwise be avoided through more readily available and faster clinical testing results.

[ patent Abstract ] to provide a method for producing a semiconductor device

The ability to detect a disease or the onset of a disease in a timely manner to manage and treat it is a deep pursuit of both patients and providers, but has not yet been realized in current healthcare systems where detection is accompanied too frequently by fatal prognosis.

It may be desirable to provide improved systems and methods for sample collection, sample preparation, assays, and/or detection. At least some embodiments herein may provide systems and apparatus that perform one or more of the steps of sample collection, preparation, assay, or detection. At least some specific examples herein may provide systems and methods for rapid, frequent, and/or more accurate diagnosis, continuous monitoring, and convenience and guidance of treatment while and where care is provided.

According to one specific example described herein, a system may comprise: a plurality of modules mounted on a support structure, wherein individual modules of the plurality of modules comprise a sample prep, an assay, and/or a detector, wherein the system is configured to perform (a) at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, separation, and chemical processing, and (b) multiple types of assays selected from the group consisting of: immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof; and wherein the plurality of types of assays are performed by means of isolated (including but not limited to fluidly isolated) assay units contained within the system. In some embodiments, the separating comprises magnetically separating.

Additional specific examples described herein may relate to a system comprising: a plurality of modules mounted on a support structure, wherein individual modules of the plurality of modules comprise a sample prep, an assay, and/or a detector, wherein the system is configured to perform (a) at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, separation, and chemical processing, and (b) one or more types of assays selected from the group consisting of: immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof; and wherein the system is configured to process or measure a sample having a volume of 250 l or less and has a coefficient of variation of 15% or less. In some embodiments, the separating comprises magnetically separating.

According to another specific example described herein, there may be provided a system comprising: a preparation instrument configured to perform sample preparation; and a meter configured to perform a plurality of types of assays selected from the group consisting of: immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof; and wherein the system is configured to perform said sample preparation and said plurality of types of assays in 4 hours or less.

In some embodiments described herein, there may be provided a system comprising: a plurality of modules mounted on a support structure, wherein individual modules of the plurality of modules comprise a sample preparation meter, an assay meter, and/or a detector, wherein the system is configured to (a) prepare a sample for at least one physical or chemical assay; and (b) performing the at least one physical or chemical assay, and wherein at least one individual module of the plurality of modules comprises a cytometer configured to count cells of the sample.

Additional specific examples described herein relate to a system comprising: a sample preparation instrument, a measuring instrument and/or a detecting instrument; and a control unit having computer executable commands for performing a point of service at a designated location with at least one of the sample preparation meter, the meter, and the probe, wherein the sample preparation meter includes a sample acquisition unit configured to acquire a biological sample, and wherein the system is configured to determine the biological sample with a coefficient of variation of less than or equal to 15%.

According to specific examples described herein, a system may include: a housing; and a plurality of modules within the housing, an individual module of the plurality of modules comprising at least one instrument selected from the group consisting of a sample prep instrument, a meter, and a probe, wherein the system comprises a liquid handling system configured to transfer a sample or reagent vessel within or from the individual module to another individual module within the housing of the system.

According to additional embodiments described herein, a plug-and-play system may be provided. The system may include: a support structure having a module mounting table configured to support a plurality of modules, the modules (a) being removable from the mounting table or interchangeable with at least one other module of the plurality of modules; (b) configured to perform, without the aid of another module in the system, (i) at least one sample preparation procedure selected from the group comprising sample processing, centrifugation, magnetic separation, or (ii) at least one type of assay selected from the group consisting of: immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof; and (c) configured to be in electrical, electromagnetic or optoelectronic communication with a controller configured to provide one or more instructions to the module or individual ones of the plurality of modules to facilitate performance of at least one sample preparation procedure or at least one type of assay.

Another specific example described herein may relate to a system comprising: a sample preparation instrument, a measuring instrument and/or a detecting instrument; and a control unit having computer-executable instructions configured to perform a point of service at a specified location, wherein the system is configured to perform a plurality of types of assays selected from the group consisting of: immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof.

Additionally, particular examples described herein may include a system comprising: a plurality of modules mounted on a support structure, wherein individual modules of the plurality of modules comprise a sample preparation instrument, a measurement instrument, and/or a detection instrument, wherein the system is configured to perform (a) at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, magnetic separation, and (b) a plurality of types of measurements selected from the group consisting of: immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof; and wherein the plurality of types of assays are performed by means of three or more assay units comprised within the system.

According to another specific example of the system, there may be provided a system comprising: a plurality of modules mounted on a support structure, wherein individual modules of said plurality of modules comprise a sample prep, an assay, and/or a probe, wherein said system is configured to perform (a) at least one sample prep procedure selected from the group consisting of sample processing, centrifugation, magnetic separation, and chemical processing, and (b) one or more types of assays selected from the group consisting of: immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof; and wherein the system is configured to process or measure a sample having a volume of 250 μ l or less and the system has a coefficient of variation of 15% or less.

Further, particular examples described herein may relate to a system comprising: a meter configured to perform at least one type of assay selected from the group consisting of immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographical assays, calorimetric assays, nephelometric assays, agglutination assays, radioisotope assays, viscometry, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof; and wherein the coefficient of variation is less than or equal to 10% when the at least one type of assay is performed with the system.

According to additional specific examples described herein, a system may include: a meter configured to perform a plurality of types of assays selected from the group consisting of immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, morphological assays, calorimetric assays, nephelometric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof; and a control unit having computer executable instructions to perform the plurality of types of assays, wherein the system is configured to assay a biological sample having a volume of less than or equal to 250 μ l.

According to additional specific examples described herein, there may be provided a system comprising: a preparation instrument configured to perform sample preparation; and a meter configured to perform a plurality of types of assays selected from the group consisting of immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographical assays, calorimetric assays, nephelometric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof, wherein the system is configured to perform the sample preparation and the plurality of types of assays in 4 hours or less.

Further, particular examples described herein may relate to a system comprising: a plurality of modules mounted on a support structure, wherein individual modules of the plurality of modules comprise a sample preparation, assay, and/or detection instrument, wherein the system is configured to perform (a) at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, magnetic separation, and chemical processing, and (b) a plurality of types of assays selected from the group consisting of immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, nephelometric assays, agglutination assays, radioisotopic assays, viscometry, thrombometry, thrombotime assays, protein synthesis assays, histological assays, culture assays, biological assays, osmolarity measurements and combinations thereof; and wherein the system is configured to process or assay a sample having a volume of 250 μ l or less, and wherein the system is configured to detect a plurality of analytes from the sample, the concentrations of the plurality of analytes differing from each other by more than an order of magnitude.

Another specific example of the system may provide a system comprising: a sample preparation instrument, a measuring instrument and/or a detecting instrument; and a control system having computer-executable instructions configured for performing a point of service at a specified location, wherein the system is configured for performing a plurality of types of assays selected from the group consisting of immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, nephelometric assays, agglutination assays, radioisotope assays, viscometric assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof.

In one specific example described herein, a system may have hardware and/or software to detect signals from multiple signal types. Light signal types include, but are not limited to, fluorescence, luminescence, absorbance, turbidity, forward scattering, and/or side scattering. The type of electrical signal includes, but is not limited to, electrochemical potential and/or electrical impedance. Mechanical signal types include, but are not limited to, liquid rheology (viscoelasticity), osmotic pressure, phase separation, and/or mobility. Thermal signal types include, but are not limited to, temperature changes.

By way of non-limiting example, a particular example of the system may use at least two different signal types to measure at least two different analyte types. Alternatively still, another embodiment of the system may use at least two different signal types for measuring at least two different analytes. Analyte types may include, but are not limited to, crystals, elements, formed elements, organic molecular compounds, inorganic molecular compounds, organisms, particles, or other analyte or analytes. Alternatively, a particular embodiment of the system may measure at least three different signal types. Alternatively, when detecting two different signal types, a particular example of a system may be configured to detect any combination of at least one optical signal type and at least one other signal type other than an electrical signal (such as a thermal signal or a mechanical signal). Alternatively still, when detecting only a single signal type or multiple signals within a single signal type, the system may have hardware and/or software to measure multiple analytes, each analyte from a different analyte type, such as but not limited to at least two classes selected from among the following classes: crystals, elements, formed elements, organic molecular compounds, inorganic molecular compounds, organisms, particles, or other analyte or analytes.

According to additional specific examples described herein, a system comprises: a plurality of modules mounted on a support structure, wherein an individual module of the plurality of modules comprises a sample prep instrument, a meter, and/or a probe; wherein the system is configured to perform a plurality of types of assays selected from the group consisting of immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscometric assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof, wherein at least one of the plurality of types of assays is a cell count or agglutination.

According to additional specific examples described herein, a system may include: a plurality of modules mounted on a support structure, wherein an individual module of the plurality of modules comprises a sample prep instrument, a meter, and/or a probe; a cytometer configured to count cells of one or more samples, wherein the system is configured to perform at least one assay selected from the group consisting of immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, nephelometric assays, agglutination assays, radioisotope assays, viscometric assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof.

Another specific example described herein may provide a system comprising: the device comprises a sample preparation instrument, a measuring instrument and a detecting instrument; and a control unit having computer executable commands for performing a point-of-service at a designated location by means of at least one of the sample preparation meter, the meter, and the probe, wherein the sample preparation meter comprises a sample collection unit configured to collect a biological sample, and wherein the system is configured to measure the biological sample with a coefficient of variation of less than or equal to 10%.

In some embodiments described herein, there may be provided a system comprising: a plurality of modules mounted on a support structure, wherein individual modules of the plurality of modules comprise a sample preparation instrument, a measurement instrument, and/or a detection instrument, wherein the system is configured to perform (a) at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, magnetic separation, and (b) at least one physical or chemical assay, and wherein the system is configured to measure a biological sample having a volume of less than or equal to 250 μ l.

A system provided according to particular examples described herein may include: a plurality of modules mounted on a support structure, wherein individual modules of the plurality of modules comprise a sample preparation, assay, and/or detection instrument, wherein the system is configured to perform (a) a plurality of sample preparation procedures selected from the group consisting of sample processing, centrifugation, magnetic separation, physical separation, and chemical separation, and (b) at least one type of assay selected from the group consisting of immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, nephelometric assays, agglutination assays, radioisotope assays, viscometric assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, molecular biology assays, biological biology assays, Culture assays, osmolarity assays, and combinations thereof.

Further, some embodiments described herein may provide a system comprising: a housing; and a plurality of modules within the housing, an individual module of the plurality of modules comprising at least one instrument selected from the group consisting of a sample prep instrument, a meter, and a probe, wherein the system comprises a liquid handling system configured to transfer a sample or reagent container within or from the individual module to another module within the housing of the system.

The above-described system, or the systems elsewhere herein, may comprise, alone or in combination, a liquid handling system, wherein the liquid handling system comprises a pipette configured to ingest, dispense, and/or transfer the biological sample.

The system described above or elsewhere herein may include an imaging device configured to image, alone or in combination, one or more of the group consisting of a collected biological sample, processing of a biological sample, and a reaction performed on the system described above or elsewhere herein. The imaging device may be a camera or sensor that detects and/or records electromagnetic radiation and an associated spatial dimension and/or temporal dimension.

The systems described above or elsewhere herein may be configured, alone or in combination, to detect multiple analytes from the sample, the multiple analytes differing from each other in concentration by more than an order of magnitude.

A sample acquisition unit configured to draw a fluid or tissue sample from a subject may be provided in the systems described above or elsewhere herein, either alone or in combination.

The systems described above or elsewhere herein, alone or in combination, can have a coefficient of variation of less than or equal to 10%.

An automated method for processing samples at a point-of-service location may be provided, the method comprising: providing a sample to the systems described above or elsewhere herein, either alone or in combination; and allowing the system to process the sample to produce a detectable signal indicative of completion of the process.

When the methods described above or elsewhere herein are performed alone or in combination, the processing step can assess the histology of the sample or the morphology of the sample. The processing step may assess the expression and/or concentration of the analyte in the sample, either alone or in combination in the methods described above or elsewhere herein.

In the systems described above or elsewhere herein, alone or in combination, the sample preparation meter can include a sample acquisition unit configured to acquire a biological sample from a subject.

The support structure may be a housing enclosing the plurality of modules, the housing selectively providing a power or communication unit, either alone or in combination, in the systems described above or elsewhere herein.

The systems described above or elsewhere herein may store and/or transmit electronic data representing images to external devices, either alone or in combination, via communication units included in the systems.

In some embodiments, the systems described above or elsewhere herein can further comprise a centrifuge, either alone or in combination.

The system described above or elsewhere herein, alone or in combination, may be configured for bi-directional communication with an external device via a communication unit included in the system, wherein the communication unit is configured to send data to the external device and receive instructions from the system.

A method of detecting the expression or concentration of an analyte suspected of being present in a biological sample from a subject may be provided, the method comprising: providing a biological sample to the system described above or elsewhere herein, either alone or in combination; and performing at least one type of assay selected from the group consisting of immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, nephelometric assays, agglutination assays, radioisotope assays, viscometric assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof, to produce a detectable signal indicative of the expression or concentration of the analyte.

The methods above or elsewhere herein, alone or in combination, may further comprise the step of generating a report containing information relating to a time-related change in the expression or concentration of the analyte.

The methods above or elsewhere herein may further comprise, alone or in combination, the step of generating a report comprising information relating to the diagnosis, prognosis and/or treatment of the physical condition of the subject based on the time-related change in the expression or concentration of the analyte.

In some cases, the chemical treatment is selected from the group consisting of heating and chromatography. In some embodiments, the receptor assay comprises a protein assay. In some embodiments, the systems provided herein are configured for automated operation, alone or in combination.

In some embodiments, the system, alone or in combination, is configured to detect multiple analytes from a sample, the multiple analytes differing from each other in concentration by more than an order of magnitude. The concentrations of the plurality of analytes may differ from each other by more than two orders of magnitude. In some cases, the concentrations of the plurality of analytes may differ from each other by more than three orders of magnitude. Various types of assays may be performed by means of four or more assay units comprised within the system. In some cases, the system is configured to draw a fluid or tissue sample from the subject. In one particular example, the system is configured to draw a blood sample from a finger of a subject.

In some embodiments, the system, alone or in combination, has a coefficient of variation of less than or equal to 5%. In other embodiments, the system, alone or in combination, has a coefficient of variation of less than or equal to 3%. In other embodiments, the systems, alone or in combination, have a coefficient of variation of less than or equal to 2%. In some cases, the coefficient of variation is based onDetermination, where 'σ' is the standard deviation and 'μ' is the average over the entire sample measurement.

In some cases, the systems provided herein are configured to perform a plurality of types of assays selected from the group consisting of immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, morphological assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscometric assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof.

In some cases, the systems provided herein have an accuracy of plus or minus 5% in the entire sample assay, or plus or minus 3% in the entire sample assay, or plus or minus 1% in the entire sample assay, or plus or minus 5% in the entire sample assay, or plus or minus 3% in the entire sample assay, or plus or minus 1% in the entire sample assay. In some embodiments, the coefficient of variation for at least one type of assay is less than or equal to 5%, or less than or equal to 3%, or less than or equal to 2%.

In some cases, the system may further comprise a plurality of modules mounted on the support structure, wherein a single module of the plurality of modules comprises the sample prep instrument, the meter, and/or the probe. The single module may include a sample preparation meter, a measurement meter, and a detection meter. In some cases, the system further includes a sample preparation meter, a measurement meter, and a probe.

In some embodiments, the systems described above or elsewhere herein, alone or in combination, are configured to perform at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, magnetic separation, and chemical processing. The chemical treatment may be selected from the group consisting of heating and chromatography.

In some embodiments, the systems described above or elsewhere herein include, alone or in combination, computer-executable instructions. The computer executable commands may be provided by a server in communication with the system.

In some embodiments, the systems described above or elsewhere herein, alone or in combination, comprise at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, magnetic separation, and chemical processing. Such systems may be configured to assay a sample at a rate of at least 0.25 assays/hour, or at least 0.5 assays/hour, or at least 1 assay/hour, or at least 2 assays/hour. Such a system may include a control unit having computer executable commands for performing point of service services at a specified location. The computer executable commands may be provided by a server in communication with the system. In some specific examples, the systems described above or elsewhere herein, alone or in combination, are configured to analyze a sample and report results to a remote system over a time period of at least about 6 hours, or 5 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 1 minute, or 30 seconds, or 10 seconds, or 5 seconds, or 1 second, or 0.1 seconds. For such systems, the concentrations of multiple analytes may differ from one another by more than two orders of magnitude or three orders of magnitude.

In some embodiments, the systems described above or elsewhere herein, alone or in combination, are configured to correlate the concentration of the analyte with compliance and non-compliance with the medical treatment.

In some embodiments, the systems described above or elsewhere herein, either alone or in combination, include a sample preparation meter and one or more sample acquisition units. The one or more sample acquisition units may include a scalpel blade and/or a needle. The needle may comprise a micro needle. The one or more sample acquisition units may be configured to acquire a biological sample.

In some embodiments, the system described above or elsewhere herein includes, alone or in combination, a sample preparation meter, a measurement meter, and a probe.

In some embodiments, the systems described above or elsewhere herein, individually or in combination, are configured for performing multiple types of assays with liquid-isolated assay units contained within the systems. In some cases, multiple types of assays can be performed on untreated tissue samples. In one example, the untreated tissue sample comprises untreated blood.

In some embodiments, the above systems, alone or in combination, are configured for performing cell counting. In other embodiments, the above systems are configured for agglutination and cell counting, either alone or in combination. In other embodiments, the above systems are configured, alone or in combination, for performing agglutination, cell counting, and immunoassay.

In some embodiments, the above systems, alone or in combination, are configured to assay a biological sample with a coefficient of variation of less than or equal to 10%, or less than or equal to 5%, or less than or equal to 3%.

In some embodiments, the above systems, alone or in combination, are configured to perform at least one physical or chemical assay, such as cell counting. In some cases, the at least one physical or chemical assay further comprises agglutination. In some cases, the at least one physical or chemical assay further comprises an immunoassay.

In some embodiments, the above systems, alone or in combination, are configured for processing or measuring volumes less than or equal toThe biological sample of (1). In other embodiments, the above systems, alone or in combination, are configured for processing or measuring volumes less than or equal toThe sample of (1). In other embodiments, the above systems, alone or in combination, are configured for processing or measuring volumes less than or equal toThe sample of (1). In other embodiments, the above systems, alone or in combination, are configured for processing or measuring a sample having a volume less than or equal to 500 nanoliters (nL).

In some embodiments, the above systems, alone or in combination, are used as a point of service system.

In some embodiments, the above systems are configured, alone or in combination, to perform two or more types of assays selected from the group consisting of immunoassays, nucleic acid assays, receptor assays, cell count assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, nephelometric assays, agglutination assays, radioisotope assays, viscometric assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof. In some cases, the system is configured, alone or in combination with other systems, to perform three or more types of assays selected from the group.

In some embodiments, the above-described systems, alone or in combination, are configured for performing at least one type of assay with a liquid-isolated assay unit contained within the system. In some cases, the liquid isolation assay unit is a tip. In some cases, each tip has at most 250 microliters (l, also referred to herein as "ul"), or at most 100 l, or at mostOr at mostOr a volume of up to 500 nanoliters (nl).

In some embodiments, a single module of the plurality of modules includes a fluid intake or retention system. In some cases, the liquid uptake and/or retention system is a pipette.

In some embodiments, the above systems, alone or in combination, are configured for bi-directional communication with a point of service server.

In some embodiments, the above systems, alone or in combination, have a liquid treatment system with a coefficient of variation of less than or equal to 10%, or less than or equal to 5%, or less than or equal to 3%, or less than or equal to 10%, or less than or equal to 5%, or less than or equal to 3%. In some embodiments, the liquid handling system includes an optical fiber.

In some embodiments, the fluid treatment system comprises a fluid intake and/or retention system. In some cases, the liquid handling system includes a pipette. In some embodimentsThe liquid handling system is attached to each individual module of the plurality of modules of the system, either alone or in combination with other systems. In some embodiments, the above systems, alone or in combination, include a housing containing a rack for supporting a plurality of modules. The size of the shell can be no more than 3m³Or not more than 2m³。

In some embodiments, the system described above includes, alone or in combination, a control system with programmed commands for performing point of service services at a specified location.

In some embodiments, the systems described above comprise liquid handling systems, either alone or in combination. In some cases, the liquid handling system includes a pipette selected from the group consisting of positive displacement pipettes, vented pipettes, and suction pipettes.

In some embodiments, the system described above includes a plurality of modules, either alone or in combination. In some cases, a single module includes a liquid handling tip configured to perform one or more procedures selected from the group consisting of: centrifugation, sample separation, immunoassay, nucleic acid assay, receptor assay, cytometric assay, colorimetric assay, enzymatic assay, electrophoretic assay, electrochemical assay, spectroscopic assay, chromatographic assay, microscopic assay, topographic assay, calorimetric assay, turbidity assay, agglutination assay, radioisotope assay, viscosity assay, coagulation assay, clotting time assay, protein synthesis assay, histological assay, culture assay, osmolarity assay, and combinations thereof. In some cases, the nucleic acid assay is selected from the group consisting of nucleic acid amplification, nucleic acid hybridization, and nucleic acid sequencing.

In some embodiments, the system described above comprises a plurality of modules, either alone or in combination, and each individual module of the plurality of modules comprises: (a) a liquid handling system configured to transfer a sample within or from the single module to another module within the system, (b) a plurality of assay units configured to perform a plurality of types of assays, and (c) a detector configured to detect signals generated from the assays. In some cases, the plurality of types of assays are selected from the group consisting of: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof.

In some embodiments, the system described above includes a plurality of modules, either alone or in combination, and each individual module includes a centrifuge.

In some embodiments, the above systems, alone or in combination, further comprise a module that provides a subset of the sample preparation procedures or assays performed by at least one module of the system.

In some embodiments, the system described above comprises, alone or in combination, a meter comprising a thermal block.

In some embodiments, the sample comprises at least one material selected from the group consisting of a liquid sample, a tissue sample, an environmental sample, a chemical sample, a biological sample, a biochemical sample, a food sample, or a pharmaceutical sample. In some cases, the sample comprises blood or other bodily fluid, or tissue.

In some embodiments, the above systems are configured, alone or in combination, for bi-directional communication with a service point server. In some cases, the two-way communication is wireless.

In some embodiments, the system described above includes a plurality of modules, either alone or in combination, and each component of the plurality of modules is interchangeable with another module.

In some embodiments, the systems described above comprise, alone or in combination, a meter comprising a discrete measurement unit. In some cases, the discrete assay unit is a liquid isolation assay unit.

In some embodiments, the systems described above, alone or in combination, are configured for longitudinal analysis with a coefficient of variation of less than or equal to 10%, or less than or equal to 5%, or less than or equal to 3%.

In some embodiments, the above systems, alone or in combination, comprise a liquid handling system comprising an optical fiber.

In some embodiments, the above systems comprise, alone or in combination, a liquid handling system comprising a pipette.

In some embodiments, the system described above includes an image analyzer, alone or in combination.

In some embodiments, the above systems, alone or in combination, include at least one camera in a housing of the system. In some cases, the at least one camera is a Charge Coupled Device (CCD) camera. In some cases, the at least one camera is a lens-less camera.

In some embodiments, the system includes, alone or in combination, a controller containing programmed commands for performing point of service services at a specified location.

In some embodiments, the above systems, alone or in combination, are plug-and-play systems configured to provide point-of-service services. In some cases, the point of service is to provide point of care service to a subject holding a prescription from a subject caregiver, the prescription being prescribed for detecting expression or concentration of an analyte in a biological sample from the subject.

In some embodiments, the system described above comprises a plurality of modules, either alone or in combination, and each member of the plurality of modules comprises a communication trolley in communication with at least one type of meter or sample preparation procedure configured to perform the at least one type of meter.

In some embodiments, the systems described above include a support structure, either alone or in combination. In some cases, the support structure is a stent. In some cases, the rack does not include power or communication cables; in other cases, the rack includes power or communication cables. In some embodiments, the support structure includes one or more mounting tables. In some cases, the support structure includes a communication cart in communication with one of the one or more mounting stations.

In some embodiments, the communication vehicle is used to provide power to individual modules of the system. In some embodiments, the communication vehicle is used to enable communication between a controller of a system (e.g., a plug-and-play system) and individual modules of the system. In some cases, the communication vehicles are used to enable communication between modules of a system or to enable communication between modules of a system.

In some embodiments, the system includes a plurality of modules, either alone or in combination, and each individual module of the plurality of modules is in wireless communication with a controller of the system. In some cases, the wireless communication is selected from the group consisting of bluetooth communication, Radio Frequency (RF) communication, and wireless network communication.

In some embodiments, a method for processing a sample includes providing the above-described system, alone or in combination with other methods. The system includes a plurality of modules configured to simultaneously perform within the same module (a) at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, magnetic separation, and chemical processing, and/or (b) at least one type of probing selected from the group consisting of immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographical assays, calorimetric assays, nephelometric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof. Next, the system (or a controller of the system) detects for the presence of resource unavailability or a failure of (a) the at least one sample preparation procedure or (b) the at least one type of assay. Upon detection of a fault within at least one module, the system performs the at least one sample preparation procedure or the at least one type of assay using another module within the system or within another system in communication with the system.

In some cases, the system processes the sample at the point-of-service location.

In some cases, a system communicates wirelessly with another system.

In some cases, multiple modules of the system are in electronic, electromagnetic, or optoelectronic communication with each other.

In some cases, multiple modules of the system communicate wirelessly with each other.

One specific example described herein includes a liquid treatment device comprising: a plurality of pipette heads, wherein an individual pipette head comprises a pipette nozzle configured to connect with a tip removable from the pipette nozzle; a plurality of individually movable plungers, wherein at least one plunger is within and movable within the pipette head; and a motor configured to effect independent movement of a single plunger of the plurality of plungers.

Another specific example described herein includes a liquid treatment device comprising: a plurality of pipette heads, wherein an individual pipette head comprises a pipette nozzle configured to connect with a tip removable from the pipette nozzle; a plurality of individually movable plungers, wherein at least one plunger is within and movable within the pipette head; and an actuator configured to effect independent movement of a single plunger of the plurality of plungers.

Yet another specific example described herein includes a liquid treatment device comprising: a plurality of pipette heads, wherein an individual pipette head comprises a pipette nozzle configured to interface with a tip removable from the pipette nozzle, wherein the liquid handling device is capable of dispensing and/or aspirating from 0.5 microliters ("uL") to 5 milliliters ("mL") of liquid while functioning with a coefficient of variation of 5% or less.

According to specific examples described herein there may be provided a liquid treatment apparatus comprising: at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to connect with a tip removable from the nozzle; at least one plunger within one of the plurality of pipette heads, wherein the plunger is configured to be movable within the pipette head; and at least one motor configured to allow movement of the plurality of plungers substantially non-parallel to the removable tip.

Another specific example described herein provides a liquid processing apparatus including: at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to connect with a tip that is removable from the nozzle; at least one plunger within one of the plurality of pipette heads, and wherein the plunger is configured to be movable within the pipette head; and at least one drive configured to allow movement of the plurality of plungers that is not substantially parallel to the removable tip.

Yet another specific example described herein may provide a liquid processing apparatus including: at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to be connected with a tip removable from said nozzle, wherein said at least one pipette head has a liquid path of a given length ending in the pipette nozzle, and wherein the length of the liquid path can be adjusted without affecting liquid movement from the tip when the tip is engaged with the pipette nozzle.

Another specific example described herein provides a liquid processing apparatus including: at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to be connected with a tip removable from said nozzle, wherein said at least one pipette head has a liquid path of a given length ending in the pipette nozzle, and wherein the length of the liquid path can be adjusted without affecting liquid movement from the tip when the tip is engaged with the pipette nozzle.

Further, particular examples described herein may include a liquid treatment device comprising: a removable tip; and at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to be connected to a tip removable from said pipette nozzle, wherein the apparatus is operatively connected to an image capture instrument configured for capturing images within and/or through the tip.

One specific example described herein may relate to a sample processing device comprising: a sample preparation instrument, a measuring instrument and/or a detecting instrument; a control unit having computer executable commands for performing a service point service at a designated location by means of at least one of the sample preparation meter, the meter and the probe; and at least one pipette having a pipette nozzle configured to connect with a tip removable from the pipette nozzle, wherein the pipette is configured to transport no more than 250uL of liquid within or between the preparation, measurement and/or detection instruments.

According to additional embodiments described herein, a liquid treatment device may be provided. The liquid treatment device may include: a plurality of pipette heads, wherein an individual pipette head comprises a pipette nozzle configured to connect with a tip removable from the pipette nozzle, wherein the liquid handling device is capable of dispensing and/or aspirating 1uL to 5mL of liquid while functioning with a coefficient of variation of 4% or less.

According to another specific example described herein, a liquid treatment device may include: at least one pipette head operably connected to the base, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; and at least one plunger within one of the plurality of pipette heads, wherein the plunger is configured to be movable within the pipette head, wherein the pipette nozzle is movable relative to the base so as to enable the pipette nozzle to have (a) a retracted position, and (b) an extended position, wherein the pipette nozzle is farther from the base in the extended position than in the retracted position.

Additionally, particular examples described herein may relate to a liquid treatment device comprising: a support from which extend a plurality of pipette heads including a positive displacement pipette head comprising a positive displacement pipette nozzle configured to connect with a first removable tip; and an air-displacement pipette head comprising an air-displacement pipette nozzle configured to connect with an air-displacement pipette tip.

Particular examples described herein may relate to a liquid treatment device comprising: a plurality of pipette heads, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; a plurality of plungers, wherein at least one plunger is within one of the plurality of pipette heads and is configured to be movable within the pipette head, and the plurality of plungers are independently movable; and a motor configured to allow independent movement of the plurality of plungers.

Additional embodiments described herein may provide a liquid treatment device comprising: a plurality of pipette heads, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; a plurality of tip removal devices, wherein at least one tip removal device is configured to be movable relative to the pipette nozzle and configured for removing an individually selected tip from the pipette nozzle, and the plurality of tip removal devices are independently movable; and a motor configured to allow independent movement of the plurality of tip removal devices.

According to another specific example described herein, there may be provided a liquid treatment apparatus comprising: a plurality of pipette heads, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip, wherein the liquid handling device has height, width, and length dimensions that each do not exceed 20 cm.

Particular examples described herein may relate to a liquid treatment device comprising: a plurality of pipette heads, wherein an individual pipette head comprises a pipette nozzle configured to connect to a removable tip, wherein the liquid handling device is capable of dispensing and/or aspirating 1uL to 3mL of liquid while functioning with a coefficient of variation of 5% or less.

Further, according to particular examples described herein, a liquid treatment device may include: at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; and at least one motor comprising a rotor and a stator, wherein the rotor is configured to rotate about an axis of rotation, wherein the axis of rotation is substantially perpendicular to the removable tip.

Another specific example described herein may relate to a liquid processing apparatus including: at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; at least one plunger within one of the plurality of pipette heads, wherein the plunger is configured to be movable within the pipette head; and at least one motor configured to allow movement of the plurality of plungers that is not substantially parallel to the removable tip.

According to additional specific examples described herein, a liquid treatment device may include: at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; and at least one plunger within one of the plurality of pipette heads, wherein the plunger is configured to be movable within the pipette head, and wherein the plunger comprises a first section and a second section, wherein at least a portion of the first section is configured to slide relative to the second section, thereby allowing the plunger to extend and/or collapse.

Another specific example described herein may relate to a liquid processing apparatus including: at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip, wherein the at least one pipette head has a liquid path of a given length terminating at the pipette nozzle, and wherein the length of the liquid path can be adjusted without affecting liquid movement from the tip when the tip is engaged with the pipette nozzle.

According to specific examples described herein, a liquid treatment device may include: at least one pipette head operably connected to the base, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; and at least one plunger within one of the plurality of pipette heads, wherein the plunger is configured to be movable within the pipette head, wherein the pipette nozzle is movable relative to the base so as to enable the pipette nozzle to have (a) a retracted position, and (b) an extended position, wherein the pipette nozzle is farther from the base in the extended position than in the retracted position.

Further, particular examples described herein may relate to a liquid treatment method including: providing at least one pipette head operably connected to the base, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; providing at least one plunger within one of the plurality of pipette heads, wherein the plunger is configured to be movable within the pipette head; and retracting the pipette tip relative to the base in the first direction prior to and/or while translating the pipette tip in a second direction that is substantially non-parallel to the first direction.

Another embodiment described herein may provide a liquid processing method, comprising: providing at least one pipette head operably connected to the base, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; retracting and/or extending the pipette nozzle relative to the base; and dispensing and/or aspirating a liquid with the tip during said retracting and/or extending.

According to some specific examples described herein, a liquid treatment device may comprise: a support from which a plurality of pipette heads extend, the plurality of pipette heads including a first pipette head of the plurality of pipette heads, the first pipette head including a first pipette nozzle configured to connect with a first removable tip; a second pipette tip of the plurality of pipette tips comprising a second pipette nozzle configured to connect with a second removable tip; wherein the first removable tip is configured to retain a first volume of liquid and the second removable tip is configured to retain a second volume of liquid, wherein the first volume is about 250 microliters and the second volume is about 2 mL.

Particular examples described herein may relate to a liquid treatment device comprising: a support from which extend a plurality of pipette heads including a positive displacement pipette head comprising a positive displacement pipette nozzle configured to connect with a first removable tip; and a vented pipette head comprising a vented pipette nozzle configured to connect to a vented pipette tip.

Another embodiment described herein may provide a method of transporting a component within a device, comprising: providing a plurality of pipette heads, wherein an individual pipette head comprises a pipette nozzle configured to connect to a removable tip, wherein the individual pipette head is capable of dispensing and/or aspirating a liquid with the tip; engaging a sample processing assembly with at least one of the plurality of pipette heads; and transporting the sample processing assembly using at least one of the plurality of pipette heads.

According to another specific example described herein, there may be provided a liquid processing apparatus including: a removable suction head; and at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip, wherein the apparatus is operably connected to a light source that provides illumination into the tip.

Further, particular examples described herein may relate to a liquid processing apparatus including: a removable suction head; and at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip, wherein the apparatus is operably connected to an image capture instrument configured to capture images within and/or through the tip.

According to specific examples described herein, a liquid treatment device may include: a removable suction head; at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; and a processor operably connected to the removable tip and/or the at least one pipette head, wherein the apparatus is configured to change and/or maintain the position of the removable tip based on instructions from the processor.

According to specific examples described herein there may be provided a liquid treatment apparatus comprising: a movable support structure; a plurality of pipette heads sharing the movable support structure, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip, wherein the plurality of pipette heads are separated by less than or equal to 4mm from center to center.

In some embodiments, the liquid treatment device, alone or in combination with other systems, operates with a coefficient of variation of less than or equal to about 10%. In some cases, the liquid handling device is capable of metering a liquid volume of 50uL or less.

In some embodiments, the system described above includes, alone or in combination, one or more pipettes having pipette tips that are flexibly movable in a certain direction. In some cases, the pipette nozzle is spring-loaded.

In some embodiments, the system described above has the following removable tips, either alone or in combination: which is a pipette tip having an inner surface, an outer surface, and an open end.

In some embodiments, the system described above has a solenoid for each plunger, either alone or in combination, to determine whether to move an individual plunger.

In some embodiments, the systems described above have a drive (or actuation device), either alone or in combination. In some cases, the drive includes a motor. The motor may cause driving of the selected actuation means.

In some embodiments, the systems described above have liquid treatment devices, either alone or in combination. The liquid handling device may be configured to aspirate or dispense no more than 250uL of liquid at a single liquid orifice. The fluid handling device may be configured to aspirate and/or dispense fluid collected from a subject via a finger prick. In some cases, the finger stick is on a point of service device.

In some embodiments, the above systems, individually or in combination, have a plurality of plungers capable of removing at least one individually selected tip from the pipette nozzle.

In some embodiments, the system comprises, either alone or in combination, a plurality of external drive devices external to a pipette head of the system, wherein the plurality of external drive devices are capable of removing at least one individually selected tip from a pipette nozzle. In some cases, additional motors allow independent movement of the multiple external drives. In some cases, the external drive device is a collar that surrounds at least a portion of the pipette head.

In some specific examples, the above system, alone or in combination, further comprises a plurality of switches, a single switch having an on position and an off position, wherein the on position allows the plunger associated with the single switch to move in response to movement caused by the motor, and wherein the off position does not allow the plunger associated with the single switch to move in response to movement caused by the motor. In some cases, the switch is a solenoid. In some cases, the switch is operated by a cam operatively connected to the additional motor.

In some embodiments, the system described above has at least one tip structure, either alone or in combination. The at least one tip removal structure is located within the pipette head and is configured to be movable within the pipette head. In some cases, the at least one tip removal structure is located external to the pipette head. In some cases, the at least one tip removal structure is a collar that surrounds at least a portion of the pipette head. In some cases, the pipette head is capable of aspirating and/or dispensing at least 150 uL.

In some embodiments, the systems described above have liquid handling systems, either alone or in combination. The liquid treatment device has a height of no more than 1cm, or 2cm, or 3cm, or 4cm, or 5cm, or 6cm, or 7cm, or 8cm, or 9cm, or 10 cm.

In some embodiments, the system comprises a plurality of plungers, alone or in combination. At least one plunger is located within one of the plurality of pipette heads and is configured to be movable within the pipette head. In some cases, the plurality of plungers are independently movable.

In some embodiments, the above systems, alone or in combination, have a liquid handling device capable of dispensing and/or aspirating no more than a minimum increment of 0.5uL or 1 uL.

In some embodiments, the above-described system comprises, alone or in combination, a plurality of plungers, wherein at least one piston is located within and configured to be movable within one of the plurality of pipette heads. In some cases, the plurality of plungers are independently movable. In some cases, the system includes a motor configured to allow the plurality of plungers to move independently.

In some embodiments, a single pipette tip of the plurality of pipette tips included in the above-described systems is capable of dispensing and/or aspirating 1uL to 3mL of liquid.

In some cases, the liquid handling devices described above have motors (or other drives) with horizontal axes of rotation, alone or in combination. In some cases, the removable tip of the liquid handling device is vertically aligned. In some cases, the liquid handling device comprises at least one plunger located within one of the plurality of pipette heads, wherein the plunger is configured to be movable within the pipette head; and at least one motor configured to allow movement of the plurality of plungers substantially non-parallel to the removable tip. In some cases, the plunger is movable in a direction substantially perpendicular to the removable tip. In some cases, the plunger is movable in a horizontal direction, and wherein the removable tip is vertically aligned.

In some embodiments, the liquid treatment device comprises a first section and a second section. The first section is configured to slide within the second section. The liquid treatment device may further comprise a heat sink surrounding the plunger of the liquid treatment device.

In some embodiments, the liquid handling device comprises at least one pipette head, wherein a single pipette head comprises a pipette nozzle configured to connect with a removable tip, wherein the at least one pipette head has a liquid path of a given length terminating at the pipette nozzle, and wherein the length of the liquid path can be adjusted when the tip is engaged with the pipette nozzle without affecting liquid movement from the tip.

The pipette nozzle is movable relative to a base operably connected to the at least one pipette head to adjust the liquid path length. In some cases, the liquid pathway is formed using a rigid component. In some cases, the liquid pathway is formed without the use of a flexible member.

In some cases, the liquid handling device further comprises a vent port in the pipette head. The vent port can have an open position and a closed position. In some cases, the vent solenoid determines whether the vent port is in an open position or a closed position. The valve may determine whether the vent port is in an open position or a closed position. The duty cycle of the valve may have a period of less than or equal to 50 ms.

In some cases, the vent port is coupled to a positive pressure source for draining liquid. The vent port may be coupled to a source of negative pressure for drawing the liquid.

In some cases, the vent port is coupled to atmospheric conditions. The ventilation port may be coupled to a switchable pump capable of providing positive or negative pressure. The pressure source is capable of providing positive or negative pressure for an extended period of time. In some cases, the removable tip includes two openings, each with a recessed passive valve. In some cases, the embedded passive valve is configured to allow liquid to flow in one direction through the first opening, through the tip body, and through the second opening.

In some cases, there is a vertical difference of at least 2cm between the retracted position and the extended position.

In some embodiments, the pipette nozzle is movable relative to the at least one plunger. In some cases, adjusting the pipette nozzle between the retracted position and the extended position changes the length of the liquid path terminating at the pipette nozzle. The liquid path is formed using only a rigid component.

In some specific examples, the plunger comprises a first section and a second section, wherein at least a portion of the first section is located within the second section when the pipette nozzle is in the retracted position, and wherein the first section is not within the second section when the pipette nozzle is in the extended position.

In some embodiments, the methods described above, alone or in combination, include extending a pipette nozzle relative to a base prior to and/or concurrently with dispensing and/or aspirating a liquid with a tip.

In some embodiments, a liquid treatment method includes: providing at least one pipette head operably connected to the base, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; providing at least one plunger within one of the plurality of pipette heads, wherein the plunger is configured to be movable within the pipette head; and retracting the pipette tip relative to the base in the first direction prior to and/or while translating the pipette tip in a second direction substantially non-parallel to the first direction. The first direction and the second direction may be substantially perpendicular. In some cases, the first direction is a substantially vertical direction and the second direction is a substantially horizontal direction.

In some embodiments, a liquid treatment method includes: providing at least one pipette head operably connected to the base, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; retracting and/or extending the pipette nozzle relative to the base; and dispensing and/or aspirating a liquid with the tip during said retracting and/or extending. In some cases, the method further comprises providing at least one plunger within one of the plurality of pipette heads, wherein the plunger is configured to be movable within the pipette head and/or to effect the dispensing and/or aspirating. In some cases, the method further comprises providing a motor that causes the at least one plunger to move within the pipette head. In some cases, the base supports at least one pipette tip. In some cases, the pipette nozzle may slide in a linear direction. The pipette nozzle may be retractable and/or extendable in a vertical direction relative to the base.

In some embodiments, a liquid handling device includes a first pipette head and a second pipette head. In some cases, the first pipette tip is a positive displacement pipette tip and the second pipette tip is a vented pipette tip.

In some embodiments, a method for transporting a component within a facility includes: providing a plurality of pipette heads, wherein an individual pipette head comprises a pipette nozzle configured to connect to a removable tip, wherein the individual pipette head is capable of dispensing and/or drawing liquid with the tip; engaging a sample processing assembly with at least one of the plurality of pipette tips; and transporting the sample processing assembly using at least one of the plurality of pipette heads. In some cases, the sample processing component is a sample preparation unit or component thereof, an assay unit or component thereof, and/or a detection unit or component thereof. In some cases, the sample processing assembly is a holder for a plurality of removable tips and/or containers. In some cases, the hardware component is picked up using a press fit between one or more pipette heads and features of the hardware component. In some cases, the hardware assembly is picked up using suction provided by one or more pipette heads and features of the hardware assembly.

In some embodiments, a liquid treatment device comprises: a removable suction head; and at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip, wherein the apparatus is operably connected to a light source that provides illumination into the tip. In some cases, the tip forms a waveguide that can provide light to the liquid contained therein through the tip, or can transmit a light signal from the liquid through the tip. In some cases, the removable tip is formed from an optically transparent material. In some cases, the liquid handling device further comprises at least one plunger located within one of the plurality of pipette heads, wherein the plunger is configured to be movable within the pipette head. In some cases, the pipette nozzle is formed with a transparent surface and/or a reflective surface. In some cases, the light source is within the device. In one example, the light source is within at least one pipette head. In some cases, the tip comprises a fiber that conducts the light. In one example, the fibers are formed of an optically transparent material. In some cases, the fibers extend along the length of the removable tip. In some cases, the optical fiber is embedded within a removable tip.

In some embodiments, a liquid handling device includes a removable tip; and at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip, wherein the apparatus is operably connected to an image capture instrument configured to capture images within and/or through the tip.

In some cases, the image capture instrument is located within the device. In some cases, the image capture instrument is located within at least one pipette tip.

In some cases, the image capture instrument is integral with the device. In some cases, the image capture instrument is a camera.

In some embodiments, the image capturer is capable of capturing electromagnetic radiation and generating an image with one or more of the visible spectrum, the infrared spectrum, the ultraviolet spectrum, the gamma spectrum.

In some cases, the liquid handling device further comprises at least one plunger located within one of the plurality of pipette heads, wherein the plunger is configured to be movable within the pipette head. The image capture instrument may be located at the end of the plunger. The plunger may comprise (or be formed from) a light-transmissive material. The plunger may be made of a transparent material.

In some cases, the pipette nozzle is formed with a transparent surface and/or a reflective surface.

In some cases, the liquid treatment device further comprises a processor located on the device.

In some cases, the liquid handling device further includes a processor located on the image capture instrument.

In some embodiments, a liquid treatment device comprises: a removable suction head; at least one pipette head, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip; and a processor operably connectable to the removable tip and/or the at least one pipette head, wherein the apparatus is configured to change and/or maintain the position of the removable tip based on instructions from the processor.

In some cases, the removable tip includes a processor. In some cases, the at least one pipette head comprises a processor. In some implementations, the first processor of the first removable tip of the device is in communication with the second processor of the second removable tip.

In some embodiments, a liquid treatment device comprises: a movable support structure; a plurality of pipette heads sharing the movable support structure, wherein an individual pipette head comprises a pipette nozzle configured to connect with a removable tip, wherein the plurality of pipette heads are separated by less than or equal to 4mm from center to center.

In some cases, the liquid handling device further comprises a plurality of plungers, wherein at least one plunger is located within one of the plurality of pipette heads and is configured to be movable within the pipette head.

In some cases, the liquid handling device further comprises a plurality of diaphragms driven by the transducer, the diaphragms enabling dispensing and/or aspiration of liquid through the removable tip.

In some cases, the plurality of pipette tips are movable along the support structure so that the lateral distance between the plurality of pipette tips is variable.

The embodiments described herein provide a method for diagnosing or treating a subject with a point of service system, comprising (a) authenticating the subject; (b) obtaining a three-dimensional depiction of the subject by means of a three-dimensional imaging device; (c) displaying, by means of a computer system comprising a processor, the three-dimensional depiction to a healthcare provider in remote communication with the subject, wherein the system is communicatively coupled to the three-dimensional imaging device; and (d) diagnosing or treating the subject by means of the displayed three-dimensional depiction of the subject.

Another embodiment described herein provides a point of service system for diagnosing or treating a subject, comprising: a service point having a three-dimensional imaging device for providing a dynamic three-dimensional space temple session of a subject; and a remote computer system configured for communicating with the three-dimensional imaging device and for retrieving the dynamic three-dimensional spatial representation of the subject, wherein the remote computer system is in turn or is configured for authenticating the subject.

Particular examples described herein provide a method for diagnosing or treating a subject with a point of care system, comprising: authenticating the subject; obtaining a three-dimensional description of the subject by means of a three-dimensional imaging device; providing the three-dimensional description to a display of a computer system of a healthcare provider, the computer system being communicatively coupled to the three-dimensional imaging device, the healthcare provider in remote communication with the subject; and diagnosing or treating the subject by means of the three-dimensional description on the display of the computer system.

Additional embodiments described herein provide a point of service system for diagnosing or treating a subject, comprising: a point of service device having a three-dimensional imaging means for providing a dynamic three-dimensional spatial description of a subject; and a remote computer system in communication with the three-dimensional imaging device, the remote computer system for authenticating the subject and retrieving a dynamic three-dimensional spatial description of the subject after said authenticating.

Further, particular examples described herein may be directed to a method for measuring percent body fat in a subject, comprising: providing a service point device having a touch screen; placing a first finger on a first side of the touch screen and a second finger on a second side of the touch screen; directing an electrical current from the service point through the subject's body, wherein the electrical current is directed through the subject's body by the first finger and the second finger; and determining the body fat percentage of the subject by measuring the electrical resistance between the first finger and the second finger with the aid of an electrical current directed through the body of the subject.

According to another specific example described herein, there may be provided a method for diagnosing a subject, the method comprising: providing a service point device having a touch screen; placing a first finger on a first side of the touch screen and a second finger on a second side of the touch screen; directing an electrical current from the service point through the subject's body, wherein the electrical current is directed through the subject's body by the first finger and the second finger; measuring the electrical resistance between the first finger and the second finger by means of an electrical current directed through the body of the subject; and diagnosing the subject based on the determined electrical resistance.

In some embodiments, the above methods, alone or in combination, comprise contacting the subject with a selected healthcare provider for the subject.

In some cases, diagnosing or treating the subject comprises contacting the subject with a healthcare provider of the subject. In some cases, diagnosing includes providing the diagnosis in real-time.

In some embodiments, the three-dimensional imaging device is part of a service point system.

In some embodiments, the methods described above, alone or in combination, further comprise identifying the subject prior to diagnosis or treatment.

In some embodiments, the above methods, alone or in combination, comprise identifying the subject by verifying a fingerprint of the subject.

In some embodiments, the methods described above, alone or in combination, comprise diagnosing or treating a subject using a touch screen display.

In some cases, diagnosing or treating comprises collecting a sample from the subject. In some cases, a sample is taken from a subject at the site of a healthcare provider. The sample may be collected from the subject at the subject's site.

In some cases, the point of service system includes an image recognition module for analyzing at least a portion of the dynamic three-dimensional spatial description of the subject for treatment. In some cases, the authentication is performed by way of one or more of a biometric scan, an insurance card of the subject, a name of the subject, a driver's license of the subject, an identification card of the subject, an image of the subject taken by way of a camera in the point-of-care system, and a gesture recognition device.

In some embodiments, the methods described above, alone or in combination, comprise diagnosing the subject by contacting the subject with a selected healthcare provider for the subject.

In some embodiments, the methods described above, alone or in combination, further comprise combining the three-dimensional description of the subject with subject-specific information. The combining may be made by means of a processor. In some cases, the point of service system includes an image recognition module for analyzing at least a portion of the dynamic three-dimensional spatial description of the subject for treatment.

In some cases, the system includes a touch screen. The touch screen may be a capacitive touch screen or a resistive touch screen. In some cases, the touch screen is at least a 60-point touch screen.

In some embodiments, for one or more of the above methods or other methods provided herein, the first finger is on a first hand of the subject and the second finger is on a second hand of the subject.

In some embodiments, the methods described above, alone or in combination, comprise diagnosing the subject by providing a percentage of body fat of the subject.

According to particular examples described herein, a container may include: a body configured to receive and confine a sample, wherein the body comprises an inner surface, an outer surface, an open end, and a tapered closed end, wherein the container is configured to engage with a pipette and comprises a soft material extending through the open end and having a slit/opening configured to prevent liquid from passing through the soft material when no object is inserted through the slit/opening.

Particular examples described herein may relate to a container comprising: a body configured to receive and confine no more than about 100 μ Ι _ of sample, wherein the body comprises an inner surface, an outer surface, and an open end, wherein the container comprises a soft material extending through the open end and having a slit/opening configured to prevent liquid from passing through the soft material when no object is inserted through the slit/opening.

According to additional specific examples described herein, there may be provided a container comprising: a body configured to receive and confine a sample, wherein the body comprises an inner surface, an outer surface, a first port, a second port, and a passageway between the first port and the second port, wherein the container comprises a material extending through the passageway, the material capable of having (1) a molten state configured to prevent liquid from passing through the material when no object is inserted through the material, and (2) a solid state configured to prevent liquid and the object from passing through the material.

Additionally, embodiments described herein may provide an injection mold plate comprising a base plate comprising a planar surface and a plurality of projections; and a counter mold comprising a plurality of indentations, wherein the projections are configured to be positioned within the indentations, wherein an individual projection of the plurality of projections comprises a cylindrical portion of a first diameter, and a funnel portion in contact with the cylindrical portion, wherein an end of the funnel portion in contact with the cylindrical portion has the first diameter and a second end of the funnel portion in contact with the planar surface has a second diameter.

According to additional specific examples described herein, a system may include: a container configured to receive and confine a sample, wherein the container comprises an inner surface, an outer surface, an open end, and an opposing closed end; and a tip configured to extend into the vessel through the open end, wherein the tip comprises a first open end and a second open end, wherein the second open end is inserted into the vessel, wherein the vessel or the tip further comprises, in addition to or at or near the closed end, a raised surface feature that prevents the second open end of the tip from contacting the bottom of the interior surface of the closed end of the vessel.

In some embodiments, the containers provided above or elsewhere herein comprise a soft material. In some cases, the soft material is a film. In some cases, the soft material is formed from a silicon-based material.

In some embodiments, the container provided above or elsewhere herein includes a lid configured to contact the body at the open end, wherein at least a portion of the lid extends into the interior of the body. In some cases, the cover includes a passage through which the soft material extends.

In some embodiments, the container provided above or elsewhere herein includes a body having a cylindrical portion of a first diameter with an open end and a closed end, and a funnel portion in contact with the open end, wherein one end of the funnel portion in contact with the open end has a first diameter and a second port of the funnel portion has a second diameter. In some cases, the second diameter is less than the first diameter. In other cases, the second diameter is greater than the first diameter. In other cases, the second diameter is equal to the first diameter. In some cases, the second port of the funnel portion is configured to engage with a removable cap.

In some embodiments, the container provided above or elsewhere herein comprises a flexible material that is a film. In some cases, the soft material is formed from a silicon-based material.

In some embodiments, the container provided above or elsewhere herein includes a lid configured to contact the body at the open end, wherein at least a portion of the lid extends into the interior of the body. In some cases, the cover includes a passage through which the soft material extends.

In some embodiments, the container provided above or elsewhere herein includes a body having a cylindrical portion of a first diameter with an open end and a closed end, and a funnel portion in contact with the open end, wherein one end of the funnel portion in contact with the open end has a first diameter and a second port of the funnel portion has a second diameter. In some cases, the second diameter is less than the first diameter. In other cases, the second diameter is greater than the first diameter. In some cases, the second port of the funnel portion is configured to engage with a removable cap.

In some embodiments, the container provided above or elsewhere herein comprises a material extending through the passageway, the material capable of having (1) a molten state configured to prevent liquid from passing through the material when no object is inserted through the material, and (2) a solid state configured to prevent liquid and the object from passing through the material. In some cases, the material is a wax. In some cases, the material has a melting point between about 50 ℃ and 60 ℃. In some cases, the object can be inserted through and removed from the material while the material is in a molten state. In some cases, the material is configured to allow the object to be inserted into and removed from the material while the material is in a molten state. In some embodiments, at least a portion of the object is coated with the material when the object is removed from the material.

In some embodiments, an injection mold plate comprises a base plate comprising a planar face surface and a plurality of projections; and a counter mold comprising a plurality of indentations, wherein the projections are configured to be positioned within the indentations, wherein an individual projection of the plurality of projections comprises a cylindrical portion of a first diameter, and a funnel portion in contact with the cylindrical portion, wherein an end of the funnel portion in contact with the cylindrical portion has the first diameter and a second end of the funnel portion in contact with the planar surface has a second diameter. In some cases, the plurality of projections are arranged in an array. In some cases, the projections have a volume of less than or equal to 100 microliters ("uL"), 50uL, 20uL, 10uL, or 1 uL. In some cases, the indentation includes a cylindrical portion and a funnel portion contacting the cylindrical portion.

In some embodiments, the systems provided above, such as the containers, individually or in combination, include surface features integrally formed on the bottom of the inner surface of the container. In some embodiments, the surface feature is a plurality of bumps on the bottom of the interior surface of the container.

In some embodiments, the devices provided above, alone or in combination, comprise a planar base plate comprising a plurality of wells; and a plurality of tips having the configurations provided above or elsewhere herein, wherein the tips are at least partially inserted into the plurality of wells and supported by a base plate. In some cases, the device forms a microtiter plate.

In some embodiments described herein, there may be provided a centrifuge comprising: a base having a bottom surface, the base configured to rotate about an axis orthogonal to the bottom surface, wherein the base comprises one or more wings configured to fold over an axis extending through the base, wherein the wings comprise an entire portion of the base on one side of the axis, wherein the wings comprise cavities to receive sample containers, wherein the sample containers are oriented in a first orientation when the base is stationary and are configured to be oriented in a second orientation when the base is rotated.

According to particular examples described herein, a centrifuge includes: a base having a bottom surface and a top surface, the base configured to rotate about an axis orthogonal to the bottom surface, wherein the base comprises one or more buckets configured to pivot about pivots configured to allow at least a portion of the buckets to pivot upwardly past the top surface, and wherein the buckets comprise cavities to receive sample containers, wherein the cavities are configured to face a first orientation when the base is stationary and are configured to face a second orientation when the base is rotating.

Further, particular examples described herein may relate to a centrifuge comprising: a base having a bottom surface and a top surface, the base configured to rotate about an axis orthogonal to the bottom surface, wherein the base comprises one or more buckets configured to pivot about a pivot, and the buckets are attached to a counterweight configured to move in a linear direction, causing the buckets to pivot, and wherein the buckets comprise a cavity to receive a sample container, wherein the cavity is configured to face a first orientation when the base is stationary, and is configured to face a second orientation when the base is rotating.

According to another specific example described herein, a centrifuge may comprise: a brushless motor assembly including a rotor configured to rotate about a rotation axis with respect to a stator; and a base comprising one or more cavities configured to receive one or more liquid samples, the base being fixed to the rotor, wherein the base rotates about the stator and a plane orthogonal to a rotational axis of the brushless motor is coplanar with a plane orthogonal to a rotational axis of the base.

Particular examples described herein may relate to a centrifuge comprising: a brushless motor assembly including a rotor configured to rotate about a rotation axis with respect to a stator, wherein the brushless motor has a height in a direction of the rotation axis; and a base comprising one or more cavities configured to receive one or more liquid samples, the base being fixed to the rotor, wherein the base rotates about the stator and the base has a height in the direction of the axis of rotation, and wherein the height of the brushless motor assembly is no more than twice the height of the base.

According to another specific example described herein, there may be provided a system comprising: at least one module mounted on the support structure, wherein the at least one module comprises a sample preparation meter, a measurement meter and/or a detection meter; and a controller operably coupled to the at least one module and an electronic display having a Graphical User Interface (GUI) for enabling a subject to interact with the system, wherein the system is configured to perform (a) at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, magnetic separation, and chemical processing, and (b) multiple types of assays selected from the group consisting of immunoassays, nucleic acid assays, receptor assays, cell count assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, nephelometric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, and the like, Histological assays, culture assays, osmolarity assays, and combinations thereof.

Particular examples described herein may relate to a system comprising: a support structure having a mounting configured to support one of a plurality of modules, the individual module configured to perform (i) at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, magnetic separation, and/or (ii) at least one type of assay selected from the group consisting of immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographical assays, calorimetric assays, nephelometric assays, agglutination assays, radioisotope assays, viscometric assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof; a controller operably coupled to the plurality of modules, wherein the controller is configured to provide one or more instructions to the module or individual ones of the plurality of modules to facilitate performance of the at least one sample preparation procedure or the at least one type of assay; and an electronic display operably coupled to the controller, the electronic display having a Graphical User Interface (GUI) for enabling a subject to interact with the system.

The systems described above or elsewhere herein, alone or in combination, may comprise a plurality of modules mounted on a support structure, with individual ones of the plurality of modules comprising a sample prep instrument, a meter, and/or a probe. A single module may be configured to perform the at least one sample preparation procedure and/or the at least one type of assay without resorting to another module in the systems described above or elsewhere herein, either alone or in combination.

In some systems of the foregoing or elsewhere herein, alone or in combination, the controller may be mounted on the support structure.

The GUI provided in the system above or elsewhere herein, alone or in combination, may be configured to provide a guided questionnaire to the subject.

In the systems described above or elsewhere herein, alone or in combination, the guidance questionnaire can include one or more graphical and/or textual items. In some embodiments, the guidance questionnaire may be configured to collect information from the subject selected from the group consisting of dietary intake, exercise, health condition, and mental condition.

In the systems described above or elsewhere herein, alone or in combination, the electronic display can be mounted on a support structure. In some embodiments, the electronic display may be mounted on a support structure of a remote system, such as the systems described above or elsewhere herein, alone or in combination. According to some embodiments described herein, the electronic display may be an interactive display. In the systems described above or elsewhere herein, alone or in combination, the interactive display may be a capacitive touch display or a resistive touch display.

A communication module may be operatively coupled to the controller for enabling the system to communicate with a remote system, which may include the above systems or elsewhere herein, alone or in combination.

The system of the foregoing or elsewhere herein, alone or in combination, can further comprise a database operatively coupled to the controller for storing information relating to dietary intake, exercise, health condition, and/or mental condition of the subject.

Particular examples described herein relate to a method of evaluating a biological sample taken from a subject, the method comprising: (a) receiving data transmitted from a device placed on or in a subject or at a retail site, wherein the device is configured to process a biological sample by: (i) receiving a biological sample; (ii) preparing a biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for subsequent qualitative and/or quantitative evaluation of the biological sample; and (iii) electronically transmitting data to an authorized analytical facility and/or an accessory thereof for performing the subsequent qualitative and/or quantitative evaluation; and (b) analyzing the data transmitted from the device at an authorized analysis facility and/or an accessory thereof to provide the qualitative and/or quantitative assessment of the biological sample.

According to another specific example described herein, a method of evaluating a biological sample collected from a subject can comprise: (a) receiving electronic data representing an image of said biological sample and/or an image of a physical process or chemical reaction with said biological sample or a part thereof, said data being transmitted from a device placed in or on a subject or in a designated sample acquiring apparatus, wherein the device is configured for processing a biological by: (i) receiving a biological sample; (ii) preparing a biological sample for subsequent qualitative and/or quantitative evaluation, wherein said preparing generates electronic data representative of an image of said biological sample and/or an image of said physical process or chemical reaction; and (iii) transmitting electronic data representative of said image to an authorized analytical facility and/or an accessory thereof for performing said subsequent qualitative and/or quantitative evaluation; wherein the process generates electronic data representative of an image necessary for subsequent qualitative and/or quantitative evaluation of said biological sample, and (b) analyzes the electronic data representative of an image transmitted from said apparatus at an authorized analysis facility and/or an accessory thereof to provide said qualitative and/or quantitative evaluation of said biological sample. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

According to another embodiment described herein, a method of evaluating multiple types of biological samples collected from a subject can be provided. The method can comprise the following steps: (a) receiving data transmitted from a device placed in or on a subject or on a designated sample acquisition instrument, wherein the device is configured to process multiple types of biological samples by: (i) receiving a plurality of types of biological samples; (ii) (ii) preparing a biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for said subsequent qualitative and/or quantitative evaluation of said plurality of types of biological samples, and (iii) electronically transmitting the data to an authorized analysis facility and/or an accessory thereof for performing said subsequent qualitative and/or quantitative evaluation; and (b) analyzing the data transmitted from the device at an authorized analysis facility and/or an accessory thereof to provide the qualitative and/or quantitative assessment of the plurality of types of biological samples.

Additional specific examples described herein can relate to a method of evaluating a biological sample taken from a subject at a specified location, the method comprising: (a) collecting and processing a biological sample at the designated location, wherein the sample is collected by a device configured to (i) receive the biological sample; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for subsequent qualitative and/or quantitative evaluation of the biological sample, and (iii) transmitting the data to a healthcare provider of an authorized analytical facility and/or an accessory device thereof for performing the subsequent qualitative and/or quantitative evaluation; and (b) transmitting data to an authorized analysis facility and/or an accessory thereof; and (c) analyzing the data transmitted from the device at an authorized analysis facility and/or an accessory thereof to provide the qualitative and/or quantitative assessment of the biological sample.

Further, particular examples described herein may relate to a method of evaluating a biological sample collected from a subject, the method comprising: (a) receiving data transmitted from a device placed in or on a subject or on a designated sample acquisition instrument, wherein the device is configured to process a biological sample by: (i) receiving a biological sample; (ii) preparing a biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for subsequent qualitative and/or quantitative evaluation of the biological sample; and (iii) transmitting the data to a healthcare provider of an authorized analytical facility and/or an accessory thereof for performing said subsequent qualitative and/or quantitative evaluation; and (b) analyzing data transmitted from the device at an authorized analysis facility and/or an accessory thereof to provide the qualitative and/or quantitative assessment of the biological sample; and (c) verifying (x) whether the subject receives a prescription request from a healthcare professional to perform the subsequent qualitative and/or quantitative evaluation of the biological sample, or (y) whether the prescription for the subsequent qualitative and/or quantitative evaluation of the biological sample is within the regulatory limits of the subsequent qualitative and/or quantitative evaluation by a payer or prescribing physician, and/or (z) whether the subject is within the coverage of health insurance for the subsequent qualitative and/or quantitative evaluation of the biological sample; wherein the step of verifying is performed before, after or simultaneously with step (a) and/or (b).

According to another embodiment described herein, a method of conducting a pathology study of a biological sample taken from a subject can be provided. The method can comprise the following steps: (a) receiving electronic data representing an image of the biological sample, a physical process and/or a chemical reaction performed with the biological sample or a portion thereof, wherein the data is received from a device placed in or on a subject or a designated sample acquisition instrument, wherein the device is configured to: (i) receiving the biological sample; (ii) preparing an acquired biological sample for subsequent qualitative and/or quantitative evaluation, wherein said preparing generates electronic data representative of an image of said biological sample and/or chemical reaction; and (iii) transmitting the electronic data representative of the image to a pathologist authorized to analyze the facility and/or its accessories; and (b) analyzing the electronic data by a pathologist of an authorized analytical facility and/or its accessories to provide said qualitative and/or quantitative assessment.

Additional embodiments described herein can relate to a method of conducting a pathology study of a biological sample collected from a subject, which can include: (a) receiving electronic data from an image representative of the biological sample and/or a chemical reaction with at least one component from the biological sample from a device placed in or on a subject or in a designated sample acquisition instrument, wherein the device is configured to: (i) receiving the biological sample; (ii) preparing an acquired biological sample for subsequent qualitative and/or quantitative evaluation, wherein said preparing generates electronic data representative of an image of said biological sample and/or chemical reaction; and (iii) transmitting the electronic data representative of the image to a pathologist at an authorized analytical facility; (b) the electronic data is analyzed by a pathologist of an authorized analytical facility to provide said subsequent qualitative and/or quantitative evaluation.

Further, particular examples described herein may relate to a method of evaluating a biological sample collected from a subject, the method comprising: (a) receiving data transmitted from a device placed in or on a subject or on a designated sample acquisition instrument, wherein the device is configured to process a biological sample by: (i) receiving a biological sample; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of said biological sample, and (iii) electronically transmitting the data to an authorized analytical facility and/or an accessory thereof; (b) analyzing the data transmitted from the device at an authorized analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative evaluation of the biological sample. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

Additional embodiments described herein can relate to a method of evaluating a biological sample collected from a subject, the method comprising: (a) receiving data transmitted from a device placed in or on a subject or at a retailer site, wherein the device is configured to process a biological sample by: (i) receiving a biological sample; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of said biological sample, and (iii) electronically transmitting the data to an authorized analytical facility and/or an accessory thereof; and (b) analyzing the data transmitted from the device at an authorized analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative evaluation of the biological sample.

According to additional specific examples described herein, a method of evaluating a biological sample can comprise: (a) processing a biological sample collected from a subject by means of a device, wherein the device is placed in or on the subject or in a designated sample collector, wherein said processing generates data necessary for a subsequent qualitative and/or quantitative evaluation of said biological sample, and wherein the device is configured for (i) receiving the biological sample; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation, and (iii) transmitting the data to an authorized analytical facility and/or an accessory thereof; (b) transmitting data from the device at an authorized analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative evaluation of the biological sample; and (c) verifying whether the subject is covered by medical insurance coverage, wherein the verifying step is performed before, after, or simultaneously with steps (a) and/or (b).

According to another embodiment described herein, a method of evaluating a biological sample collected from a subject may be provided. The method can comprise the following steps: (a) receiving electronic data representing an image of said biological sample and/or a chemical reaction with at least one component from said biological sample transmitted from a device placed in or on a subject or in a designated sample acquisition instrument, wherein the device is configured for processing the biological sample by: (i) receiving the biological sample; (ii) preparing a biological sample for subsequent qualitative and/or quantitative evaluation, wherein said preparing generates electronic data representative of an image of said biological sample and/or chemical reaction; and (iii) transmitting the electronic data representative of the image to an authorized analytical facility and/or an accessory thereof; wherein the processing generates electronic data representative of an image necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample, and (b) analyzes the electronic data representative of an image transmitted from the apparatus at an authorized analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative evaluation of the biological sample. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

An additional specific example can relate to a method of evaluating a biological sample collected from a subject, the method comprising: (a) receiving data transmitted from a device placed in or on a subject or on a designated sample acquisition instrument, wherein the device is configured to process a biological sample by: (i) receiving a biological sample; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of said biological sample, and (iii) transmitting the data to a healthcare provider of an authorised analysis facility and/or an accessory device thereof; and (b) analyzing the data transmitted from the device at an authorised analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative assessment of the biological sample; (c) verifying whether the subject received a prescription from a healthcare professional requiring said subsequent qualitative and/or quantitative evaluation of said biological sample, wherein said verifying step is performed before, after or simultaneously with steps (a) and/or (b).

In addition, particular examples described herein may relate to a method of evaluating a biological sample, the method comprising: (a) processing a biological sample collected from a subject who has received a prescription requiring a subsequent qualitative and/or quantitative evaluation of the biological sample by means of a device, wherein the device is placed in or on the subject or in a designated sample collector, wherein said processing generates data necessary for the subsequent qualitative and/or quantitative evaluation of said biological sample, and wherein the device is configured for (i) receiving the biological sample; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation, and (iii) transmitting the data to an authorised analysis facility and/or an accessory device thereof; (b) transmitting data from the device for analysis at an authorized analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative evaluation of the biological sample; and (c) verifying whether the prescription for the subsequent qualitative and/or quantitative evaluation of the biological sample is within the regulatory limits of the subsequent qualitative and/or quantitative evaluation by a payer or prescribing physician, wherein the verifying step is performed before, after, or simultaneously with steps (a) and/or (b). By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

Another specific example described herein provides a method of evaluating a biological sample collected from a subject, the method comprising: (a) receiving data transmitted from a device placed in or on a subject or on a designated sample acquisition instrument, wherein the device is configured to process a biological sample by: (i) receiving a biological sample; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate information necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample, and (iii) electronically transmitting the data to an authorized analytical facility and/or an accessory thereof; and (b) analyzing the data transmitted from the device at an authorized analytical facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative assessment of the biological sample, wherein the subsequent qualitative and/or quantitative assessment of the biological sample results in a determination of the presence or concentration of one or more analytes selected from the group consisting of: sodium, potassium, chloride, TCO₂Anionic interstitium, ionic calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO₂、PO₂、HCO₃Alkali residue, sulfur dioxide, kaolin ACT, diatomaceous earth ACT, PT/INR, cTnl, CK-MB, or BNP.

In addition, particular examples described herein may relate to a method of evaluating multiple types of biological samples collected from a subject, the method comprising: (a) receiving data transmitted from a device placed in or on a subject or on a designated sample acquisition instrument, wherein the device is configured to process multiple types of biological samples by: (i) receiving a plurality of types of biological samples; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of said plurality of types of biological sample, and (iii) electronically transmitting the data to an authorized analytical facility and/or an accessory thereof; and (b) analyzing the data transmitted from the device at an authorized analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative evaluation of the plurality of types of biological samples.

In the practice of any of the methods described above or elsewhere herein, either alone or in combination, qualitative and/or quantitative evaluation of the biological sample can be achieved without the need to transport the sample from the site at which the sample is collected to an authorized analytical facility and/or an ancillary device thereof.

The methods described above or elsewhere herein may include, alone or in combination, methods wherein the biological sample is selected from the group consisting of: blood, serum, plasma, nasal swab sampling or nasopharyngeal irrigation, saliva, urine, tears, gastric fluid, spinal fluid, stool, mucus, sweat, cerumen, oil, glandular secretions, cerebrospinal fluid, tissue, semen, and vaginal secretions, pharyngeal swab sampling, respiration, hair, nails, skin, biopsy, placental fluid, amniotic fluid, umbilical cord blood, emphatic fluid, body cavity fluid, sputum, mucus, pus, microflora, meconium, milk, and/or other excretions.

Any of the above or elsewhere herein methods can be practiced, alone or in combination, wherein the biological sample has a volume of 250 microliters (uL) or less.

In the individual or combined implementations of the methods above or elsewhere herein, the methods may further include the step of providing supervision by a health care professional of an authorized analytical facility and/or by a software program.

In some embodiments, the methods described above or elsewhere herein, alone or in combination, further comprise verifying insurance eligibility of the subject prior to, after, or simultaneously with the analysis.

The methods above or elsewhere herein, alone or in combination, may further comprise generating a report comprising a treatment analysis of the subject based on the qualitative and/or quantitative assessment.

In the practice of the above or elsewhere herein, alone or in combination, the analysis can determine the presence or concentration of an analyte present in the biological sample.

The methods provided above or elsewhere herein may include, alone or in combination, an analyte selected from the group consisting of: proteins, nucleic acids, drugs, drug metabolites, gases, ions, particles, small molecules and metabolites thereof, elements, toxins, lipids, carbohydrates, prions, tangible elements, and combinations thereof.

A given sample collector may be a retail site or a doctor's office, implemented according to any of the methods described above or elsewhere herein, alone or in combination. In some embodiments, a given sample collector can be the subject's home when any of the methods described above or elsewhere herein are performed, alone or in combination. In the methods described above or elsewhere herein, alone or in combination, the designated sample acquiring instrument may be an employer's site, provider's office, or hospital.

In the implementations of the methods described above or elsewhere herein, either alone or in combination, the aggregated data can be provided to produce a longitudinal analysis over time.

The methods described above or elsewhere herein may utilize biological samples collected from a finger prick, either alone or in combination.

In implementations of the methods described above or elsewhere herein, alone or in combination, processing of the biological sample does not involve, in some cases, display of expression or concentration levels of one or more analytes selected for determination of a cardiac marker, chemical constituent, blood gas, electrolyte, lactate, hemoglobin, coagulation, or hematology.

The methods described above or elsewhere herein may include, alone or in combination, a device configured to verify whether a subject is within the coverage of medical insurance for the qualitative and/or quantitative assessment of the biological sample.

In a separate or combined implementation of any of the methods above or elsewhere herein, the device may be configured to verify whether the subject has received a prescription request from a healthcare professional to perform said qualitative and/or quantitative evaluation of said biological sample.

In some embodiments, the methods described above or elsewhere herein, alone or in combination, may comprise a device configured to verify the identity of a subject prior to receiving a biological sample, electronically transmitting data, or analyzing the transmitted data. In some embodiments, the verification of the identity of the subject may comprise receiving a genetic signature of the subject. In some of the methods described above or elsewhere herein, alone or in combination, the genetic marker can be obtained by nucleic acid amplification of a biological sample from the subject. In the individual or combined implementations of the methods above or elsewhere herein, the verification of the identity of the subject may comprise one or more biometric measurements of the subject. In some embodiments of the methods described above or elsewhere herein, alone or in combination, the verification of the identity of the subject can be performed by an authorized technician.

In a separate or combined implementation of the above or elsewhere herein, the identity of an authorized technician may be verified prior to receiving a biological sample, electronically transmitting data, or analyzing the transmitted data.

In a separate or combined implementation of the above or elsewhere herein, the apparatus may be configured to receive one or more cartridges configured for qualitative and/or quantitative evaluation as required by a medical care professional.

In some embodiments, one or more of the methods described above or elsewhere herein, alone or in combination, can provide a cartridge with one or more identifiers readable by the device.

The method above or elsewhere herein, alone or in combination, may further comprise receiving identifier information from the device.

Performing the above or elsewhere herein, either alone or in combination, may further comprise providing one or more protocols to the device based on the received identifier information, wherein the protocols affect preparation of the biological sample.

The device may be contained within a housing, in the practice of the above or elsewhere herein, either alone or in combination.

The methods described above or elsewhere herein may include, alone or in combination, qualitative and/or quantitative assessments that involve the determination of clinical relevance or lack of relevance of a biological sample.

In the practice of the above or other methods elsewhere herein, either alone or in combination, the designated sample collector may be a retailer site. In some embodiments described herein, including the above or elsewhere herein methods alone or in combination, the designated sample acquiring instrument is a chain store, pharmacy, supermarket, or department store. In the methods above or elsewhere herein, taken alone or in combination, the designated sample acquisition instrument can be the subject's home.

The performance of the methods described above or elsewhere herein, either alone or in combination, can include data containing electronic bits representative of the sample. In the methods above or elsewhere herein, alone or in combination, this data can be aggregated and can be used for longitudinal analysis over time to facilitate diagnosis, treatment, and/or disease prevention.

In the methods described above or elsewhere herein, alone or in combination, the biological sample can have a volume of 250 microliters ("uL") or less. In some embodiments, the biological sample in the methods above or elsewhere herein, alone or in combination, can be blood, serum, saliva, urine, tears, gastric fluid and/or digestive fluid, stool, mucus, sweat, cerumen, oil, glandular secretions, semen, or vaginal secretions. In the individual or combined implementations of the methods described above or elsewhere herein, the biological sample can be a tissue sample. The methods described above or elsewhere herein may include, alone or in combination, a biological sample taken from a finger prick.

The methods described above or elsewhere herein may include, alone or in combination, generating a report based on the qualitative and/or quantitative assessment of the biological sample. In some embodiments, performing one or more of the methods described above or elsewhere herein, alone or in combination, can further comprise transmitting the report to an additional medical care professional. The additional medical care professional may have provided the subject with a prescription requiring the qualitative and/or quantitative evaluation of the biological sample in the methods described above or elsewhere herein, alone or in combination. In some cases, additional healthcare professionals are located at a different location than the authorized analysis facility, in the performance of the methods described above or elsewhere herein, either alone or in combination.

In the practice of the methods described above or elsewhere herein, either alone or in combination, the treatment may include the addition of one or more reagents or fixatives.

In some embodiments, the data is transmitted to the cloud-computing-based infrastructure in the methods described above or elsewhere herein, alone or in combination.

The methods described above or elsewhere herein may include, alone or in combination, an image, wherein the image is a video image. In implementations of the above or other methods elsewhere herein, either alone or in combination, the data may comprise electronic data representing an image and/or audio signal.

In a separate or combined implementation of the above or other methods elsewhere herein, the payer may receive an electronic bill from a designated sample collector.

In the implementation of the above or other methods elsewhere herein, either alone or in combination, an authorized medical care professional at the analysis facility can receive an electronic payment from a designated sample collector.

The devices utilized in the methods above or elsewhere herein, alone or in combination, can be configured to additionally prepare a biological sample based on at least one of: pre-preparation of biological samples, analysis of data at authorized analytical facilities and/or their accessories.

In the performance of the methods described above or elsewhere herein, either alone or in combination, the authorized analytical facility may be separate from the sample collector.

When one or more of the methods described above or elsewhere herein are performed, alone or in combination, the preparation of the biological sample can be automated.

The methods described above or elsewhere herein, alone or in combination, may further comprise monitoring the subsequent qualitative and/or quantitative evaluation. In the methods described above or elsewhere herein, alone or in combination, the step of supervising can be performed by a medical care professional of an authorized analysis facility and/or by a software program. In some embodiments, the transmission of data from the device may also be used, alone or in combination, in some of the methods described above or elsewhere herein, to supervise the subsequent qualitative and/or quantitative evaluation. The methods described above or elsewhere herein may be provided alone or in combination, with supervision being provided by a healthcare professional of an authorized analytical facility and/or by a software program.

The data utilized in the above-described or elsewhere herein, alone or in combination, can be representative of a biological sample and/or any portion thereof. In some embodiments, the data may represent the preparation of a collected biological sample. The data may include information on one or more conditions under which the collected biological sample is prepared. The one or more conditions may include one or more characteristics listed in the following group: the amount of the biological sample, the concentration of the biological sample, the mass of the biological sample, the temperature, or the humidity.

In some of the methods described above or elsewhere herein, alone or in combination, the data represents a reaction run by the apparatus. The data may include information on the rate of reaction. In some cases, the data may include information about control reactions and chemical reactions involving the biological sample.

In the practice of the above or elsewhere herein, alone or in combination, such methods may further comprise (c) supervising one or more of steps (i) - (iii) to improve the quality of the assessment, wherein the supervising is performed before, after, or simultaneously with any of steps (i) - (iii).

The methods above or elsewhere herein may, alone or in combination, further comprise (iv) monitoring one or more of steps (i) - (iii) to improve the quality of the assessment, wherein the monitoring is performed before, after, or simultaneously with any of steps (i) - (iii).

In some embodiments, the methods described above or elsewhere herein can be provided alone or in combination, wherein the monitoring is of data representative of a biological sample and/or any portion thereof. The supervision may be a supervision of data representing the biological sample and/or any part thereof. The supervision may be a supervision of data representing a preparation of the collected biological sample. In some examples, the monitoring is monitoring of data representative of the preparation of the collected biological sample. The supervision may be a supervision of information on one or more conditions under which the biological sample is to be collected. In the methods described above or elsewhere herein, alone or in combination, the monitoring can be of information on one or more conditions under which the biological sample is prepared for collection. The supervision may be supervision of data representing chemical reactions run by the apparatus. In some embodiments, the monitoring may be monitoring data representative of a chemical reaction run by the device. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

In the performance of the above or other methods elsewhere herein, either alone or in combination, the medical care coverage is provided by a medical insurance company.

The methods described above or elsewhere herein may include, alone or in combination, preparatory steps involving one or more types of chemical reactions selected from: immunoassay, nucleic acid assay, receptor assay, cytometric assay, colorimetric assay, enzymatic assay, electrophoretic assay, electrochemical assay, spectroscopic assay, chromatographic assay, microscopic assay, topographic assay, calorimetric assay, turbidimetric assay, agglutination assay, radioisotope assay, viscometric assay, blood clotting time assay, protein synthesis assay, histological assay, culture assay, or osmolarity assay.

The apparatus may also be configured for processing a biological sample by electronically transmitting data representative of one or more biometric measurements of a subject according to the methods described above or elsewhere herein, alone or in combination.

In some of the above or elsewhere herein methods, alone or in combination, the processing of the biological sample does not comprise analysis of the expression or concentration levels of three or more analytes belonging to the classes of cardiac markers, blood gas, electrolytes, lactate, hemoglobin, and clotting factors.

In some embodiments, the processing of the biological sample does not comprise analysis of the expression or concentration levels of three or more analytes belonging to: sodium, potassium, chloride, TCO₂Anionic interstitium, ionic calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO₂、PO₂、HCO₃Alkali residue, sulfur dioxide, kaolin ACT, diatomaceous earth ACT, PT/INR, cTnl, CK-MB, and BNP.

In implementations of some of the methods above or elsewhere herein, alone or in combination, the sample acquiring device may be one or more of: a hospital, clinic, military location, or the home of a subject.

In some embodiments, for the methods described above or elsewhere herein, alone or in combination, the data can be displayed on a touch screen after analysis.

The methods described above or elsewhere herein may include imaging data of various parts of the body, which data may be used for analysis concurrently with biochemical analysis.

Particular examples described herein may relate to a system for evaluating a biological sample collected from a subject, the system comprising: (a) a communication unit configured to receive data from a device placed in or on a subject or in a designated sample collector, wherein the device is configured to process a biological sample, thereby generating data necessary for a subsequent qualitative and/or quantitative evaluation of said biological sample, and wherein the device comprises (i) a sample collection unit configured to receive a biological sample; (ii) a sample preparation unit configured for preparing a biological sample for subsequent qualitative and/or quantitative evaluation; and (iii) a transmission unit configured to transmit data to an authorised analysis facility and/or an accessory device thereof; and (b) a processor that processes the data at the authorized analysis facility and/or an accessory thereof for qualitative and/or quantitative evaluation of the biological sample, and wherein the processor is in communication with a record database containing one or more medical records and/or insurance information for a subject.

Additional embodiments described herein may relate to a system for evaluating a biological sample collected from a subject, the system comprising: (a) a communication unit configured to receive data from a device placed in or on a subject or in a designated sample collector, wherein the device is configured to process a biological sample, thereby generating data necessary for a subsequent qualitative and/or quantitative evaluation of said biological sample, and wherein the device comprises (i) a sample collection unit configured to receive a biological sample; (ii) a sample preparation unit configured for preparing a biological sample for subsequent qualitative and/or quantitative evaluation; and (iii) a transmission unit configured to transmit data to an authorised analysis facility and/or an accessory device thereof; and (b) a processor that processes the data at the authorized analysis facility and/or its accessories for subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the processor is in communication with a record database containing one or more medical records of the subject, and/or wherein the processor is in communication with a payer database containing insurance information for the subject. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

According to another embodiment described herein, a system for evaluating a blood sample collected from a subject may be provided. The system may include: (a) a communication unit configured to receive data from a device placed in or on a subject or in a designated sample collector, wherein the device is configured to process a blood sample so as to generate data necessary for a subsequent qualitative and/or quantitative evaluation of said blood sample, and wherein the device comprises (i) a sample collection unit configured to receive a blood sample; (ii) a sample preparation unit configured for preparing a biological sample for subsequent qualitative and/or quantitative evaluation, wherein the sample preparation unit allows the addition of at least one reagent to a blood sample; and (iii) a transmission unit configured to transmit data to an authorised analysis facility and/or an accessory device thereof; and (b) a processor that processes the data at an authorized analysis facility and/or an accessory thereof for subsequent qualitative and/or quantitative evaluation of the blood sample, and wherein the processor accesses a records database containing one or more medical records of the subject, and/or wherein the processor accesses a payer database containing insurance information for the subject.

According to additional embodiments described herein, a system for rapid evaluation of a biological sample taken from a subject to aid in the diagnosis, treatment, or prevention of a disease may be provided. The system may include: a communication unit for receiving electronic data from a device representative of an image of the biological sample and/or a chemical reaction with at least one component from the biological sample; the device is placed in or on a subject or in a designated sample collector, wherein the device is used for processing a biological sample, thereby generating electronic data representing an image of the biological sample necessary for a subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device comprises within a housing (i) a sample collection unit for receiving the biological sample; (ii) a sample preparation unit for preparing a biological sample for subsequent qualitative and/or quantitative evaluation, wherein the preparation of the biological sample is automated; (iii) (iii) an imaging unit for recording an image of a biological sample and/or a chemical reaction with at least one component from the biological sample, and (iv) a transmission unit for transmitting electronic data representative of the image and/or chemical reaction; and a processor that processes the electronic data representative of the image for subsequent qualitative and/or quantitative evaluation of the biological sample.

In a separate or combined implementation of the above or elsewhere herein, the processor may be configured to communicate with a payer database that includes insurance information for the subject.

The systems described above or elsewhere herein may include, alone or in combination, a device configured to receive information related to the qualitative and/or quantitative assessments and, in turn, or display the information on the device.

In a separate or combined implementation of the above or elsewhere herein, the apparatus may include a processing unit configured to verify whether the subject is covered with medical insurance coverage for said qualitative and/or quantitative evaluation of the biological sample.

In some embodiments, the system described above or elsewhere herein, alone or in combination, may comprise a device configured to verify whether the subject has received a prescription request from a medical care professional to perform said qualitative and/or quantitative evaluation of the biological sample.

In the systems described above or elsewhere herein, alone or in combination, a processor is provided that can access the record database prior to providing the qualitative and/or quantitative assessments. Still alternatively, in the system above or elsewhere herein, alone or in combination, the processor accesses the payer database prior to providing the qualitative and/or quantitative assessment.

The system described above or elsewhere herein, either alone or in combination, can determine which record databases to access before providing the qualitative and/or quantitative assessments.

In a separate or combined implementation of the above or elsewhere herein, the apparatus may be configured to receive one or more cartridges configured for qualitative and/or quantitative evaluation by a medical care professional prescribing a prescription requirement.

In some embodiments, the device is contained within a housing in the systems described above or elsewhere herein, alone or in combination.

In the systems described above or elsewhere herein, alone or in combination, the qualitative and/or quantitative assessment may involve determination of clinical relevance of the biological sample or lack thereof.

In the systems described above or elsewhere herein, alone or in combination, the designated sample acquiring instrument is a chain store, pharmacy, supermarket or department store. In some embodiments, the designated sample collector is the subject's home.

The systems described above or elsewhere herein can include, alone or in combination, a biological sample having a volume of 250uL or less. The biological sample may be blood, serum, saliva, urine, tears, gastric juice and/or digestive juice, stool, mucus, sweat, cerumen, oil, glandular secretions, semen or vaginal secretions. In some cases, the biological sample may be a tissue sample.

In some systems of the foregoing or elsewhere herein, alone or in combination, the biological sample can be collected from a finger prick.

In some embodiments, the systems described above or elsewhere herein may utilize a designated sample collector, which may be a retailer. In the systems described above or elsewhere herein, alone or in combination, the designated sample acquiring instrument may be an employer's site, provider's office, or hospital.

In some systems of the foregoing or elsewhere herein, alone or in combination, the authorized analytical facilities may be separate from the sample collector.

In the systems described above or elsewhere herein, alone or in combination, a medical care professional may access a user interface for and/or overseeing the subsequent qualitative and/or quantitative assessments.

In the systems described above or elsewhere herein, alone or in combination, the processor may further provide supervision for such subsequent qualitative and/or quantitative evaluation.

In the systems described above or elsewhere herein, alone or in combination, the sample preparation unit can comprise (i) a pipette, and, in addition or alternatively, (ii) one or more of: a centrifuge, a magnetic separator, a filter, a container, a vessel, an assay unit, a reagent unit, a heater, a thermal controller, a cell counter, an electromagnetic source, a temperature sensor, a motion sensor, or a sensor for an electrical property.

In some embodiments, the systems described above or elsewhere herein may include images, either alone or in combination. The image may be static. In some embodiments, the image may be a video image. The systems described above or elsewhere herein may include, alone or in combination, a transmission unit configured to wirelessly transmit electronic data representing an image.

In the systems described above or elsewhere herein, alone or in combination, the data may include electronic data representing image and audio signals.

The apparatus in the above or other systems elsewhere herein, alone or in combination, may be configured to receive one or more cassettes configured for qualitative and/or quantitative analysis. In some specific examples, the cassette may have one or more identifiers that are readable by the apparatus.

In some systems of the foregoing or elsewhere herein, alone or in combination, at least one component can be a biological analyte consisting of a carbohydrate, a lipid, a protein, or combinations thereof.

In the use of the above or elsewhere herein systems, alone or in combination, chemical reactions can be carried out without the need for a biological sample.

In some embodiments, for systems of the above or elsewhere herein, alone or in combination, the data can be displayed on a touch screen after analysis.

The system described above or elsewhere herein may include imaging data of various parts of the body that are processed for analysis concurrently with biochemical analysis.

Some embodiments described herein may relate to a method of conducting a pathology study of a biological sample collected from a subject, the method may include: (a) receiving electronic data from an image representative of the biological sample and/or a chemical reaction with at least one component of the biological sample from a device placed in or on a subject or in a designated sample acquisition instrument, wherein the device is configured to: (i) receiving the biological sample; (ii) preparing a collected biological sample for subsequent qualitative and/or quantitative evaluation, wherein said preparing generates electronic data representative of an image of said biological sample and/or chemical reaction; and (iii) transmitting the electronic data representative of the image to a pathologist at an authorized analytical facility; and (b) analyzing the electronic data by a pathologist of an authorized analytical facility to provide said subsequent qualitative and/or quantitative assessment.

One embodiment described herein relates to a method of evaluating a biological sample collected from a subject. The method comprises (a) receiving data transmitted from a device placed in or on a subject or on a designated sample acquisition instrument, wherein the device is configured to process a biological sample by: (i) receiving a biological sample; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of said biological sample, and (iii) electronically transmitting the data to an authorized analytical facility and/or an accessory thereof; and (b) analyzing the data transmitted from the device at an authorized analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative evaluation of the biological sample. This may be in contrast to conventional devices, which may only transmit the results of the analysis, rather than data for subsequent qualitative and/or quantitative evaluation of the sample. Such traditional devices that merely transmit results may not be relied upon by one or more medical care professionals in the diagnosis, treatment, and/or prevention of disease for a subject.

In some embodiments, the processing of the biological sample does not include analysis of the expression or concentration levels of three or more analytes belonging to the classes of cardiac markers, blood gas, electrolytes, lactate, hemoglobin, and clotting factors. In some cases, the processing of the biological sample does not include analysis of the presence or concentration levels of three or more analytes belonging to: sodium, potassium, chloride, TCO₂Anionic interstitium, ionic calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO₂、PO₂、HCO₃Alkali residue, sulfur dioxide, kaolin ACT, diatomaceous earth ACT, PT/INR, cTnl, CK-MB, and BNP.

According to another embodiment described herein, there is provided a method of evaluating a biological sample collected from a subject. The method comprises (a) receiving data transmitted from a device placed in or on a subject or at a retailer site, wherein the device is configured to process a biological sample by: (i) receiving a biological sample; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of said biological sample, and (iii) electronically transmitting the data to an authorized analytical facility and/or an accessory thereof; and (b) analyzing the data transmitted from the device at an authorized analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative evaluation of the biological sample.

An additional embodiment described herein is a method of evaluating a biological sample, the method comprising: (a) processing a biological sample collected from a subject by means of a device, wherein the device is placed in or on the subject or in a designated sample collector, wherein said processing generates data necessary for a subsequent qualitative and/or quantitative evaluation of said biological sample, and wherein the device is configured for (i) receiving the biological sample; (ii) (ii) preparing a biological sample for subsequent qualitative and/or quantitative evaluation, and (iii) transmitting data to an authorized analytical facility and/or its accessories; (b) transmitting data from the device at the authorized analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative evaluation of the biological sample; and (c) verifying whether the subject is covered by medical insurance coverage, wherein the verifying step is performed before, after, or simultaneously with steps (a) and/or (b).

Another specific example described herein is a method of evaluating a biological sample collected from a subject, the method comprising (a) receiving electronic data representing an image of the biological sample and/or a chemical reaction performed on a device, wherein the electronic data is transmitted from the device placed in or on the subject or on a designated sample collector, wherein the device is configured to process the biological sample by: (i) receiving the biological sample; (ii) preparing a biological sample for subsequent qualitative and/or quantitative evaluation, wherein said preparing generates electronic data representative of an image of said biological sample and/or chemical reaction; and (iii) transmitting the electronic data representative of the image to an authorized analytical facility and/or an accessory thereof; wherein the processing generates electronic data representative of an image necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample, and (b) analyzes the electronic data representative of an image transmitted from the apparatus at an authorized analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative evaluation of the biological sample.

According to yet another embodiment described herein, a system for evaluating a biological sample collected from a subject is provided. The system comprises (a) a communication unit configured to receive data from a device placed in or on a subject or in a designated sample collector, wherein the device is configured to process a biological sample, thereby generating data necessary for a subsequent qualitative and/or quantitative evaluation of said biological sample, and wherein the device comprises (i) a sample collection unit configured to receive a biological sample; (ii) a sample preparation unit configured for preparing a biological sample for subsequent qualitative and/or quantitative evaluation; and (iii) a transmission unit configured to transmit data to an authorised analysis facility and/or an accessory device thereof; and (b) a processor that processes the data at an authorized analysis facility and/or an accessory thereof for subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the processor is in communication with a records database containing one or more medical records of the subject, and/or wherein the processor is in communication with a payer database containing insurance information for the subject.

Further, a method of evaluating a biological sample collected from a subject is provided. The method comprises (a) receiving data transmitted from a device placed in or on a subject or in a designated sample acquisition instrument, wherein the device is configured to process a biological sample by (i) receiving the biological sample; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample, and (iii) transmitting the data to a medical care provider of an authorized analysis facility and/or an accessory device thereof; and (b) analyzing the data transmitted from the device at an authorised analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative assessment of the biological sample; and (c) verifying whether the subject received a prescription request from a medical care professional to perform the subsequent qualitative and/or quantitative evaluation of the biological sample, wherein the verifying step is performed before, after, or simultaneously with steps (a) and/or (b).

Additional specific examples described herein relate to a method of evaluating a biological sample, the method comprising (a) processing a biological sample collected from a subject who has received a prescription requiring a subsequent qualitative and/or quantitative evaluation of the biological sample by means of a device, wherein the device is placed in or on the subject or in a designated sample collector, wherein the processing generates data necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device is configured for (i) receiving the biological sample; (ii) (ii) preparing a biological sample for subsequent qualitative and/or quantitative evaluation, and (iii) transmitting data to an authorized analytical facility and/or its accessories; (b) transmitting data from the device for analysis at an authorized analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative evaluation of the biological sample; and (c) verifying whether the prescription for the subsequent qualitative and/or quantitative evaluation of the biological sample is within the regulatory limits of the subsequent qualitative and/or quantitative evaluation by a payer or prescribing physician, wherein the verifying step is performed before, after, or simultaneously with steps (a) and/or (b).

A method of evaluating a biological sample collected from a subject is illustrated according to one embodiment described herein. The method comprises (a) receiving data transmitted from a device placed in or on a subject or in a designated sample acquisition instrument, wherein the device is configured to process a biological sample by (i) receiving the biological sample; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate information necessary for the subsequent qualitative and/or quantitative evaluation of the biological sample, and (iii) electronically transmitting the data to an authorized analytical facility and/or its accessories; and (b) analyzing the data transmitted from the device at an authorized analytical facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative assessment of the biological sample, wherein the subsequent qualitative and/or quantitative assessment of the biological sample results in a determination of the presence or concentration of an analyte belonging to one or more selected from the group consisting of: sodium, potassium, chloride, TCO₂Anionic interstitium, ionic calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO₂、PO₂、HCO₃Alkali residue, sulfur dioxide, kaolin ACT, diatomaceous earth ACT, PT/INR, cTnl, CK-MB, or BNP.

In another embodiment, the present invention provides a system for evaluating a blood sample collected from a subject, said system comprising (a) a communication unit configured to receive data from a device placed in or on the subject or in a designated sample collector, wherein the device is configured to process the blood sample, thereby generating data necessary for a subsequent qualitative and/or quantitative evaluation of said blood sample, and wherein the device comprises (i) a sample collection unit configured to receive the blood sample; (ii) a sample preparation unit configured for preparing a biological sample for subsequent qualitative and/or quantitative evaluation, wherein the sample preparation unit allows the addition of at least one reagent to a blood sample; and (iii) a transmission unit configured to transmit data to an authorised analysis facility and/or an accessory device thereof; and (b) a processor that processes the data at an authorized analysis facility and/or an accessory thereof for subsequent qualitative and/or quantitative evaluation of the blood sample, and wherein the processor accesses a records database containing one or more medical records of the subject, and/or wherein the processor accesses a payer database containing insurance information for the subject.

Another method of evaluating multiple types of biological samples collected from a subject is provided. The method comprises (a) receiving data transmitted from a device placed in or on a subject or on a designated sample acquisition instrument, wherein the device is configured to process multiple types of biological samples by: (i) receiving a plurality of types of biological samples; (ii) (ii) preparing the biological sample for subsequent qualitative and/or quantitative evaluation to generate data necessary for the subsequent qualitative and/or quantitative evaluation of said plurality of types of biological sample, and (iii) electronically transmitting the data to an authorized analytical facility and/or an accessory thereof; and (b) analyzing the data transmitted from the device at an authorized analysis facility and/or an accessory thereof to provide the subsequent qualitative and/or quantitative evaluation of the plurality of types of biological samples.

In some specific examples, the processing of the biological sample does not involve the display of the presence or concentration levels of one or more analytes selected for the determination of cardiac markers, chemical composition, blood gas, electrolytes, lactate, hemoglobin, coagulation, or hematology. In some embodiments, the processing of the biological sample does not involve the display of the presence or concentration levels of three or more analytes belonging to: sodium, potassium, chloride, TCO₂Anionic interstitium, ionic calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO₂、PO₂、HCO₃Alkali residue, sulfur dioxide, kaolin ACT, diatomaceous earth ACT, PT/INR, cTnl, CK-MB, and BNP. After subsequent analysis, such information may be transmitted back to the device, e.g., for display, storage, or analysis.

Further, in some embodiments, the device is configured to verify whether the subject has medical insurance coverage for the qualitative and/or quantitative assessment of the biological sample. The device may comprise a processing unit configured for verifying whether the subject has a medical insurance coverage for said qualitative and/or quantitative evaluation of the biological sample. The device may be configured to verify whether the subject has received a prescription request from a medical care professional to perform said qualitative and/or quantitative evaluation of the biological sample.

In some cases, the processor accesses the record database prior to providing the qualitative and/or quantitative assessment. The processor may access a payer database prior to providing the qualitative and/or quantitative rating. In some embodiments, the system determines which record databases to access prior to providing the qualitative and/or quantitative assessment.

In some embodiments, the device is configured to verify the identity of the subject prior to receiving the biological sample, electronically transmitting the data, or analyzing the transmitted data. The verification of the identity of the subject may comprise receiving a genetic signature of the subject. The genetic marker may be obtained by nucleic acid amplification of a biological sample from the subject. Verification of the identity of the subject may include one or more biometric measurements of the subject. Verification of the subject's identity may be performed by an authorized technician. The identity of the authorized technician may be verified prior to receiving the biological sample, electronically transmitting the data, or analyzing the transmitted data.

According to some specific examples described herein, the apparatus may be configured to receive one or more cartridges configured for qualitative and/or quantitative evaluation required by a medical care professional. The apparatus may be configured to receive one or more cartridges configured for qualitative and/or quantitative evaluation as required by a medical care professional. The cassette may have one or more identifiers that are readable by the device. In some cases, the provided methods may also include receiving identifier information from the apparatus. Such methods may also further include providing one or more protocols to the device based on the received identifier information, wherein the protocols enable preparation of a biological sample. The protocol may be provided wirelessly from a server to facilitate preparation and/or processing of the biological sample. The procedure may be provided from the cloud or from any external device.

In some embodiments, the apparatus may be contained within a housing.

The qualitative and/or quantitative evaluation may involve the determination of clinical relevance of the biological sample or lack thereof.

In some embodiments described herein, the designated sample collector is a retailer point of presence. The designated sample acquiring instrument may be a chain store, a pharmacy, a supermarket or a department store. The designated sample collector may be the subject's home.

In some embodiments, the data includes electronic bits representing the sample. This data can be aggregated and used for longitudinal analysis over time to facilitate diagnosis, progression therapy, and/or disease prevention. This data can also be used and can be seen in longitudinal analysis over time to facilitate diagnosis, progression of treatment and/or disease prevention, and to better understand disease progression or regression, or to understand the efficacy of interventions including treatment or lifestyle changes.

The biological sample may have a volume of 250uL or less. The biological sample is blood, serum, saliva, urine, tears, gastric juice and/or digestive juice, stool, mucus, sweat, cerumen, oil, glandular secretions, semen or vaginal secretions. The biological sample may be a tissue sample. The biological sample may be collected from a finger prick.

In some specific examples, a method may further comprise generating a report based on the qualitative and/or quantitative assessment of the biological sample. The method may further include transmitting the report to an additional medical care professional. In some cases, the additional medical care professional provides a prescription to the subject that requires it to perform the qualitative and/or quantitative evaluation of the biological sample. The additional medical care professional may be located at a different location than the authorized analysis facility.

In some embodiments, the treatment comprises the addition of one or more reagents or fixatives.

According to one specific example described herein, data may be transmitted to a cloud computing-based infrastructure. The image may be a video image. The data may include electronic data representing image and/or audio signals. Cloud computing based infrastructure may learn itself. The data may be fed to a model that may be re-fitted and re-adjusted based on the acquired data. The cloud computing-based infrastructure may perform the analysis.

In some embodiments, the processor accesses a payer database. The payer may receive an electronic bill from a designated sample collector. An authorized medical care professional of the analysis facility may receive an electronic payment from a designated sample collector.

The apparatus may be configured to additionally prepare the biological sample based on at least one of prior preparation of the biological sample, analysis of the data at an authorized analysis facility or an accessory thereof.

In some embodiments, the authorized analytical facility is separate from the sample collector.

The preparation of the biological sample may be automated. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

A method may be provided which further comprises supervising said subsequent qualitative and/or quantitative evaluation. The step of supervising may be performed by an authorized medical care professional of the analysis facility and/or by a software program. The data transmitted from the device may also be used to supervise the subsequent qualitative and/or quantitative evaluation. The supervision may be provided by a medical care professional of an authorized analysis facility and/or by a software program. A user interface accessible by a medical care professional for and/or supervising the subsequent qualitative and/or quantitative evaluation may be provided. The processor may also provide supervision for the subsequent qualitative and/or quantitative evaluation. By way of non-limiting example, such oversight may be associated with certain devices, such as those shown in FIGS. 1-23. A particular example is that the analysis station providing the final test results remotely controls these devices.

In some embodiments, the data represents a biological sample and/or any portion thereof. The data may represent the preparation of the collected biological sample. The data may include information of one or more conditions under which the collected biological sample is prepared. The one or more conditions may include one or more characteristics listed in the following group: the amount of the biological sample, the concentration of the biological sample, the mass of the biological sample, the temperature, or the humidity. The data may represent a reaction run by the device. The data may include information on the rate, quality and/or performance of the reaction. The data may include information about control reactions and chemical reactions involving the biological sample. The data collected may be photons as a result of a chemical reaction. Other examples of data may include electrons, photons, intensity, frequency, color, sound, or temperature. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

In some embodiments, the provided methods further comprise (c) supervising one or more of steps (i) - (iii) to improve the quality of the assessment, wherein the supervising is performed before, after, or simultaneously with any of steps (i) - (iii). Further, the provided methods further comprise (iv) supervising one or more of steps (i) - (iii) to improve the quality of the evaluation, wherein the supervising is performed before, after, or simultaneously with any of steps (i) - (iii). The supervision may be supervision of data representing the biological sample and/or any part thereof. The supervision may be supervision of data representing the preparation of the collected biological sample. The supervision may be supervision of information on one or more conditions under which preparation of the collected biological sample is performed. The supervision may be supervision of data representing reactions run by the device. The supervision may be of data representing the operation of reactions occurring within the system. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

In some embodiments, the medical care insurance coverage is provided by a medical insurance company and/or employer.

In some embodiments, the preparing step involves one or more types of reactions selected from the group consisting of: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, spectroscopic assays (e.g., mass spectrometry, infrared spectroscopy, X-ray photoelectron spectroscopy), electrophoretic assays, nucleic acid sequencing, agglutination assays, chromatographic assays, coagulation function assays, electrochemical assays, histological assays, or cellular assays (including dead cell and/or living cell assays), molecular biological assays, chemical assays, turbidity assays, coagulation function assays, radioisotope assays, viscosity assays, coagulation function assays, coagulation time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, microscopic assays, topographic assays, calorimetric assays, and/or other types of assays, or combinations thereof.

The device may also be configured to process a biological sample by electronically transmitting data representative of one or more biometric measurements of a subject.

In some embodiments, the sample collector is one or more of: a hospital, clinic, emergency room, military location, or the home of the subject.

One particular example described herein can relate to a system for rapid evaluation of a biological sample taken from a subject to aid in the diagnosis, treatment, or prevention of a disease, the system comprising: a communication unit for receiving electronic data from a device representative of an image of the biological sample and/or a chemical reaction with at least one component from the biological sample; the device is placed in or on a subject or in a designated sample collector, wherein the device is used for processing a biological sample, thereby generating electronic data representing an image of the biological sample necessary for a subsequent qualitative and/or quantitative evaluation of the biological sample, and wherein the device comprises within a housing (i) a sample collection unit for receiving the biological sample; (ii) a sample preparation unit for preparing a biological sample for subsequent qualitative and/or quantitative evaluation, wherein the preparation of the biological sample is automated; (iii) an imaging unit for recording an image of a biological sample and/or a chemical reaction with at least one component from the biological sample; and (iv) a transmission unit for transmitting electronic data representing the image and/or the chemical reaction; and a processor that processes the electronic data representative of an image for subsequent qualitative and/or quantitative evaluation of the biological sample. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

In some embodiments, the sample preparation unit may comprise (i) a pipette, and either (ii) one or more of: a centrifuge, a magnetic separator, a filter, a container, a vessel, an assay unit, a reagent unit, a heater, a thermal controller, a cell counter, an electromagnetic source, a temperature sensor, a motion sensor, or a sensor for an electrical property.

The images may be still and/or video images. The data may include electronic data representing image and audio signals.

The biological sample may be one or more selected from: blood, serum, saliva, urine, tears, gastric and/or digestive fluids, stool, mucus, sweat, cerumen, oil, glandular secretions, semen or vaginal secretions. In some embodiments, the biological sample has a volume of 250uL or less. The component of the biological sample may be a biological analyte consisting of carbohydrates, lipids, proteins, or combinations thereof. The chemical reaction can be performed without a biological sample.

The transmission unit may be configured to wirelessly transmit electronic data representing an image.

The apparatus may be configured to receive one or more cartridges configured for qualitative and/or quantitative evaluation. In some embodiments, the cassette may have one or more identifiers that are readable by the device.

In one specific example described herein, there is provided a system comprising a housing containing therein (i) a plurality of modules mounted on a support structure, wherein an individual module of the plurality of modules comprises: a sample preparation instrument configured to implement at least one sample preparation procedure; and a meter configured to perform one or more types of assays, wherein the meter is configured to receive a plurality of individually addressable assay units, each assay unit being fluidly isolated from each other, and each assay unit being configured to perform one or more types of assays, wherein a given type of assay performed within the individually addressable assay units is configured to produce a detectable signal; a detection system configured to detect a plurality of signals associated with a plurality of types of assays; and a sample processing system configured to transfer the individually addressable assay units from the assay to a position where the signal is detectable by the detection system. As described herein, the system can be configured to perform (a) at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, separation, and chemical processing, and (b) multiple types of assays.

It should be understood that one or more of the following features may be suitable for use with any of the specific examples described herein. By way of non-limiting example, the detection system and/or the sample processing system are integrated with a single module. Alternatively still, the detection system and/or sample processing system are separate from the single module and contained within the housing. Alternatively still, the housing further comprises a cytometer configured to perform a cytometry assay, wherein the sample processing system is configured to move the individually addressable assay units from the assay to the cytometer contained within the housing. Still alternatively, the system includes a cytometer that receives an aliquot from a common sample. Still alternatively, the housing has one or more of the following characteristics: (a) volume less than or equal to 2m³(ii) a (b) The occupied area is less than or equal to 1.5m²(ii) a Or (c) a lateral dimension or height of less than or equal to about 1.5 m. Alternatively still, the detection system comprises a plurality of detectors, a single detector of said plurality of detectors detecting a unique signal from a given type of assay performed in a given addressable assay unit, and wherein the sample processing system is configured to cluster the individually addressable assay units producing said unique detectable signal to a range where the signal is detectable by the single detector. Still alternatively, the sample processing system is configured to transfer samples or reagents between individual modules of the plurality of modules. Still alternatively, the detectable signal is selected from the group consisting of an optical signal, a thermal signal, an electrical signal, a chemical signal, and an audio signal. Alternatively or additionally, each individual module includes a communication exchangeA vehicle configured to communicate with a controller programmed to control execution of the individual modules to implement the at least one sample preparation procedure and the plurality of types of assays. Alternatively, the communication ac vehicle provides power to a single module. Still alternatively, at least one of the plurality of modules is configured to perform an assay that is different from any of the remaining modules of the system. Still alternatively, the controller is programmed to (i) receive a response from the single module to evaluate a sample or a pointer to system performance, and (ii) based on the evaluation, send instructions to the system as needed to implement the at least one sample preparation procedure and the plurality of types of assays with another function within the same module, another module within the system, or another system in communication with the system. Still alternatively, the controller is external to the system. Alternatively still, the controller is integral with the support structure. Still alternatively, the evaluation identifies a fault with one or more instruments, and wherein the instructions effect correction of the fault in real time.

In a specific example of the present invention, a computer-implemented method for probing network connectivity for a network device comprises: connecting to a network provider; performing network reachability probing ("ping") with a first server having a static Internet Protocol (IP) address with a network provider; performing network reachability probing on a second server having a static Uniform Resource Locator (URL) with a network provider; and determining whether to maintain connectivity with the network provider based on whether the network device receives a response from the first server and/or whether the network device receives a response from the second server. In one particular example, the determination of whether connectivity is maintained with the network provider is based on whether the network device receives a response from the first server and whether the network device receives a response from the second server.

In some cases, the computer-implemented method further comprises connecting to another network provider based on at least one criterion selected from the group consisting of: bandwidth of another network provider, cost of maintaining connectivity with another network provider, cost of transferring information by another network provider, download rate of another network provider, and upload rate of another network provider. In one embodiment, the at least one criterion is location based, time based, or bandwidth based. It should be understood that any device may be equipped with any of the network connection techniques described herein, such as, but not limited to, those shown in fig. 1-23. Network connectivity techniques may provide increased network reliability and/or performance for communication between diagnostic instruments and remote servers, devices, or other systems for any purpose.

In one particular example, network reachability probing the first server includes sending a network reachability probe ("ping") packet to the first server. In another particular example, network reachability probing the second server includes sending a network reachability probe packet to the second server. In yet another specific example, connectivity with a network provider is maintained if a first server responds to a network device in response to network reachability probes to the first server and/or a second server responds to a network device in response to network reachability probes to the second server. In another particular example, the computer-implemented method further includes connecting to another network provider if the first server does not respond to the network device in response to the network reachability probe being made to the first server and/or the second server does not respond to the network device in response to the network reachability probe being made to the second server. In yet another embodiment, the network provider is selected from the group consisting of a wireless router, a bluetooth router, a wired router, a cellular network router, a Radio Frequency (RF) device, and an opto-electronic device.

In some cases, the computer-implemented method further comprises: connecting to an additional network provider; performing network reachability probing on the first server by means of the additional network provider; performing network reachability probing of the second server by means of the additional network provider; and determining whether to maintain connectivity with the additional network provider based on whether the network device received a response from the first server and/or whether the network device received a response from the second server. In one particular example, determining whether to maintain connectivity with the additional network provider is based on whether the network device received a response from the first server and whether the network device received a response from the second server. In another specific example, connecting to the second network provider includes terminating connectivity with the network provider.

In one embodiment, the network provider is selected from the group consisting of a wireless router, a bluetooth router, a wired router, a cellular network router, a Radio Frequency (RF) device, and an opto-electronic device. In another particular example, network reachability probes are performed simultaneously to the first server and the second server.

In some embodiments, a computer-implemented method for probing network connectivity for a network device comprises: connecting to a network provider; directing a first data packet from a network device to a first server having a static Internet Protocol (IP) address, wherein the first data packet is directed by means of a network provider; directing a second data packet from the network device to a second server having a static Uniform Resource Locator (URL), wherein the second data packet is directed by means of the network provider; and determining whether to maintain connectivity with the network provider based on a comparison of one or more data packets received by the network device from the first server and the second server. In one particular example, the first server comprises a Domain Name System (DNS) server. In another embodiment, the first data packet is a loopback request packet. In yet another embodiment, the second data packet is a loopback request packet. In another particular example, directing the first data packet from the network device to the first server includes network reachability probing of the first server. In yet another specific example, directing the second data packet from the network device to the second server includes performing network reachability probing of the second server. In another particular example, if a first received data packet of the one or more data packets received by the network device is the same as a first data packet directed to the first server, connectivity to the network provider is maintained. In yet another specific example, if a second received data packet of the one or more data packets received by the network device is the same as a second data packet directed to a second server, connectivity to the network provider is maintained. It should be understood that any device may be equipped with any of the network connection techniques described herein, such as, but not limited to, those shown in fig. 1-23. Network connectivity techniques may provide increased network reliability and/or performance for communication between diagnostic instruments and remote servers, devices, or other systems for any purpose.

In some cases, the computer-implemented method further includes receiving a first receive data packet from the first server and/or receiving a second receive data packet from the second server. In one embodiment, if the checksum of the first received packet matches the predetermined packet, connectivity to the network provider is maintained. In another embodiment, connectivity to the network provider is maintained if the checksum of the second received data packet matches the predetermined data packet. In a specific example, the computer-implemented method further comprises connecting to another network provider if the first received data packet is different from the first data packet and/or the second received data packet is different from the second data packet.

In some cases, the computer-implemented method further comprises: connecting to another network provider; directing a first data packet from the network device to the first server, wherein the first data packet is directed by means of the further network provider; directing a second data packet from the network device to a second server, wherein the second data packet is directed by means of the other network provider; and determining whether to maintain connectivity with another network provider based on a comparison of one or more data packets received by the network device from the first server and the second server. In one particular example, connecting to the other network provider includes terminating connectivity with the network provider. It should be understood that any device may be equipped with any of the network connection techniques described herein, such as, but not limited to, those shown in fig. 1-23. Network connectivity techniques may provide increased network reliability and/or performance for communication between diagnostic instruments and remote servers, devices, or other systems for any purpose.

In one particular example, connecting to the network provider includes locating the network provider. In one embodiment, the network provider is selected from the group consisting of a wireless router, a bluetooth router, a wired router, a cellular network router, a Radio Frequency (RF) device, and an opto-electronic device.

In one particular example, the computer-implemented method further comprises determining whether to maintain connectivity with a network provider based on at least one criterion selected from the group consisting of: bandwidth, cost of maintaining connectivity with a network provider, cost of transferring information by means of a network provider, download rate, and upload rate. In one embodiment, the at least one criterion is location based, time based, or bandwidth based.

In some cases, the computer-implemented method further comprises connecting to another network provider based on at least one criterion selected from the group consisting of: bandwidth of another network provider, cost of maintaining connectivity with another network provider, cost of transferring information by means of another network provider, download rate of another network provider, and upload rate of another network provider. In one embodiment, connectivity to the network provider is maintained based on a comparison of the download rate or the upload rate to a predetermined limit. In one embodiment, the network device is selected from the group consisting of a Personal Computer (PC), a tablet PC, a slate PC, a server, a mainframe, and a smart phone.

In some embodiments, a computer-implemented method for selecting a network provider for a network device includes: connecting to a network provider; performing network reachability probes by a network provider for a first server having a static Internet Protocol (IP) address and a second server having a static Uniform Resource Locator (URL); and terminating the connection with the network provider based on any network termination condition selected from the group consisting of: (a) a network device does not receive a response from the first server and/or the second server after the network reachability probe, (b) another network provider has a network bandwidth (or delay, performance, or cost related factor) that is higher than the network bandwidth of the network provider, (c) another network provider has a network cost that is lower than the network cost of the network provider, (d) the network ingress and egress provided by another network provider is more robust than the network provided by the network provider, (e) connectivity between a network device and another network provider is via a wired connection and connectivity between a network device and the network provider is via a wireless connection, and (f) another network provider is closer to a network device than the network provider. In a specific example, the connection with the network provider is terminated based on at least any two network termination conditions selected from the group. In another specific example, the connection with the network provider is terminated based on at least any three network termination conditions selected from the group. In yet another specific example, the computer-implemented method further comprises connecting to another network provider. In another specific example, the connectivity between the network device and the first network provider is via a wired or wireless network access point. In yet another specific example, network reachability probes are performed simultaneously to the first server and the second server. It should be understood that any device may be equipped with any of the network connection techniques described herein, such as, but not limited to, those shown in fig. 1-23. Network connectivity techniques may provide increased network reliability and/or performance for communication between diagnostic instruments and remote servers, devices, or other systems for any purpose.

In some embodiments, a computer-implemented method for establishing network connectivity for a network device includes the steps of: (a) connecting to a first network provider; (b) performing network reachability detection on the first server and the second server by means of the first network provider; and (c) if a second network provider meets the criteria not met by the first network provider, selecting the second network provider in preference to the first network provider. In one particular example, the selecting is in response to a network reachability probe. In another embodiment, the criteria is location-based, time-based, or bandwidth-based criteria. In yet another specific example, the first server has a static Internet Protocol (IP) address. In another specific example, the second server has a static Uniform Resource Locator (URL). In yet another embodiment, the criterion is selected from the group consisting of: (a) whether a network device receives a response from the first server and/or the second server after the network reachability probe, (b) whether the network bandwidth of the second network provider is higher than the network bandwidth of the first network provider, (c) whether the network cost of the second network provider is lower than the network cost of the first network provider, (d) whether the network ingress and egress provided by the second network provider is more robust than the network provided by the first network provider, (e) whether the connectivity between the network device and the second network provider is robust via a wired connection and the connectivity between the network device and the first network provider is via a wireless connection, and (f) whether the second network provider is closer to a network device than the first network provider. It should be understood that any device may be equipped with any of the network connection techniques described herein, such as, but not limited to, those shown in fig. 1-23. Network connectivity techniques may provide increased network reliability and/or performance for communication between diagnostic instruments and remote servers, devices, or other systems for any purpose.

In some embodiments, a computer-implemented method for establishing network connectivity for a network device includes: connecting to a first network provider; locating a second network provider having a higher level of prioritization than the first network provider based on one or more predetermined network connectivity criteria; and connecting to a second network provider. In one particular example, the locating includes network reachability probing of the first server and the second server. In another specific example, the first server has a static Internet Protocol (IP) address. In yet another specific example, the second server has a static Uniform Resource Locator (URL). In another embodiment, the one or more predetermined network connectivity criteria are selected from the group consisting of network bandwidth, network cost, and proximity of the network device to the network provider. In yet another embodiment, the one or more predetermined network connectivity criteria are location based, time based, or bandwidth based. It should be understood that any device may be equipped with any of the network connection techniques described herein, such as, but not limited to, those shown in fig. 1-23. Network connectivity techniques may provide increased network reliability and/or performance for communication between diagnostic instruments and remote servers, devices, or other systems for any purpose.

In some embodiments, one or more steps of the methods provided herein are performed with a processor. In one example, a network device is connected to a first network provider via a processor. In some embodiments, any network reachability detection, selection, and location is by way of one or more processors, which may be located in a network device provided herein or remotely, such as in a remote computer system.

In another specific example of the present invention, a system for establishing network connectivity for a network device includes a network connectivity controller for locating a network provider, the network connectivity controller having a processor for executing machine readable code configured to: establishing a connection with a network provider; performing network reachability probing on a first server having a static Internet Protocol (IP) address with a network provider; performing network reachability probing on a second server having a static Uniform Resource Locator (URL) with a network provider; and determining whether to maintain connectivity with the network provider based on whether the network device receives a response from the first server and/or whether the network device receives a response from the second server. The system also includes a Graphical User Interface (GUI) for displaying to a user a list of network providers, the list of network providers generated by means of one or more network connectivity criteria. In one embodiment, the one or more network connectivity criteria are selected from the group consisting of: bandwidth of another network provider, cost of maintaining connectivity with another network provider, cost of transferring information by means of another network provider, download rate of another network provider, and upload rate of another network provider. In another embodiment, the one or more network connectivity criteria are location based, time based, or bandwidth based. In yet another specific example, the machine-readable code is configured to determine whether to maintain connectivity with the network provider based on whether the network device received a response from the first server and whether the network device received a response from the second server. It should be understood that any device may be equipped with any of the network connection techniques described herein, such as, but not limited to, those shown in fig. 1-23. Network connectivity techniques may provide increased network reliability and/or performance for communication between diagnostic instruments and remote servers, devices, or other systems for any purpose.

In another embodiment of the present invention, a computer readable medium includes code for implementing a method comprising: establishing a connection with a network provider; performing network reachability probing on a first server having a static Internet Protocol (IP) address with a network provider; performing network reachability probing on a second server having a static Uniform Resource Locator (URL) with a network provider; and determining whether to maintain connectivity with the network provider based on whether the network device receives a response from the first server and/or whether the network device receives a response from the second server. In some cases, a connection is established with a network provider by way of a processor.

In yet another specific example described herein, an apparatus includes a plurality of network connectivity interfaces installed on the apparatus, wherein at least two of the interfaces use different connection technologies; a programmable processor programmed to: a) direct a first network connectivity request using a first one of the network connectivity interfaces to verify end-to-end connectivity; b) direct a second network connectivity request using a first one of the network connectivity interfaces to verify end-to-end connectivity; and determining whether to switch network connectivity to another of the network connectivity interfaces based on the status of the network connectivity request.

In one particular example, there is provided a computer-implemented method for calibrating user responses to questions relating to dietary intake, exercise, health condition, or mental condition, the method comprising: (a) presenting a query to a user by way of a computer system and an interactive display operatively coupled to the computer system, the query relating to a dietary intake, exercise, health condition, or mental condition of the user; (b) receiving, by way of the computer system and interactive display, a response to the query from the user; and (c) interpreting, by means of a computer processor, the response based on a set of reference information, wherein the set of reference information includes a pictorial depiction of the dietary portion of the dietary intake, the exertion level of the exercise, the present state of health, or the present state of mental status. The method may comprise, subsequent to step (c), monitoring the health of the user.

In another embodiment, a computer-implemented method for calibrating user responses to questions relating to dietary intake, exercise, health condition, or mental condition is provided, the method comprising: (a) presenting a query to a user by way of a computer system and an interactive display operatively coupled to the computer system, the query relating to a dietary intake, exercise, health condition, or mental condition of the user; (b) receiving, by way of the computer system and interactive display, a response to the query from the user; and (c) interpreting, by means of the computer system, the response based on a calibration matrix having a set of reference information generated by means of a pictorial depiction of the dietary portion of the dietary intake, the exertion level of the exercise, the present state of health or the present state of mental condition. The method may comprise, subsequent to step (c), monitoring the health of the user.

In yet another embodiment, provided herein is a computer-readable medium comprising machine-executable code implementing a method for calibrating user response to questions related to dietary intake, exercise, health condition, or mental condition, comprising: (a) presenting a query to a user by way of a computer system and an interactive display operatively coupled to the computer system, the query relating to a dietary intake, exercise, health condition, or mental condition of the user; (b) receiving, by way of the computer system and interactive display, a response to the query from the user; and (c) interpreting, by means of the computer system, the response based on a set of reference information, wherein the set of reference information includes a pictorial depiction of the dietary portion of the dietary intake, the exertion level of the exercise, the present state of health, or the present state of mental status. The method for calibrating user response to questions relating to dietary intake, exercise, health condition or mental condition may comprise monitoring the health of the user subsequent to step (c).

In another embodiment, a system for calibrating user responses to questions relating to dietary intake, exercise, health condition, or mental condition is provided, the system comprising: an interactive display configured to present machine-generated graphical items to a user; and a computer system operatively coupled to the interactive display, the computer system having a memory location containing machine executable code, the code implementing a method by means of a processor of the computer system, comprising: (a) presenting a query to a user by way of the computer system and interactive display, the query relating to a dietary intake, exercise, health condition, or mental condition of the user; (b) receiving, by way of the computer system and interactive display, a response to the query from the user; and (c) interpreting, by means of the computer system, the response based on a set of reference information, wherein the set of reference information includes a pictorial depiction of the dietary portion of the dietary intake, the exertion level of the exercise, the present state of health, or the present state of mental status. The method may comprise, subsequent to step (c), monitoring the health of the user.

In some embodiments, in the methods, systems, or computer-readable media described above or elsewhere herein relating to reference information, the reference information is obtained by providing a user with a selection of at least two picture elements, wherein the picture elements depict a serving size, a exertion level, a present state of health, or a present state of mental status.

In some embodiments, in methods, systems, or computer-readable media described above or elsewhere herein that relate to reference information, the reference information is utilized to generate a calibration matrix to calibrate a user's response to a query regarding the user's dietary intake, exercise, health condition, or mental condition.

In some embodiments, in the methods, systems, or computer readable media described above or elsewhere herein relating to an interactive display, the interactive display is a capacitive touch display or a resistive touch display.

In some embodiments, in the methods, systems, or computer-readable media described above or elsewhere herein relating to reference information, the reference information is obtained or presented prior to a query to the user regarding the user's dietary intake, exercise, health condition, or mental condition.

In some embodiments, in the methods, systems, or computer-readable media described above or elsewhere herein relating to reference information, the reference information is obtained or presented after a query to the user regarding the user's dietary intake, exercise, health condition, or mental condition.

In some embodiments, in the methods, systems, or computer-readable media described above or elsewhere herein relating to reference information, the reference information is obtained or presented concurrently with a query for the user regarding the user's dietary intake, exercise, health condition, or mental condition.

In some embodiments, in the methods, systems, or computer-readable media described above or elsewhere herein that relate to a user's response to a query regarding the user's dietary intake, exercise, health condition, or mental condition, the response is interpreted by means of a calibration matrix residing on a memory location of a computer system.

In some particular examples, in methods, systems, or computer-readable media described above or elsewhere herein that involve a user's response to a query regarding the user's dietary intake, exercise, health condition, or mental condition, the query is presented to the user by way of a Graphical User Interface (GUI) on an interactive display.

In some embodiments, in the methods, systems, or computer-readable media described above or elsewhere herein relating to a GUI, the GUI includes a customizable menu screen containing a selection of at least one, two, three, or four of the following applications: (a) a food intake component comprising information about a user's diet and an interface for inputting food, beverages, or other related information; (b) a exertion component having information related to a user's activity habits or schedule and an interface for entering user-specific activity information, exercise or other user-specific activity-related information; (c) a health component having information about the health of the user and an interface for responding to queries or inputting information related to the health of the user; (d) a mental condition component having information about a user's mental condition and an interface for responding to queries or entering information related to the user's mental condition; and (e) a calibration questionnaire component, wherein the user is presented with at least one selection of picture elements regarding dietary intake, exercise, health condition, or mental condition, and the user's selection of picture elements is used to establish a calibration matrix to interpret the user's perception of dietary allowance for dietary intake, exertion, state of health, or state of mental condition.

In some embodiments, in methods, systems, or computer-readable media described above or elsewhere herein that relate to calibration matrices, the calibration matrices reside in memory locations of a computer system.

In some embodiments, in the methods, systems, or computer-readable media described above or elsewhere herein relating to a user's response to a question regarding dietary intake, exercise, health condition, or mental condition, the response is interpreted using an internal calibration matrix of the user's perception of the dietary intake, the exertion level of the exercise, the present state of health condition, or the present state of mental condition.

In some embodiments, in methods, systems, or computer-readable media described above or elsewhere herein that relate to an internal calibration matrix, the internal calibration matrix is stored in a memory location of a computer system.

In some embodiments, in the methods, systems, or computer-readable media described above or elsewhere herein relating to a customizable menu screen, the customizable menu screen includes a selection of at least two of the applications.

In some embodiments, in methods, systems, or computer readable media described above or elsewhere herein relating to a system, the system is a point of service system configured to perform one or more assays on a sample.

In some embodiments, in methods, systems, or computer readable media described above or elsewhere herein relating to a point of service system, the point of service system is configured to perform one, two, three, or more assays on a sample.

In one particular example, there is provided a method of creating a data repository for records of individual subjects, the method comprising: correlating, using a processor, a genetic signature of a subject with at least one record of the subject, wherein the genetic signature is obtained by: (i) obtaining a biological sample comprising at least one nucleic acid molecule of a subject, and (ii) generating a genetic marker from the at least one nucleic acid molecule, wherein the genetic marker is indicative of the identity of the subject; and storing the gene signature and record in one or more databases. The method may be used to create a data repository for records of individual subjects. The method may further comprise repeating the above steps for at least one additional subject. The method may further comprise performing nucleic acid amplification of the at least one nucleic acid molecule on the sample processing device.

In another embodiment, a method of verifying the identity of an individual is provided, the method comprising: comparing, with the aid of a processor, a genetic signature of the individual with a pre-collected genetic signature of the individual stored in a memory unit, wherein the genetic signature is obtained by analyzing a biological sample of the individual submitted to a point of service site, the point of service site comprising a sample processing device configured to receive the biological sample from the individual and process the sample to produce the genetic signature, and a match between the genetic signature and the pre-collected genetic signature verifies the identity of the individual. The processor and the memory unit may or may not be part of the same device.

In another embodiment, a method of verifying the identity of an individual is provided, the method comprising: comparing, by means of a processor, a genetic signature of the individual with a pre-collected genetic signature of the individual stored in a memory unit, wherein the genetic signature is obtained by analyzing a biological sample of the individual, wherein an amount of time between collecting the biological sample from the individual and completing the comparison of the genetic signature with the pre-collected genetic signature does not exceed 24 hours, and wherein a match between the genetic signature and the pre-collected genetic signature verifies the identity of the individual. The processor and the memory unit may or may not be part of the same device.

In another embodiment, a method of verifying the identity of an individual is provided, the method comprising: comparing, by means of a processor, a genetic signature of the individual with a pre-collected genetic signature of the individual stored in a memory unit, wherein the genetic signature is obtained by analyzing a biological sample of the individual, wherein an amount of time between collecting the biological sample from the individual and completing the comparison of the genetic signature with the pre-collected genetic signature does not exceed 24 hours, and wherein a match between the genetic signature and the pre-collected genetic signature verifies the identity of the individual. The processor and the memory unit may or may not be part of the same device.

In yet another embodiment, a method of associating a genetic marker of an individual with a medical record is provided, comprising: comparing, by means of a processor, a genetic signature of an individual with a pre-collected genetic signature of the individual stored in a memory unit, wherein the genetic signature is obtained by analyzing a biological sample of the individual submitted at a point-of-service location and a match between the genetic signature and the pre-collected genetic signature verifies an identity of the individual, the pre-collected genetic signature having one or more medical records associated therewith, and the verification of the identity of the individual allows association of the genetic signature with the one or more medical records.

In another embodiment, there is provided a method of providing an individual with access to a secure location or device, comprising: comparing, by means of a processor, a genetic signature of the individual with a pre-collected genetic signature of the individual stored in a memory unit, wherein the genetic signature is obtained by analyzing a biological sample of the individual submitted to the point-of-service location, a match between the genetic signature and the pre-collected genetic signature verifies the identity of the individual, and if the verified identity of the individual belongs to a set of identities containing one or more identities that are allowed to use the secure location or device, the individual is provided access to the secure location or device.

In another embodiment, a method of verifying the identity of an individual is provided, comprising: comparing, by means of a processor, a genetic signature of an individual with a pre-collected genetic signature of the individual stored in a memory unit, and comparing a dynamic biometric signature of the individual with a pre-collected dynamic biometric signature of the individual stored in a memory unit, wherein the genetic signature and the dynamic biometric identifier are obtained by analyzing one or more biological samples of the individual submitted to a point of service location, and wherein a match between the genetic signature and the pre-collected genetic signature, and a degree of variation between the dynamic biometric identifier and the pre-collected dynamic biometric identifier, verifies an identity of the individual.

In another particular example, there is provided a method of creating a data repository with a unique identifier for records of individual subjects, the method comprising: associating, using a processor, a genetic signature of a subject with at least one record of the subject, wherein the genetic signature is a unique identifier of the subject, and wherein the genetic signature is obtained by: (i) obtaining a biological sample comprising at least one nucleic acid molecule of a subject, and (ii) generating a genetic signature from the at least one nucleic acid molecule, wherein the genetic signature is indicative of the identity of the subject, storing the genetic signature and record in one or more databases; and using the genetic signature as an index to provide access to records in the one or more data repositories.

In yet another specific example, there is provided a system for creating a data repository for records of individual subjects, the system comprising: a sample collection unit configured to obtain a biological sample suspected of containing at least one nucleic acid molecule of a subject; an identity generator configured to generate a genetic signature from the at least one nucleic acid molecule, wherein the genetic signature is indicative of the identity of the subject; a processor configured to associate the genetic signature with at least one record of an individual; and one or more databases configured to store the genetic markers and records.

In another specific example, there is provided a system for verifying the identity of an individual, the system comprising: a sample processing device configured to receive a biological sample from an individual; a memory unit configured to store a pre-collected genetic signature of an individual; a processor configured to compare a genetic signature of an individual with a pre-collected genetic signature; a sample collection unit configured to obtain a biological sample suspected of containing at least one nucleic acid molecule of a subject; an identity generator configured to generate a genetic signature from the at least one nucleic acid molecule, wherein the genetic signature is indicative of the identity of the subject; wherein the genetic marker is obtained by analyzing a biological sample of the individual submitted to a point of service location, the point of service location comprising a sample processing device configured to receive the biological sample from the individual and process the sample to produce the genetic marker, and a match between the genetic marker and the pre-collected genetic marker verifies the identity of the individual.

In another specific example, provided herein is a system for verifying the identity of an individual, the system comprising: a memory unit configured to store a pre-collected genetic signature of an individual; and a processor configured to compare a genetic signature of the individual with a pre-collected genetic signature, wherein the genetic signature is obtained by analyzing a biological sample of the individual, an amount of time between collecting the biological sample from the individual and completing the comparison of the genetic signature with the pre-collected genetic signature does not exceed 24 hours, and a match between the genetic signature and the pre-collected genetic signature verifies the identity of the individual.

In another specific example, there is provided a system for associating a genetic marker of an individual with a medical record, the system comprising: a memory unit configured to store a pre-collected genetic signature of an individual; and a processor configured to compare a genetic signature of the individual with a pre-collected genetic signature, wherein the genetic signature is obtained by analyzing a biological sample of the individual, a match between the genetic signature and the pre-collected genetic signature verifies the identity of the individual, the pre-collected genetic signature has one or more medical records associated therewith, and verification of the identity of the individual allows association of the genetic signature with the one or more medical records.

In some embodiments, there is provided a system for providing an individual with access to a secure location or device, the system comprising: a memory unit configured to store a pre-collected genetic signature of an individual; and a processor configured to compare the genetic signature of the individual with the pre-collected genetic signature, wherein the genetic signature is obtained by analyzing a biological sample of the individual, a match between the genetic signature and the pre-collected genetic signature verifies the identity of the individual, and if the verified identity of the individual belongs to a set of identities containing one or more identities that are allowed to use the secure location or device, the individual is provided access to the secure location or device. The system may also include a sample acquisition unit configured to obtain a biological sample suspected of containing at least one nucleic acid molecule of the subject; and a marker generator configured to generate a genetic marker from the at least one nucleic acid molecule, wherein the genetic marker is indicative of the identity of the subject.

In another specific example, there is provided a system for verifying the identity of an individual, the system comprising: one or more memory units configured to store a pre-collected genetic signature and a pre-collected protein signature of the individual; and a processor configured to compare a genetic signature of the individual with the pre-collected genetic signature, and to compare a protein signature of the individual with a pre-collected protein signature of the individual, wherein the genetic signature and the protein signature are obtained by analyzing one or more biological samples of the individual submitted to a point-of-service location, and wherein a match between the genetic signature and the pre-collected genetic signature, and a degree of change between the protein signature and the pre-collected protein signature that is within an acceptable range, verifies the identity of the individual.

In another particular example, there is provided a system for creating a data repository with unique identifiers for records of individual subjects, the system comprising: a marker generator configured to generate a genetic marker from at least one nucleic acid molecule from a personal subject, wherein the genetic marker is indicative of the identity of the subject; a processor configured to associate the genetic signature with at least one record of a subject, wherein the genetic signature is a unique identifier of the subject; and one or more databases configured to store genetic markers and records, wherein the genetic markers are indices to records in the one or more databases. The system may also include a sample acquisition unit configured to obtain a biological sample suspected of containing at least one nucleic acid molecule of the subject.

In yet another embodiment, a tangible computer-readable medium is provided that contains machine-executable code for implementing a method of creating a data repository for medical records of individual subjects, the method comprising: correlating, using a processor, a genetic signature of a subject with at least one record of the subject, wherein the genetic signature is obtained by: (i) obtaining a biological sample comprising at least one nucleic acid molecule of a subject, and (ii) generating a genetic marker from the at least one nucleic acid molecule, wherein the genetic marker is indicative of the identity of the subject; and storing the genetic markers and records in one or more databases, thereby creating a data repository for records of individual subjects.

In another embodiment, a tangible computer-readable medium is provided that contains machine-executable code for implementing a method for verifying the identity of a person, the method comprising: comparing, with the aid of a processor, a genetic signature of an individual with a pre-collected genetic signature of the individual stored in a memory unit, wherein the genetic signature is obtained by analyzing a biological sample of the individual submitted to a point of service location, the point of service location comprising a sample processing device configured to receive the biological sample from the individual and process the sample to produce the genetic signature, and a match between the genetic signature and the pre-collected genetic signature verifies the identity of the individual.

In yet another embodiment, a tangible computer-readable medium is provided that contains machine-executable code for implementing a method for verifying the identity of a person, the method comprising: comparing, by means of a processor, a genetic signature of an individual with a pre-collected genetic signature of the individual stored in a memory unit, wherein the genetic signature is obtained by analyzing a biological sample of the individual, wherein an amount of time between collecting the biological sample from the individual and completing the comparison of the genetic signature with the pre-collected genetic signature does not exceed 24 hours, and wherein a match between the genetic signature and the pre-collected genetic signature verifies the identity of the individual.

In another embodiment, a tangible computer-readable medium is provided that contains machine-executable code for implementing a method for verifying the identity of a person, the method comprising: comparing, by means of a processor, a genetic signature of an individual with a pre-collected genetic signature of the individual stored in a memory unit, wherein the genetic signature is obtained by analyzing a biological sample of the individual submitted at a point-of-service location, a match between the genetic signature and the pre-collected genetic signature verifies the identity of the individual, the pre-collected genetic signature has one or more medical records associated therewith, and the verification of the identity of the individual allows the association of the genetic signature with the one or more medical records.

In yet another embodiment, a tangible computer-readable medium is provided that contains machine-executable code for implementing a method for verifying the identity of a person, the method comprising: comparing, with the aid of a processor, a genetic signature of an individual with a pre-collected genetic signature of the individual stored in a memory unit, and a protein signature of an individual with a pre-collected protein signature of the individual stored in a memory unit, wherein the genetic signature and the protein signature are obtained by analyzing one or more biological samples of the individual submitted to a point-of-service location, a match between the genetic signature and the pre-collected genetic signature, and a degree of variation between the protein signature and the pre-collected protein signature within an acceptable range, verifying the identity of the individual.

In another embodiment, a tangible computer-readable medium is provided that contains machine-executable code for implementing a method of creating a data repository with unique identifiers for records of individual subjects, the method comprising: associating, using a processor, a genetic signature of a subject with at least one record of the subject, wherein the genetic signature is a unique identifier of the subject, and wherein the genetic signature is obtained by: (i) obtaining a biological sample comprising at least one nucleic acid molecule of a subject, and (ii) generating a genetic marker from the at least one nucleic acid molecule, wherein the genetic marker is indicative of the identity of the subject; storing the genetic markers and records in one or more databases; and using the genetic markers as an index to provide access to records in the one or more databases.

In some embodiments, the biological sample described above or elsewhere herein may be obtained via finger prick, scalpel, swab, or breath capture.

In some embodiments, the biological sample described above or elsewhere herein may contain at least one material selected from the group consisting of: blood, serum, saliva, urine, gastric fluid, tears, feces, semen, vaginal secretions, interstitial fluid derived from tumor tissue, ocular fluid, sweat, mucus, cerumen, oil, glandular secretions, hair, nails, skin, spinal fluid, plasma, nasal swab, or nasopharyngeal wash, spinal fluid, cerebrospinal fluid, tissue, pharyngeal swab, respiration, biopsy, placental fluid, amniotic fluid, umbilical cord blood, forceful fluid, body cavity fluid, sputum, pus, microbiota, meconium, milk, and any combination thereof.

In some embodiments, the biological sample described above or elsewhere herein may be obtained by a sample acquisition unit of a sample processing device.

In some embodiments, the sample processing device may generate the genetic marker in a system, method, or tangible computer-readable medium described above or elsewhere herein that relates to generating the genetic marker.

In some embodiments, in the systems, methods, or tangible computer-readable media described above or elsewhere herein that relate to generating genetic markers, the genetic markers may be generated on an external device at a location different from the sample processing device.

In some embodiments, in the systems, methods, or tangible computer-readable media described above or elsewhere herein relating to biological sample acquisition, a biological sample may be obtained at a point-of-service location.

In some specific examples, in systems, methods, or tangible computer-readable media described above or elsewhere herein that involve a sample processing device, the sample processing device may be located at a point-of-service location.

In some specific examples, in a system, method, or tangible computer-readable medium described above or elsewhere herein that involves one or more databases, the one or more databases can use a genetic signature as a unique identifier for at least one medical record.

In some embodiments, in the systems, methods, or tangible computer-readable media described above or elsewhere herein that relate to a pre-acquired genetic signature, the pre-acquired genetic signature can be associated with at least one medical record of an individual.

This summary is provided to introduce a selection of concepts in a simplified form that are further described below in the detailed description. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter.

Is incorporated by reference

All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

[ brief description of drawings ]

The novel features which are characteristic of at least some of the specific examples described herein are set forth with particularity in the appended claims. A better understanding of the features and advantages of the specific examples described herein may be obtained by reference to the detailed description that sets forth illustrative specific examples, in which at least some of the principles of the specific examples are utilized, and the accompanying drawings of which:

fig. 1 illustrates an example of a system including a sample processing device and an external controller, according to one specific example described herein.

Fig. 2 shows an example of a sample processing device.

FIG. 3 shows an example of a module having a sample preparation meter, a probe, and a liquid handling system.

Fig. 4 provides an example of a rack supporting a plurality of modules having a vertical arrangement.

Fig. 5 provides an example of a rack supporting a plurality of modules in an array arrangement.

Fig. 6 illustrates a plurality of modules having a staggered arrangement.

FIG. 7 shows an example of a sample processing device having multiple modules.

Fig. 8 shows a plurality of racks supporting one or more modules.

FIG. 9 shows an example of a module with one or more components in communication with a controller.

Fig. 10 illustrates a system having a plurality of modules mounted in a rack (e.g., including being mounted on a rack).

FIG. 11 shows a plurality of plots illustrating a parallel processing convention.

Fig. 12 shows an exploded view of a positive displacement pipette.

Fig. 13 shows a side view of a positive displacement pipette in the full pipette position.

Fig. 14 shows a side view of the positive displacement pipette in the full dispensing position.

Fig. 15 shows an external view of the vented pipette.

Fig. 16 shows a cross-sectional view of a vented pipette.

Fig. 17 shows a close-up of the interface between the pipette tip and the nozzle.

Fig. 18 shows an example of a drive removing device.

Fig. 19A shows a multiheaded pipette in accordance with one specific example described herein.

Fig. 19B shows a side view of the pipette.

Fig. 20 shows a cross-sectional view of a vented pipette.

Fig. 21 shows a plurality of pipettes with removal means.

Fig. 22 shows an example of a multiheaded pipette in accordance with one specific example described herein.

Fig. 23 provides an example of a multiheaded pipette provided in accordance with another specific example described herein.

FIG. 24 provides a diagram of a vessel that can be used for nucleic acid assays, according to one embodiment described herein.

Fig. 25 illustrates a method for using a container according to another specific example described herein.

FIG. 26A provides an illustration of a vessel that can be used for centrifugation, according to one specific example described herein.

FIG. 26B provides a pictorial view of a tip that may be used for centrifugation, according to one embodiment described herein.

Figure 27 provides a pictorial view of a pipette tip that may be used in liquid handling.

Figure 28 shows an example of a cavity.

Fig. 29 illustrates an example of a bulk handling tip according to one specific example described herein.

FIG. 30 is an example of an assay tip that can provide a colorimetric reading.

Fig. 31 illustrates an example of a sample tip for processing or fractionating a sample, such as a blood sample.

Figure 32 is an example of a current reaction tip.

FIG. 33 illustrates the interface between the mini-tip nozzle and the mini-tip.

FIG. 34 provides an example of a mini-tip.

FIG. 35 provides an illustration of a microcard and substrate plate with a microcap tip according to one embodiment described herein.

Fig. 36 illustrates an example of a centrifuge provided according to one specific example described herein.

Fig. 37 provides another example of a centrifuge according to one specific example described herein.

Fig. 38 illustrates an additional example of a centrifuge provided in accordance with another specific example described herein.

Fig. 39 shows a system including a device that communicates with an external device through a network.

FIG. 40 illustrates a method of processing a sample provided in accordance with one specific example described herein.

Fig. 41A shows an SPI bridge procedure with a master bridge and a parallel-serial SPI (serial peripheral interface) slave bridge. Fig. 41B shows an example of an SPI bridge. Fig. 41C shows a modular component diagram with the various components of the interconnect module pin and the master and slave bridges. Fig. 41D shows a slave bridge connected to the master bridge. FIG. 41E shows a device having a plurality of modules installed on the SPI link of the communication exchange vehicle of the device.

Fig. 42 shows an operation matrix of the service point system.

FIG. 43 is an example of an operational matrix of a service point system and/or one or more modules of the service point system.

Fig. 44 shows an operation matrix and a conventional matrix.

45A-45C illustrate examples of operation matrices with normal and processing states.

Fig. 46 illustrates an example of a fluid treatment device in a retracted position provided in accordance with one specific example described herein.

FIG. 46A shows the fluid treatment device in a fully retracted position, retracted as previously described.

FIG. 46B shows the retracted fluid treatment device in a fully Z-down position.

Fig. 47 illustrates an example of a liquid treatment device in an extended position, according to one specific example described herein.

Fig. 48 shows a front view of a liquid treatment device.

Fig. 49 shows a side view of a liquid treatment device.

Fig. 50 shows another side view of the liquid treatment device.

Fig. 51 shows a rear perspective view of the liquid handling device.

Fig. 52 provides an example of a liquid handling device for carrying a sample processing assembly.

FIG. 53 shows a side view of a liquid handling device for carrying a sample processing assembly.

Fig. 54 shows an example of a cam switch arrangement according to one specific example described herein. FIG. 54A shows an example of a binary cam in the null position, where the cam has rotated 0 degrees. Fig. 54B shows an example of a binary cam in position 1, where the cam has rotated 22.5 degrees. Fig. 54C shows an example of a binary cam in position 5, where the cam has rotated 112.5 degrees. Fig. 54D shows an example of a binary cam in position 15, where the cam has rotated 337.5 degrees. Fig. 54E illustrates a motor mounted selection cam according to one specific example described herein.

FIG. 55 shows an example of a liquid treatment device using one or more light sources according to one specific example described herein. Fig. 55A shows a plurality of pipette tips. Fig. 55B shows a side cross-sectional view of the liquid treatment device. Fig. 55C shows a close-up of a light source that may be provided within a liquid treatment device. Fig. 55D shows a close-up of the plunger and pipette nozzle. Fig. 55E shows a perspective view of the liquid handling device.

FIG. 56 illustrates a point of service device having a display according to one specific example described herein. The display includes a Graphical User Interface (GUI).

Fig. 57 shows a table listing sample preparation examples.

Fig. 58 shows a table listing examples of possible assays.

Fig. 59 shows an example of a tip interface, which includes an example of a threaded arrangement.

Fig. 60 provides an additional example of a nozzle-tip interface using a press-fit interface.

Fig. 61 shows an example of an internal thread pick-up interface.

FIG. 62 illustrates an example of an O-ring tip pick-up interface.

Fig. 63 provides an example of expanding/contracting a smart material tip pick-up interface.

Fig. 64 provides an example of an expanding/contracting elastomeric deflected tip pick-up interface.

Fig. 65 provides an example of a vacuum gripper tip pick-up interface.

Fig. 66 provides an example of a pipette module according to one specific example described herein.

Fig. 67A shows an example of a modular pipette with a raised shuttle in a full dispense position.

Fig. 67B shows an example of a modular pipette with a lowered shuttle in a full dispense position.

Fig. 68A provides a top view of an example of a magnetic control.

FIG. 68B provides a side view of the magnetic control.

Fig. 69 provides an example of a cuvette and cuvette holder.

Fig. 70A illustrates an example of a rack (e.g., cuvette) according to one specific example described herein.

Fig. 70B shows an additional view of a holder (e.g., cuvette).

Figure 71 shows an example of a cleaner head.

Fig. 72 shows an example of a vial strip.

Fig. 73 shows another example of a vial strip.

Fig. 74A-74D show spectrophotometers.

Fig. 75A shows a protocol involving a laboratory, a sample collector, and a healthcare professional.

Fig. 75B shows a retailer having a processing device in communication with an actual authorization device (e.g., without limitation, a CILA or ISO certified laboratory).

Fig. 76 illustrates a processing device that may be placed at a designated sample acquisition instrument and configured to communicate with one or more other devices over a network.

FIG. 77A illustrates various exemplary components of a processing device.

Fig. 77B illustrates another example of a device.

Fig. 78 shows an example of a sample collection, processing, and analysis method.

FIG. 79 illustrates a laboratory welfare manager in communication with a payer and a sample collector.

Fig. 80 illustrates a laboratory welfare system provided in accordance with one specific example described herein.

FIG. 81 illustrates an example of a laboratory welfare manager/wholesaler model according to one specific example described herein.

FIG. 82 illustrates an example of a system that provides sample processing, analysis, and supervision.

FIG. 83 illustrates a method for connecting a network-enabled device (also referred to herein as a "network device") to a network, according to one embodiment described herein.

Fig. 84 illustrates a method for connecting a network device to a network, according to a specific example described herein.

Fig. 85 illustrates a method for generating a ranked list of network providers, according to a specific example described herein.

FIG. 86 illustrates a system with an electronic device and a network provider, according to a specific example described herein.

FIG. 87 illustrates a functional block diagram icon of a general computer hardware platform, according to a specific example described herein.

FIG. 88 illustrates a first network enabled device in communication with a second network enabled device according to a specific example described herein.

[ embodiment ] A method for producing a semiconductor device

While various specific examples have been shown and described herein, it will be obvious to those skilled in the art that such specific examples are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the specific examples described herein may be employed in practicing the invention.

The term "module" as used herein refers to a device, component, or apparatus that includes one or more components or stand-alone units configured as part of a larger device or apparatus. In some cases, a module works independently and independently of another module. In other cases, a module works in conjunction with other modules (e.g., modules within a module) to perform one or more tasks, such as assaying a biological sample.

The term "sample processing system" as used herein refers to an apparatus or system configured to facilitate imaging, probing, positioning, repositioning, retaining, capturing, and depositing of a sample. In one example, the robot with pipetting capability is a sample processing system. In another example, a pipette that may or may not have (other) robotic capabilities is a sample processing system. The sample processed by the sample processing system may or may not include a liquid. The sample processing system may be capable of transporting bodily fluids, secretions, or tissues. The sample processing system may be capable of transporting one or more substances within the apparatus that are not necessarily samples. For example, the sample processing system may be capable of transporting a powder that is reactive with one or more samples. In some cases, the sample processing system is a liquid processing system. The liquid handling system may include various types of pumps and valves or pipettes, which may include, but are not limited to, positive displacement pipettes, vented pipettes, and suction pipettes. The sample processing system may transport samples or other substances by means of robots as described elsewhere herein.

The term "healthcare provider" as used herein refers to a doctor or other healthcare professional who provides medical treatment and/or medical advice to a subject. The healthcare professional can include a person or entity associated with the healthcare system. Examples of healthcare professionals can include doctors (including general and specialist doctors), surgeons, dentists, audiologists, speech pathologists, physician assistants, nurses, midwives, pharmacists/pharmacists, dieticians, therapists, psychologists, therapists, clinical physicians, physical therapists, phlebotomists, occupational therapists, optometrists, emergency medical technicians, paramedics, medical laboratory technicians, medical prosthesis technicians, radiology technicians, social workers, and numerous other human resources trained to provide some type of healthcare service. The healthcare professional may or may not prescribe a qualification. Healthcare professionals may be working at or affiliated with hospitals, healthcare sites, and other service providers, or may also work in academic training, research, and management departments. Some healthcare professionals can provide care and treatment services to patients at private or public places, cell centers, or gathering sites or mobile units. The community health care workers may work outside of the formal healthcare facilities. The healthcare service manager, medical records and health information technician, and other support personnel may also be healthcare professionals or affiliated with the healthcare provider. A healthcare professional may be an individual or a device that provides preventive, therapeutic, promotional, or rehabilitative healthcare services to an individual, home, or community.

In some embodiments, the healthcare professional may already be familiar with the subject or have communicated with the subject. The subject may be a patient of a healthcare professional. In some cases, a healthcare professional may have prescribed a subject to undergo clinical testing. A healthcare professional may have instructed or advised the subject to undergo clinical testing at a point-of-service site or by a laboratory. In one example, the healthcare professional can be a basic healthcare physician of the subject. The healthcare professional may be any type of physician of the subject (including a general practitioner, referred to as a medical practitioner, or a physician who the patient selects and connects with, either by himself or by a telemedicine service, and/or a specialist). The healthcare professional can be a healthcare professional.

The term "rack" as used herein refers to a frame or housing for mounting a plurality of modules. The bracket is configured to allow the module to be secured to or engaged with the bracket. In some cases, the dimensions of the stent are standardized. In one example, the spacing between modules is normalized to a multiple of at least about 0.5 inches, or 1 inch, or 2 inches, or 3 inches, or 4 inches, or 5 inches, or 6 inches, or 7 inches, or 8 inches, or 9 inches, or 10 inches, or 11 inches, or 12 inches.

The term "cell" as used in the context of biological samples includes samples that are substantially similar in size to a single cell, including but not limited to vesicles (such as liposomes), cells, virosomes, and substances associated with small particles such as beads, nanoparticles, or microspheres. Characteristics include, but are not limited to, size; a shape; temporal and dynamic changes such as cell movement or proliferation; particle size; whether the cell membrane is intact; cellular contents including, but not limited to, protein content, protein modifications, nucleic acid content, nucleic acid modifications, organelle content, nuclear structure, nuclear contents, internal cellular structures, internal vesicle content, ion concentration, and expression of other small molecules such as steroids or drugs; and cell surface (cell membrane and cell wall) markers including proteins, lipids, carbohydrates and modifications thereof.

One specific example described herein provides a system and method for multipurpose analysis of a sample or health parameter. A sample may be collected and one or more sample preparation steps, assay steps, and/or detection steps may be performed on the device. The specific examples described herein may be applicable to any of the specific applications, systems, and devices set forth below. The invention may be applied as a stand-alone system or method, or as part of an integrated system, such as in a system involving point-of-service healthcare. In some embodiments, the system may include external directional imaging techniques (such as ultrasound or MRI), or be integrated with peripherals for integrated imaging and other health detection or services. It is to be understood that the various embodiments described herein may be understood and implemented individually, collectively, or in any combination.

According to one specific example described herein, a system for one or more multipurpose analyses and/or sample processing may be provided.

FIG. 1 illustrates an example of a system. A system may include one or more sample processing devices 100, which sample processing devices 100 may be configured to receive a sample and/or perform multipurpose analysis of one or more samples or one or more types of samples, either sequentially or simultaneously. The analysis may occur within the system. The analysis may or may not occur on the device. The system may contain one, two, three or more sample processing devices. The sample processing devices may or may not be in communication with each other or external devices. The analysis may or may not occur on the external device. The analysis may be effected by means of a software program and/or a healthcare professional. In some cases, the external device may be the controller 110.

A system for multi-purpose analysis may include one or more sets of sample processing devices. A sample processing device suite may contain one or more devices 100. The devices may be grouped according to geography, associated entities, facilities, space, routers, hubs, healthcare providers, or may have any other grouping means. The devices within the groups may or may not communicate with each other. The devices within each group may or may not communicate with one or more external devices.

The sample processing apparatus may include one, two, or more modules 130. The modules may be removably provided to the device. The module may be capable of performing a sample preparation step, an assay step, and/or a detection step. In some embodiments, each module may be capable of performing a sample preparation step, an assay step, and/or a detection step. In some embodiments, one or more modules may be supported by a support structure 120 (such as a rack). Zero, one, two or more holders may be provided for the device.

A module may contain one, two or more components 140, which components 140 may be capable of performing sample preparation steps, assay steps and/or detection steps. The cartridge assembly may also include reagents and/or containers or vessels that may perform the sample preparation steps, the assay steps, and/or the detection steps. The cartridge assembly may assist in the sample preparation step, the assay step, and/or the detection step. A device may contain one or more components that are not provided within a module. In some cases, the assembly may be useful for only one of the sample preparation steps, the assay steps, and/or the probing steps. Examples of components are provided in more detail elsewhere herein. A component may have one or more subcomponents.

In some cases, a hierarchy may be provided in a system comprising one or more sets of devices, a set of devices comprising one or more devices, a device may in turn or comprise one or more racks, the racks may comprise one or more modules, a device may comprise one or more modules, a module and/or device may comprise one or more components, and/or a component may comprise one or more subcomponents of the component. One or more levels of hierarchy are optional and need not necessarily be provided in the system. Alternatively, all levels of the hierarchy described herein may be provided within the system. Any discussion herein that applies to one level of the hierarchy may also apply to other levels of the hierarchy.

According to one specific example described herein, a sample processing device is provided. The sample processing apparatus may include one or more components. The sample processing device may be configured to receive a sample and/or perform one or more sample preparation steps, assay steps, and/or detection steps. The sample preparation step, the assay step and/or the detection step may be performed automatically without human intervention.

In some embodiments, the device may be or contain a cassette. The cassette is removable from the large apparatus. Alternatively, the cartridge may be permanently attached to or integral with the device. The device and/or cartridge (both) may be components of a disposable such as a patch or pill.

The cassettes may be generic cassettes that may be configured for the same detection options. The universal cassette can be dynamically programmed for certain detections by remote or onboard protocols. In some cases, the cartridge may be loaded with all reagents and, in turn, or alternatively, have server-side (or local) control over a two-way communication system. In this case, the apparatus or cassette may not require tubing, replaceable tanks, or other specific instances that require manual maintenance, calibration, and compromise quality due to manual intervention and processing steps.

In some embodiments, the cartridge contains a chemical reaction package for locally generating heat to enhance kinetics, or for cooling the mixture. The cartridge may have isolated regions under temperature control (e.g., regions with high temperatures for nucleic acid detection) without affecting other parts of the cartridge/apparatus. The cassette may also be transitioned to a different configuration based on external or internal stimuli. The stimulus may be sensed via a sensor on the cassette body or as part of the cassette. More common sensors, such as RFID tags, may also be part of the cassette. For example, if sample acquisition and analysis are performed at two different locations (e.g., for a patient in intensive care, a sample is acquired from the patient and then transferred to a device for analysis), the cassette may be equipped with a biometric sensor. This allows associating patient samples with the cartridge, thereby preventing errors. The cassettes may have electrical and/or fluidic interconnections to communicate signals and/or fluids between different containers, tips, etc. on the cassette. The cassette may also contain detectors and/or sensors.

The intelligent cassette design with feedback, self-learning, and sensing means enables compact form factor, waste reduction, and higher efficiency with point of service utility.

In one specific example, a separate external robotic system may be utilized in situ to assemble new cassettes as needed in real time. Alternatively, such capability may be part of the device or cassette.

Fig. 2 shows an example of a device 200. The device may have a sample acquisition unit 210. The apparatus may include one or more support structures 220, which support structures 220 may support one or more modules 230a, 230 b. The device may include a housing 240, which housing 240 may support or contain the remainder of the device. The device may also include a controller 250, a display 260, a power unit 270, and a communication unit 280. The device may be able to communicate with the external device 290 through the communication unit. A device may have a processor and/or memory that may be capable of performing or providing instructions for one or more steps to be performed by the device, and/or may be capable of storing one or more instructions.

Sample collection

The apparatus may comprise a sample acquisition unit. The sample acquisition unit may be configured to receive a sample from a subject. The sample acquisition unit may be configured to receive the sample directly from the subject, or may be configured to receive the sample that has been acquired from the subject indirectly.

One or more collection devices may be used in the collection of a sample from a subject. The collection device may use one or more principles in the collection of the sample. For example, the sample acquisition device may use gravity, capillary action, surface tension, suction, vacuum force, pressure differential, density differential, thermal differential, or any other mechanism or combination thereof in sample acquisition.

The body fluid may be drawn from the subject and provided to the device in a variety of ways, including but not limited to: finger stick, incision, injection, aspiration, wiping, pipetting, breath, and/or any other technique described elsewhere herein. A body fluid collector may be used to provide body fluid. The body fluid collector may comprise a scalpel, a capillary tube, a test tube, a pipette, a syringe, a needle, a micro-needle, a pump, a laser, a porous membrane, or any other collector described elsewhere herein. The body fluid collector may be integrated into the cartridge or onto the device, such as by containing a scalpel and/or capillary tube on the cartridge body or one or more containers, or by a pipette that can draw a biological sample directly from the patient. The harvester can be operated directly or remotely by a human or automated. One means of achieving automation or remote human manipulation may be by incorporating a camera or other sensing device into the collector itself or the device or cassette or any component thereof and using the sensing device to guide sample collection.

In one particular example, a scalpel pierces the skin of a subject and draws a sample, for example, using gravity, capillary action, suction, pressure differential, and/or vacuum force. The scalpel or any other body fluid collector may be part of the device, part of the cartridge of the device, part of the system, or a separate component. In another embodiment, a laser may be used to pierce the skin or cut a tissue sample from the patient. Lasers may also be used at the anesthesia sample collection site. In yet another specific example, the sensor may take an optical measurement through the skin rather than invasively obtaining the sample. In some embodiments, the patch may include a plurality of micro needles that may pierce the skin of the subject. The scalpel, patch, or any other body fluid collector may be activated by various mechanical, electrical, electromechanical, or other known activation mechanisms, or any combination of such methods, as desired.

In some cases, the body fluid collector may be a lancing device that may be provided on or may be a disposable. The lancing device can be used to communicate the sample or information about the sample to a non-disposable device that can process the sample. Alternatively, the disposable puncturing device itself may process and/or analyze the sample.

In one example, a finger of a subject (or other part of the subject's body) may be pierced to obtain a body fluid. The body fluid may be collected using a capillary tube, pipette, swab, dropper, or any other mechanism known in the art. The capillary or pipette may be separate from the device and/or the cartridge of the device, may be inserted into or attached to the device, or may be part of the device and/or cartridge. In another specific example where an enabling mechanism (outside the body) is not required, the subject may simply provide a body fluid to the device and/or cartridge, e.g. as may be done with a saliva sample or a finger prick sample.

The body fluid may be drawn from the subject and provided to the device in a variety of ways, including but not limited to: finger prick, incision, injection and/or pipetting. Body fluids may be collected using intravenous or non-intravenous methods. Body fluids may be provided using a body fluid collector. The body fluid collector may comprise a scalpel, a capillary tube, a test tube, a pipette, a syringe, an intravenous hemospast, or any other collector described elsewhere herein. In one particular example, a scalpel pierces the skin and draws a sample, for example, using gravity, capillary action, suction, or vacuum force. The scalpel may be part of the reader device, part of the cartridge, part of the system or a separate component, which may be disposable. The scalpel may be activated by a variety of mechanical, electrical, electromechanical or any other known activation mechanisms or any combination of such methods, as desired. In one particular example, a finger of a subject (or other part of the subject's body) may be pierced to obtain a body fluid. Examples of other parts of the subject's body may include, but are not limited to: the subject's hand, wrist, arm, torso, leg, foot, ear, or neck. The body fluid may be collected using a capillary tube, pipette, or any other mechanism known in the art. The capillary or pipette may be separate from the device and/or cartridge or may be part of the device and/or cartridge or container. In another specific example where an enabling mechanism is not required, the subject may simply provide a body fluid to the device and/or cartridge, e.g., as may be done with a saliva sample. The collected liquid may be placed in the device. The body fluid collector may be attached to the device, removably attached to the device, or may be provided separately from the device.

In some embodiments, the sample may be provided directly to the device, or additional containers or components may be used that may serve as conduits or means for providing the sample to the device. In one example, the waste may be wiped onto the cartridge or may be provided to a receptacle on the cartridge. In another example, the urine cup may be ejected from a cartridge of the device, a peripheral of the device, or a device. Alternatively, the capsule may be pushed out, pulled out and/or twisted out of the cassette or a peripheral of the cassette of the apparatus. Urine may be provided directly to the small container or from a urine cup. In yet another example, a nasal swab collection may be inserted into the cassette. The cartridge may include a buffer that can interact with a nasal swab collection. In some cases, the cartridge may include one or more reservoirs or reservoirs with one or more reagents, diluents, detergents, buffers, or any other solution or material. The tissue sample may be placed on a slide that may be embedded within a cassette to process the sample. In some cases, the tissue sample may be provided to the cassette by any means (e.g., opening, tray), and the slide is automatically prepared within the cassette. The liquid sample may be provided to the cartridge and the cartridge may in turn or be prepared as a slide within the cartridge. Any description of providing a sample to a cartridge or container therein may also apply to providing a sample directly to an apparatus without a cartridge. Any step described herein as being performed by a cassette may be performed by the apparatus without the cassette.

Containers for sample collection may be configured for obtaining samples from a wide range of different biological, environmental and any other substrates. The container may be configured to receive a sample directly from a body part, such as a finger or arm, by contacting the body part with the container. The sample may also be introduced by a sample transfer device which may in turn or be designed for a single step process in the transfer of the sample into a container or cassette or into a device. The collection container may be designed and customized for each different sample matrix (such as urine, feces, or blood) being processed. For example, the sealed container may be twisted off or ejected from a conventional urine cup so that it can be placed directly into the cartridge without pipetting the sample. The container for sample collection may be configured for obtaining blood from a finger prick (or other puncture site). The collection container may be configured with one or more access ports, each of which is connected to one or more isolation chambers. The collection container may be configured with only a single access port connected to one or more of the isolated chambers. The collected sample may flow into the chamber via capillary action. Each isolation chamber may contain one or more reagents. Each isolated chamber may contain a different reagent than the other chambers. The reagent in the chamber may be coated on the chamber walls. Reagents may be deposited in certain regions of the chamber and/or in a gradient to control the mixing and distribution of the reagents in the sample. The chamber may contain an anticoagulant (e.g., lithium heparin, EDTA (ethylenediaminetetraacetic acid), citric acid). The chambers may be arranged such that no mixing of the sample between the chambers occurs. The chambers may be arranged such that an appropriate amount of mixing occurs between the chambers. Each chamber may be the same or different size and/or volume. The chambers may be configured to be filled with the sample at the same or different rates. The chamber may be connected to an entry port via an opening or port that may have a valve. Such a valve may be configured to allow liquid flow in one direction or in both directions. The valve may be passive or active. The sample collection container may be transparent or opaque in certain areas. The sample collection container may be configured with one or more opaque regions to allow for automated and/or manual evaluation of the sample collection process. The sample in each chamber may be extracted by the apparatus via a sample processing system equipped with a tip or container for interfacing with a sample collection container. The sample in each chamber may be forced out of the chamber by a plunger. Samples may be extracted or expelled from each chamber individually or simultaneously.

The sample may be collected from the environment or any other source. In some cases, the sample is not taken from the subject. Examples of samples may include liquids (such as liquids, gases, gels), solids, or semi-solid materials that can be detected. In one scenario, a food product may be tested to determine if the food is safe to eat. In another scenario, environmental samples (e.g., water samples, soil samples, air samples) may be tested to determine if there are any contaminants or poisons. Such samples may be collected using any device, including those described elsewhere herein. Alternatively, such samples may be provided directly to the apparatus, cartridge or container.

The collected liquid may be placed in the device. In some cases, the collected liquid is placed within a cartridge of the device. The collected liquid may be placed in any other area of the device. The device may be configured to receive a sample, whether it is directly from the subject, from a body fluid collector, or from any other means. The sample acquisition unit of the device may be configured to receive the sample.

The body fluid collector may be attached to the device, removably attached to the device, or may be provided separately from the device. In some cases, the body fluid collector is integral with the device. The body fluid collector may be attached or removably attached to any part of the device. The body fluid collector may be in fluid communication with, or rendered in fluid communication with, the sample collection unit of the device.

The cartridge may be inserted into or otherwise interface with the sample processing device. The cassette may be attached to the device. The cassette is removable from the apparatus. In one example, the sample may be provided to a sample acquisition unit of the cartridge. The sample may or may not be provided to the sample collection unit via the body fluid collector. The body fluid collector may be attached to the cartridge, removably attached to the cartridge, or may be provided separately from the cartridge. The body fluid collector may or may not be integral with the sample collection unit. Then, the cassette may be inserted into the apparatus. Alternatively, the sample may be provided directly to the apparatus, which may or may not use a cartridge. The cartridge may contain one or more reagents which may be used in the operation of the apparatus. The reagents may be self-contained within a cartridge. The reagent may be provided to the apparatus via the cartridge without pumping the reagent into the apparatus via the cuvette and/or buffer reservoir. Alternatively, one or more reagents may already be provided on the device. The cartridge may comprise a housing and insertable test tubes, containers or tips. The vessel or tip may be used to store reagents required for running the probe. Some containers or tips may be preloaded onto the cassette. Other containers or tips may be stored within the apparatus, possibly in a cooled environment as desired. At the time of detection, the apparatus can assemble the on-board stored containers or tips with specific cassettes as needed by using a robotic system within the apparatus.

The body fluid collector or any other collecting device may be disposable. For example, the body fluid collector may be used once and discarded. The body fluid collector may have one or more disposable components. Alternatively, the body fluid collector may be reusable. The body fluid collector can be reused any number of times. In some cases, the body fluid collector may include both a reusable component and a disposable component. To reduce the environmental impact of disposal, the material of the cassette or other body fluid collector may be made of a decomposable material or other "green" material.

Any components inserted into the system or device may be identified based on identification tags or labels and/or other communication means. Based on the identification of such components, the system may ensure that the components are suitable for use (e.g., have not exceeded their validity period). The system may cross-reference an onboard database and/or a remote database containing data and information about the components.

The components inserted into the system or device may include on-board sensors. Such sensors may be responsive to temperature, humidity, light, pressure, vibration, acceleration, and other environmental factors. Such sensors may be sensitive to a combination of absolute levels, exposure level duration, cumulative exposure levels, and other factors. When the component is inserted into a system or apparatus or interfaced with a user interface, the system or apparatus may read and/or communicate with such sensors to determine how and if the one or more components are suitable for use in the system/apparatus based on a set of rules.

The sample acquisition unit and/or any other part of the apparatus may be capable of receiving a single type of sample or multiple types of samples. For example, the sample collection unit may be capable of receiving two different types of bodily fluids (e.g., blood, tears). In another example, the sample acquisition unit may be capable of receiving two different types of biological samples (e.g., urine samples, stool samples). Various types of samples may or may not be liquid, solid, and/or semi-solid. For example, the sample collection unit may be capable of receiving one or more, two or more, or three or more bodily fluid, exudate and/or tissue samples.

The device may be capable of receiving a single type of sample or multiple types of samples. The device may be capable of processing a single type of sample or multiple types of samples. In some cases, a single body fluid collector may be used. Alternatively, multiple and/or different body fluid collectors may be used.

Sample(s)

In one specific example described herein, a sample may be received by a device. Examples of the sample include various liquid samples. In some cases, the sample may be a sample of bodily fluid from the subject. The sample may be an aqueous sample or a gaseous sample. The sample may be a gel. The sample may include one or more liquid components. In some cases, a solid or semi-solid sample may be provided. The sample may comprise tissue collected from a subject. The sample may include body fluids, secretions, and/or tissues of the subject. The sample may be a biological sample. The biological sample may be a bodily fluid, exudate and/or tissue sample. Examples of biological samples may include, but are not limited to: blood, serum, saliva, urine, gastric and digestive fluids, tears, feces, semen, vaginal secretions, interstitial fluid derived from tumor tissue, ocular fluid, sweat, mucus, cerumen, oil, glandular secretions, breath, spinal fluid, hair, nails, skin cells, plasma, nasal swab biopsy (nasal swab) or nasopharyngeal wash, spinal fluid, cerebrospinal fluid, tissue, pharyngeal swab, biopsy, placental fluid, amniotic fluid, umbilical cord blood, forceful fluid, body cavity fluid, sputum, pus, microorganisms, meconium, milk, and/or other excretions. The sample may be provided from a human or animal. The sample may be provided from a mammal, vertebrate, such as a murine, simian, human, farm animal, sport animal or pet. Samples may be taken from live subjects or from dead subjects.

The sample may be freshly collected from the subject, or may have been subjected to some form of pre-treatment, storage or transport. The sample may be provided from the subject to the apparatus without intervention or for a prolonged period of time. The subject may contact the device, cartridge, and/or container to provide the sample.

The subject may provide a sample, and/or the sample may be collected from the subject. The subject may be a human or an animal. The subject can be a mammal, a vertebrate, such as a murine, simian, human, farm animal, sport animal, or pet. The subject may be alive or dead. The subject may be a patient, a clinical subject, or a preclinical subject. The subject may be undergoing diagnostic, therapeutic and/or disease management or lifestyle or preventive care. The subject may or may not be a subject under the care of a healthcare professional.

The sample may be collected from the subject by puncturing the skin of the subject or without puncturing the skin of the subject. A sample may be collected through the orifice of a subject. A tissue sample, whether it be an internal tissue sample or an external tissue sample, may be collected from a subject. The sample may be taken from any part of the subject including, but not limited to, the subject's fingers, hands, arms, shoulders, torso, abdomen, legs, feet, neck, ears, or head.

In some embodiments, the sample may be an environmental sample. Examples of environmental samples may include air samples, water samples, soil samples, or plant samples.

Additional samples may include food products, beverages, manufacturing materials, textiles, chemicals, treatments, or any other sample.

The apparatus may receive and/or process one type of sample. Alternatively, the device may receive and/or process multiple types of samples. For example, the device may be capable of receiving one or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, twelve or more, fifteen or more, twenty or more, thirty or more, fifty or more, or one hundred or more types of samples. The device may be capable of receiving and/or processing any of these number of sample types from different or the same substrates simultaneously and/or at different times. For example, the device may be capable of preparing, assaying, and/or probing one or more types of samples.

Any volume of sample may be provided from the subject or from another source. Examples of volumes may include, but are not limited to: about 10mL or less, 5mL or less, 3mL or less, 1 μ L or less, 500 μ L or less, 300 μ L or less, 250 μ L or less, 200 μ L or less, 170 μ L or less, 150 μ L or less, 125 μ L or less, 100 μ L or less, 75 μ L or less, 50 μ L or less, 25 μ L or less, 20 μ L or less, 15 μ L or less, 10 μ L or less, 5 μ L or less, 3 μ L or less, 1 μ L or less, 500nL or less, 250nL or less, 100nL or less, 50nL or less, 20nL or less, 10nL or less, 5nL or less, 1nL or less, 500pL or less, 100pL or less, 50pL or less, or 1nL or less, 500pL or less, 100pL or less, or 50pL or less, or 1pL or less, or 1pL or less. The amount of sample may be about 1 drop of sample. The amount of sample can be about 1-5 drops of sample, 1-3 drops of sample, 1-2 drops of sample, or less than 1 drop of sample. The amount of sample may be the amount collected from a pricked finger or a finger prick. Any volume, including those described herein, may be provided to the apparatus.

Sample to apparatus

The sample acquisition unit may be integral with the apparatus. The sample acquisition unit may be separate from the apparatus. In some embodiments, the sample acquisition unit is removable from and/or insertable into the device. The sample acquisition unit may or may not be provided in the cartridge. The cartridge may or may not be removable and/or insertable from the device.

The sample acquisition unit may be configured to receive a sample. The sample acquisition unit may be capable of containing and/or confining a sample. The sample acquisition unit may be capable of transferring the sample to another part of the apparatus.

The sample acquisition unit may be in fluid communication with one or more modules of the apparatus. In some cases, the sample acquisition unit may be in permanent liquid communication with one or more modules of the apparatus. Alternatively, the sample acquisition unit may be caused to enter and/or exit liquid communication with the module. The sample acquisition unit may or may not be selectively fluidly isolated from one or more of the modules. In some cases, the sample acquisition unit may be in fluid communication with each module of the apparatus. The sample acquisition unit may be in permanent fluid communication with each module, or may be brought into and/or out of fluid communication with each module.

The sample acquisition unit can be selectively brought into and/or out of fluid communication with one or more modules. The fluid communication may be controlled according to one or more protocols or a set of instructions. The sample acquisition unit may be brought into liquid communication with the first module and out of liquid communication with the second module, and vice versa.

Similarly, the sample acquisition unit may be in fluid communication with one or more components of the apparatus. In some cases, the sample acquisition unit may be in permanent liquid communication with one or more components of the apparatus. Alternatively, the sample acquisition unit may be brought into and/or out of liquid communication with the apparatus assembly. The sample acquisition unit may or may not be selectively fluidly isolated from one or more components. In some cases, the sample acquisition unit may be in fluid communication with each component of the apparatus. The sample acquisition unit may be in permanent fluid communication with each component, or may be brought into and/or out of fluid communication with each component.

One or more means may be provided for transferring the sample from the sample acquisition unit to the probe site. In some embodiments, a flow-through device may be used. For example, a channel or conduit may connect the sample acquisition unit with the detection point of the module. The channel or conduit may or may not have one or more valves or devices that selectively allow or block the flow of liquid.

Another device that may be used to transfer a sample from a sample acquisition unit to a probe site may use one or more liquid-isolated components. For example, the sample acquisition unit may provide the sample to one or more tips or vessels that are movable within the device. The one or more tips or vessels can be transferred to one or more modules. In some embodiments, the one or more tips or containers may be transported to the one or more modules via a robotic arm or other component of the apparatus. In some embodiments, a tip or a container may be received in one module. In some embodiments, the liquid handling device at the module may operate a tip or a vessel. For example, a pipette at the module may draw and/or aspirate a sample provided to the module.

The device may be configured to receive a single sample, or may be configured to receive multiple samples. In some cases, the plurality of samples may or may not be a plurality of types of samples. For example, in some cases, a single device may process a single sample at a time. For example, the device may receive a single sample and may perform one or more sample processing steps, such as sample preparation steps, assay steps, and/or detection steps, using the sample. The device may complete processing or analyzing the sample before admitting a new sample.

In another example, the device may be capable of processing multiple samples simultaneously. In one example, a device may receive multiple samples simultaneously. The plurality of samples may or may not be a plurality of types of samples. Alternatively, the device may receive the samples sequentially. The samples may be provided to the device one after the other, or may be provided to the device after any amount of time has elapsed. The device may be able to start sample processing of a first sample, receive a second sample during said sample processing, and process the second sample in parallel with the first sample. The first and second samples may or may not be the same type of sample. The device may be capable of processing any number of samples in parallel, including but not limited to: greater than and/or equal to about 1 sample, 2 samples, 3 samples, 4 samples, 5 samples, 6 samples, 7 samples, 8 samples, 9 samples, 10 samples, 11 samples, 12 samples, 13 samples, 14 samples, 15 samples, 16 samples, 17 samples, 18 samples, 19 samples, 20 samples, 25 samples, 30 samples, 40 samples, 50 samples, 70 samples, 100 samples.

In some embodiments, an apparatus may include one, two, or more modules that may be capable of processing one, two, or more samples in parallel. The number of samples that can be processed in parallel may be determined by the number of modules and/or components available in the device.

When multiple samples are processed simultaneously, the samples may begin and/or end processing at any time. The samples do not have to start and/or end processing at the same time. The first sample may have completed processing while the second sample is still in process. The second sample may not begin processing until after the first sample has begun processing. When the sample has completed processing, additional samples may be added to the device. In some cases, the device may be able to continue to run by adding samples to the device when each sample has completed processing.

Multiple samples may be provided simultaneously. The multiple samples may or may not be the same type of sample. For example, a plurality of sample acquisition units may be provided to the apparatus. For example, one, two, or more scalpels may be provided on the device, or may be brought into fluid communication with a sample acquisition unit of the device. The plurality of sample acquisition units may receive samples simultaneously or at different times. A plurality of any of the sample acquisition devices described herein can be used. The same type of sample acquisition device or different types of sample acquisition devices may be used.

Multiple samples may be provided in sequence. In some cases, multiple sample acquisition units or a single sample acquisition unit may be used. Any combination of the sample acquisition devices described herein can be used. The device may receive one sample at a time, two samples at a time, or more samples. The sample may be provided to the device after any amount of time has elapsed.

Module

A device may contain one or more modules. The module may be capable of performing one or more, two or more, or all three of the sample preparation steps, the assay steps, and/or the detection steps. Fig. 3 shows an example of a module 300. The module may contain one or more, two or more, or three or more sample prep instruments 310, and/or assay instruments 320, and/or detection instruments 330. In some embodiments, a plurality of sample prep meters, and/or probes are provided. The module may also include a liquid handling system 340.

The module may include one or more sample prep instruments. The sample preparation instrument may include one or more components configured for chemical and/or physical processing. Examples of such sample preparation processes may include dilution, concentration/enrichment, separation, sorting, filtering, lysis, chromatographic analysis, incubation, or any other sample preparation step. The sample preparation instrument may include one or more sample preparation components, such as a separation system (including but not limited to a centrifuge), a magnet (or other magnetic field induction device) for magnetic separation, a filter, a heater, or a diluent.

One or more meters may be provided for the module. The meter may include one or more components configured to perform one or more of the following assays or steps: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and/or other types of assays or combinations thereof. The assay instrument may be configured for use in protein assays, including immunoassays and enzymatic assays or any other assay involving interaction with a protein component. Topography measurements in some cases include morphological measurements. Examples of other components included in the module are (but are not limited to) one or more of the following: a temperature control unit, a heater, a thermal block, a cytometer, an electromagnetic energy source (e.g., X-ray, light source), an assay unit, a reagent unit, and/or a support. In some embodiments, the module includes one or more assays capable of performing nucleic acid assays and protein assays (including immunoassays and enzymatic assays). In some embodiments, the module includes one or more meters capable of performing fluorescence assays and cell counts.

The meter may or may not be located separately from the prep meter. In some cases, the meter may be integrated within the prep meter. Alternatively, they may be different meters, and samples or other substances may be transferred from one meter to another.

An assay unit may be provided and may have one or more of the characteristics described further elsewhere herein. The assay unit may be capable of receiving and/or confining a sample. The assay units may be fluidly isolated or hydraulically independent from each other. In some embodiments, the assay unit may have tip specifications. The assay tip may have an inner surface and an outer surface. The assay tip may have a first open end and a second open end. In some embodiments, the assay units may be provided as an array. The assay unit may be movable. In some embodiments, the individual assay units may be movable relative to each other and/or other components of the apparatus. In some cases, one or more assay units may be moved simultaneously. In some embodiments, the assay unit may have one or other reagents coated on the surface. In some embodiments, a series of reagents may be coated or deposited on a surface, such as a tip surface, and may be used for a continuous reaction. Alternatively, the assay unit may comprise beads or other surfaces coated with or absorbed onto, or absorbed or adhered to, reagents or other reactants. In another example, the assay unit may comprise beads or other surfaces coated or formed with soluble reagents or other reactants.

A reagent unit may be provided and may have one or more characteristics as further described elsewhere herein. The reagent unit may be capable of receiving and/or confining a reagent or a sample. The reagent units may be fluidly isolated or hydraulically independent from each other. In some embodiments, the reagent unit may have a container format. The reagent container may have an inner surface and an outer surface. The reagent unit may have an open end and a closed end. In some embodiments, the reagent units may be provided as an array. The reagent unit may be mobile. In some embodiments, the individual reagent units may be movable relative to each other and/or other components of the apparatus. In some cases, one or more reagent units may be moved simultaneously. The reagent unit may be configured to receive one or more assay units. The reagent unit may have an inner region into which the assay unit may be at least partially inserted.

A holder may be provided for the assay unit and/or the reagent unit. In some embodiments, the holder may have a cassette format or a miniature card format. In some specific examples, the support may be of a patch gauge or may be integrated into a patch or implantable sensing and analysis unit. One or more assay/reagent unit holders may be provided within the module. The holder may be shaped for supporting one or more assay units and/or reagent units. The holder may keep the assay unit and/or the reagent unit aligned in a vertical direction. The support may allow the assay unit and/or the reagent unit to be moved or movable. The assay unit and/or the reagent unit may be removed from and/or placed on the support. The devices and/or systems may include one or more features, components, characteristics, or steps provided in U.S. patent publication No. 2009/0088336, which is incorporated herein by reference in its entirety.

The module may include one or more detectors. The detector may comprise one or more sensors that may detect visual/optical signals, infrared signals, thermal/temperature signals, ultraviolet signals, any signal along the electromagnetic spectrum, electrical signals, chemical signals, audio signals, pressure signals, motion signals, or any other type of detectable signal. The sensors provided herein may or may not include any other sensors described elsewhere herein. The detector may be located separate from the sample preparation meter and/or the meter. Alternatively, the monitor may be positioned in an integrated manner with the sample preparation meter and/or the meter.

In some embodiments, the sample may be provided to one or more sample prep meters before being provided to the meter. In some cases, the sample may be provided to sample preparation after being provided to the meter. The sample may be subjected to probing before, after, or during its provision to the sample preparation meter and/or the meter.

A liquid handling system may be provided for the module. The liquid handling system may allow movement of samples, reagents or liquids. The liquid handling system may allow dispensing and/or aspiration of a liquid. The liquid handling system may draw a desired liquid from a selected location and/or may dispense the liquid at the selected location. The liquid handling system may allow for mixing and/or reaction of two or more liquids. In some cases, the liquid handling device may be a pipette. Examples of pipettes or liquid handling devices are provided in more detail elsewhere herein.

Any description herein of a liquid processing system may also be applicable to other sample processing systems, and vice versa. For example, the sample processing system may transport any type of sample, including but not limited to a bodily fluid, exudate, or tissue sample. The sample processing system may be capable of processing liquids, solids, or semi-solids. The sample processing system may be capable of receiving, storing, and/or moving samples, and/or any other substance within the device useful and/or necessary for sample processing within the device. The sample processing system may be capable of receiving, storing, and/or moving containers (e.g., assay units, reagent units) that may contain samples and/or any other substances within the device.

The liquid handling system may comprise a pipette tip. For example, a pipette tip may be removably connected to a pipette. The tip may be attached to a pipette nozzle. Examples of tip/nozzle interfaces are provided in more detail elsewhere herein.

Another example of a liquid treatment system may use a flow-through design. For example, a liquid treatment system may include one or more channels and/or conduits through which a liquid may flow. The channel or conduit may contain one or more valves that can selectively stop and/or allow the flow of liquid.

The liquid handling system may have one or more portions that may result in liquid isolation. For example, the liquid handling system may use pipette tips that are fluidly isolatable from other components of the apparatus. The liquid-insulated portion may be movable. In some embodiments, the liquid handling system tip may be an assay tip as described elsewhere herein.

The module may have a housing and/or a support structure. In some embodiments, a module may have a support structure on which one or more components of the module may be placed. The support structure may support the weight of one or more components of the module. The components may be provided above the support structure, to the sides of the support structure and/or below the support structure. The support structure may be a base plate that may connect and/or support the various components of the module. The support structure may support one or more sample prep instruments, meters, and/or probes of the module. The modules may be self-contained. Multiple modules may be moved together. The various components of the module may be able to move together. The various components of the module may be connected to each other. The components of the module may share a common support.

The modules may be closed or open. The housing of the module may enclose the module therein. The housing may completely enclose the module or may partially enclose the module. The housing may form an airtight enclosure around the module. Alternatively, the housing need not be airtight. The housing may enable temperature, humidity, pressure, or other characteristics within the module or within one or more components to be controlled.

Electrical connections may be provided for the modules. The module may be electrically connected to the rest of the device. The plurality of modules may or may not be electrically connected to each other. When the module is inserted/attached to the device, the module may enter into an electrical connection with the device. The device may provide power (or electricity) to the module. When the module is removed from the device, it may be disconnected from the power source. In one case, when the module is inserted into the device, the module is electrically connected to the rest of the device. For example, the module may be inserted into a cradle of the device. In some cases, a support (e.g., a housing) of the device may provide power and/or power to the module.

The module may also be capable of forming a fluid connection with the rest of the device. In one example, the module may be fluidly connected to the rest of the device. Alternatively, the module may be brought into liquid communication with the rest of the apparatus, e.g. via a liquid handling system as disclosed herein. The module may be brought into liquid communication when the module is inserted/attached to the device, or may be selectively brought into liquid communication at any time after the module is inserted/attached to the device. The module may be disconnected from liquid communication with the device when the module is removed from the device and/or selectively disconnected from liquid communication with the device if the module is attached to the device. In one example, the module may be in or may enter into liquid communication with a sample acquisition unit of the device. In another example, a module may be in or may enter liquid communication with other modules of the device.

The modules may be of any size and shape, including those described elsewhere herein. The module may have a size equal to or smaller than the device. The equipment module can enclose less than or equal to about 4m³、3m³、2.5m³、2m³、1.5m³、1m³、0.75m³、0.5m³、0.3m³、0.2m³、0.1m³、0.08m³、0.05m³、0.03m³、0.01m³、0.005m³、0.001m³、500cm³、100cm³、50cm³、10cm³、5cm³、1cm³、0.5cm³、0.1cm³、0.05cm³、0.01cm³、0.005cm³Or 0.001cm³Total volume of (c). The module may have any volume described elsewhere herein.

The module and/or the module housing may have a footprint that covers a lateral area of the device. In some embodiments, the equipment footprint may be less than or equal to about 4m²、3m²、2.5m²、2m²、1.5m²、1m²、0.75m²、0.5m²、0.3m²、0.2m²、0.1m²、0.08m²、0.05m²、0.03m²、100cm²、80cm²、70cm²、60cm²、50cm²、40cm²、30cm²、20cm²、15cm²、10cm²、7cm²、5cm²、1cm²、0.5cm²、0.1cm²、0.05cm²、0.01cm²、0.005cm²Or 0.001cm²。

The module and/or module housing can have a transverse dimension (e.g., width, length, or diameter) or height of less than or equal to about 4m, 3m, 2.5m, 2m, 1.5m, 1.2m, 1m, 80cm, 70cm, 60cm, 50cm, 40cm, 30cm, 25cm, 20cm, 15cm, 12cm, 10cm, 8cm, 5cm, 3cm, 1cm, 0.5cm, 0.1cm, 0.05cm, 0.01cm, 0.005cm, or 0.001 cm. The lateral dimensions and/or heights may be different from each other. Alternatively, they may be the same. In some cases, the modules may be tall and thin, or may be short and wide. The ratio of height to transverse dimension may be greater than or equal to 100:1, 50:1, 30:1, 20:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:30, 1:50, or 1: 100. The modules and/or module housings may be proportionally tall and thin.

The module and/or the module housing may have any shape. In some embodiments, the modules may have a rectangular or square cross-sectional shape. In other specific examples, the modules may have a cross-sectional shape that is circular, elliptical, triangular, trapezoidal, parallelogram, pentagonal, hexagonal, octagonal, or any other shape. The modules may have a longitudinal cross-sectional shape that is circular, oval, triangular, rectangular, square, trapezoidal, parallelogram, pentagonal, hexagonal, octagonal, or any other shape. The module may or may not have a box shape.

Any number of modules may be provided for a device. The device may be configured to receive a fixed number of modules. Alternatively, the device may be configured to accept a variable amount of modules. In some embodiments, each module of the device may have the same components and/or configuration. Alternatively, different modules of the device may have different components and/or configurations. In some cases, different modules may have the same housing and/or support structure specifications. In another example, different modules may still have the same overall dimensions. Alternatively, they may have different sizes.

In some cases, a device may have a single module. The single module may be configured to receive a single sample at a time, or may be capable of receiving multiple samples simultaneously or sequentially. The single module may be capable of performing one or more sample preparation steps, assay steps, and/or detection steps. The single module may or may not be swapped out to provide different functionality.

Further details and descriptions of modules and module components are further described elsewhere herein. Any such specific examples of such modules may be provided in combination with other specific examples or separately.

Support frame

In one specific example described herein, a system having a plurality of modules is provided. The system is configured for assaying a biological sample, such as a fluid and/or tissue sample from a subject.

In some embodiments, the system includes a plurality of modules mounted on a support structure. In one embodiment, the support structure is a rack having a plurality of mounting stations, a single one of which is used to support a module.

In one particular example, the rack includes a controller communicatively coupled to the plurality of modules. As described below, in some cases, the controller is communicatively coupled to the liquid handling system. The controller is configured to control operation of the module to prepare and/or process the sample, such as assaying the sample by one or more of the techniques described herein.

A single module of the plurality of modules contains a sample preparation meter, a measurement meter, and/or a detection meter. The system is configured to perform (a) a plurality of sample preparation procedures selected from the group consisting of sample processing, centrifugation, separation, physical separation, and chemical separation, and (b) at least one type of assay selected from the group consisting of: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and/or other types of assays or combinations thereof. In some embodiments, the separation comprises magnetic separation, such as separation by means of a magnetic field, for example.

In one particular example, the support structure is a rack-type structure for removably retaining or securing individual ones of the plurality of modules. The rack-type structure includes a plurality of racks configured to receive and removably secure the modules. In one example, as shown in fig. 4, a rack 400 may have one or more modules 410a, 410b, 410c, 410d, 410e, 410 f. The modules may have a vertical arrangement in which they are located on top of each other. For example, six modules may be stacked on top of each other. The modules may have a horizontal arrangement in which they are adjacent to each other. In another example, the modules may form an array. Fig. 5 illustrates an example of a stent 500 having a plurality of modules 510 in a tangible array. For example, the modules may form a vertical array of M modules high and/or N modules wide, where M, N is a positive integer. In other embodiments, the rack may support an array of modules, wherein a horizontal array of modules is formed. For example, the modules may form a horizontal array of N modules wide and/or P modules long, where N and P are positive integers. In another example, a three-dimensional array of modules may be supported by a rack, where the modules form a block of M modules high, N modules wide, and P modules long, where M, N and P are positive integers. The rack may be capable of supporting any number of modules having any number of configurations.

In some embodiments, a rack may have one or more racks, each configured to receive one or more modules. The device may be capable of operating when the rack has received a module. The device may still be able to operate even if one or more racks have not received a module.

Fig. 6 shows another specific example of the bracket mounting configuration. One or more modules 600a, 600b may be provided adjacent to each other. Any number of modules may be provided. For example, the modules may be stacked vertically on top of each other. For example, N modules may be vertically stacked on top of each other, where N is any positive integer. In another example, the modules may be horizontally connected to each other. Any combination of vertical and/or horizontal connections between modules may be provided. The modules may be in direct contact with each other or may have connection interfaces. In some cases, modules may be added to or removed from the stack/group. This configuration may be able to accommodate any number of modules. In some embodiments, the number of modules may or may not be limited by the device housing.

In another specific example, the support structure is disposed below the first module, and successive modules may be mounted on each other with or without mounting members disposed on each module. The mounting member may be a connection interface between the modules. In one example, each module includes a magnetic mounting member for securing a top surface of a first module to a bottom surface of a second module. Other connection interfaces may be employed, which may include magnetic features, adhesives, sliding features, locking features, tie bars, snaps, hook and loop fasteners, twist features, or plugs. The modules may be mechanically and/or electrically connected to each other. In this way, modules may be stacked on top of each other or next to each other to form a system for assaying samples.

In other embodiments, a system for assaying a sample includes a housing and a plurality of modules within the housing. In one particular example, the housing is a rack having a plurality of mounting stations, a single one of which is used to support a module. For example, the bracket may be formed integrally with the housing. Alternatively, the housing may contain or enclose the support. The housing and the bracket may or may not be formed from separate pieces that may or may not be connected to each other. Individual modules of the plurality of modules include at least one instrument selected from the group consisting of a sample preparation instrument, a measurement instrument, and a detection instrument. The system includes a liquid handling system configured to transfer sample or reagent containers within or from a single module to another module within the system housing. In one particular example, the liquid handling system is a pipette.

In some embodiments, all modules may be shared within a device or between devices. For example, a device may have one, some, or all of its modules as dedicated modules. In this case, the sample may be transported from one module to another as needed. This movement may be sequential or random.

Any module may be a shared resource or may contain a specified shared resource. In one example, the specified shared resource may be a resource that is not available to all modules, or may be a resource that is available in a limited number of modules. The shared resource may or may not be removable from the device. An example of a shared resource may include a cytometer.

In one embodiment, the system further comprises a cytometer for performing cell counting on one or more samples. The cytometer may be supported by the support and operatively coupled to each of the plurality of modules by the sample processing system.

Cytometry assays are commonly used to optically measure properties of individual cells. The cells monitored may be live and/or dead cells. Cell counts can be used to determine the expression, quantity, and/or modification of particular proteins, nucleic acids, lipids, carbohydrates, or other molecules by using appropriate dyes, stains, or other labeling molecules. Properties that can be measured by cell counting also include measurements of cell function or activity, including but not limited to: phagocytosis, active transport of small molecules, mitosis or meiosis, protein translation, gene transcription, DNA replication, DNA repair, protein secretion, apoptosis, chemotaxis, mobility, adhesion, antioxidant activity, RNAi, protein or nucleic acid degradation, drug response, infectivity, and specific pathway or enzyme activity. Cell counts can also be used to determine information about cell populations including, but not limited to: variation in cell count, total population percentage, and any of the above characteristics in a sample population. The assays described herein can be used to measure one or more of the above-described properties of each cell, which facilitates the determination of correlations or other relationships between different properties. The assays described herein can also be used to independently measure multiple cell populations, for example, by labeling a mixed cell population with antibodies specific to different cell lines.

Cell counting may be useful for determining characteristics of cells in real time. The properties of the cells can be monitored continuously and/or at different time points. The different points in time may be at regular or irregular intervals. The different points in time may be according to a predetermined schedule or may be triggered by one or more events. Cell count can use one or more imaging techniques or other sensing techniques described herein to detect changes in cells over time. This may include cell movement or morphology. The kinematics or kinetics of the sample can be analyzed. Time-series analysis can be provided for the cells. Such real-time detection may be useful for calculation of clotting, coagulation, prothrombin time. The presence of one or more molecules and/or diseases, responses to diseases and/or drugs can be ascertained from the time-based analysis.

In one example, cytometric analysis is performed by flow cytometry or by microscopy. Flow cytometers typically use a flowing liquid medium that sequentially carries individual cells to an optical detector. Microscopic cells are typically detected by optical means, typically by recording at least one magnified image. It should be understood that flow cytometry and microscopic microscopy are not completely repulsive. As an example, flow cytometry assays use microscopy to record images of cells passing through an optical detector. Many targets, reagents, assays, and detection methods may be the same for flow cytometry and microscopy. As such, unless otherwise specified, the description provided herein should be considered applicable to these and other forms of cytometric analysis known in the art.

In some embodiments, up to about 10,000 cells of any given type may be measured. In other embodiments, a different number of cells of any given type is determined, including but not limited to: greater than and/or equal to about 10 cells, 30 cells, 50 cells, 100 cells, 150 cells, 200 cells, 300 cells, 500 cells, 700 cells, 1000 cells, 1500 cells, 2000 cells, 3000 cells, 5000 cells, 6000 cells, 7000 cells, 8000 cells, 9000 cells, 10000 cells.

In some embodiments, cell counting is performed within a microfluidic channel. For example, flow cytometry analysis is performed in a single channel or in multiple channels in parallel. In some embodiments, the flow cytometer measures multiple cellular characteristics sequentially or simultaneously. In some cases, cell counting can occur within one or more tips and/or vessels described herein. Cell counting may be combined with cell sorting, wherein detected cells satisfying a particular set of characteristics are transferred from the stream and collected for storage, additional analysis and/or processing. Such sorting can separate multiple cell populations based on different sets of characteristics, such as 3-way or 4-way sorting.

FIG. 7 shows a system 700 having a plurality of modules 701-706 and a cytometer 707, according to one specific example described herein. The plurality of modules includes a first module 701, a second module 702, a third module 703, a fourth module 704, a fifth module 705, and a sixth module 706.

The cytometer 707 is operatively coupled to each of the plurality of modules 701-706 through the sample processing system 708. As described herein, the sample processing system 708 may include a pipette, such as a positive displacement, vented, or aspirated pipette.

As described above and in other specific examples described herein, the cytometer 707 includes a cell counter for performing cell counting on a sample. The cytometer 707 can perform cell counting on a sample while one or more of the modules 701-706 perform other preparation and/or assay procedures on another sample. In some cases, the cytometer 707 performs cell counting on the sample after the sample has undergone sample preparation within one or more of the modules 701-706.

The system 700 includes a support structure 709 having a plurality of racks (or mounting tables). The plurality of racks is used to interface the modules 701-706 to the support structure 709. As shown, support structure 709 is a stent.

Each module is fixed to a bracket 709 by means of an attachment member. In one particular example, the attachment member is a hook secured to the module or the rack. In such a case, the hook is configured to slide into a receptacle of the module or rack. In another specific example, the attachment member includes a fastener, such as a screw fastener. In yet another specific example, the attachment member is formed of a magnetic material. In such a case, the module and the chassis may include magnetic materials of opposite polarity to provide an attractive force to secure the module to the chassis. In another specific example, the attachment member includes one or more rails or tracks in the frame. In such a case, the module includes one or more structures for mating with one or more rails or tracks to secure the module to the bracket 709. Still alternatively, power may be provided by the rail.

Examples of structures that may allow the module to mate with the bracket may include one or more pins. In some cases, the module receives power directly from the rack. In some cases, the module may be a power source that internally powers the device, such as a lithium ion battery or a fuel cell powered battery. In one example, the module is configured to mate with the rack by way of rails, while the power of the module comes directly from the rails. In another example, the module mates with the cradle by means of attachment members (rails, pins, hooks, fasteners), but provides power to the module wirelessly, such as inductively (i.e., inductive coupling).

In some embodiments, the module that mates with the bracket does not necessarily require a pin. For example, inductive electrical communication may be provided between the module and the cradle or other support. In some cases, wireless communication may be used, such as by way of ZigBee communication or other communication protocols.

Each module is removable from the rack 709. In some cases, a module may be replaced with the same, similar, or different module. In one embodiment, the module is removed from the rack by sliding the module out of the rack 709. In another specific example, the module is removed from the bracket 709 by twisting or turning the module so that the attachment members of the module disengage from the bracket 709. Removal of the module from the cradle 709 may terminate any electrical connectivity between the module and the cradle 709.

In one particular example, the module is attached to the bracket by sliding the module into the rack. In another specific example, the module is attached to the bracket by twisting or turning the module so that the attachment member of the module engages the bracket 709. Attaching the module to the bracket 709 may establish an electrical connection between the module and the bracket. The electrical connections may be used to provide power to or from the module to the rack or to the device and/or to provide a communications communication vehicle between the module and one or more other modules or controllers of the system 700.

Each rack of the rack may or may not be occupied. As shown, all of the racks of rack 709 are occupied by modules. However, in some cases, one or more racks of rack 709 are unoccupied by a module. In one example, the first module 701 has been removed from the rack. In such a case, the system 700 may operate without the module being removed.

In some cases, the chassis may be configured to receive a subset of the module types that system 700 is configured to use. For example, the rack may be configured to receive a module capable of running an agglutination assay instead of a cell count assay. In such a case, the module may be "dedicated" to agglutination. In other cases, the rack may be configured to receive all types of modules that the system 700 is configured to use, ranging from probes to supporting electrical systems.

Each module may be configured to function (or execute) independently of the other modules. In one example, the first module 701 is configured to execute independently of the second module 702, the third module 703, the fourth module 704, the fifth module 705, and the sixth module 706. In other cases, a module is configured to execute with one or more other modules. In such a case, the module may support parallel processing of one or more samples. In one example, the second module 702 performs an assay on the same or a different sample while the first module 701 prepares the sample. This may support minimizing and eliminating downtime between modules.

The support structure (or cradle) 709 may have a server type configuration. In some cases, the dimensions of the stent are standardized. In one example, the spacing between modules 701-706 is normalized to a multiple of at least about 0.5 inches, or 1 inch, or 2 inches, or 3 inches, or 4 inches, or 5 inches, or 6 inches, or 7 inches, or 8 inches, or 9 inches, or 10 inches, or 11 inches, or 12 inches.

The bracket 709 may support the weight of one or more of the modules 701-706. Further, the support 709 has a center of gravity selected such that the module 701 (top) is mounted on the support 709 without creating a moment arm that may cause the support 709 to rotate or tip over. In some cases, the center of gravity of rack 709 is arranged between the vertical midpoint of the rack and the bottom of the rack, with the vertical center being 50% from the bottom of rack 709 to the top of the rack. In a particular example, the center of gravity of the cradle 709 is disposed at least about 0.1%, or 1%, or 10%, or 20%, or 30%, or 40%, or 50%, or 60%, or 70%, or 80%, or 90%, or 100% of the height of the cradle as measured from the bottom of the cradle 709 as measured along a longitudinal axis away from the bottom of the cradle 709.

The rack may have a plurality of racks (or mounting tables) configured to receive one or more modules. In one example, the rack 709 has six mounting stations for allowing each of the modules 701-706 to be mounted to the rack. In some cases, the racks are located on the same side of the rack. In other cases, the racks are located on alternating sides of the rack.

In some embodiments, system 700 includes electrical connectivity components for electrically connecting modules 701-706 to one another. The electrical connectivity component may be a communications ac vehicle, such as a system communications ac vehicle. In some cases, the electrical connectivity components also enable the modules 701-706 to communicate with each other and/or with a controller of the system 700.

In some embodiments, system 700 includes a controller (not shown) for facilitating processing of the sample via one or more of modules 701-706. In one particular example, the controller facilitates parallel processing of samples in modules 701-706. In one example, the controller directs the sample processing system 708 to provide samples in the first module 701 and the second module 702 in order to run different assays on the samples simultaneously. In another example, the controller directs the sample processing system 708 to provide a sample within one of the modules 701-706, and also to provide the sample (e.g., a portion of a finite volume of the sample) to the cytometer 707, such that cell counting of the sample and one or more other sample preparation procedures and/or assays are performed in parallel. In this manner, the system minimizes, if not eliminates, downtime between the modules 701-706 and the cytometer 707.

Each individual module of the plurality of modules may include a sample processing system for providing and removing samples to and from each of the processing modules and assay modules of the individual module. Further, each module may include various sample processing and/or assay modules, in addition to other components for facilitating processing and/or assaying of samples via the module. The sample processing system of each module may be separate from the sample processing system 708 of the system 700. That is, sample processing system 708 transfers samples to and from modules 701-706, while the sample processing system of each module transfers samples to and from the various sample processing and/or assay modules included within each module.

In the example illustrated in fig. 7, the sixth module 706 includes a sample processing system 710, the sample processing system 710 including a pipetting pipette 711 and a positive displacement pipette 712. The sixth module 706 includes a centrifuge 713, a spectrophotometer 714, a nucleic acid assay (such as a Polymerase Chain Reaction (PCR) assay) instrument 715, and a PMT 716. An example of spectrophotometer 714 is shown in fig. 70 (see below). The sixth module 706 further comprises a cassette 717, the cassette 717 being adapted to hold a plurality of tips for facilitating sample transfer to and from each processing or assay module of the sixth module.

In a particular example, the pipette 711 includes 1 or more, or 2 or more, or 3 or more, or 4 or more, or 5 or more, or 6 or more, or 7 or more, or 8 or more, or 9 or more, or 10 or more, or 15 or more, or 20 or more, or 30 or more, or 40 or more, or 50 or more heads. In one example, the suction pipette 711 is an 8-head pipette having eight heads. The suction pipette 711 may be as described in other specific examples described herein.

In some specific examples, the positive displacement pipette 712 has a coefficient of variation less than or equal to about 20%, 15%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.3%, or 0.1% or less. The coefficient of variation is determined in terms of σ/μ, where "σ" is the standard deviation and "μ" is the average over the entire sample measurement.

In one embodiment, all modules are identical to each other. In another embodiment, at least some of the modules are different from each other. In one example, the first, second, third, fourth, fifth, and sixth modules 701-706 include positive displacement pipettes and pipette pipettes as well as various assays, such as nucleic acid assays and spectrophotometers. In another example, at least one of modules 701-706 may have a different assay and/or sample preparation instrument than the other modules. In one example, the first module 701 includes an agglutination assay but does not include a nucleic acid amplification assay, while the second module 702 includes a nucleic acid assay but does not include an agglutination assay. The module may not include any assays.

In the example illustrated in FIG. 7, modules 701-706 include the same assay and sample preparation (or manipulation) instruments. However, in other specific examples, each module includes any number and combination of the assays and processors described herein.

The modules may be stacked vertically or horizontally with respect to each other. Two modules are oriented perpendicularly with respect to each other if they are oriented along a plane parallel, substantially parallel, or nearly parallel to the gravitational acceleration vector. Two modules are horizontally oriented with respect to each other if they are oriented along a plane that is orthogonal, substantially orthogonal, or nearly orthogonal to the gravitational acceleration vector.

In one embodiment, the modules are stacked vertically, i.e., one module on top of another module. In the example illustrated in FIG. 7, the bracket 709 is oriented such that the modules 701-706 are disposed vertically with respect to each other. In other cases, however, the modules are disposed horizontally with respect to each other. In such a case, the bracket 709 may be oriented such that the modules 701-706 may sit horizontally alongside one another.

In some embodiments, the modules 701-706 communicate with each other and/or with the controller of the system 700 through communication vehicles ("communication vehicles"), which may include electronic circuitry and components for facilitating communication between the modules and/or the controller. The communication vehicles include subsystems that transfer data between the modules and/or controllers of the system 700. The communication vehicle may bring the components of the system 700 into communication with a Central Processing Unit (CPU), memory (e.g., internal storage, system cache), and storage location (e.g., hard disk) of the system 700.

The communications communication interchange vehicle may include a parallel wire having a plurality of connections, or any physical arrangement that provides a logical function as a parallel communications communication interchange vehicle. The communications vehicles may include parallel connections and bit-serial connections and may be connected online in a multi-drop (i.e., electrically parallel) or daisy topology, or through a switching hub. In one particular example, the communication vehicle may be a first generation communication vehicle, a second generation communication vehicle, or a third generation communication vehicle. The communications communication vehicles allow communication between each module and other modules and/or controllers. In some cases, the communication exchange vehicle supports communication between multiple systems, such as between multiple systems similar or identical to system 700.

The system 700 may include one or more serial communication ac vehicles, parallel communication ac vehicles, or self-healing communication ac vehicles. The communication vehicles may include a master scheduler that controls data traffic, such as traffic to or from the modules (e.g., modules 701-706), controllers, and/or other systems. The communication vehicles may include an external communication vehicle that connects external devices and systems to a main system board (e.g., a motherboard); and an intercom communicating vehicle connecting the internal components of the system to the system board. An intercom connects the internal components to one or more Central Processing Units (CPUs) and an internal memory.

In some embodiments, the communication vehicle may be a wireless communication vehicle.

In some embodiments, system 700 includes one or more communication vehicles selected from the group consisting of: media communication AC vehicle, computer automatic measurement and control (CAMAC) communication AC vehicle, Industry Standard Architecture (ISA) communication AC vehicle, Extended ISA (EISA) communication AC vehicle, low pin count communication AC vehicle, MBus, micro-channel communication AC vehicle, multi-communication AC vehicle, NuBus or IEEE1196, OPTi local communication AC vehicle, Peripheral Component Interconnect (PCI) communication AC vehicle, parallel Advanced Technology Attachment (ATA) communication AC vehicle, Q-communication AC vehicle, S-100 communication AC vehicle (or IEEE696), SBus (or IEEE1496), SS-50 communication AC vehicle, STE communication AC vehicle, STD communication AC vehicle (for STD-80[ 8-bit ] -communication]And STD32[ 16-/32-position]) The vehicle comprises a single communication AC vehicle, a VESA local communication AC vehicle, a VME communication AC vehicle, a PC/104Plus communication AC vehicle, a PC/104Express communication AC vehicle, a PCI-104 communication AC vehicle, a PCIe-104 communication AC vehicle, a 1-line communication AC vehicle, an ultra-transmission communication AC vehicle and a mutual integrated circuit (I)²C) A communication interchange car, a PCI Express (or PCIe) communication interchange car, a Serial ATA (SATA) communication interchange car, a serial peripheral interface communication interchange car, a UNI/O communication interchange car, a SMBus, a 2-wire or 3-wire interface, a self-healing flexible interface communication interchange car, and variations and/or combinations thereof.

In some cases, system 700 includes a Serial Peripheral Interface (SPI), which is the interface between one or more microprocessors and peripheral or I/O components (e.g., modules 701-706) of system 700. The SPI may be used to attach 2 or more, or 3 or more, or 4 or more, or 5 or more, or 6 or more, or 7 or more, or 8 or more, or 9 or more, or 10 or more, or 50 or more, or 100 or more SPI-compatible I/O components to a microprocessor or microprocessors. In other cases, system 700 includes RS-485 or other standards.

In one particular example, an SPI is provided having an SPI bridge with a parallel and/or series topology. Such bridging allows selection of one of many SPI components on an SPI I/O communication vehicle without proliferation of chip selection. This is accomplished by applying appropriate control signals as described below to allow for daisy-chaining of devices or chip selection for devices on the SPI communication bus. However, it does not maintain a parallel data path, so there is no daisy-chained data to be transferred between the SPI component and the microprocessor.

In some embodiments, an SPI bridging component is provided between a microprocessor and multiple SPII/O components connected in a parallel and/or serial (or series) topology. The SPI bridge component supports parallel SPI using MISO and MOSI lines, as well as serial (daisy-chained) local chip select connections (CSL /) to other slave devices. In one particular example, the SPI bridge component provided herein addresses any issues associated with multi-chip selection for multiple slave devices. In another specific example, the SPI bridge component provided herein supports 4, 8, 16, 32, 64 or more individual chip selections for 4 SPI-enabled devices (CS 1/-CS 4 /). In yet another specific example, the SPI bridge component provided herein supports 4-fold concatenation with an external address line arrangement (ADR 0-ADR 1). In some cases, the SPI bridge component provided herein provides the ability to control up to 8, 16, 32, 64, or more general output bits for control or data. The SPI bridge component provided herein, in some cases, supports control of up to 8, 16, 32, 64, or more general output bits for control or data, and may be used for device identification of the master and/or diagnostic communication to the master.

Fig. 41A illustrates an SPI bridging procedure with a master bridge and a parallel-serial SPI slave bridge, according to one specific example described herein. The SPI communication bus is enhanced by adding local chip select (CSL /), module select (MOD _ SEL), and select data input (DIN _ SEL) to the SPI bridge, allowing for the addition of various system features including essential and non-essential system features, such as cascading of multiple slave devices, virtual daisy chaining of device chip select to keep module-to-module signal counts at an acceptable level, support for module identification and diagnostics, and communication with non-SPI components on the module while maintaining compatibility with embedded SPI-compatible slave components. Fig. 41B shows an example of SPI bridging according to one specific example described herein. The SPI bridge includes internal SPI control logic, control buffers (8 bits as shown), and various input and output pins.

In a parallel-serial configuration, each slave bridge is connected to a master (also referred to herein as an "SPI master" or "master bridge"). Each slave bridge MOSI pin is connected to the master bridge MOSI pin, and the slave bridge MOSI pins are connected to each other. Similarly, the MISO pin of each slave bridge is connected to the MISO pin of the master bridge, and the MISO pins of the slave bridges are connected to each other.

Each slave bridge may be a module (e.g., one of modules 701-706 of fig. 7) or a component in a module. In one example, the first slave bridge is the first module 701, the second slave bridge is the second module 702, and so on. In another example, the first slave bridge is a component of a module (e.g., one of components 910 of fig. 9).

Fig. 41C shows a module assembly diagram with interconnected module pins and various components of the master and slave bridges, according to one specific example described herein. Fig. 41D illustrates a slave bridge connected to a master bridge, according to one specific example described herein. The MISO pin of each slave bridge is in electrical communication with the MOSI pin of the master bridge. Each slave bridge MOSI pin is in electrical communication with the master bridge MISO pin. The DIN _ SEL pin of the first slave bridge (left) is in electrical communication with the MOSI pin of the first slave bridge. The DOUT _ SEL pin of the first slave bridge is in electrical communication with the DIN _ SEL pin of the second slave bridge (right). The additional slave bridges may be connected as second slaves by bringing the DIN _ SEL pin of each additional slave bridge into electrical communication with the DOUT _ SEL pin of the preceding slave bridge. In such a case, the slave bridges are connected in a parallel-series configuration.

In some embodiments, when the module select line (MOD _ SEL) is asserted, the CLK pulse directed to the connected SPI bridge captures the state of the bit shifted to DIN _ SEL in the bridge. The number of DIN _ SEL bits corresponds to the number of modules connected together on the parallel-to-serial SPI links. In one example, if two modules are connected in a parallel-series configuration, the number of DIN _ SEL is equal to 2.

In one embodiment, the SPI that latches a "1" during a module selection sequence bridges into a "selected module," which is configured to receive an 8-bit control word during a subsequent component selection sequence. Each SPI bridge can access up to 4 cascaded SPI slave devices. Further, each SPI bridge may have an 8-bit GP receive port and an 8-bit GP transmit port. The "element select" sequence writes an 8-bit word into the "select module" SPI bridge control register to support subsequent transactions with a particular SPI device or to read and write data via the SPI bridge GPIO port.

In one specific example, component selection is performed by asserting a local chip select line (CSL /) and then clocking the first byte of a MOSI transferred data word into a control buffer. In some cases, the format of the control buffer is CS4CS3CS2CS1AD1AD0R/W N. In another embodiment, the second byte is data to be transmitted or received. When CSL/is deasserted, the loop is complete.

In an SPI transaction, following a component selection sequence, a subsequent SPI slave data transaction is started. The SPI CS/(which may be referred to as SS /) is routed to one of 4 possible bridging devices according to the true state of CS4, CS3, CS2, or CS 1. The jumper bits AD0, AD1 are compared to the control registers AD0, AD1, allowing up to 4 SPI bridges on the module.

Fig. 41E shows a device having a plurality of modules installed on the SPI link of a communication vehicle of the device, according to one specific example described herein. The figure shows 3 modules, module 1, module 2 and module 3. Each module includes one or more SPI bridges for bringing the various components of the module into electrical connection with the SPI link, including a master controller (including one or more CPUs) in electrical communication with the SPI link. Module 1 includes a plurality of SPI slaves in electrical communication with each of SPI bridge 00, SPI bridge 01, SPI bridge 10, and SPI bridge 11. In addition, each module includes a receive data controller, a transmit data controller, and a module ID jumper.

In other specific examples, modules 701-706 are configured to communicate with each other and/or one or more controllers of system 700 via wireless communication vehicles (or interfaces). In one example, modules 701-706 communicate with each other via a wireless communication interface. In another example, one or more of modules 701-706 communicate with a controller of system 700 via a wireless communication cart. In some cases, modules 701-706 and/or one or more controllers of the system communicate with each other solely through wireless communication. This may advantageously eliminate the need for a wired interface in the rack for receiving modules 701-706. In other cases, system 700 includes a wired interface that works in conjunction with a wireless interface of system 700.

Although system 700 is shown with a single rack, a system (such as system 700) may have multiple racks. In some specific examples, a system has at most 1, or 2, or 3, or 4, or 5, or 6, or 7, or 8, or 9, or 10, or 20, or 30, or 40, or 50, or 100, or 1000, or 10000 scaffolds. In one embodiment, the system has a plurality of racks disposed in a side-by-side configuration.

Fig. 8 shows an example of a multi-rack system. For example, first bracket 800a may be connected and/or adjoined to second bracket 800 b. Each rack may include one or more modules 810. In another specific example, the system includes a plurality of racks disposed vertically with respect to each other — i.e., one rack atop another rack. In some embodiments, the scaffold may form a vertical array (e.g., one or more scaffold heights and one or more scaffold widths), a horizontal array (one or more scaffold widths, one or more scaffold lengths), or a three-dimensional array (one or more scaffold heights, one or more scaffold widths, and one or more scaffold lengths).

In some specific examples, the modules may be mounted on the rack according to a rack configuration. For example, if vertically oriented brackets are placed adjacent to each other, the modules may be installed vertically along the brackets. If horizontally oriented racks are placed on top of each other, the modules may be installed horizontally along the racks. The brackets may be connected to each other via any kind of connection interface, including those previously described for the modules. The brackets may or may not be connected to each other. The brackets may be mechanically and/or electrically connected to each other.

In another specific example, the system includes a plurality of racks, and each rack among the plurality of racks is configured for a different use, such as sample processing. In one example, a first scaffold is configured for sample preparation and cell counting, and a second scaffold is configured for sample preparation and agglutination. In another specific example, the bracket is installed horizontally (i.e., along an axis orthogonal to the force acceleration vector). In yet another specific example, the system includes a plurality of racks, and two or more racks among the plurality of racks are configured for the same purpose, such as sample preparation or processing.

In some cases, a system having multiple racks includes a single controller configured to direct (or facilitate) sample processing in each rack. In other cases, each individual rack of the plurality of racks includes a controller configured to facilitate sample processing in the individual rack. The controllers may be in network or electrical communication with each other.

A system having a plurality of racks may include a communication cart (or interface) for communicating the plurality of racks with one another. This allows parallel processing between the shelves. For example, for a system comprising two racks interchangeably coupled to each other by means of a communication trolley, the system processes a first sample in a first of the two racks, while the system processes a second sample in a second of the two racks.

Systems having multiple racks may include one or more sample processing systems for transferring samples to and from the racks. In one example, the system includes three racks and two sample handling systems to transfer samples to and from each of the first, second, and third racks.

In some embodiments, the sample processing system is a robot or robotic arm for facilitating sample transfer between supports, between modules in a support, and/or within a module. In some specific examples, each module may have one or more robots. The robot may be useful for moving components within or between different modules or other components of the system. In other embodiments, the sample processing system is an actuator (e.g., electric motors, pneumatic actuators, hydraulic actuators, linear actuators, comb actuators, piezoelectric and amplifying piezoelectric actuators, thermal bimorph chips, micro-mirror devices, and electroactive polymers) device for facilitating sample transfer between the supports or modules in the supports. In other embodiments, the sample processing system includes a pipette, such as a positive displacement, aspiration, or air displacement pipette, which may in turn be either robotically capable or robot possessing pipetting capabilities. One or more robots may be useful for transferring the sampling system from one location to another.

Robotic arms (also referred to herein as "arms") are configured to transfer samples to and from modules, or in some cases between racks. In one example, an arm transfers samples between a plurality of vertically oriented modules in a rack. In another example, an arm transfers samples between a plurality of horizontally oriented modules in a rack. In yet another example, an arm transfers samples between a plurality of horizontally and vertically oriented modules in a rack.

Each arm may include a sample manipulation device (or member) for supporting a sample during transfer to and from the module and/or one or more other racks. In a particular example, the sample manipulation device is configured to support a tip or container (e.g., container, vial) having a sample. The sample manipulation device may be configured to support a sample support, such as a microcard or cassette. Alternatively, the manipulation device may have one or more features that may allow the manipulation device to act as a sample holder. The sample manipulation apparatus may or may not include a platform, a holder, a magnet, a fastener, or any other device that may be useful for transfer.

In some embodiments, the arm is configured to transfer modules from one rack to another rack. In one example, an arm transfers a module from a first rack in a first rack to a first rack in a second rack, or from a first rack in a first rack to a second rack in a second rack.

The arm may have one or more drive means which may allow the arm to transfer the sample and/or the module. For example, one or more motors may be provided, which may allow movement of the arm.

In some cases, the arm may move along a track. For example, vertical and/or horizontal tracks may be provided. In some cases, the robotic arm may be a magnetic mount with a motion lock mount.

In some specific examples, a robot, such as a robotic arm, may be provided within the device housing. The robot may be provided in a cradle and/or in a module. Alternatively, they may be external to the rack and/or module. They may allow movement within the device, between tracks, between modules, or within modules. The robot may move one or more components including, but not limited to, a sample processing system such as a pipette, container/tip, cartridge, centrifuge, cytometer, camera, detection unit, thermal control unit, meter or system, or any other component described elsewhere herein. The components may be movable within the module, within the rack, or within the device. The components may still be movable within the device even if no support or module is provided within the device. The robot may move one or more modules. The module may be movable within the device. The robot may move one or more carriages, which may be movable within the apparatus.

The robot may be moved using one or more different drives. Such driving means may use mechanical components, electromagnetic, magnetic, thermal, piezoelectric, optical or any other properties or combinations thereof. For example, the drive device may use a motor (e.g., linear motor, stepper motor), lead screw, track, or any other drive device. In some cases, the robot may be electronically, magnetically, thermally, or optically controlled.

Fig. 68A provides an example of a magnetic manner of controlling the position of a robot or other object. The top view identifies an array of magnets 6800. A coil support structure 6810 can be provided adjacent to the magnets. The coil support structure may be made of an electrically conductive, magnetically weak material.

The magnet array may comprise a magnet strip or an m x n array of magnets, wherein m and/or n is greater than or equal to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 40, 50, or 100.

FIG. 68B provides a side view of the magnetic control. The coil support structure 6810 can have 1, 2, 3, 4, 5, 6, 7, 8, or more conductive coils 6820 thereon. The coil support structure may abut the array of magnets 6800.

Passive damping may be provided as well as the use of conductive magnetic materials.

The drive means may be able to move with very high precision. For example, the robot may be capable of moving with an accuracy within about 0.01nm, 0.05nm, 0.1nm, 0.5nm, 1nm, 5nm, 10nm, 30nm, 50nm, 75nm, 100nm, 150nm, 200nm, 250nm, 300nm, 400nm, 500nm, 600nm, 700nm, 800nm, 900nm, 1 μm, 1.5 μm, 2 μm, 3 μm, 4 μm, 5 μm, 7 μm, 10 μm, 15 μm, 20 μm, 25 μm, 30 μm, 40 μm, 50 μm, 75 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, 500 μm, 750 μm, 1mm, 2mm, or 3 mm.

The robot may be able to move in any direction. The robot may be capable of moving in a lateral direction (e.g., a horizontal direction) and/or a vertical direction. The robot may be able to move within a horizontal plane and/or a vertical plane. The robot may be capable of moving in x, y, and/or z directions, where the x, y, and z axes are orthogonal to each other. Some robots may move in only one dimension, two dimensions, and/or three dimensions.

Plug and play

In one particular example described herein, a plug-and-play system is described. The plug-and-play system is configured for assaying at least one sample, such as a tissue sample or a liquid sample, from a subject.

In some embodiments, a plug-and-play system includes a support structure having a mounting table configured to support a module of a plurality of modules. The module is detachable from the mounting station. In some cases, the module may be removably detachable — that is, the module may be detached from the mounting table and returned to its original position on the mounting table. Alternatively, a module may be replaced with another module.

In one particular example, the module is configured to perform, without the aid of another module in the system, (a) at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, magnetic separation, or (b) at least one type of assay selected from the group consisting of: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and/or other types of assays or combinations thereof.

In a particular example, the module is configured to be in electrical, electromagnetic, or opto-electrical communication with the controller. The controller is configured to provide one or more instructions to the module or individual ones of the plurality of modules to facilitate performance of at least one sample preparation procedure or at least one type of assay.

In one particular example, the system communicates with a controller to coordinate or facilitate processing of the sample. In one particular example, the controller is part of the system. In another embodiment, the controller is remotely located with respect to the system. In one example, the controller is in network communication with the system.

In a particular example, the module is configured to be coupled to a support structure. The support structure may be a rack having a plurality of racks for receiving a plurality of modules. The support structure is part of a system configured to receive the module. In one embodiment, the modules are hot pluggable-that is, the modules may be interchanged with one another or removed from the support structure while the system is processing other samples.

In some embodiments, after a user hot swaps a first module to a second module, the system can detect and identify the second module and update a list of modules available for use by the system. This allows the system to determine which resources are available for use by the system to process the sample. For example, if the cell count module is exchanged for an agglutination module and the system has no other cell count module, the system will know that the system is not capable of performing cell counting on the sample.

The plurality of modules may include the same module or different modules. In some cases, the plurality of modules are multi-function (or multi-purpose) modules configured for various preparation and/or processing functions. In other cases, the plurality of modules may be application-specific (or function-specific) modules configured for fewer functions than the multi-function modules. In one example, the one or more modules are application-specific modules configured for cell counting.

In some embodiments, the system is configured to detect the type of module without any user input. Such plug-and-play functionality advantageously enables a user to plug a module into the system for use without having to enter any commands or instructions.

In some cases, the controller is configured to detect the module. In such a case, when a user inserts a module into the system, the system probes the module and determines whether the module is a multi-purpose module or a special-purpose module. In some cases, the system can probe the module by using an electronic identifier, which may include a unique identifier. In other cases, the system can detect the module by means of a physical identifier, such as a bar code or an electronic component configured to provide a unique Radio Frequency Identification (RFID) code, such as an RFID number or unique ID, for communicating with the vehicle through the system.

The system may probe the module automatically or upon request from a user or another system or electronic component in communication with the system. In one example, system 700 detects a module 701 after a user inputs the module into system 700, which may allow system 700 to determine the type of module (e.g., a cell count module).

In some cases, the system is also configured to determine the location of the modules, which may allow the system to construct a virtual map of the modules, such as to facilitate parallel processing (see below), for example. In one example, system 700 is configured to probe the physical location of each of modules 701-706. In such a case, the system 700 understands that the first module 701 is located in the first port (or chassis) of the system 700.

Modules may have the same components or different components. In one specific example, each module has identical components, such as those described above in the context of fig. 7. That is, each module includes a pipette and various sample handlers. In another embodiment, the modules have different components. In one example, some modules are configured for a cell count assay, while other modules are configured for an agglutination assay.

In another specific example, the shared module may be a dedicated cooling or heating unit that provides cooling or heating capabilities to the device or other modules as needed.

In yet another specific example, the shared resource module may be a rechargeable battery pack. Examples of batteries may include, but are not limited to: zinc-carbon, zinc-chlorine, alkaline, oxy-nickel hydroxide, lithium, mercury oxide, zinc-air, silver oxide, NiCd, lead-acid, NiMH, NiZn, or lithium ions. These batteries may or may not be hot-pluggable. The rechargeable battery may be coupled to an external power source. The rechargeable battery module can be recharged when the device is plugged into an external power source, or the battery module can be removed from the device and recharged in a dedicated recharger external to the device, or plugged directly into an external power source. The dedicated recharging meter may be the device or may be operatively connected to the device (e.g., recharging may be by induction without direct physical contact). The recharger may be a solar recharger or may be powered by other clean or conventional power sources. The recharger may be powered by a conventional generator. The battery module may provide a uninterruptible power supply system (UPS) for a device or group of devices in case power from an external supply is interrupted.

In another embodiment, the shared resource module may be a "computing center," or some high-performance general-purpose or special-purpose processor that is assembled together by appropriate cooling into a module that is dedicated to high-performance computing within the device or shared by some devices.

In yet another specific example, a module may be a combination of high performance and/or high capacity storage devices to provide a large amount of storage space on the device (e.g., 1TB, 2TB, 10TB, 100TB, 1PB, 100PB, or larger) for sharing by all modules, modules in other devices that may share resources with the device, or even shared by an external controller for caching large amounts of data locally to the device or to a physical site or sites or to some site or to any other group of devices.

In another particular example, the sharing module may be a satellite communication module that is capable of providing communication capabilities to communicate with a satellite from devices or other devices that may be sharing resources.

In yet another specific example, the module may be an internet router and/or a wireless router that provides full routing and/or hotspot capabilities to a device or group of devices allowed to share the device's resources.

In some embodiments, a module may act, alone or in combination with other modules (or systems) provided herein, as a "data center" for a device or group of devices that are allowed to share the resources of the device, thereby providing high performance computing, high capacity storage, high performance networking, satellite communication capabilities, or other forms of dedicated communication capabilities in a device for a given location or site or locations.

In one particular example, the shared module may be a recharger for a wireless or wired peripheral for use with the device.

In one embodiment, the shared module may be a small refrigerated or temperature controlled storage unit for storing samples, cassettes, or other supplies for the device.

In another specific example, the module may be configured to automatically dispense prescriptions or other medications. The module may also have other components such as a package capper and a label printer to make packaging and dispensing of the medication safe and efficient. The modules may be remotely programmed or programmed in the device to automatically dispense the drugs-based on real-time diagnostics on the biological sample or any other algorithm or method that determines such a need. The system may have a pharmacy decision support analysis to support the module around treatment decisions, dosages, and other pharmacy-related decision support.

The module may have a swappable component. In one example, the module has a positive displacement pipette that is interchangeable with the same type of pipette or a different type of pipette such as a suction pipette. In another example, the module has a meter that can be exchanged with the same type of meter (e.g., a cell count meter) or a different type of meter (e.g., an agglutination meter). The modules and systems are configured to identify modules and components within the modules, and to update or modify processing conventions, such as parallel processing conventions, in view of the modules coupled to the system and the components within each module.

In some cases, the module may be external to the device and connected to the device through a communications communication vehicle of the device (e.g., via a USB port).

Fig. 9 shows an example of a module 900 having one or more components 910. The module may have one or more controllers. The components 910 are electrically coupled to each other and/or to a controller via a communication ac vehicle ("communication ac vehicle"), such as the communication ac vehicle described in the context of fig. 7 above, for example. In one example, module 900 includes one or more communication vehicles selected from the group consisting of: media communication vehicle, computer automatic measurement and control (CAMAC) communication vehicle, Industry Standard Architecture (ISA) communicationCommunication vehicle, Extended ISA (EISA) communication vehicle, low pin count communication vehicle, MBus, micro-channel communication vehicle, multi-communication vehicle, NuBus or IEEE1196, OPTi local communication vehicle, Peripheral Component Interconnect (PCI) communication vehicle, parallel Advanced Technology Attachment (ATA) communication vehicle, Q-communication vehicle, S-100 communication vehicle (or IEEE696), SBus (or IEEE1496), SS-50 communication vehicle, STE communication vehicle, STD communication vehicle (for STD-80[ 8-bit)]And STD32[ 16-/32-position]) The vehicle comprises a single communication AC vehicle, a VESA local communication AC vehicle, a VME communication AC vehicle, a PC/104Plus communication AC vehicle, a PC/104Express communication AC vehicle, a PCI-104 communication AC vehicle, a PCIe-104 communication AC vehicle, a 1-line communication AC vehicle, an ultra-transmission communication AC vehicle and a mutual integrated circuit (I)²C) A communication interchange vehicle, a PCI Express (or PCIe) communication interchange vehicle, a Serial ATA (SATA) communication interchange vehicle, a serial peripheral interface communication interchange vehicle, a UNI/O communication interchange vehicle, a SMBus, a self-healing elastic interface communication interchange vehicle, and variations and/or combinations thereof. In one particular example, a communication AC cart is configured to communicatively couple components 910 to each other and to a controller. In another specific example, a communication cart is configured to communicatively couple the component 910 to a controller. In one particular example, a communication cart is configured to communicatively couple components 910 to one another. In some specific examples, module 900 includes a power communication ac cart that provides power to one or more of components 910. The power communication AC vehicle can be separated from the communication AC vehicle. In another embodiment, one or more components are powered by means of a communications communication vehicle.

In one particular example, the component 910 can be exchangeable, such as hot-pluggable. In another specific example, the component 910 may be removed from the module 900. The component 910 is configured for sample preparation, processing, and probing. Each of the components 910 may be configured to process a sample via one or more sample processing, preparation, and/or probing conventions.

In the illustrated example, the module 900 includes 6 components 910: a first component (component 1), a second component (component 2), a third component (component 3), a fourth component (component 4), a fifth component (component 5), and a sixth component (component 6). Module 900 typically includes 1 or more, or 2 or more, or 3 or more, or 4 or more, or 5 or more, or 6 or more, or 7 or more, or 8 or more, or 9 or more, or 10 or more, or 20 or more, or 30 or more, or 40 or more, or 50 or more, or 100 or more components 910. The assembly 910 is configured for serial and/or parallel processing of samples by means of a controller communicatively (and electrically) coupled to the assembly 910.

In one example, component 1 is a centrifuge, component 2 is a spectrophotometer, component 3 is a nucleic acid meter, and component 4 is a PMT meter, component 5 is a pipette holder, and component 6 is a sample washer.

In one embodiment, the component is configured to process the samples in a sequence. In such a case, the sample is processed in the modules (i.e., module 1, module 2, etc.) in sequence. In another specific example, the sample processing is not necessarily sequential. In one example, the samples are first processed in component 4 and then processed in component 1.

In one specific example, component 910 processes samples in parallel. That is, a component may process a sample while one or more other components process the sample or a different sample. In one example, component 1 processes the sample while component 2 processes the sample. In another embodiment, the component 910 processes the samples sequentially. That is, while one component processes a sample, the other component does not process the sample.

In some embodiments, the module 900 includes a sample processing system configured to transfer samples to and from the assembly 910. In one embodiment, the sample processing system is a positive displacement pipette. In another embodiment, the sample processing system is a pipette. In yet another embodiment, the sample processing system is an air displacement pipette. In another specific example, the sample processing system includes one or more of a suction pipette, a positive displacement pipette, and an air displacement pipette. In yet another specific example, the sample processing system includes any two of a suction pipette, a positive displacement pipette, and an air displacement pipette. In another specific example, the sample processing system includes a suction pipette, a positive displacement pipette, and an exhaust pipette.

The components 910 may be connected via the communication bus architecture provided herein. In one example, the components 910 are connected via a parallel-serial configuration described in the context of fig. 41A-41E. That is, each component 910 may be connected to an SPI slave bridge, which in turn is connected to a master bridge. In other embodiments, the components 910 are connected in a series (or daisy) configuration. In other embodiments, the components 910 are connected in a parallel configuration.

In some embodiments, the component 910 may be swapped with other components. In one particular example, each component may be swapped with the same component (i.e., another component having the same function). In another specific example, each component may be exchanged with a different component (i.e., a component having a different function). When the module 900 is closed, the components 910 may be hot-pluggable or removable.

Fig. 10 illustrates a system 1000 having a plurality of modules mounted to a rack of the system 1000, according to one specific example described herein. The system includes a first module (module 1), a second module (module 2), and a third module (module 3). The system 1000 includes a communications communication cart ("communication cart") for communicating a controller of the system 1000 with each module. The communication vehicles of system 1000 (also referred to herein as "system communication vehicles") are also configured to enable the modules to communicate with each other. In some cases, the controller of system 1000 is optional.

With continued reference to FIG. 10, each module includes a plurality of meters (or sub-modules) designated by Mxy, where "x" designates the module and "y" designates the meter. Each module may alternatively include a controller communicatively coupled to each instrument via a communication vehicle (also referred to herein as a "module communication vehicle"). In some cases, the controller is communicatively coupled to the system communication vehicle through the module communication vehicle.

The module 1 includes a first meter (M11), a second meter (M12), a third meter (M13), and a controller (C1). The module 2 includes a first meter (M21), a second meter (M22), a third meter (M23), and a controller (C2). Module 3 includes a first meter (M31) and a controller (C3). The controller of the module is communicatively coupled to each meter via a communications trolley. The instrument is selected from the group consisting of a preparation instrument, a measuring instrument, and a detection instrument. The preparation instrument is configured for sample preparation; the analyzer is configured for sample measurement; and the probe is configured to analyze the probe.

In one particular example, each module communication trolley is configured to allow the meter to be removed in such a way that the module can still function without the meter being removed. In one example, M11 may be removed from module 1 while allowing M12 and M13 to function. In another specific example, each meter may be hot swapped with another meter — that is, one meter may be replaced with another meter without removing the module or shutting down system 1000.

In some embodiments, the meter is removable from the module. In other embodiments, the meter may be replaced by another meter. In one example, M11 is replaced by M22.

Each meter may be different, or two or more meters may be the same, with respect to a particular module. In one example, M11 is a centrifuge and M12 is a agglomerator. As another example, M22 is a nucleic acid analyzer and M23 is an x-ray photoelectron spectrometer.

Two or more modules may have the same instrument configuration or different configurations. In some cases, the module may be a dedicated module. In the embodiment illustrated in fig. 10, module 3 has a single meter M31 communicatively coupled to C3 by meter M31.

The system 1000 includes a sample processing system for transferring samples to and from the cartridge. The sample processing system includes a positive displacement pipette, a suction pipette, and/or an exhaust pipette. The sample processing system is controlled by a controller of the system 1000. In some cases, a sample processing system may be exchanged by another sample processing system, such as by a sample processing system dedicated for certain uses.

With continued reference to FIG. 10, each module includes a sample handling system for transferring samples to and from the meter. The sample processing system includes a positive displacement pipette, a suction pipette, and/or an exhaust pipette. The sample processing system is controlled by a controller in the module. Alternatively, the sample processing system is controlled by a controller of the system 1000.

Parallel processing and dynamic resource sharing

In another specific example described herein, a method for processing a sample is provided. The method is used to prepare a sample and/or perform one or more sample analyses.

In some embodiments, a method for processing a sample includes providing a system having a plurality of modules as described herein. The modules of the system are configured to simultaneously perform (a) at least one sample preparation procedure selected from the group consisting of sample processing, centrifugation, magnetic separation, and chemical processing, and/or (b) at least one type of assay selected from the group consisting of: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and/or other types of assays or combinations thereof. Next, the system detects for the presence of resource unavailability or failure of (a) the at least one sample preparation procedure or (b) the at least one type of assay. After detecting a fault within at least one module, the system performs the at least one sample preparation procedure or the at least one type of assay using another module of the system or of another system in communication with the system.

In some specific examples, the system 700 of fig. 7 is configured to allocate resource sharing to facilitate sample preparation, processing, and probing. In one example, one of modules 701-706 is configured to perform a first sample preparation procedure, while another of modules 701-706 is configured to perform a second sample preparation procedure that is different from the first sample preparation procedure. This enables the system 700 to process the first sample in the first module 701 while the system 700 processes the second sample or a portion of the first sample. This advantageously reduces or eliminates downtime (or dead time) between modules where processing in the modules (or components within the modules) conventionally requires different time periods to complete. Even if processing is done routinely within the same time period, parallel processing enables the system to optimize system resources in multiple situations without the time periods overlapping. This may apply to the case where one module is put into use after another module or if one module has a different start time than another module.

The system 700 includes various devices and apparatuses for facilitating sample transfer, preparation, and probing. Sample processing system 708 enables transfer of samples to and from each of modules 701-706. The sample processing system 708 enables a sample to be processed in one module while a portion of the sample or a different sample is transferred to or from another module.

In some cases, system 700 is configured to probe each of modules 701-706 and determine whether a rack configured to receive the module is empty or occupied by the module. In one particular example, the system 700 can determine whether a chassis of the system 700 is occupied by a general purpose or multi-function module, such as a module configured to perform multiple probes, or a special purpose module, such as a module configured to perform selective probes. In another specific example, the system 700 can determine whether a rack or a module in a rack is defective or malfunctioning. The system may then use other modules to perform sample processing or probing.

"multifunction modules" are configured for a wide range of uses such as sample preparation and processing. The multifunctional module may be configured for at least 2, or 3, or 4, or 5, or 6, or 7, or 8, or 9, or 10, or 20, or 30, or 40, or 50 uses. A "special-purpose module" is a module configured for one or more selected uses or a subset of uses, such as for at most 1, or 2, or 3, or 4, or 5, or 6, or 7, or 8, or 9, or 10, or 20, or 30, or 50 uses. Such uses may include sample preparation, processing, and/or detection (e.g., assays). The module may be a multi-function module or a special purpose module.

In some cases, a special purpose module may include sample preparation procedures and/or probing not included in other modules. Alternatively, special purpose modules include a subset of the sample preparation procedures and/or probes included in other modules.

In the example illustrated in fig. 7, module 706 may be a special purpose module. Particular uses may include, for example, one or more assays selected from a cytometric assay, an agglutination assay, a microscopic assay, and/or any other assay described elsewhere herein.

In one example, the module is configured to perform only cell counting. The module is configured for use by the system 700 to perform cell counting. The cell count module may be configured to prepare and/or process the sample prior to performing cell counting on the sample.

In some embodiments, a system configured for parallel processing of multiple samples is provided. The samples may be different samples or portions of the same sample (e.g., portions of a blood sample). Parallel processing enables the system to use system resources in situations when such resources would otherwise be unavailable. In this manner, the system is configured to minimize or eliminate lag periods between processing protocols, such as preparation and/or assay protocols. In one example, the system measures (e.g., by way of cell count) the first sample in the first module while the system is centrifuging the same or different samples in different modules.

In some cases, the system is configured to process the first sample in the first component of the first module while the system processes the second sample in the second component of the first module. The first sample and the second sample may be portions of a bulk sample, such as portions of a blood sample, or different samples, such as a blood sample from a first subject and a blood sample from a second subject, or a urine sample from a first subject and a blood sample from a first subject. In one example, the system determines the first sample in the first module while the system is centrifuging the second sample in the first module.

FIG. 11 shows a plurality of plots illustrating parallel processing conventions according to the specific examples described herein. Each plot illustrates processing in a single module as a function of time (abscissa, or "x-axis"). In each module, a step increase over time corresponds to the start of the process, and a step decrease over time corresponds to the end (or completion) of the process. The top plot shows processing in the first module, the middle plot shows processing in the second module, and the bottom plot shows processing in the third module. The first, second, and third modules are part of the same system (e.g., system 700 of fig. 7). Alternatively, the first, second and/or third modules may be part of a stand-alone system.

In the illustrated example, while a first module processes a first sample, a second module processes a second sample and a third module processes a third sample. The first module and the third module start processing at the same time, but the processing time is different. This may be the case, for example, if the first module processes the sample with a different assay or preparation routine than the third module (e.g., centrifugation in the first module and cell counting in the third module). In addition, the first module takes twice as long to complete. During this time, the third module processes the second sample.

The second module starts processing the sample at a time later than the start time of the first and third modules. This may be the case, for example, if the second module requires a different period of time to complete sample processing than the first and third modules, or if the second module encounters a failure.

The modules may have the same dimensions (e.g., length, width, height) or different dimensions. In one example, one general or special purpose module has a length, width, and/or height that is different from another general or special purpose module.

In some cases, systems and modules for processing biological samples are configured to communicate with other systems to facilitate sample processing (e.g., preparation, assay). In one particular example, the system communicates with another system, for example, by way of a wireless communication interface such as a wireless network router, bluetooth, Radio Frequency (RF), opto-electronic, or other wireless communication mode. In another embodiment, the system communicates with another system via wired communication means such as a wired network (e.g., the internet or an intranet).

In some embodiments, service point devices in a predetermined area communicate with each other to facilitate network connectivity, such as connectivity to an internet or intranet. In some cases, a plurality of service point devices communicate with each other by means of an internal network, such as an internal network established by one of the plurality of service point devices. This may allow a subset of the plurality of service point devices to connect to the network without a direct (e.g., wired, wireless) network connection — the subset of the plurality of service point devices being connected to the network by way of the network connectivity of the service point devices connected to the network. With such shared connectivity, the service point device can retrieve data (e.g., software, data files) without connecting to a network. For example, a first service point device that is not connected to the wide area network may retrieve a software update by forming a local area connection or a point-to-point connection with a second service point device. The first service point device may then connect to a wide area network (or cloud) by means of the network connectivity of the second service point device. Alternatively, the first point of service device may retrieve a copy of the software update directly from the second point of service device.

In one example of shared connectivity, a first point of service device connects (e.g., wirelessly connects) to a second point of service device. The second service point device is connected to the network by means of a network interface of the second service point device. The first service point device may connect to the network through a network connection of the second service point device. It should also be appreciated that the devices herein may implement the network connectivity techniques described herein using any network connectivity hardware and/or software. This includes the network connectivity techniques described in text and icons in association with fig. 83-88.

Record-based logging and failure recovery

Another specific example described herein provides a method for enabling devices and systems, such as point of service devices, to maintain transaction records and/or operation records. Such methods, for example, enable the systems and devices provided herein to recover from a fault condition.

In some cases, the point of service devices and modules have an operational state that characterizes the state of operation of such devices, such as, for example, sample centrifugation, sample transfer from a first component to a second component, or nucleic acid amplification. In one particular example, the operational state is an individual (or discrete) condition of the state of operation of the service point device.

The operational state may capture operations at various levels, such as a device level or a system level. In one example, the operational state includes use of a device (e.g., pipette). In another example, the operational state includes moving a component of the device (e.g., moving the pipette two inches to the left).

In some embodiments, the service point device has a processing directory (or operations directory) with one or more operations matrices. Each of the one or more matrices has discrete operating states of a service point system (or device) or one or more modules of a system. The processing catalog may be generated by a service point system or device or by another system located on or associated with the service point system or device. In one example, the processing catalog is generated after initial system startup or setup. In another example, the processing catalog is generated upon request by a user or other system, such as a maintenance system.

In one embodiment, the service point system generates a processing directory configured to record operational data corresponding to one or more discrete operational states of the service point system. The one or more discrete operating states may be selected from the group consisting of sample preparation, sample assay, and sample probing. Next, the operation data of the service point system is sequentially recorded in the processing directory.

In some cases, the operational data is recorded in real-time. That is, when a change or update in the operating state of the service point system is detected, the operational data may be recorded.

In some cases, the operational data is recorded in the sample processing catalog prior to the service point system performing a processing routine corresponding to the operational state of the service point system. In other cases, the operational data is recorded in the sample processing catalog after the point-of-service system performs the processing routine. As an alternative, the operational data is recorded in the sample processing catalog while the point-of-service system is performing the processing routine. In some cases, logging data is logged before, during, or after completion of a transaction to provide a finest level of granularity of logging for each action across time and space for overall system level logging or for purposes of system integrity and system recovery.

The service point system is configured to record the progress of the respective processes of the respective components of the service point system and/or the modules of the service point system. In some cases, the service point system makes a record in the processing catalog when the processing routine has been completed by the service point system.

The processing directory may be provided by way of one or more matrices stored on the service point system or another system associated with the service point system. In some cases, a service point device (e.g., system 700 in fig. 7) or module (e.g., first module 701 in fig. 7) may include an operational matrix with discrete operational states for the service point device or module. The operation matrix includes discrete states, i.e., state 1, state 2, state 3, etc., of individual modules or components of modules of the service point system. The rows (if a row matrix) or columns (if a column matrix) of the operation matrix are reserved for each module or component. Further, each state may include one or more sub-states, and each sub-state may include one or more sub-states. For example, a module having a first state (state 1) may have components that perform various functions. The state of each component has a state denoted by state mn, where "m" denotes the module and "n" denotes the component of the module. In one example, for a first module of a service point device, a first component may have a first state, state 11, and a second component may have a second state, state 12; and for a second module of the service point device, the first component may have a first state, state 21, and the second component may have a second state, state 22. Each module may have any number of components (or sub-modules), such as at least 1 component (e.g., a single centrifuge), at least 10 components, or at least 100 components.

FIG. 42 illustrates an operational matrix of a service point system according to one specific example described herein. The operation matrix may be for a service point system, or a module of a system, or any component of a system or any module. The operation matrix includes a first column having a number corresponding to a Sequence number ("Sequence no"), and a second column having a string corresponding to an operational state of the system (e.g., "state 1"). Each operating state includes one or more conventional-conventional n, where "n" is an integer greater than or equal to 1. In the illustrated example, the first state ("state 1") includes at least 3 conventions- "convention 1", "convention 2", and "convention 3". In one particular example, a routine comprises one or more instructions that, alone or in conjunction with other routines, cause a system or module in a system to conform to a particular state of the system.

The matrix may be located on (or stored on) a physical storage medium of or associated with a controller of the point of service device. The physical storage medium may be part of a database of the point of service device. The database may include one or more components selected from the group consisting of a Central Processing Unit (CPU), a hard disk, and memory (e.g., flash memory). The database may be onboard the device and/or contained within the device. Alternatively, data may be transmitted from the device to an external device and/or cloud computing infrastructure. The matrix may be provided by way of one or more spreadsheets, data files, having one or more rows and columns. Alternatively, the matrix may be defined by one or more rows and one or more columns residing in a memory or other storage location of a controller or other system on or associated with the service point device.

FIG. 43 is an example of an operational matrix of a service point system and/or one or more modules of a service point system. The operation matrix includes 3 processing states of the module, namely "centrifuge sample", "perform cell count on sample", and "perform agglutination assay on sample". Each processing state includes one or more conventions. For example, the first processing state ("centrifuged sample") has six conventions as shown, i.e., "remove sample from sample processing system", "provide sample in centrifugal tip", and so on. The convention is listed in increasing order of time. That is, the "removing a sample from a sample processing system" routine is performed prior to the "providing a sample in a centrifugal tip" routine.

In some cases, the operational data is provided in a one-dimensional matrix (i.e., a column matrix or a row matrix). In other cases, the operational data is provided in a two-dimensional matrix, where the rows correspond to conventional and the columns correspond to a single system or system module.

The operation matrix allows the service point system to determine what processing conventions the system has done with the finest level of detail in the system. This advantageously enables the system to recover from a fault condition in the event that which processing is conventionally completed in a particular state prior to the system logging the fault condition (e.g., power outage, system crash, module crash).

In some embodiments, a method for updating an operational log of a service point system includes accessing an operational log of the service point system, the operational log configured to record operational data corresponding to one or more discrete operational states of the service point system. The operational log may be accessible by the service point system, a controller of the service point system, or another system of or associated with the service point system (collectively referred to as "the system"). The one or more discrete operating states include one or more predetermined processing regimes (e.g., centrifugation, PCR, one or more assays). Next, the system generates one or more processing conventions to be performed by the service point system. The processing conventionally corresponds to one or more operating states of the service point system. The system then records data corresponding to the one or more processing conventions in an oplog.

In some cases, the operation log may be part of an operating system of the system. Alternatively, the oplog is a software or other computer-implemented application that resides on the system or cloud.

In some cases, the log is implemented (or resident) on a hard disk or a flash disk that is not part of the hard disk. In addition to an external power source, the log system may be separately powered by a battery, providing an uninterruptible power supply system to the log system in the event of a system crash or interruption of power from an external or other source. In other cases, the oplog resides on a storage medium (hard disk, flash drive) of another system, such as a remote system.

In another particular example, a method for processing a sample with a service point system includes accessing an oplog of the service point system. The oplog has operational data corresponding to one or more discrete operational states of the service point system. The one or more discrete operating states include one or more predetermined processing conventions. The system sequentially executes processing conventions from the one or more predetermined processing conventions and removes data corresponding to completed processing conventions for the operating state of the service point system from the oplog.

In one specific example, data corresponding to a completed processing routine is removed from the oplog before, after, or during sequential execution of the processing routine.

In some embodiments, a computer-assisted method for restoring an operating state of a point of service system includes accessing a sample processing catalog after a fault condition of the point of service system; identifying a last minute operational state of the service point system from the sample processing catalog; identifying a last-minute sample processing routine from the one or more predetermined sample processing routines, the last-minute sample processing routine corresponding to a last-minute operating state of the point-of-service system; and executing a next-time sample processing routine selected from the one or more predetermined sample processing routines, the next-time sample processing routine immediately following the last-time sample processing routine. The sample processing catalog is configured to record operational data corresponding to one or more discrete operational states of the point-of-service system. In some cases, the operation data is recorded in a sample processing directory after completion of a sample processing routine sequentially selected from one or more predetermined sample processing routines. The one or more operating states of the point of service system are selected from the group consisting of sample preparation, sample metering, and sample probing. In some cases, the fault condition is selected from the group consisting of a system crash, a power outage, a hardware fault, a software fault, and an operating system fault.

In other particular examples, a computer-assisted method for restoring an operating state of a service point system includes accessing an operational log of the service point system after a fault condition of the service point system. Next, one or more processing conventions corresponding to the operation data are sequentially played back from the operation log. The one or more process conventions are played back without the service point system executing the one or more process conventions. When a certain processing routine from the one or more processing routines corresponds to an operational state of the point-of-service system prior to the fault condition, the system stops playing back the one or more processing routines. The system then restores the point of service system to the pre-fault condition operating state. In some cases, the oplog has operational data corresponding to one or more discrete operational states of the service point system. The one or more discrete operating states include one or more predetermined processing conventions.

FIG. 44 shows a planning matrix and a conventional matrix. The planning matrix and the regular matrix may be part of one or more operational matrices of the service point system. The planning matrix includes predetermined conventions to be executed by the service point system or modules of the service point system ("the system"). The conventions for a plan (a "plan") are listed sequentially from top to bottom in the order in which such plans are to be executed by the system. The routine matrix includes a routine (or plan) that has been executed by the system. When the system performs a particular routine, the system records the routine in a routine matrix. Conventions are recorded in the convention matrix in the order of their execution. The convention at the bottom of the list is that performed last minute. In some cases, once one or more of the steps necessary to complete the lineage have been completed by the system, the routine is marked as completed.

In one example, the system accesses the routine matrix after a fault condition to determine a routine performed at a last instance. The system then begins processing the plan (from the plan matrix) selected after the routine performed at the last instance. In the illustrated example, the system begins processing by providing a centrifuge tip in a centrifuge.

In one embodiment, the system provides a pointer to indicate the last minute processing routine to be completed before the fault condition. Fig. 45A shows an operation matrix with a processing state. Each processing state has one or more conventions in a convention matrix. In the illustrated example, completed conventions are shown in black text and incomplete conventions are shown in gray text. As described above, the conventions to be completed may be filled in by referencing the planning matrix. The horizontal arrows are pointers that mark the position in the conventional matrix immediately following the last moment. After the fault condition, the system begins processing at the location indicated by the horizontal arrow. Here, the system provides a centrifugation tip in a centrifuge. In other cases, the system includes pointers that mark the current and pending processing routine locations. In fig. 45B, the horizontal arrow is a pointer marking the location of the incomplete process routine ("providing the sample in the centrifugal tip"). The system may be performing such processing conventions between 0% to less than 100% completion. Once completed, the horizontal arrow is incremented to the next convention (the arrow is incremented along the convention matrix). After the fault condition, the system begins processing at the location indicated by the horizontal arrow. As another alternative, the system includes a pointer that marks the location of the pending process routine that immediately follows the current process routine. In fig. 45C, the horizontal arrow is a pointer marking the location of the processing routine to be processed next ("providing a centrifugal tip in a centrifuge"). In the illustrated example, the system is still performing the previous processing routine (as shown in gray "provide centrifugal tips in centrifuge"). As described above, the to-do routine may be populated by referencing the planning matrix.

In some embodiments, the tracking process may also conventionally include tracking the precise location of one or more components. Tracking the processing routine may include tracking each step or location associated with tracking the processing routine. For example, tracking the position of the component may keep track of the precise distance the component has moved (e.g., per mm, μm, nm, or less). The distance that the component has moved on its journey can still be tracked even if it has not yet reached its destination. Thus, even if an error occurs, the precise location of the component may still be known and may be useful for determining the next steps. In another example, the amount of time a certain object has been centrifuged may be tracked-even if the centrifugation process has not been completed.

Assembly

A device may include one or more components. One or more of these components may be modular components, which may be provided to a module. One or more of these components are not modular components and may be provided to the device, but outside the module.

Examples of equipment components may include liquid handling systems, tips, containers, mini cards, assay units (which may be in the form of tips or containers), reagent units (which may be in the form of tips or containers), dilution units (which may be in the form of tips or containers), wash units (which may be in the form of tips or containers), contamination reduction equipment, lysis equipment, filters, centrifuges, temperature controls, probes, housings/supports, controllers, displays/user interfaces, power supplies, communication units, equipment tools, and/or equipment identifiers.

One, two or more of the device components may also be modular components. In some embodiments, some components may be provided at both the device level and the module level, and/or the device and module may be the same. For example, a device may have its own power supply, while a module may also have its own power supply.

Fig. 2 provides a high-level illustration of a device 200. The device may have a housing 240. In some embodiments, one or more components of the apparatus may be contained within an apparatus housing. For example, the apparatus may include one or more support structures 220, and the support structures 220 may have one or more modules 230a, 230 b. The apparatus may also have a sample acquisition unit 210. The device may have a communication unit 280 that can allow the device to communicate with one or more external devices 290. The apparatus may also include a power unit 270. The device may have a display/user interface 260, which display/user interface 260 may be visible to an operator or user of the device. In some cases, user interface 260 displays a user interface, such as a Graphical User Interface (GUI), to the subject. The device may also have a controller 250 that may provide instructions to one or more components of the device.

In some embodiments, the display unit on the device may be detachable. In some embodiments, the display unit may also have a CPU, memory, a graphics processor, a communication unit, a rechargeable battery, and other peripherals, enabling it to operate like a "tablet computer" or "tablet computer" to enable it to communicate wirelessly with the device. In some embodiments, separate displays/tablets may be a resource shared among all devices in a location or group, so that one "tablet" may control, input, and interact with 1, 2, 5, 10, 100, 1000, or more devices.

In some embodiments, the separate display may serve as a companion device for the healthcare professional, not only for controlling the device, but also as a touch input device for collecting patient signatures, absences, and other authorizations, as well as collaborating with other patients and healthcare professionals.

The housing may enclose (or enclose) one or more components of the device.

The sample acquisition unit may be in fluid communication with one or more modules. In some embodiments, the sample acquisition unit may be in selective fluid communication with the one or more modules. For example, the sample acquisition unit may be selectively brought into and/or out of fluid communication with the cartridge. In some embodiments, the sample acquisition unit may be fluidly isolated from the cartridge. The liquid handling system may assist in transporting the sample from the sample acquisition unit to the module. The fluid handling system can transport fluid while the sample acquisition unit remains in fluid or hydraulic isolation from the module. Alternatively, the liquid handling system may allow the sample acquisition unit to be fluidically connected to the module.

The communication unit may be capable of communicating with an external device. Two-way communication may be provided between the communication unit and the external device.

The power unit may be an internal power source or may be connected to an external power source.

Further description of the diagnostic device and one or more device components may be discussed in more detail elsewhere herein.

Liquid treatment system

The apparatus may have a liquid handling system. As previously noted, any discussion herein of a liquid processing system may be applicable to any sample processing system or vice versa. In some embodiments, the liquid handling system may be contained within an equipment enclosure. The liquid handling system or portions of the liquid handling system may be contained within a module housing. The liquid handling system may allow for collection, delivery, handling and/or transport of liquids, dissolution of dry reagents, mixing of liquids and/or dry reagents with liquids, and collection, delivery, handling and/or transport of non-liquid components, samples or materials. The liquid may be a sample, a reagent, a diluent, a detergent, a dye or any other liquid that may be used by the apparatus. The liquid being treated by the liquid treatment system may comprise a homogeneous liquid, or a liquid having a particulate or solid component therein. The liquid being treated by the liquid treatment system may have at least a portion of the liquid therein. The liquid handling system may be capable of handling dissolution of dry reagents, mixing of dry reagents in liquids, and/or liquids. "liquid" may include, but is not limited to, various liquids, emulsions, suspensions, and the like. Different liquids can be treated using different liquid transfer devices (tips, capillaries, etc.). Liquid handling systems, including but not limited to pipettes, may also be used to transport containers around the device. The liquid treatment system may be capable of treating a flowing material, including but not limited to a liquid or a gaseous liquid, or any combination thereof. The liquid handling system may dispense and/or draw liquid. The fluid handling system may dispense and/or aspirate a sample or other fluid, which may be a bodily fluid or any other type of fluid. The sample may comprise one or more particulate or solid matter floating within the liquid.

In one example, the liquid handling system may use a pipette or similar device. The liquid handling device may be part of a liquid handling system and may be a pipette, a syringe or any other device. The liquid treatment device may have a portion with an inner surface and an outer surface and an open end. The liquid handling system may also comprise one or more pipettes, wherein each pipette has a plurality of orifices through which simultaneous aeration and/or liquid flow may occur. In some cases, the portion comprising the inner and outer surfaces and the open end may be a tip. The tip may or may not be removable from the pipette nozzle. The open end can collect liquid. Liquid can be dispensed through the same open end. Alternatively, the liquid may be dispensed through the other end.

The collected liquid may optionally be contained within a liquid handling device. When desired, a liquid may be dispensed from the liquid treatment device. For example, the pipette may selectively aspirate liquids. The pipette may draw a selected amount of liquid. The pipette may be capable of actuating the stirring device to mix the liquid within the tip or within the container. Pipettes may incorporate tips or vessels to create a continuous flow loop for mixing, including mixing of materials or reagents in non-liquid form. Pipette tips can also facilitate mixing by metering multiple liquids simultaneously or sequentially, such as in a 2-part substrate reaction. The liquid may be contained within the pipette tip until it is desired to dispense the liquid from the pipette tip. In some embodiments, all of the liquid within the liquid treatment apparatus may be dispensed. Alternatively, a portion of the liquid within the liquid treatment device may be dispensed. A selected amount of liquid within the liquid handling device may be dispensed or retained in the tip.

The liquid handling device may comprise one or more liquid handling orifices and one or more suction heads. For example, the liquid handling device may be a pipette with a pipette nozzle and a removable/detachable pipette tip. The tip is connectable to a liquid handling orifice. The tip may be removable from the liquid handling orifice. Alternatively, the tip may be integrally formed on the liquid handling orifice or may be permanently fixed to the liquid handling orifice. When connected to the liquid handling orifice, the pipette tip forms a liquid tight seal. In some embodiments, the liquid handling orifice is capable of receiving a single tip. Alternatively, the liquid handling orifice may be configured to receive a plurality of tips simultaneously.

The liquid treatment apparatus may comprise one or more liquid-insulated or hydraulically-independent units. For example, the liquid handling device may comprise one, two or more pipette tips. Pipette tips can be configured to receive and confine liquids. The tips may be fluidly isolated or hydraulically independent from each other. The liquids contained in the tip may be isolated or hydraulically independent from each other or from other liquid liquids in the device. The hydraulically isolated or hydraulically independent units may be movable relative to other parts of the apparatus and/or relative to each other. The liquid-isolated or hydraulically independent units can be moved individually.

For dispensing and/or aspirating liquids, the liquid handling apparatus may comprise one, two, three, four or more types of devices. For example, the liquid handling apparatus may comprise a positive displacement pipette and/or a vented pipette. Liquid handling devices may include piezoelectric or acoustic dispensers, as well as other types of dispensers. The liquid handling device may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more positive displacement pipettes. The liquid handling device may be capable of metering (aspirating) very small liquid droplets from a pipette nozzle/tip. The liquid handling apparatus may comprise 1 or more, 2 or more, 4 or more, 8 or more, 12 or more, 16 or more, 20 or more, 24 or more, 30 or more, 50 or more, 100 or more air displacement pipettes. In some embodiments, the same number of positive displacement pipettes and air displacement pipettes may be used. Alternatively, more positive displacement pipettes may be provided than positive displacement pipettes, or vice versa. In some embodiments, one or more positive displacement pipettes may be integrated into a "fin" style (or modular) pipette format to save space and provide additional custom configurations.

In some embodiments, a liquid handling device, such as a pipette as described elsewhere herein (e.g., positive displacement pipette, vented pipette, piezoelectric pipette, acoustic pipette, or other type of pipette or liquid handling device), may have the ability to draw several different liquids that are separated with or without an air "plug. The liquid handling device may have the ability to facilitate/accelerate reactions with reagents attached to a surface (e.g., pipette tip surface) by reciprocating the enclosed liquid, thereby disrupting the non-agitated layer. The reciprocating motion may be pneumatically driven. This motion may be equivalent or comparable to the orbital movement of a microtiter plate to accelerate the binding reaction in an ELISA assay.

The liquid treatment apparatus may comprise one or more susceptors or supports. The base and/or support may support one or more pipette tips. The pipette head may include a pipette body and a pipette nozzle. The pipette nozzle may be configured to interface with and/or connect to a removable tip. The base and/or support may connect one or more pipette tips of the liquid handling apparatus to one another. The base and/or support may support and/or carry the weight of the pipette head. The base and/or support may allow the pipette head to move together. One or more pipette tips may extend from the base and/or the support. In some embodiments, one or more positive displacement pipettes and one or more vented pipettes may share a base or support.

Positive displacement pipette

Fig. 12 shows an exploded view of a positive displacement pipette provided in accordance with one specific example described herein. Positive displacement pipettes may include a lower portion that includes a positive displacement pipette tip 1200, a nozzle 1202, and a slotted sleeve 1204. Positive displacement pipettes may also include an inner portion that includes a collet 1212, a collet sleeve 1214, a collet spring 1216, and a collet cap and hammer 1218. A positive displacement pipette may include an upper portion including a threaded solenoid 1220 with a hammer blade pivot pin 1222, a base 1228, and a DC gear motor 1230.

Positive displacement pipettes may allow for liquid dispensing or aspiration with high precision and accuracy. For example, by using a positive displacement pipette, the amount of liquid dispensed or aspirated can be controlled to within about 1mL, 500 microliters (μ L, also used herein as "ul"), 300 μ L, 200 μ L, 150 μ L, 100 μ L, 50 μ L, 30 μ L, 10 μ L, 5 μ L, 1 μ L, 500nL, 300nL, 100nL, 50nL, 10nL, 5nL, 1nL, 500pL, 100pL, 10pL, or 1 pL.

Positive displacement pipettes may have a low Coefficient of Variation (CV). For example, the CV may be 10% or less, 8% or less, 5% or less, 3% or less, 2% or less, 1.5% or less, 1% or less, 0.7% or less, 0.5% or less, 0.3% or less, 0.1% or less, 0.05% or less, 0.01% or less, 0.005% or less, or 0.001% or less. In some cases, positive displacement pipettes with such coefficients of variation may be configured to handle a sample (e.g., liquid) volume of less than or equal to 10mL, 5mL, 3mL, 2mL, 1mL, 0.7mL, 0.5mL, 0.4mL, 0.3mL, 250 μ L, 200 μ L, 175 μ L, 160 μ L, 150 μ L, 140 μ L, 130 μ L, 120 μ L, 110 μ L, 100 μ L, 70 μ L, 50 μ L, 30 μ L, 20 μ L, 10 μ L, 7 μ L, 5 μ L, 3 μ L, 1 μ L, 500nL, 300nL, 100nL, 50nL, 10nL, 5nL, 1nL, 500pL, 100pL, 50pL, 10pL, 5pL, 1 pL. In other cases, positive displacement pipettes with such coefficients of variation are configured to handle sample volumes greater than 10mL, 20mL, 30mL, 40mL, 50mL, 100mL, or more.

Positive displacement pipettes dispense and/or aspirate liquid by collecting a fixed amount of liquid and expel the liquid by changing the volume of the chamber in which the liquid is collected. Positive displacement pipettes can collect liquid without collecting air. In another embodiment, a single pipette may be able to collect multiple amounts or types of liquids by separating the collected liquids with an air "plug". The tip of a positive displacement pipette may include a plunger that directly displaces the liquid. In some embodiments, the tip of a positive displacement pipette may function as a microsyringe, wherein the internal plunger may displace liquid directly.

Positive displacement pipettes can have a variety of specifications. For example, the plunger may slide up and down based on various actuation mechanisms. The use of a threaded solenoid 1220 with a hammer pin 1222 advantageously allows a large degree of control over the volume dispensed and/or aspirated. This may be very useful in the case of handling small volumes of liquid. The threaded solenoid may be mechanically coupled to a motor 1230. The motor may rotate, causing the threaded solenoid to rotate. In some embodiments, the threaded solenoid may be directly coupled to the motor such that the amount of rotation of the threaded solenoid is the same as the amount of rotation of the motor. Alternatively, the threaded solenoid may be indirectly coupled to the motor such that the amount of rotation of the solenoid is proportional to the amount of rotation of the motor.

The hammer blade pivot 1222 may be positioned through the threaded solenoid 1220. The hammer pin may have an orthogonal orientation with respect to the threaded helical tube. For example, if the threaded coilpipe is vertically aligned, the hammer blade axis pin may be horizontally aligned. The hammer pin may pass through the threaded helical tube at two points. In some embodiments, the threaded solenoid and the hammer pin may be positioned within the slotted sleeve 1204. One end of the hammer pin may fit into a slot of the sleeve. In some embodiments, the slotted sleeve may have two slots and the blade pin may have two ends. The first port of the hammer plate pin may be located in the first slot of the sleeve and the second port of the hammer plate may be located in the second slot of the sleeve. The slot prevents the hammer pin from rotating. Thus, as the threaded solenoid is rotated by the motor, the hammer pin can move up and down along the slot.

The hammer blade pin 1222 may alternatively pass through the collet cap and hammer 1218. The collet cap may be connected to the collet directly or indirectly. The collet may be capable of passing into and through at least a portion of the pipette nozzle 1202. Because the hammer pin can move up and down along the slot, the collet can also move up and down along the slot. The collet pin can move up and down the same amount as the hammer blade pivot pin. Alternatively, the distance the collet pins move may be proportional to the distance the hammer pin moves. The collet pin may be coupled directly or indirectly to the ram pin.

The collet preferably does not directly contact the liquid collected and/or dispensed by the pipette tip. Alternatively, the collet may contact the liquid. The collet may contact a plunger, which may preferably directly contact the liquid collected and/or dispensed by the pipette tip. Alternatively, the plunger may not be in direct contact with the liquid. The amount the collet can be moved up and down can determine the amount of liquid dispensed.

The use of a threaded solenoid may provide a high degree of control over the amount of liquid dispensed and/or aspirated. The large amount of movement that causes the screw to rotate can be converted to a small amount of movement that causes the hammer pin to slide up and down and thereby cause the plunger in the pipette tip to slide up and down.

Positive displacement pipettes may have a full aspirating position and a full dispensing position. The collet can be in a top position when the pipette is in the full suction position. The collet may be in a bottom position when the pipette is in the full dispensing position. The pipette may be capable of transitioning between a full aspirating position and a full dispensing position. The pipette may be capable of any position between the full aspirate position and the full dispense position. The pipette may have a partial aspiration position and a partial dispense position. The pipette can be stopped smoothly at any position therebetween in an analog manner. Alternatively, the pipette may be stopped at a particular position therebetween in fixed increments by digital means. To aspirate or draw in liquid, the pipette may be moved from the dispensing position to the aspirating position (e.g., moving the collet assembly upward toward the motor). To dispense or squirt some of the liquid, the pipette may be moved from the aspirating position to the dispensing position (e.g., moving the collet assembly downward away from the motor).

Figure 13 shows an outside view and a side cross-sectional view of a positive displacement pipette tip in a top position (e.g., full suction position). For clarity, the pipette tips are not shown. The motor 1300 may be coupled to a solenoid 1310. The solenoid may be located below the motor. The helical tube may be located between the motor and the positive displacement pipette tip. The collet assembly 1320 may be located within the coil. The coil may surround or enclose the collet assembly.

A plunger spring 1330 may be provided between the collet assembly 1320 and the solenoid 1310. The collet assembly may have a shelf or ledge on which one end of the plunger spring may be supported or seated. Pipette nozzle 1340 may have another shelf or protrusion on which one end of a plunger spring may be supported or seated. The plunger spring may be located between the pipette nozzle and the top of the collet.

The plunger spring may be in an extended state when the positive displacement pipette is in its full aspirate position. The plunger spring may hold the collet assembly in the upper position when the pipette is in the aspirating position.

Fig. 14 illustrates an outside view and a side cross-sectional view of a positive displacement pipette tip in a bottom position (e.g., a full dispensing position). The motor 1400 may be coupled to a solenoid 1410. The solenoid may be located below the motor. The helical tube may be located between the motor and the positive displacement pipette tip. The collet assembly 1420 may be positioned within the coil or at least partially below the coil. The coil may surround or enclose the collet assembly.

A plunger spring 1430 may be provided at least partially between the collet assembly 1420 and the solenoid 1410. The collet assembly may have a shelf or ledge on which one end of the plunger spring may be supported or seated. The pipette nozzle 1440 may have another shelf or ledge on which one end of the plunger spring may be supported or seated. The plunger spring may be located between the pipette nozzle and the top of the collet. The plunger spring may surround at least a portion of the collet assembly.

The plunger spring may be in a compressed state when the positive displacement pipette is in its full dispensing position. The collet assembly can be pushed downward toward the tip, thereby compressing the spring. The pipette may have two (or more) plungers and/or collets that support the aspiration/dispensing and subsequent mixing of the two materials; for example, a treated epoxy resin, which is a copolymer formed from two different chemicals; mixing and metering can be carefully controlled with respect to volume and time.

A positive displacement tip plunger 1450 may be connected to the collet assembly 1420. The plunger may be located below the collet assembly. The plunger may be located between the collet assembly and the tip. The positive displacement tip plunger may include an elongated portion that may be capable of extending at least partially through the pipette tip. In some embodiments, the elongate portion may be long enough to extend completely through the pipette tip when in the full dispensing position. In some embodiments, the elongate portion of the plunger can extend beyond the pipette tip when in the full dispensing position. The end of the plunger may or may not be in direct contact with the liquid aspirated and/or dispensed by the positive displacement pipette. In some embodiments, the plunger may have a ledge or shelf that may be positioned on the collet assembly. The plunger may move up and down the same amount as the collet assembly.

The pipette tip may have any tip configuration as described elsewhere herein. For example, the pipette tip may have a positive displacement tip as shown in fig. 14 or fig. 27. The positive displacement tip can be configured to confine and receive any volume of liquid, including the volumes of liquid described elsewhere herein.

Air-exhaust type pipette

Fig. 15 illustrates an external view of an air displacement pipette provided in accordance with one specific example described herein. The vented pipette may include a pipette tip 1500 and an external removal device 1510 for removing the pipette tip from a pipette nozzle 1520.

Vented pipettes may allow for liquid dispensing or aspiration with high accuracy and precision. For example, by using a vented pipette, the amount of liquid dispensed or aspirated can be controlled to within about 3mL, 2mL, 1.5mL, 1mL, 750 μ L, 500 μ L, 400 μ L, 300 μ L, 200 μ L, 150 μ L, 100 μ L, 50 μ L, 30 μ L, 10 μ L, 5 μ L, 1 μ L, 500nL, 300nL, 100nL, 50nL, 10nL, or 1 nL. In some embodiments, positive displacement pipettes may have greater accuracy and/or precision than air displacement pipettes.

In some embodiments, one or more pipettes, such as one or more air displacement pipettes, positive displacement pipettes, and suction pipettes, may have a low Coefficient of Variation (CV). For example, the CV may be 15% or less, 12% or less, 10% or less, 8% or less, 5% or less, 3% or less, 2% or less, 1.5% or less, 1% or less, 0.7% or less, 0.5% or less, 0.3% or less, or 0.1% or less. In some cases, a pipette (e.g., a positive displacement pipette, vented pipette, or aspirated pipette) having such a coefficient of variation may be configured to handle a sample (e.g., liquid) volume of less than or equal to 10mL, 5mL, 3mL, 2mL, 1mL, 0.7mL, 0.5mL, 0.4mL, 0.3mL, 250 μ L, 200 μ L, 175 μ L, 160 μ L, 150 μ L, 140 μ L, 130 μ L, 120 μ L, 110 μ L, 100 μ L, 70 μ L, 50 μ L, 30 μ L, 20 μ L, 10 μ L, 7 μ L, 5 μ L, 3 μ L, 1 μ L, 500nL, 300nL, 100nL, 50nL, 10nL, 5nL, 1nL, 500pL, 100pL, 50pL, 10pL, 5pL, 1 pL. In other cases, pipettes with such coefficients of variation (e.g., positive displacement pipettes, vented pipettes, or suction pipettes) are configured to handle sample volumes greater than 10mL, 20mL, 30mL, 40mL, 50mL, 100mL, or higher. Various types and combinations of pipettes provided herein (e.g., positive displacement pipettes, vented pipettes, or suction pipettes) are configured to have such a coefficient of variation while processing the sample volumes set forth herein.

The vented pipette may have a low Coefficient of Variation (CV). For example, the CV may be 10% or less, 8% or less, 5% or less, 3% or less, 2% or less, 1.5% or less, 1% or less, 0.7% or less, 0.5% or less, 0.3% or less, 0.1% or less, 0.05% or less, 0.01% or less, 0.005% or less, or 0.001% or less. In some cases, an air displacement pipette having such a coefficient of variation can be configured to process a sample (e.g., liquid) volume of less than or equal to 10mL, 5mL, 3mL, 2mL, 1mL, 0.7mL, 0.5mL, 0.4mL, 0.3mL, 250 μ L, 200 μ L, 175 μ L, 160 μ L, 150 μ L, 140 μ L, 130 μ L, 120 μ L, 110 μ L, 100 μ L, 70 μ L, 50 μ L, 30 μ L, 20 μ L, 10 μ L, 7 μ L, 5 μ L, 3 μ L, 1 μ L, 500nL, 300nL, 100nL, 50nL, 10nL, 5nL, 1nL, 500pL, 100pL, 50pL, 10pL, 5pL, 1 pL. In other cases, an air displacement pipette having such a coefficient of variation is configured to handle sample volumes greater than 10mL, 20mL, 30mL, 40mL, 50mL, 100mL, or higher.

Vented pipettes may cause liquid to be dispensed and/or aspirated by generating a vacuum by movement of a plunger within an air-tight sleeve. As the plunger moves upward, a vacuum is created in the void space left by the plunger. Air rises from the cleaner head to fill the void space left behind. The tip air is then replaced by liquid which can be drawn into the tip and made available for transport and distribution elsewhere. In some embodiments, the vented pipette may be subjected to a constantly changing environment, such as temperature. In some embodiments, the environment may be controlled in order to provide improved accuracy.

Air displacement pipettes may have a variety of specifications. For example, the vented pipette may be adjustable or fixed. The suction head may be conical or cylindrical. The pipette may be standard or locked. The pipette may be electronically or automatically controlled, or may be manual. The pipette may be single channel or multichannel.

Fig. 16 shows a cross-sectional view of the vented pipette. The air displacement pipette may include a pipette tip 1600 and an external removal device 1610 for removing the pipette tip from a pipette nozzle 1620. The removal device may be positioned in contact with the end of the pipette tip. The removal device may be positioned above the pipette tip at an end opposite the end of the pipette dispensing and/or aspirating liquid. The pipette tip may have a shelf or projection on which the removal device can be placed.

The pipette tip may have any tip of any of the specifications described elsewhere herein. For example, the tip may be a nucleic acid tip, a centrifugal extraction tip, a bulk processing tip, a chromogenic tip, a blood tip, a mini-tip, a micro-tip, a nano-tip, a femto-tip, a pico-tip, etc., or may have the features or characteristics of any of the tips described in fig. 24-34.

Fig. 17 illustrates a close-up of the interface between the pipette tip 1700 and the nozzle 1720. The removal device 1710 may be positioned in contact with the pipette tip.

The pipette nozzle may have a protrusion 1730 or shelf that may contact the removal device. The nozzle shelf may prevent the removal device from moving too far upwards. The nozzle shelf may provide a desired location for the removal device.

The pipette tip may also have one or more sealing assemblies 1740. The sealing assembly may be one or more O-rings or other similar materials known in the art. The sealing assembly may contact the pipette tip when the pipette tip is attached to the nozzle. The sealing assembly may allow a liquid-tight seal to be formed between the pipette tip and the nozzle. The seal assembly can keep the pipette tip attached to the nozzle without external forces. The pipette tip may be friction fit to the pipette nozzle.

An internal channel 1750 or chamber may be provided within the pipette nozzle. The pipette tip may have an interior surface 1760 and an interior region 1770. The internal channel of the pipette nozzle may be in fluid communication with an internal region of the pipette tip. The plunger may be moved through a channel of the pipette nozzle and/or an interior region of the pipette tip. The plunger may allow aspiration or dispensing of liquid from the pipette tip. The plunger may or may not be in direct contact with the liquid. In some embodiments, air may be provided between the plunger and the liquid.

Fig. 18 shows an example of actuation of the removal device 1810. The removal device can cause the pipette tip 1800 to be removed from the nozzle 1820. The removal means may be provided outside the pipette tip and the nozzle. To push away the pipette tip from the nozzle, the removal device can be moved downwards. Alternatively, the pipette nozzle may be moved upwards, causing the pipette tip to be caught by the removal device and pushed away. The removal device is movable relative to the pipette nozzle.

The removal device may contact the pipette tip at the top of the pipette tip. The removal device may contact the pipette tip at a side of the pipette tip. The removal device may partially or completely surround the pipette tip.

Fig. 19A shows a plurality of pipettes with external removal means. For example, 8 pipette tips may be provided. In other embodiments, any other number of pipette tips may be used, including those described elsewhere herein.

Fig. 19B shows a side view of the pipette head. The pipette head may include a pipette tip 1900. The pipette tip may be removably coupled to the pipette nozzle 1920. External removal means 1910 may be provided. The external removal device may be in contact with the pipette tip or may be in contact with the pipette tip. The pipette nozzle may be coupled to a mount 1930 of the pipette. The pipette support may be coupled to a motor 1940 or other drive means.

Fig. 20 shows a cross-sectional view of a vented pipette. The vented pipette may include a pipette tip 2000 and an external removal device 2010 for removing the pipette tip from a pipette nozzle 2020. The removal device may be positioned in contact with the end of the pipette tip. The removal device may be positioned at an end above the pipette tip opposite the end of the pipette tip that dispenses and/or aspirates the liquid. The pipette tip may have a shelf or a projection on which the removal device can be placed.

The removal device 2010 can be moved up and down to remove the pipette tip from the nozzle. The removal device may be coupled to a drive device that may allow the removal device to move up and down. In some embodiments, the removal device may be directly coupled to the drive device. Alternatively, the removal device may be indirectly coupled to the drive device. One or more switches may be provided between the removal device and the drive device, which may determine whether the removal device is responsive to the drive device. The switch may be a solenoid or other device.

The vented pipette may also include an inner plunger 2030. The plunger is movable through an interior portion of the pipette nozzle. The plunger may be coupled to a drive means which may allow the plunger to move up and down. In some embodiments, the plunger may be directly coupled to the drive device. Alternatively, the plunger may be indirectly coupled to the drive means. One or more switches may be provided between the plunger and the drive means, which may determine whether the plunger is responsive to the drive means. The switch may be a solenoid or other device.

Fig. 20A shows the plunger in a down position and the removal device in a down position, thereby pushing the tip downward relative to the pipette nozzle.

Fig. 20B shows the plunger in the intermediate position and the removal device in the up position, allowing the tip to be attached to the pipette nozzle.

Fig. 20C shows the plunger in the up position and the removal device in the up position, allowing the tip to be attached to the pipette nozzle.

Fig. 21 shows a plurality of pipettes with removal means. For example, 8 pipette tips may be provided. In other embodiments, any other number of pipette tips may be used, including the pipette tips described elsewhere herein.

A support structure 2100 for a pipette may be provided. One or more pipette sleeves 2110 can be provided through which the plunger can extend. A spring 2120 according to specific examples described herein may be provided. The spring may be compressed when the plunger moves downward. The spring may be extended when the plunger is in the up position.

One or more switching devices, such as a solenoid 2130, may be provided. A drive means, such as a motor 2140, may be provided for a plurality of pipettes. The drive means may be coupled to the plunger of the pipette and/or the removal means. In some embodiments, the drive device may be directly coupled to the plunger and/or the removal device. Alternatively, the drive means may be indirectly connected to the plunger and/or the removal means. In some embodiments, one or more switches may be provided between the drive means and the plunger and/or the removal means. The switch may determine whether the plunger and/or the removal device is responsive to the drive device. In some embodiments, the switch may be a solenoid.

In some embodiments, a single drive device may be used to control each pipette piston for a multiheaded pipette. A switch may be provided for each pipette piston so that actuation of each pipette piston can be individually controlled. In some instances, the pipette piston may dynamically change its volume, thereby optimizing the ability to dispense a desired volume of sample using aspiration techniques (but not limited to such techniques); for example, the piston may be a tube within a tube that can expand to dynamically control the volume. In some embodiments, a switch may be provided for groups of pipette pistons such that actuation between each of the groups of pipette pistons may be individually controlled. A single drive means may be used to control each pipette piston. In some embodiments, a single drive device may be used to control groups of pipette pistons. Alternatively, each pipette piston may be connected to its own separate drive means. Thus, 1, 2, 3, 4 or more drive means (such as motors) may be provided for the pipette piston.

Fig. 22 shows an example of a multiheaded pipette in accordance with one specific example described herein. Individual pipette tips on the multiheaded pipette may be individually actuated or may have individually actuatable components. For example, the removal device 2200 for one of the pipette heads may be in the up position, while the other removal device 2210 may be in the down position. The switch, such as solenoid 2220, for this one pipette head may be disengaged while the switches for the other pipette heads may be engaged. Thus, when a drive means such as motor 2230 is engaged to move a removal device downward to remove a pipette tip from a pipette nozzle, this disengaged switch may cause this one removal device to not move downward with the other movement devices. The detached removal device may remain in its place. This can result in the pipette tip remaining on the detached pipette, while other pipette tips are removed from other pipettes.

In another example, the plunger 2250 for one of the pipette heads may be in the up position, while the other plunger 2260 may be in the down position. The switch, such as a solenoid, for the one pipette head may be disengaged and the switch for the other pipette head may be engaged. Thus, when a drive means such as a motor is engaged to move the plunger downward to dispense liquid or remove a pipette tip from a pipette nozzle, the one disengaged switch may cause the one plunger not to move downward with the other plunger. The disengaged plunger may remain in its place. This can result in the pipette tip remaining on the detached pipette when other pipette tips are removed from other pipettes, or can prevent liquid from being dispensed from the detached pipette when liquid is dispensed at other pipettes.

In some embodiments, the disengaged switch may prevent removal of the pipette tip or dispensing of liquid. In some embodiments, the disengaged switch may prevent the pipette tip from being picked up. For example, an engaged switch may cause the pipette head to be driven downward to pick up a pipette tip, while the pipette head coupled with the disengaged switch remains in the retracted position. In another example, an engaged switch may cause the device that picks up one or more pipette heads to actuate to pick up the heads, while a disengaged switch prevents operation of the device that picks up one or more pipette tips.

In some additional embodiments, the disengaged switch prevents the pipette tip from aspirating liquid. For example, an engaged switch may cause an internal plunger or other device to move upward to draw liquid. The disengaged switch may cause the plunger to remain in its home position. Thus, the aspiration of liquid in a multiheaded pipette can be individually controlled while using one or more drive means.

The removal means may be provided outside the pipette nozzle or inside the pipette nozzle. Any description herein of any type of removal device may also refer to other types of removal devices. For example, the description of an individually drivable external removal device may also apply to an internal removal device which may have the form of a plunger or other form which may be provided within a nozzle.

The drive means may be configured to drive components in a plurality of pipettes. For example, the drive device may be configured to drive the removal device. The drive means may be capable of driving both the first removal means and the second removal means. A first solenoid may be operatively provided between the drive means and the first removal means. A second solenoid may be operatively provided between the drive means and the second removal means. The first solenoid may be engaged or disengaged to determine whether the drive caused by the drive means may result in movement of the removal device. The second solenoid may be engaged or disengaged to determine whether actuation by the actuation means may result in movement of the removal device. The first and second solenoids may be engaged or disengaged independently of each other. Each of the solenoids for the individual pipettes or groups of pipettes controlled by the drive device may be engaged or disengaged in response to one or more signals received from the controller.

In some embodiments, the drive device may be located at the top of the pipette. The drive means may be located on a support structure at an end opposite the pipette tip. The drive means may be located on the support structure at an end opposite the pipette nozzle. The drive means may comprise one or more shafts which may be oriented parallel to one or more pipette tips. The drive means may have a rotational axis which may be parallel to an axis extending along the height of the pipette tip or tips.

Fig. 23 shows an example of a multiheaded pipette 2300 provided in accordance with another specific example described herein. The drive 2310 may be located on any part of the pipette. For example, the drive means may be located on one side of the support structure. Alternatively, it may be located on the top or bottom of the support structure. The drive means may be located on the side of the support structure opposite the pipette nozzle 2320. The drive means may comprise one or more shafts 2330 that may be oriented perpendicular to one or more pipette tips 2340. The drive means may have a rotational axis which may be perpendicular to an axis extending along the height of the pipette tip or tips. For example, the pipette tip may have a vertical orientation, while the drive device may have a shaft or a rotational axis having a horizontal orientation. Alternatively, the drive device shaft or shaft may be at any angle relative to the pipette tip or tips.

One or more pipette heads or pipette supports 2350 can have a curved configuration. For example, the pipette support may have a horizontal component 2350a that meets with a vertical component 2350 b. In some embodiments, liquid may be provided only to the vertical component of the pipette. Alternatively, the liquid may or may not flow to the horizontal component of the pipette. Pipettes may have a single piston or plunger that may be coupled with two or more nozzles or tips, and may use valves or switches to support aspiration/dispensing through one or more of the nozzles or tips.

One or more switches 2360 may be provided. The switches may be individually controllable. The examples of switches and controls described elsewhere herein are applicable. The drive device may be capable of driving one or more pipette drive assemblies, such as a pipette tip remover, one or more pipette tip installers, one or more liquid dispensing devices, and/or one or more liquid aspiration devices. The switch may determine whether one or more of the pipette drive assemblies are moving.

Having a side-mounted drive device can reduce one or more dimensions of the multiheaded pipette. For example, a side-mounted drive device can reduce the vertical dimension of a multiheaded pipette while maintaining the same barrel volume and thus pipette capacity. Top-mounted, side-mounted, or bottom-mounted drive means may be selected depending on the desired displacement of the pipette within the device and/or module, or other constraints in the device and/or module.

Having a single drive means that results in the actuation of all pipette drive assemblies can also reduce the size of a multiheaded pipette. A single drive device can control multiple pipette drive assemblies. In some embodiments, one or more drive devices may be provided to control a plurality of pipette drive assemblies.

Fig. 46 illustrates an example of a liquid handling device in a retracted position provided in accordance with another specific example described herein. The liquid handling device may include one or more tips 4610, 4612, 4614. In some embodiments, a plurality of tip types may be provided. For example, a positive displacement tip 4610, a vented nozzle tip 4612 may be provided, and a vented micro nozzle tip 4614 may be provided. A base 4620 supporting one or more pipette tips may be provided. Positive displacement motor 4630 may be coupled to positive displacement pipette tip 4635.

The liquid handling device may include a manifold 4640. The manifold may include one or more vent ports 4642. The vent port is fluidly connectable to the fluid path of the pipette head. In some embodiments, each pipette head may have a vent port. In some cases, each vented pipette head may have a vent port. The conduits 4644 may be connected to a manifold. Still alternatively, the conduit may connect the manifold to a source of positive or negative pressure, the ambient atmosphere, or a reversible positive/negative pressure source.

A heat sink 4650 may be provided for the liquid handling device. The heat sink may provide isothermal control. In some embodiments, the heat sink may be in thermal communication with a plurality of pipette heads. The heat sink can assist in equalizing the temperature of multiple pipette tips.

The liquid treatment device may have one or more support portions. In some specific examples, the support portion may include an upper clamshell 4660 and a lower clamshell 4665.

FIG. 46A shows the fluid treatment device in a fully retracted position, retracted as previously described. FIG. 46B shows the retracted liquid handling device in a fully Z-lowered position. In the fully Z-down position, the entire lower clamshell 4665 may be lowered relative to the upper clamshell 4660. The lower clamshell can support the pipette head and the nozzle. The pipette head and nozzle are movable with the lower clamshell member. The lower clamshell can include a front 4667 that supports the pipette head and a rear 4668 that supports the drive and switch devices.

Fig. 47 illustrates an example of a liquid handling device in an extended position, according to particular examples described herein. The fluid handling devices may include one or more tips 4710, 4712, 4714. A positive displacement type tip 4710, a vented nozzle tip 4712 and a vented micro nozzle tip 4714 may be provided. The liquid handling device may also include one or more nozzles 4720, 4722, 4724. Positive displacement nozzles 4720, vented nozzles 4722, and vented micro nozzles 4724 may be provided. The nozzles may be connected to their respective tips. In some cases, the nozzles may be connected to their respective tips via a press fit or any other engagement means. One or more tip ejectors 4732, 4734 can be provided. For example, a conventional tip ejector 4732 may be provided for removing the vented tip 4712. One or more micro ejectors 4734 may be provided for removing the vented mini-tips 4714. The ejector may form a collar. The ejector may be designed to push the cleaner head open. The ejector may be located below the nozzle.

The liquid handling device may be in a fully Z-lowered position with the lower clamshell 4765 lowered relative to the upper clamshell 4760. Additionally, a Z-clutch lever 4770 may be provided, which Z-clutch lever 4770 may engage any or all pipettes for individual and/or combined nozzle lowering (i.e., nozzle extension). Fig. 47 shows an example in which all the nozzles are lowered. However, the nozzles may be individually selected in order to determine which nozzle to lower. The nozzle may be lowered in response to a single drive means such as a motor. The switching means can determine which pipettes are engaged with the rod. The illustrated trip lever 4770 shows the nozzle in a lowered position with the trip lever lowered. A Z-motor encoder 4780 may be provided. The encoder may allow tracking of motor movement position.

According to some specific examples, an x-axis slide 4790 may be provided. The x-axis slide may allow lateral movement of the liquid handling device. In some embodiments, the liquid handling device is slidable along the track.

Fig. 48 shows a front view of a liquid treatment device. A protective plate 4810 may be provided in some embodiments. The protective plate protects parts of the pipette tip. The protective plate can protect the liquid path of the pipette tip. In one example, a protective plate may be provided for a hard conduit connecting the pipette lumen to the nozzle. The protective plate may be connected to the heat sink or may be incorporated with the heat sink.

As mentioned above, various types of pipettes and/or tips may be provided. One or more positive displacement pipettes and/or one or more air displacement pipettes may be used. In some cases, the protective plate may cover only the vented pipette. Alternatively, the protective plate may cover the positive displacement pipette, or may cover both.

Fig. 49 shows a side view of a liquid treatment device. The liquid handling device may comprise a pipette head, which may comprise a nozzle head 4902, which nozzle head 4902 may be configured for connection to a tip 4904. The tip may be removably connected to the pipette nozzle.

One or more pipette nozzles may be supported by nozzle-drop shaft 4920. A Z-motor 4922 may be provided that, when driven, may cause one or more nozzles to descend (e.g., extend). One or more solenoids 4924 may be provided, or other switching devices may be provided for selectively connecting the Z-motor with the nozzle-lowering shaft. When the solenoid is in the "on" position, actuation of the Z-motor may cause the nozzle-lowering shaft to lower or raise. When the solenoid is in the "off" position, the actuation of the z-motor does not cause movement of the nozzle-lowering shaft.

A conduit 4910 may be provided through the pipette head and terminating at the pipette nozzle. The conduit may have a portion with a rigid inner conduit 4910a and a rigid outer conduit 4910 b. In some cases, the rigid inner conduit may be movable while the rigid outer conduit is fixed. In other embodiments, the rigid inner conduit may be movable or fixed and the rigid outer conduit may be movable or fixed. In some embodiments, the inner conduit may be movable relative to the outer conduit. The total length of the conduit may be variable.

A plunger 4930 may be provided within the liquid treatment device. The plunger may provide a metered amount within the pipette chamber. An extension of the pipette lumen 4935 may be provided. In some cases, the extension of the pipette lumen may be in liquid communication with the conduit 4910. Alternatively, the conduit is not in liquid communication with the pipette lumen. In some embodiments, the pipette lumen and the tubing are parallel to each other. In other embodiments, the pipette lumen and the tubing are not substantially parallel to each other. They may be substantially perpendicular to each other. The conduit may have a substantially vertical orientation and the pipette lumen may have a substantially horizontal orientation, or vice versa. In some embodiments, the pipette and tip may function in a push/pull fashion, such as in a multilumen tubing arrangement, for simultaneous or sequential aspiration and dispensing.

One or more valves 4937 may be provided for controlling access to the vent port of the pipette. In some cases, the valve may correspond to an associated pipette. The valve may determine whether the vent port is open or closed. The valve may determine the extent to which the vent port is open. The vent port may be in communication with a pressure source, such as a positive pressure source or a negative pressure source. The vent port may be in communication with the ambient atmosphere. The vent port may provide access to the conduit 4910 from the manifold.

Clutch levers 4940 for individual metering may be provided. The trip lever may be connected to a motor that may be used to drive liquid metering. Still alternatively, a guide shaft 4942 may be provided. One or more solenoids 4945 or other switching devices may be provided in communication with the trip lever. The solenoid or other switching device may be provided for selectively connecting the motor with the plunger 4930. When the solenoid is in the "on" position, actuation of the metering motor may cause the plunger to be engaged and moved, thereby dispensing and/or aspirating the liquid. When the solenoid is in the "off" position, actuation of the metering motor does not cause movement of the plunger. A plurality of plungers may be provided, each plunger being associated with its respective solenoid, which may be selectively in an on or off position. Thus, when the motor is driven, only the plunger associated with the "on" solenoid will respond.

Fig. 50 shows another side view of the liquid treatment device. This view includes a view of the motor 5010 for metering. The motor may be used to meter liquid in a vented pipette. An encoder 5020 for the motor is also illustrated. The encoder may allow for tracking of motor movement. This ensures that the plunger position is always known.

FIG. 51 illustrates a rear perspective view of the liquid handling device. The liquid treatment device can include a pump 5110. The pump may be in fluid communication with a pipette lumen. In some cases, the pump can be brought into or out of liquid communication with the pipette lumen. The pump may be in fluid communication with the manifold and/or the vent port. The pump may draw (or effect movement of) liquid or air.

The pump may provide positive and/or negative pressure. The pump may be a reversible pump, which may be capable of providing both positive and negative pressure. The pump can be actuated in a pipette containing a piston to allow the pipette to aspirate or dispense any volume of liquid without being limited by the positive displacement that can be generated for a given piston size. This factor, in combination with a large volume tip, can allow a small pipette to aspirate or dispense large volumes of liquid for certain applications. The pump may allow the pipette to function without the need for a motor or piston, while still providing fine control through pulse width modulation.

The liquid handling device can also include an accumulator 5120 having one or more valves that can be connected to a pressure source or ambient conditions. Still alternatively, the accumulator may be connected to a reversible pump that can provide either positive or negative pressure.

A multi-headed liquid handling device, such as a multi-headed pipette, may be capable of picking up multiple tips/containers simultaneously on several pipette nozzles. For example, multiple pipette nozzles may be extended to pick up multiple tips/containers. The plurality of pipette nozzles may be individually controlled to determine which tips/containers to pick up. Multiple tips/containers can be picked up simultaneously. In some cases, all pipette nozzles may pick up pipette tips/containers substantially simultaneously.

In some embodiments, the pipette does not include a plunger. The sample (e.g., liquid) may be moved in or with the aid of a pipette using positive and/or negative pressure. In some cases, positive or negative pressure is provided by means of gas or vacuum, respectively. A vacuum system having one or more vacuum pumps may be used to provide the vacuum. The positive pressure may be provided by means of pressurized air. A compressor may be used to pressurize the air.

Size/range

One or more dimensions (e.g., length, width, or height) of the pipette may be less than or equal to about 1mm, 5mm, 10mm, 15mm, 20mm, 25mm, 30mm, 35mm, 40mm, 45mm, 50mm, 55mm, 60mm, 70mm, 80mm, 90mm, 100mm, 112mm, 12cm, 15cm, 20cm, 25cm, 30cm, or any other dimension described elsewhere herein. One or more dimensions may be the same or may be different. For example, the height of the pipette may not exceed 1mm, 1cm, 2cm, 3cm, 4cm, 5cm, 5.5cm, 6cm, 6.5cm, 7cm, 8cm, 9cm, 10cm, 11cm, 12cm, 13cm, 15cm, 17cm, 20cm, 25cm, or 30 cm.

In some embodiments, the pipette may have a 1cm length³Or less, 5cm³Or smaller, 8cm³Or smaller, 10cm³Or smaller, 15cm³Or smaller, 20cm³Or smaller, 25cm³Or smaller, 30cm³Or less, 35cm³Or smaller, 40cm³Or smaller, 50cm³Or smaller, 60cm³Or smaller, 70cm³Or smaller, 80cm³Or smaller, 90cm³Or smaller, 100cm³Or smaller, 120cm³Or smaller, 150cm³Or smaller, 200cm³Or smaller, 250cm³Or smaller, 300cm³Or less, or 500cm³Or a smaller total volume.

The pipette may have one or more pipette heads. In some embodiments, a single pipette head of a pipette may be capable of dispensing any volume of liquid. For example, the single pipette tip may be capable of dispensing and/or aspirating no more than and/or equal to about 10mL, 5mL, 3mL, 2mL, 1mL, 0.7mL, 0.5mL, 0.4mL, 0.3mL, 250 μ L, 200 μ L, 175 μ L, 160 μ L, 150 μ L, 140 μ L, 130 μ L, 120 μ L, 110 μ L, 100 μ L, 70 μ L, 50 μ L, 30 μ L, 20 μ L, 10 μ L, 7 μ L, 5 μ L, 3 μ L, 1 μ L, 500nL, 300nL, 100nL, 50nL, 10nL, 5nL, 1nL, 500pL, 100pL, 50pL, 10pL, 5pL, 1pL, or any other volume of liquid described elsewhere herein. The pipette may be capable of dispensing no more than and/or equal to any volume of liquid, such as those described herein, while having any size, such as those described elsewhere herein. In one example, the liquid handling device may have a height, width and/or length of no more than 20cm and may be capable of aspirating and/or dispensing at least 150 μ Ι _.

The liquid handling system may be capable of dispensing and/or aspirating liquids with high accuracy and/or precision. For example, the coefficient of variation of the liquid treatment system can be less than or equal to 20%, 15%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1.5%, 1%, 0.7%, 0.5%, 0.4%, 0.3%, 0.2%, 0.1%, 0.07%, 0.05%, 0.01%, 0.005%, or 0.001%. The liquid handling device may be capable of dispensing and/or aspirating a liquid while functioning with the coefficient of variation values described herein. The liquid handling system may be capable of controlling the volume of liquid dispensed to within 5mL, 3mL, 2mL, 1mL, 0.7mL, 0.5mL, 0.3mL, 0.1mL, 70 μ L, 50 μ L, 30 μ L, 20 μ L, 10 μ L, 7 μ L, 5 μ L, 3 μ L, 1 μ L, 500nL, 300nL, 100nL, 50nL, 10nL, 5nL, 1nL, 500pL, 100pL, 50pL, 10pL, 5pL, or 1 pL. For example, the liquid handling device may be capable of dispensing and/or aspirating no more than a minimum increment of any volume described herein.

The liquid handling system may be capable of operating with any of the coefficients of variation described herein and/or controlling the volume of liquid dispensed at any of the values described herein while having one or more of the other described features (e.g., having any of the dimensions described herein or being capable of dispensing and/or aspirating any of the volumes described herein). For example, a liquid handling device may be capable of dispensing and/or aspirating 1 μ L to 3mL of liquid while functioning with a coefficient of variation of 4% or less.

The liquid handling device may comprise a pipette head or a plurality of pipette heads. In some embodiments, the plurality of pipette heads may include a first pipette head and a second pipette head. The first and second pipette tips may be capable of and/or configured to dispense and/or aspirate the same amount of liquid. Alternatively, the first and second pipette heads may be capable of and/or configured for dispensing different amounts of liquid. For example, the first pipette head may be configured to dispense and/or aspirate up to a first volume of liquid and the second pipette head may be configured to dispense and/or aspirate up to a second volume of liquid, wherein the first and second volumes are different or the same. In one example, the first volume may be about 1mL and the second volume may be about 250 μ L.

In another example, the liquid handling device may comprise a plurality of pipette heads, wherein a first pipette head may comprise a first pipette nozzle configured for connection with a first removable tip, and a second pipette head may comprise a second pipette nozzle configured for connection with a second removable tip. The first removable tip may be configured to hold up to a first volume of liquid, and the second removable tip may be configured to hold up to a second volume of liquid. The first and second volumes may be the same or may be different. The first volume and the second volume may have any of the values described elsewhere herein. For example, the first volume may be about 1mL, and the second volume may be about 250 μ L.

Multiple pipette tips may be provided for a liquid handling device. The plurality of pipette heads may be spaced apart any distance. In some specific examples, the liquid handling device can be less than or equal to about 0.1mm, 0.3mm, 0.5mm, 0.7mm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm, 4.5mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 12mm, 15mm, 20mm, 30mm, or 50 mm. The distance between the pipette tips may be the center-to-center distance of the pipette tips. The distance between the pipette tips from center to center may be the pitch of the pipette tips.

Pipette heads may share a support structure. In some embodiments, the support structure may be a movable support structure. One, two or more pipette heads may be movable along the support structure such that the lateral distance between the pipette heads may be variable. In some cases, the pitch of the pipette tips may be variable so as to encompass or be limited to one or more of the previously described dimensions. In one example, the pipette head is slidable along the support so that the distance of the pipette head from center to center can be varied. Each of the pipette tips may be variable so that they are spaced apart by the same distance; or may be individually variable so that they may be spaced apart by various distances. The lateral distance ratio between the pipette tips may remain constant or may change as the pipette tip position changes. The pipette, fin or nozzle may change its relative position (move in or out, expand or contract) to obtain different pitches as desired and to access resources in multiple planes at a time.

In some embodiments, the form factor of a pipette (e.g., positive displacement pipette, suction pipette, air displacement pipette) may be adapted to a so-called "miniature" pipette. In such cases, the form factor may be reduced or optimized for space throughout the horizontal or clamshell configurations. The system or apparatus may include one or more micropipettes. The micropipette may be modular and removable from a support structure having the micropipette.

In some specific examples, the micropipette is configured to process samples of 1uL, 0.9uL, 0.8uL, 0.7uL, 0.6uL, 0.5uL, 0.4uL, 0.3uL, 0.2uL, 0.1uL, 10nL, 1 nL.

In some embodiments, a micropipette is provided that supports macro-scale protocols and/or treatments of various chemical components at a point-of-service site, as opposed to micro-liquid confinement treatments of non-replicable laboratory protocols. In some cases, the protocol and/or treatment is selected from, but not limited to: centrifugation, separation, precipitation, denaturation, extraction, coagulation, flocculation, chromatography, column-based processing, lysis, dilution, mixing, incubation, cell lysis, cell immobilization, heating, cooling, sample distribution, separate processing or assay or detection systems, modularity, sample utilization, sedimentation, concentration of analytes on a solid phase, immunoassay, nucleic acid amplification, nuclear magnetic resonance, microscopy, spectrometry, calorimetry, sequencing, pathology surveillance and analysis, and culture.

Pipette arrangement

The liquid handling device may be a pipette. In some embodiments, the liquid handling device may comprise one or more pipette tips. The liquid handling device may comprise a support, and the one or more pipette heads extending therefrom. As previously described, the support may support the weight of the one or more pipette tips. The support may comprise means for moving the pipette head in one or more dimensions, either individually or together. The support may allow the pipette head to move together. The support may also be flexible or "serpentine" and/or robotic in nature, allowing a wide range of movement of the pipette head in multiple (or infinite) planes of directions. Such a range of movement may allow the pipette to act as a robotic end effector for a device possessing one or more liquid handling functions or non-liquid handling functions. The support may connect pipette tips to each other. The shared support may or may not be integral with the pipette head. The support body may or may not also support the drive means. The support may or may not be capable of supporting the weight of a drive device operably connected to one or more pipette heads.

The pipette head may include a pipette nozzle configured for connection with a removable tip. The pipette head may also include a pipette body. The pipette nozzle may be coaxial with the pipette body. The pipette body may support a pipette nozzle. The pipette nozzle may comprise an opening. The pipette head may also include a fluid pathway therein. The liquid path may or may not be contained within the pipette body. The liquid path may pass through the pipette body. The liquid path may have a given length. The liquid path may terminate at a pipette nozzle. The liquid pathway may be in the inner conduit. The inner conduit may be rigid or flexible.

The pipette nozzle may be connected to the removable tip by any means. For example, a pipette nozzle may be connected with a removable tip to form a liquid-tight seal. The removable tip may be friction fit to the pipette nozzle. The tip may interface with the pipette nozzle along an outer surface of the pipette nozzle, an inner surface of the pipette nozzle, or within a recess or intermediate portion of the pipette nozzle. Alternatively, the pipette nozzle may interface with the tip along an outer surface of the tip, an inner surface of the tip, or within a recess or intermediate portion of the tip.

In some embodiments, a plunger may be provided within the pipette head. The plunger may allow dispensing and/or aspiration of the liquid. The plunger is movable within the pipette head. The pipette may be able to load the desired plunger from a selected set of plungers stored in or picked up from a storage area outside the pipette. The plunger is movable along the liquid path. The plungers may be held in the same orientation or may have different orientations. In an alternative embodiment, a transducer driven diaphragm may be provided which may function to cause liquid to be dispensed and/or aspirated through the tip. Alternative dispensing and/or suction devices may be used, which may include a positive pressure source and/or a negative pressure source that may be coupled to the liquid path.

In some embodiments, the tip of the pipette head may have a length. The direction of the nozzle may be along the length of the nozzle. In some embodiments, the liquid treatment device may include a motor having a rotor and a stator. The rotor may be configured to rotate about an axis of rotation. The axis of rotation may have any orientation relative to the cleaner head. For example, the axis of rotation may be substantially parallel to the cleaner head. Alternatively, the axis of rotation may be substantially non-parallel to the cleaner head. In some cases, the axis of rotation may be substantially perpendicular to the tip, or at any other angle relative to the tip, including but not limited to 15 degrees, 30 degrees, 45 degrees, 60 degrees, or 75 degrees. In one example, the axis of rotation may be horizontal and the removable tip may be vertically aligned. Alternatively, the axis of rotation may be vertical, with the removable tip being horizontally aligned. This arrangement may provide a "curved" pipette arrangement in which the tip is curved relative to the motor. The motor may be useful for metering liquid within the tip. In some embodiments, the motor may allow movement of one or more plungers within the pipette head.

In some embodiments, the liquid handling device may include a motor that may be capable of allowing movement of a plurality of plungers that are not substantially parallel to the removable tip. Alternatively, the movement of the plurality of plungers may be substantially parallel to the removable tip. In some cases, the movement of the plurality of plungers may be substantially perpendicular to the removable tip, or at any other angle, including but not limited to those angles described elsewhere herein. In one example, the plunger may be able to move in a horizontal direction while the removable tip is aligned vertically. Alternatively, the plunger may be able to move in a vertical direction, with the removable tip being horizontally aligned.

The liquid path may terminate at a pipette nozzle. In some cases, another end point of the liquid path may be provided at the plunger. In some embodiments, the liquid path may be curved or bent. The first portion of the liquid path may have a different orientation than the second portion of the liquid path. The first and second portions may be substantially perpendicular to each other. The angles of the first and second portions may be fixed relative to each other, or may be variable.

Drive the

The liquid treatment device may comprise a drive device. In some embodiments, a single drive means may be provided for the liquid treatment device. Alternatively, a plurality of drive means may be provided. In some cases, only a single drive means may be provided depending on the particular application (e.g., tip removal, plunger control, switch control). Alternatively, a plurality of driving means may be provided for a specific use. In one example, the drive means may be a motor. The motor may include a rotor and a stator. The rotor may be able to rotate about an axis of rotation.

A single drive means such as a motor may be useful for individualized dispensing and/or aspiration. The liquid handling device may comprise a plurality of pipette heads. A plurality of plungers can be provided, wherein at least one plunger can be within the pipette head and can be configured to be movable within the pipette head. In some cases, each of the pipette tips may have one or more plungers therein. The plurality of plungers may be independently movable. In some cases, the plunger may move along a fluid path within the pipette head. The drive means may be operatively connected to the plunger. The drive means may allow independent movement of the plurality of plungers. Still alternatively, movement of such a plunger may result in dispensing and/or aspiration of the liquid. A single motor or other drive device may control the independent movement of multiple plungers. In some cases, a single motor or other drive device may control the independent movement of all of the plurality of plungers.

A single drive means such as a motor may be useful for individualized removal of a tip from a pipette nozzle. The liquid handling device may comprise a plurality of pipette heads. A plurality of tip removal devices may be provided, wherein at least one tip removal device is configured to remove individually selected tips from the pipette nozzle. The tip removal device may be configured to be movable relative to the pipette nozzle in order to effect said removal. The tip removal device may be independently movable. Alternatively, the tip removal device need not be mobile, but may be individually controllable so as to allow removal of the tip. The drive means may be operatively connected to the tip removal means. The drive means may allow independent movement of the plurality of tip removal devices. A single motor or other drive means may control the independent movement of the plurality of tip removal devices. In some cases, a single motor or other drive device may control the independent movement of all tip removal devices of the plurality of tip removal devices.

In some embodiments, the tip removal device can be within the pipette head. The internal tip removal device may be configured to be movable within the pipette head. For example, the tip removal device may be a plunger. In other embodiments, the tip removal device may be external to the pipette head. For example, the tip removal device may be a collar that surrounds at least a portion of the pipette head. The collar may contact a portion of the pipette nozzle, pipette body, and/or pipette tip. Another example of an external removal device may be a peel plate. The tip removal device may or may not contact the tip when causing the tip to be removed from the pipette.

A single drive means, such as a motor, may be useful for individualized retraction and/or extension of the pipette nozzle. The liquid handling device may comprise a plurality of pipette heads. The pipette head may include a pipette nozzle, which may or may not be movable relative to the support body. The plurality of pipette nozzles may be independently movable. The drive means may be operatively connected to the pipette nozzle or other part of the pipette head, thereby allowing retraction and/or extension of the pipette nozzle. The drive means may allow independent movement of a plurality of pipette nozzles. A single motor or other drive means may control the independent movement of multiple pipette nozzles. In some cases, a single motor or other drive device may control the independent movement of all pipette nozzles of the plurality of pipette nozzles.

In some embodiments, a tip may be attached to a pipette nozzle based on the position of the pipette nozzle. For example, the pipette nozzle may be extended and lowered to contact the tip. The pipette nozzle and tip may be press fit to each other. The tip connected to the device may be controllable if the selected pipette nozzle is independently controllable in the extended position. For example, one or more pipette tips may be selected to extend. The tip may be connected to an extended pipette nozzle. Thus, a single drive may allow for independent selection and attachment/pick-up of tips.

Alternatively, a single motor or other drive device may control independent movement of a single plunger, tip removal device, and/or pipette nozzle. In some cases, multiple drive devices may be provided to control the movement of multiple plungers, tip removal devices, and/or pipette nozzles.

The liquid treatment device may comprise one or more switches. A single switch may have an on position and an off position, wherein the on position allows action or movement in response to movement caused by the drive means, and wherein the off position does not allow action or movement in response to movement caused by the drive means. The on position of the switch may allow an operable connection between the drive device and another part of the liquid handling device, such as a plunger, a tip removal device and/or a pipette nozzle moving device. The off position of the switch may not allow an operable connection between the drive device and another part of the liquid handling device, such as a plunger, tip removal device and/or pipette nozzle moving device. For example, the off position may allow the drive device to move, but the other portions of the liquid treatment device selected do not provide a response. In one example, one or more plungers associated with the single switch may be movable in response to movement caused by the motor when the switch is in the on position, and the one or more plungers associated with the single switch may not be permitted to move in response to movement caused by the motor when the switch is in the off position. In another example, one or more tip removal devices associated with the single switch may cause a tip to be removed in response to movement caused by the motor when the switch is in the on position, and one or more tip removal devices may not cause a tip to be removed in response to movement caused by the motor when the switch is in the off position. Similarly, when the switch is in the on position, the one or more pipette nozzles associated with the single switch may be extended and/or retracted in response to movement caused by the motor, and when the switch is in the off position, the one or more pipette nozzles associated with the single switch are not allowed to be extended and/or retracted in response to movement caused by the motor.

The switch may be a binary switch that may have only an on position and an off position. One, two or more actuations may occur when the switch is in the on position and not when the switch is in the off position. In alternative embodiments, the switch may have multiple positions (e.g., 3, 4, 5, 6, 7, 8, or more positions). The switch may be fully off, fully on, or partially on. In some embodiments, the switch may have different degrees of depression. Different switch positions may or may not allow different drive combinations. In one example, when the motor is driven, the switch in position 0 may not allow for actuation of the plunger and tip removal device, the switch in position 1 may allow for actuation of the plunger but not of the tip removal device, the switch in position 2 may not allow for actuation of the plunger but of the tip removal device, and the switch in position 3 may allow for actuation of the plunger and allow for actuation of the tip removal device. In some embodiments, the switch may include a control pin that may extend to different degrees to represent different positions of the switch.

In some embodiments, the switch may be a solenoid. The solenoid may have an on position and/or an off position. In some embodiments, the solenoid may have an extension assembly for an on position and a retraction assembly for an off position. A single solenoid may be provided for each pipette head. For example, a single solenoid may or may not allow movement of a single plunger associated with the solenoid, tip removal device associated with the solenoid, or pipette nozzle associated with the solenoid.

Another example of a switch may include the use of one or more binary cams. Fig. 54 shows an example of a cam-switch arrangement. The cam-switch arrangement may include a plurality of binary cams 5410a, 5410b, 5410c, 5410 d. The dual cam may have one or more protruding sections 5420 and one or more notched sections 5422. One or more control pins 5430 may be provided. In some embodiments, each cam may have a control pin operatively connected thereto.

A single control pin 5430 may contact a single binary cam 5410. In some embodiments, a biasing force may be provided on the control pin that may cause the control pin to remain in contact with the cam surface. Thus, the control pin may contact the protruding section 5420 of the cam or the notched section 5422 of the cam. The cam may be rotated, causing the cam portion contacting the control pin to change. The cam may have a rotational axis. As the cam rotates, the control pin may contact the protruding or notched segment, which may cause the control pin to move in response. When the control pin contacts the protruding section, the control pin shaft may extend further from the rotational axis of the cam than if the control pin contacts the notched section.

A plurality of cams may be provided. In one example, each cam may share an axis of rotation. In some examples, the cams may have a common shaft. The cams may be configured to rotate at the same rate. The cam may have a protruding section and a notched section at different angles around the cam. For example, fig. 54A shows a first cam 5410a having one protruding section and one notched section. The second cam 5410b may have two protruding sections and two notched sections. The third cam 5410c may have four protruding sections and four notched sections. The fourth cam 5410d may have eight protruding sections and eight notched sections. In some cases, any number of cams may be provided. For example, n cams may be provided, where n is any positive integer. From the first cam up to the nth cam may be provided. Any selected cam i of the plurality of cams may be provided. In some cases, the ith cam may have 2ⁱ¹A convex section and 2ⁱ¹A notch section. The protruding sections and the notch sections may be radially and evenly distributed around the cam. The configuration of the control pin, which may or may not protrude from the cam, may form a binary configuration.

Fig. 54A shows an example of a binary cam in position 0, where the cam is rotated 0 degrees. Each control pin is contacting the notched portion, which allows each control pin to have a retracted position. Fig. 54B shows an example of a binary cam in position 1, where the cam has rotated 22.5 degrees. Each of the control pins other than the fourth control pin is contacting the notched portion. The fourth control pin is contacting the protruding section, which causes the fourth control pin to extend. A binary reading can be generated where the retracted pin is 0 and the extended pin is 1. Fig. 54C shows an example of a binary cam in position 5, where the cam has rotated 112.5 degrees. The first and third control pins are contacting the notched portion, and the second and fourth pins are contacting the protruding portion. The second pin and the fourth pin are extended. Fig. 54D shows an example of a binary cam in position 15, where the cam has rotated 337.5 degrees. Each control pin is contacting a protruding section of the cam. Each control pin is in the extended position and therefore each has a reading of 1. The cam may be rotated any amount, which may allow for any combination of extended and retracted pins.

The extended control pin may allow an operable connection between the drive means and another part of the liquid treatment device. For example, a control pin for the extension of a particular cam may allow a motor to move the plunger, tip removal device, and/or pipette nozzle associated with this single cam.

FIG. 54E illustrates a motor mounted selection cam according to the specific example described herein. One or more cams 5410 may be provided with one or more control pins 5430. The cams may share shaft 5440. A motor 5450 with an encoder may be provided. Pulley 5460 may operatively connect the motor to the cam. In some embodiments, the motor may be capable of rotating, which may cause the cam to rotate. The shaft may rotate, which may cause the cams to rotate together. The cam may be rotated to a desired position to provide a desired arrangement of the extended control pins. The extended control pin may allow an operable connection between the further motor and another part of the pipette. An attachement-free pipette body 5470 may also be provided. In some embodiments, the extended control pin may be a switch in the on position and the retracted control pin may be a switch in the off position, or vice versa.

In some embodiments, aspiration and dispensing are controlled independently of each other. This can be achieved by means of a single drive. In one example, one drive device provides sample (e.g., liquid) aspiration, while another drive device provides sample dispensing.

Ventilation

The one or more liquid handling devices may comprise a vent. For example, the pipette may include a vent. For example, the pipette nozzle and/or pipette tip may include a vent opening. The vent opening may allow the inner plunger device to move inside without expelling or drawing liquid. In some embodiments, the vent opening may allow the plunger to move without causing liquid within the liquid path to move substantially along the liquid path. For example, the vent may be able to allow the plunger to move downward within the pipette nozzle or tip without draining the liquid. The plunger may or may not be in direct contact with the liquid at all times. In some cases, the plunger may move downward without expelling liquid until the plunger contacts the liquid. In another example, the vent opening may allow the plunger to move upward away from the liquid and draw in air while allowing the liquid to remain in its original position within the pipette nozzle or tip.

The vent may allow for improved pipette accuracy and/or precision. The vent may be included in a vented pipette. The vent may improve the accuracy and/or precision of the vented pipette by allowing air to be vented, depending on environmental conditions, which may cause inherent inaccuracies in the liquid. Alternatively, a positive displacement pipette may comprise a vent. Ventilation may reduce inaccuracies associated with variable conditions. The vent may allow for the ejection of a liquid-filled pipette tip without loss of liquid from the tip. Venting the liquid-filled tip without loss of liquid can support incubation of the tip when it is detached from the pipette, thereby freeing the pipette to perform other tasks. In one embodiment, the pipette tip may be vented and then subsequently picked up for further processing of the internal liquid.

In some embodiments, the liquid treatment device may include one or more vent ports. In some cases, one or more pipette heads may have a vent port. In one example, each pipette head of a liquid handling device can have a vent port. Each particular type of pipette tip (e.g., vented pipette tip) may have a vent port.

The vent port may be capable of having an open position and a closed position. In some cases, a switch may be used to determine whether the vent port is in an open or closed position. In one example, the switch may be a solenoid, a valve, or any other switching device described elsewhere herein. The vent port switch may have one or more characteristics that provide for any other switching device described elsewhere herein, or vice versa. The vent port switch may be a binary switch or may have multiple positions. The vent ports may be open or closed, or may have different degrees of openness. The vent port is open or closed, or the degree of opening of the vent port may be controlled by a controller. In one example, the vent solenoid may determine whether the vent port is in an open position or a closed position. In another example, the valve may determine whether the vent port is in an open position or a closed position. A valve, solenoid, or any other switch may be duty cycled. The duty cycle can have any period including, but not limited to, a period of 5s or less, 3s or less, 2s or less, 1s or less, 500ms or less, 300ms or less, 200ms or less, 100ms or less, 75ms or less, 60ms or less, 50ms or less, 40ms or less, 30ms or less, 20ms or less, 10ms or less, 5ms or less, or 1ms or less. The duty cycle may be controlled according to one or more instructions from the controller.

In some embodiments, a vent solenoid, valve, or other switch may determine the extent to which the vent may be open. For example, the switch may only determine whether the vent port is open or closed. Alternatively, the switch may determine whether the vent port is open to an intermediate degree, such as about 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% open. The vent port may be open to a fixed degree, or may be open to any degree along a continuous range. The degree of openness may be controlled in response to one or more signals from the controller. The controller may be used to determine a desired degree of pressure to be provided in the liquid path.

The vent port may be coupled to a pressure source. The pressure source may be a positive pressure source or a negative pressure source. A positive pressure source may be useful for the discharge of liquid from within the pipette head. A negative pressure source may be useful for aspiration of liquid into the pipette tip. In some cases, the vent port may be coupled to atmospheric conditions. For example, a vent port may selectively connect the interior of the pipette tip with ambient air.

The positive or negative pressure may be delivered by any technique known in the art. In one example, the ventilation port may be coupled to a reversible pump capable of delivering positive or negative pressure. The pump may be capable of delivering positive or negative pressure for extended periods of time. For example, the pump may deliver positive pressure until all liquid is discharged. The pump can deliver positive pressure for as long as desired to allow the desired amount of liquid to be discharged through the pipette head. In another example, the pump can deliver negative pressure as long as desired to allow a desired amount of liquid to be drawn through the pipette tip. Reversible pumps may allow for switching between providing positive and negative pressure under selected conditions.

The positive or negative pressure may be provided by a liquid. For example, the negative pressure may be provided by air or another gas. In other embodiments, the positive or negative pressure may be provided by a liquid or any other liquid.

In some cases, the pipette head has a single vent port. Alternatively, the pipette head may have multiple vent ports. The plurality of vent ports may be connected to a positive pressure source, a negative pressure source, an ambient condition, or any combination thereof.

Retraction

The liquid handling device may include one or more pipette heads, wherein an individual pipette head has a liquid path of a specified length. The fluid path can be entirely within the pipette head or one or more portions of the pipette head can be external to the pipette head. The liquid path length may terminate at the pipette nozzle. The liquid path length may terminate at an orifice of the liquid handling device. In some cases, the fluid path length may terminate at the end of a tip connected to the fluid handling device. In some cases, the liquid path length may terminate at the end of the plunger (e.g., the end of the plunger closer to the tip). Alternatively, the fluid path length may terminate at the tip of the pipette tip or base or support. The liquid pathway may have two or more terminal ends, which may be any combination of the above terminal locations. In some cases, the liquid path length may be determined by two terminal ends.

The length of the liquid path may be adjustable. In some cases, the length of the liquid path may be adjustable when the tip is engaged with the pipette nozzle without affecting liquid movement from the tip. The liquid path length may be adjusted while the liquid in the tip remains in substantially the same position. The liquid path length may be increased and/or decreased.

The liquid path length may be adjusted by changing the position of 1, 2 or more termination points of the liquid path. In one example, the liquid path may have two termination points: a remote termination point closer to the point at which the tip or liquid is expelled and/or aspirated and a proximal termination point further from the point at which the tip or liquid is expelled and/or aspirated. The remote termination point may be moved to adjust the liquid path length. Alternatively, the proximal termination point may be moved to adjust the liquid path length. In some cases, the distal termination point and the proximal termination point may be moved relative to each other to adjust the liquid path length.

In one example, the remote termination point may be a pipette tip and the proximal termination point may be a piston tip closer to the pipette tip. The pipette nozzle may be connected to a tip that may contain a liquid therein. The pipette nozzle may be retracted or extended relative to the plunger and/or the rest of the pipette head. The liquid path length of the pipette tip can be adjusted. In some cases, extending and/or retracting the pipette nozzle need not cause substantial movement of the liquid within the tip. In another example, the plunger may be driven towards or away from the tip. This can also result in the liquid path length of the pipette tip being adjusted. The plunger can be actuated without causing substantial movement of the liquid in the tip.

As previously described, the liquid handling device may include at least one pipette head connected to the base, wherein an individual pipette head contains a pipette nozzle configured for connection with a removable tip. A plunger may be provided within the pipette head and may be configured to be movable within the pipette head. The pipette nozzle may be movable relative to the base so as to enable the pipette nozzle to have a retracted position and an extended position in which the pipette nozzle is further from the base than in the retracted position. The pipette nozzle may be movable relative to the plunger, relative to the motor, relative to the rest of the pipette head, relative to a switch or relative to any other part of the liquid handling device. Adjusting the pipette nozzle between the retracted position and the extended position may change the length of the liquid path terminating at the pipette nozzle. In some cases, only a stiff component may be used to form the liquid path length.

Any difference in position may be provided between the retracted position and the extended position. For example, there may be no more than and/or equal to about a 1mm, 3mm, 5mm, 7mm, 1cm, 1.5cm, 2cm, 2.5cm, 3cm, 4cm, 5cm, or 10cm difference between the retracted position and the extended position. The difference in position may be in the vertical direction, the horizontal direction, or any combination thereof. The difference in position may be in a direction parallel to the length of the cleaner head, perpendicular to the length of the cleaner head or any combination thereof.

In some embodiments, this may be accomplished by venting, such as the venting or other devices described elsewhere herein. The vent port may be positioned along the liquid path.

The liquid path may be formed by one or more components. In some embodiments, the liquid pathway may be formed entirely of the rigid component. In other embodiments, the liquid path may be formed by a flexible member. Alternatively, the liquid path may be formed by a combination of a hard component and a soft component. The liquid path may be formed by a rigid component without using a soft component. The liquid path may be formed by a soft component without using a hard component.

Examples of hard components may include hard tubes, pipes, conduits or channels. The liquid path may be formed by a single rigid component or by a plurality of rigid components. The plurality of rigid components may or may not be moveable relative to each other. The rigid components may slide relative to each other. In one example, a plurality of rigid components may be provided in a telescoping configuration, wherein one or more rigid components are slidable within another rigid component. The length of the liquid path may be varied by moving one or more rigid components relative to each other.

Examples of flexible components may include flexible tubes, pipes, conduits or channels. For example, a bendable plastic tube may be used. The liquid path may be formed by a single flexible member or a plurality of flexible members. The plurality of flexible members may be movable relative to each other. For example, they may slide relative to each other and/or may have a telescopic arrangement.

The liquid handling device may have a plunger within one or more pipette heads. The plunger may be configured to be movable within the pipette head. The plunger may be movable along the liquid path. The plunger may be movable in a vertical direction and/or a horizontal direction. The plunger may be movable in a direction parallel to the length of the tip and/or perpendicular to the length of the tip. The plunger may form a liquid-tight connection with one or more walls of the liquid pathway. Thus, as the plunger is movable along the liquid path, the pressure within the liquid path may be varied and/or maintained.

The plunger may be formed of a hard component, a soft component, or any combination thereof. The plunger may be formed from a single unitary piece. Alternatively, the plunger may be formed from multiple sections. For example, the plunger may include a first section and a second section. At least a portion of the first section may be configured to slide relative to the second section, thereby allowing the plunger to extend and/or retract. In one example, the first section may be configured to slide within the second section. A telescoping configuration may be provided. The length of the plunger may be fixed or may be variable. The plunger may have any number of sections (e.g., 1, 2, 3, 4, 5, 6, 7, 8, or more sections) that may or may not be movable relative to each other. The plunger may form a double needle and/or a multiple needle configuration.

In some embodiments, the heat sink may surround the plunger. The heat sink may assist in maintaining the plunger at a desired temperature or within a desired temperature range. This may be beneficial when precise control of the volume dispensed and/or aspirated is desired. The heat sink may assist in reducing and/or controlling thermal expansion of one or more components of the liquid handling device, such as the plunger. In other embodiments, a pipette nozzle and/or tip may be used to transfer heat to and/or from a pipette for heating and/or cooling operations. A pipette may also be used to deliver/apply cold air to control the temperature of the cartridge, container, pipette tip, etc. A pump may be used to accomplish this function.

Particular examples described herein may relate to a liquid treatment method that may include providing a liquid treatment device having one or more of the features described herein. For example, the method can include providing at least one pipette head operably connected to the base, wherein an individual pipette head includes a pipette nozzle configured for connection with a removable tip. The method may further comprise retracting and/or extending the pipette nozzle relative to the base. The method may include retracting and/or extending the pipette nozzle any distance, which may be determined by the controller.

Still alternatively, the method may comprise dispensing and/or aspirating the liquid with a tip. Aspiration and/or dispensing may occur while the pipette nozzle is retracted and/or extended. Aspiration and/or dispensing may occur while the pipette nozzle is retracted and/or extended in a vertical direction, a horizontal direction, a direction parallel to the length of the tip, a direction perpendicular to the length of the tip, a direction away from/toward the base, or any combination thereof.

The speed of dispensing and/or aspirating may depend on the speed of retraction and/or extension of the pipette nozzle, or vice versa. In systems with small volumes of liquid and small containers, it may be beneficial to dispense and/or aspirate during retraction and/or extension of the pipette nozzle. For example, a small container may be provided in which the liquid is at or near the topmost layer of the container. When the tip meets the top of the liquid surface at the container, overflow may occur if suction does not occur. If aspiration occurs when the tip encounters liquid and is lowered into the container, the aspiration prevents overflow. In some specific examples, dispensing and/or aspiration may occur at a rate sufficient to prevent overflow or to have any other desired effect.

In some embodiments, the pipette tip may be extended and/or retracted before, after, and/or simultaneously with translating the pipette head. The pipette nozzle may be extended and/or retracted in a first direction, and pipette head translation may occur in a second direction. The first and second directions may or may not be substantially parallel to each other. In some cases, the first direction and the second direction may be substantially non-parallel to each other. The first direction and the second direction may be substantially perpendicular to each other. In one example, the first direction is a substantially vertical direction and the second direction is a substantially horizontal direction. In another example, the first direction is substantially parallel to the length of the cleaner head and the second direction is substantially perpendicular to the length of the cleaner head.

The pipette nozzle may be extended and/or retracted relative to the base before, after, and/or simultaneously with dispensing and/or aspirating liquid with the tip. The liquid can be dispensed and/or aspirated before, after, and/or simultaneously with translating the pipette tip.

In one example, the pipette nozzle may be retracted prior to and/or concurrently with translating the pipette head. The pipette nozzle may then be extended prior to and/or concurrently with dispensing and/or aspirating liquid with the tip. While translating the pipette head, the pipette tip may be retracted a sufficient amount to clear any objects that may be encountered. The pipette tip may be sufficiently extended to contact the liquid to be aspirated and/or to dispense the liquid to a specified location.

The pipette tip may or may not be extended and/or retracted while translation of the pipette tip occurs. In some cases, individual pipette nozzles in multiple pipette heads that translate together may or may not extend and/or retract together. In some cases, individual pipette nozzles may be independently retracted and/or extended. The pipette nozzle may be extended and/or retracted based on a known path to be moved, which may or may not include a known obstruction that needs to be cleared. The pipette nozzle may be extended and/or retracted based on one or more measurements provided by the sensor (e.g., if the sensor encounters an obstruction during translation of the pipette head).

In some cases, the pipette may include one or more sensors for providing various data to a control system operating the pipette. In one example, the one or more sensors provide position measurements that enable the pipette to be extended and retracted. In another example, the one or more sensors provide temperature, pressure, humidity, conductivity data. In yet another example, the one or more sensors include a camera for taking images, video, and/or audio from within the pipette.

A multiheaded pipette may have multiple pipette heads. One or more of the pipette heads and/or each pipette head may comprise a pipette nozzle. One or more of the pipette tips and/or each pipette tip may have a pipette tip attached thereto. One or more of the pipette tips and/or each pipette tip may be capable of receiving or connecting to a pipette tip. In one example, each pipette head may be connected to one pipette tip. In other examples, each pipette head may be capable of connecting to one or more pipette tips. The pipette tip may be press fit onto the pipette tip and/or may be connected by any other means known in the art, including but not limited to: magnetic elements, fasteners, hook and loop fasteners, elastic elements, tie bars, sliding devices, locking devices, clamps, drive mechanism assemblies, and/or adhesives.

One or more pipette tips may be provided in a row. For example, 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, or 12 or more pipette tips may be provided in a row. One or more pipette tips may be provided in a column. For example, 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, or 12 or more pipette tips may be provided in columns. An array of pipettes may be provided, wherein the array has 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, or 12 or more pipettes in rows and 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, or 12 or more pipettes in columns. In some embodiments, the pipette tips may be arranged in staggered rows, straight, angled, or curved rows, concentric shapes, or any other configuration. The pipette tip may be configured and/or sized to match one or more of the arrangements on the microcard described elsewhere herein.

A multiheaded pipette may have an air displacement pipette having a pipette head configuration as described elsewhere herein. Alternatively, a multiheaded pipette may have a positive displacement pipette with a pipette head configuration as described elsewhere herein. Alternatively, the multiheaded pipette may comprise both a vented pipette and a positive displacement pipette. One or more vented pipettes may be provided in one region and one or more positive displacement pipettes may be provided in another region. Alternatively, an air displacement pipette and a positive displacement pipette may be interspersed. A vented pipette may be provided in one format and a positive displacement pipette may be provided in another format. For example, a row of air displacement pipettes may be provided, and a single positive displacement pipette may be provided. In one embodiment, a bank of 8-headed vented pipettes may be provided with a single positive displacement pipette.

One or more air displacement pipettes and one or more positive displacement pipettes may be provided on the same pipette support. Alternatively, they may be provided on different pipette holders. The vented and positive displacement pipettes may be in fixed positions relative to each other. Alternatively, they may be movable relative to each other.

1, 2, 3, 4, 5, 6 or more pipettes and/or other liquid handling devices may be provided within the apparatus. The liquid treatment device may have a fixed position within the apparatus. Alternatively, the liquid treatment device may be movable within the apparatus.

1, 2, 3, 4, 5, 6 or more pipettes and/or other liquid handling devices may be provided within a module. The liquid treatment device may have a fixed position within the module. Alternatively, the liquid handling device may be movable within the module. In some embodiments, the liquid handling device may be movable between modules. Alternatively still, the liquid treatment device may be provided outside the module but within the apparatus.

The liquid handling device may transfer a sample or other liquid from one portion of the apparatus and/or module to another. The liquid handling device may transfer liquid between modules. The liquid handling device may enable liquid to be transported from one part of the apparatus to another, thereby effecting one or more sample handling steps. For example, the liquid may be subjected to a sample preparation step in a first part of the apparatus and may be transferred by the liquid handling system to a second part of the apparatus, where additional sample preparation steps, assay steps or detection steps may occur. In another example, the liquid may be subjected to an assay in a first portion of the apparatus and may be transferred by the liquid handling system to a second portion of the apparatus, where additional assay steps, detection steps, or sample preparation steps may occur. In some cases, the liquid handling device is configured to transfer a liquid, solid, or semi-solid (e.g., a gel). Thus, the term "liquid treatment" is not necessarily limited to liquids, but may encompass substances of different viscosities or consistencies.

Liquid handling may allow for the transfer of liquid where the liquid is contained within one or more pipette tips and/or containers. The tip and/or the container containing the liquid may be moved from one part of the apparatus to another. For example, a pipette tip may draw liquid in one portion of the device and move to a second portion of the device where the liquid may be dispensed. Alternatively, parts of the apparatus may be movable relative to the liquid treatment device. For example, a portion of the device may be moved to a pipette, where the pipette may draw liquid. Then another part of the device can be moved to the pipette where it can dispense the liquid. Similarly, the liquid handling device may be movable to pick up and/or remove pipette tips and/or containers at different locations.

Liquid treatment suction head

In one example, the pipette nozzle may be configured to receive one or more types of pipette tips. The pipette nozzle may be shaped to complement one or more types of pipette tips. In some embodiments, pipette tips may have tips with the same diameter, even though other pipette tip shapes or sizes may vary. In another example, the pipette nozzle may have one or more shaping features that may selectively contact the pipette tip depending on the pipette tip. For example, the pipette nozzle may have a first portion that contacts a first type of pipette tip, and a second portion that contacts a second type of pipette tip. In such cases, the pipette nozzles may have the same configuration. Alternatively, the pipette nozzle may be specially shaped to fit one type of pipette tip. Different pipette nozzles can be used for different pipette tips.

The pipette tip may be formed of a material that enables one or more signals to be detected from the pipette tip. For example, the pipette tip may be transparent and may allow optical detection of the liquid within the pipette tip. The pipette tip may be optically read or detected in any other way while the pipette tip is attached to the pipette nozzle. Alternatively, the pipette tip may be optically read or detected in any other way when it has been removed from the pipette nozzle. When read by the probe, the pipette tip may or may not have liquid contained therein. The pipette tip may have one or more configurations, dimensions, characteristics, or features as described in more detail elsewhere herein.

In some embodiments, the pipette tip may receive or emit light from a light source. The tip may function as a lens to focus the light emitted by the pipette. In some embodiments, the light source may be operably connected to the liquid treatment device. The light source may be external to the liquid treatment device or may be internal to the liquid treatment device. In some embodiments, one or more light sources can be provided within a pipette head of a liquid handling device. In some embodiments, the or each pipette tip may have a light source. The plurality of light sources may or may not be independently controllable. One or more characteristics of the light source may or may not be controlled, including but not limited to: whether the light source is on or off, the brightness of the light source, the wavelength of the light, the intensity of the light, the illumination angle, the position of the light source. The light source may provide light into the tip.

The light source may be any instrument capable of emitting energy in the electromagnetic spectrum. The light source may emit light along the visible spectrum. In one example, the light source may be a Light Emitting Diode (LED) (e.g., a gallium arsenide (GaAs) LED, an aluminum gallium arsenide (AlGaAs) LED, a gallium arsenide phosphide (GaAsP) LED, an aluminum gallium indium phosphide (AlGaInP) LED, a gallium phosphide (III) (GaP) LED, an indium gallium nitride (InGaN)/gallium nitride (III) (GaN) LED, or an aluminum gallium phosphide (AlGaP) LED). In another example, the light source may be a laser, such as a Vertical Cavity Surface Emitting Laser (VCSEL) or other suitable light emitter, such as an indium gallium aluminum phosphide (InGaAIP) laser, a gallium arsenic phosphide/gallium phosphide (GaAsP/GaP) laser, or an aluminum gallium arsenide/gallium arsenide (GaAIAs/GaAs) laser. Other examples of light sources can include, but are not limited to, an electronically excited light source (e.g., cathodoluminescence, electron stimulated luminescence (ESL bulb), cathode ray tube (CRT monitor), nixie tube, incandescent light source (e.g., carbon filament lamp, conventional incandescent bulb, halogen lamp, silicon carbide rod, nernst lamp), Electroluminescent (EL) light source (e.g., light emitting diode-organic light emitting diode, polymer light emitting diode, solid state lighting, LED lamp, electroluminescent sheet, electroluminescent wire), gas discharge light source (e.g., fluorescent lamp, induction lighting, hollow cathode lamp, neon and argon lamp, plasma lamp, xenon flash lamp), or high intensity discharge light source (e.g., carbon arc lamp, ceramic discharge metal halide lamp, mercury dielectric-arc iodine lamp, mercury vapor lamp, metal halide lamp, sodium vapor lamp, xenon arc lamp), alternatively, the light source may be a bioluminescent light source, a chemiluminescent light source, a phosphorescent light source, a fluorescent light source.

The light source may be capable of emitting electromagnetic waves in any spectrum. For example, the light source may have a wavelength falling between 10nm and 100 μm. The light wavelength may fall between 100nm to 5000nm, 300nm to 1000nm, or 400nm to 800 nm. The light wavelength may be less than and/or equal to 10nm, 100nm, 200nm, 300nm, 400nm, 500nm, 600nm, 700nm, 800nm, 900nm, 1000nm, 1100nm, 1200nm, 1300nm, 1500nm, 1750nm, 2000nm, 2500nm, 3000nm, 4000nm, or 5000 nm.

One or more of the plurality of light sources may be provided. In some specific examples, each of the plurality of light sources may be identical. Alternatively, one or more of the light sources may be different. The light characteristics of the light emitted by the light sources may be the same or may be different. The light sources may be independently controllable.

The tip may form a waveguide that is capable of providing light to the liquid contained therein through the tip, or of transmitting a light signal from the liquid through the tip. The tip may be capable of transmitting light from a light source to the liquid contained therein. The light source may be infrared light. The infrared light may be used to heat the sample or the reaction in the tip or elsewhere. The tip may be capable of transmitting light. The tip may be formed from a light-transmissive material. In some embodiments, the tip can transmit all waves in the electromagnetic spectrum. Alternatively, the tip may transmit selected waves of the electromagnetic spectrum. For example, the tip may transmit light of a selected wavelength. The tip may or may not transmit light along the entire length of the tip. A portion of the tip or the entire tip may be formed from a light-transmissive material. The cleaning head may be transparent, translucent and/or opaque.

In some embodiments, the tip may comprise a fiber capable of conducting light. The fibers may be formed of an optically transparent material. The fibres may extend along a part of or the entire length of the removable tip. The optical fiber may be embedded in a removable tip. The optical fiber can be embedded in an opaque tip, a transparent tip, and/or a translucent tip.

The pipette nozzle may be formed of transparent and/or reflective surfaces. The pipette nozzle may be configured to allow light transmission through the pipette nozzle. For example, light from a light source may pass through the pipette nozzle to the tip. In some embodiments, the pipette nozzle may have a reflective surface. Light from the tip may be reflected back into the tip by the pipette nozzle, creating a high illumination level within or adjacent to the tip.

Fig. 55 shows an example of a liquid treatment apparatus using one or more light sources. Fig. 55A shows a plurality of pipette tips. Each pipette head may include a nozzle 5510. An ejection sleeve 5512 may be provided for each pipette head.

Fig. 55B shows a side cross-sectional view of the liquid handling device with plunger 5520 in a bottom position. The device may include a pipette housing 5530. A solenoid 5540 may be provided, the solenoid 5540 may affect the actuation of the ejection sleeve 5512 or plunger 5520.

Fig. 55C shows a close-up of a light source that may be provided within a liquid treatment device. For example, an LED5550 or other light source may be provided within the pipette housing. Any description herein of LEDs may also apply to any other light source, and vice versa. The LED may be located at the end of the plunger 5520. The LED may be located at the top end of the plunger or at the bottom end of the plunger. The LED may be coaxial with the plunger. The LED may be integral with the plunger or may be a separate part from the plunger. The LED may or may not be in direct contact with the plunger. In some embodiments, the LED may move with the plunger. Alternatively, the LED may remain fixed and the plunger may be movable.

A plunger retainer 5560 may be provided that may assist in aligning and/or controlling the position of the plunger. The plunger retainer may have one or more features 5565 that may place the plunger in an extended or retracted position. When the plunger is in the extended position, it may be located closer to the pipette nozzle and/or tip than when the plunger is in the retracted position.

Fig. 55D shows a close-up of the plunger 5520 and pipette tip 5510. In some cases, an O-ring 5570 may be provided on the pipette head. The plunger may be formed of a light transmissive material. In some embodiments, the plunger may be formed of a transparent material. The plunger may be a light pipe plunger that may function as a light guide. The plunger may transmit light from the light source to the tip and/or to a liquid contained within the tip. The plunger may or may not transmit light from the liquid within the tip to another location.

Fig. 55E shows a perspective view of the liquid handling device.

The liquid handling device may be operatively connected to the image capture instrument. The image capture instrument may be capable of capturing an image of the liquid within the tip. Alternatively, the image capture instrument may be capable of capturing images through the tip. The image capture instrument may be external to the liquid handling device or may be internal to the liquid handling device. In some embodiments, one or more image capture instruments may be provided within a pipette head of a liquid handling device. In some embodiments, multiple or each pipette tip may have an image capture instrument. In some embodiments, the image capture instrument may be integrally formed with the device. The device itself may be capable of functioning as an image capture instrument. In some embodiments, the tip and/or plunger may be capable of functioning as a lens of an image capture instrument. The tip and/or plunger may be formed of a light transmissive material that may be shaped to provide a desired optical effect.

The plurality of image capturing instruments may or may not be independently controllable. The image capture instruments may be the same or may be different.

Any description of the image capture instrument is applicable to any electromagnetic spectrum detection instrument. The image capture instrument may be capable of capturing electromagnetic radiation and generating an image along one or more of: visible spectrum, infrared spectrum, ultraviolet spectrum, or gamma spectrum. In some embodiments, the image capture instrument is a camera. Any description of the camera or other detection instruments described elsewhere herein may be applicable. In one example, the image capture instrument may be a digital camera. The image capture instrument may also include a Charge Coupled Device (CCD) or photomultiplier tube and photocell, or a light monitor or other detection instrument, such as a scanning microscope (whether back-illuminated or front-illuminated). In some cases, the camera may use a CCD, CMOS, may be a lensless (computational) camera (e.g., a frankencam camera), an open source camera, or may use any other visual detection technique known in the art or later developed. The camera may include one or more features that may, in use, bring the camera into focus, or may take images that may be later gathered. In some embodiments, the imaging modality may employ 2-D imaging, 3-D imaging, and/or 4-D imaging (including changes over time). The imaging modality may take still images. The static images may be captured at 1 or more time points. The imaging modality may also take video and/or dynamic images. The video images may be continuously captured over 1 or more time periods. Any other description of the imaging apparatus and/or the detection unit may also apply.

In one example, the image capture instrument may be located at the end of the plunger. In some examples, the image capture instrument may be located at the bottom or top end of the plunger. The image capture instrument may be coaxial with the plunger. The image capture instrument may be integral with the plunger or may be a separate component from the plunger. The image capture instrument may or may not be in direct contact with the plunger. In some embodiments, the image capture instrument is movable with the plunger. Alternatively, the image capture instrument may remain stationary and the plunger may be movable. The image capture instrument may be located at the position of, or adjacent to or near the light source as provided in fig. 55B and 55C.

The plunger and/or tip may comprise a light transmissive material. The plunger and/or the tip may be made of a transparent material. The plunger and/or tip may be shaped to have desired optical properties. The plunger and/or tip may be a lens of an image capture instrument. Movement of the plunger and/or tip may or may not affect the focus of the image captured by the image capture instrument. The image capture instrument may be directed in a longitudinal direction along the length of the tip. Alternatively, the image capture device may be directed in a transverse direction perpendicular to the length of the tip, or at any other angle.

In some embodiments, the image capture instrument may be capable of capturing an image of the liquid within the tip. Alternatively, the image capture instrument may be capable of capturing an image of any sample within the instrument. In some embodiments, the image capture instrument may capture an image of a sample located at the tip of the tip. For example, the sample may be located at the end of the tip opposite the pipette nozzle. The image capture instrument may capture an image of the sample passing through the tip. The sample may be a liquid sample, a tissue sample, or any other sample described elsewhere herein. In some embodiments, the image capture instrument may operate in conjunction with a light source. The light source may illuminate the sample, which allows the image capture instrument to capture an image of the sample.

The processor may be operatively connected to a tip of the liquid handling device. The processor may be located within the liquid handling device, within a pipette head associated with the tip, or on the tip itself. The liquid handling device may change and/or maintain the position of the removable tip based on instructions from the processor. The processor may be connected to sensors on or near the liquid treatment device that measure environmental conditions, such as temperature, humidity or vapor pressure, and may adjust the movement of the liquid treatment apparatus to compensate or optimize for such conditions.

In one example, a plurality of tips can be provided, wherein individual tips of the plurality of tips can have a processor located on and/or operatively connected to the tips. In some embodiments, each tip may have a processor attached or operatively connected thereto. The tip processors may be capable of communicating with the controller and/or each other. For example, a first processor of a first removable tip may be in communication with a second processor of a second removable tip.

In some embodiments, the position of the tip may be controllable based on the communication. The position of the tip may be controllable when the tip is engaged with the pipette tip. Alternatively, the position of the tip may be controllable when the tip is detached from the pipette head. The tip may be able to change and/or maintain its position when the tip is engaged with the pipette tip and/or when the tip is disengaged from the pipette tip.

The nozzle may comprise 1, 2 or more openings. The tip may be of any useful shape that can interface with a pipette or one or more pipette nozzles. The tip may take many forms such as cylindrical, oval, square, "T" or circular. A single tip may have multiple sub-compartments or cavities. Such sub-compartments may be used to contain various useful chemicals such as reagents. Useful chemicals such as reagents may be stored in or on the tip or any of its subcompartments in liquid, solid, film or other form. The tip may contain vesicles of chemical substances such as reagents that can be released on command (e.g. when puncturing). The tip may also be used for chemical and physical processing steps such as reagent and/or sample filtration. One or more of the openings may include a switch, such as a valve. In one example, the suction head may have two openings, wherein each opening may include a recessed passive valve. A switch, such as an embedded passive valve, may be configured to allow liquid to flow in one direction through the first opening, then through the tip body, and then through the second opening. The valve controls the direction of the liquid flow. The liquid may flow completely through the tip or may flow through a portion of the tip. For example, the tip may have a switch at one opening that allows liquid to flow in a certain direction (e.g., allowing liquid to flow into the tip to allow aspiration while not allowing liquid to exit the tip; or allowing liquid to flow out of the tip to allow dispensing while not allowing liquid to be aspirated into the tip). The valve may be controlled to determine the direction of liquid flow, the magnitude of liquid flow, or whether any liquid flow is permitted.

The liquid handling system may be capable of dispensing and/or aspirating one or more liquids simultaneously. In some cases, a liquid handling system may dispense, aspirate, and/or transport multiple types of liquids simultaneously. Liquid handling may provide a modular technique for tracking and handling different liquids for one or more concurrent steps or detections.

Multipurpose transport

Liquid handling devices may be useful for dispensing, aspirating and/or transferring one or more liquids. The liquid handling device may also be useful for one or more additional functions, including non-liquid handling functions. The connection of the components or the suction head may allow the liquid handling apparatus to function as a robot capable of performing one or more non-liquid handling functions. Alternatively, the pipette itself may be employed to perform one or more such non-liquid functions by one or more drive means. Such non-liquid handling functions may include the ability to transmit power to move components, tools or other objects (such as a cuvette body) or a cartridge or specimen or any component thereof. When combined with a flexible support (described herein) or other configuration that allows for a wide range of movement, the device may be able to perform such functions in multiple dimensions within the device or even outside the device.

For example, a liquid handling device may be useful for transferring components from one location to another within an apparatus. The component that can be transferred can be a sample processing component. The sample processing component may be a sample preparation unit or component thereof, an assay unit component thereof, and/or a detection unit or component thereof. Examples of components may include, but are not limited to, tips, vessels, support structures, miniature cards, sensors, temperature control instruments, image capture units, optical instruments, cell counters, centrifuges, or any other component described elsewhere herein.

The liquid handling device may pick up the sample processing assembly. The liquid handling device may move the sample processing assembly to different locations of the apparatus. The liquid handling device may discharge the sample processing assembly to its new location within the device.

The liquid handling device may be capable of transferring the sample processing assembly within the module. The liquid handling device may or may not be limited to a module. Alternatively, the liquid handling device may be capable of transferring sample processing components between modules, and need not be limited to a single module. In some cases, the liquid handling device may be capable of transferring the sample processing assembly within the rack and/or may be confined to the rack. Alternatively, the liquid handling device may be capable of transferring sample processing components between racks and need not be limited to a single rack.

The liquid handling device may use a variety of devices to pick up and move the sample processing assembly. For example, a press-fit between one or more pipette heads and features of the sample processing assembly can be used to pick up the sample processing assembly. For example, the pipette nozzle may interface with the tip by a press-fit arrangement. The same press-fit arrangement can be used to allow the pipette nozzle to engage with features of the sample processing assembly. Alternatively, a press-fit interface may be present between any other part of the liquid handling device and the sample processing assembly. In some cases, the press-fit features of the sample processing assembly may protrude to meet with the liquid handling device. The press-fit feature of the sample processing assembly can have a shape that is complementary to the press-fit portion of the liquid handling device.

Another example of an engagement device may be a pressure driven device, such as a suction device. The sample processing assembly can be picked up using suction provided by one, two, or more pipette heads. Suction may be provided by one or more pipette tips, may be provided by internal actuation of a plunger or a source of negative pressure coupled to the fluid path. The pipette head providing the suction force may contact any portion of the sample processing assembly, or may contact a particular feature of the sample processing assembly. Features of the sample processing assembly may or may not protrude to meet the liquid handling device.

An additional example of an engagement means may be a magnetic means. The liquid handling device may include a magnet that may be switched on to interface with the magnet of the sample processing assembly. The magnet may be turned off when it is desired to unload the sample processing assembly. Additional devices known in the art may be used, including but not limited to adhesives, hook and loop fasteners, screws, or a lock slot arrangement.

In some embodiments, a component removal device may be provided to assist in unloading the specimen processing components. Alternatively, a separate component removal device may not be required. In some cases, a tip removal device may be used as the component removal device. In another example, a plunger may be used as the component removal device. Alternatively, a separate component removal device may be provided. The component removal device may use gravity, friction, pressure, temperature, viscosity, magnetic principles, or any other principle. A large number of tips can be stored in the apparatus as a shared resource of pipettes or robots to be utilized when needed. The suction heads can be stored in hoppers, magazines, bags used when needed. Alternatively, the tips may be stored in a nested manner to save space within the device. In another embodiment, the module may be configured to provide additional tips or any other resources as needed as a shared module in the device.

The liquid handling device may interface with the sample processing assembly at any number of interfaces. For example, the liquid handling device may interface with the sample processing assembly at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more interfaces. Each interface may be the same kind of interface or may be any combination of various interfaces (e.g., press fit, suction, magnetic, etc.). The number and/or type of interfaces may depend on the sample processing component. The fluid handling device may be configured to interface with the sample processing assembly with one type of interface, or may have multiple types of interfaces. The liquid handling device may be configured to pick up and/or transfer a single type of sample processing component, or may be capable of picking up and transferring multiple types of sample processing components. With the assistance of the application of various types of tips, the liquid handling device can facilitate or perform various sample processing tasks, including physical and chemical processing steps, for or with the sample processing assembly.

Fig. 52 provides an example of a liquid handling device for carrying a sample processing assembly. The sample processing component may be a cuvette holder 5210. The cuvette holder may have one or more interface features 5212, which interface features 5212 may be configured to interface with a liquid handling device. In some specific examples, the interface feature can contact a pipette nozzle 5220 of the liquid handling apparatus. The plurality of interface features may contact the plurality of pipette nozzles.

In some embodiments, the tip removal device 5230 may be useful for removing the cuvette holder from the pipette nozzle. A plurality of tip removal devices may be driven simultaneously or sequentially.

FIG. 53 shows a side view of a liquid handling device useful for carrying a sample processing assembly. The cuvette holder 5310 may be connected to a liquid handling apparatus. For example, the nozzle 5320 can engage a cuvette holder. The nozzles may have the same shape and/or configuration. Alternatively, the nozzles may have different configurations. The cuvette holder may have one or more complementary shapes 5330, which complementary shapes 5330 may be configured to receive the nozzle. The nozzle may engage the carrier by friction and/or vacuum assistance. The nozzle may be used with a vented pipette.

The cuvette holder may interface with one or more cuvettes 5340 or other types of containers. The cuvette may have a configuration as shown in fig. 70A-70B.

The liquid treatment device may also be connected to a series of connected containers. One such configuration is shown in fig. 69, in which a liquid handling device may interface with a pick port 6920 for picking up a strip of containers.

In some embodiments, a micro-container is provided that can be interfaced with a pipette for various processing and analysis functions. In some cases, the various processing and analysis functions may be performed at a point-of-service site.

Pick-up interface

The liquid handling device may be configured for interfacing with a pipette tip or any other component. As previously mentioned, the liquid handling device may comprise a pipette nozzle which may be press-fitted to a pipette tip. Additional devices may be used to connect the pipette tip or other components to the liquid handling equipment, including but not limited to: magnetic elements, fasteners, hook and loop fasteners, elastic elements, tie bars, sliding devices, locking devices, clamps, drive mechanism assemblies, and/or adhesives. The connection of the components or tips may allow the liquid handling device to function as a robot capable of performing one or more liquid handling or non-liquid handling functions. Such functions may include the ability to transmit power to move a tool such as a cassette or other object. When combined with a flexible support (as described above), the device may be able to perform such functions across a large range of movement.

The pipette nozzle may be capable of interfacing with a single tip and/or container. For example, a particular pipette nozzle may be configured to interface with a particular tip and/or container. Alternatively, a single pipette nozzle may be capable of interfacing with multiple tips and/or containers. For example, the same pipette nozzle may be able to interface with both large and small pipette tips and/or containers. Pipette nozzles may be capable of interfacing with tips and/or containers having different configurations, sizes, volumetric capacities, materials, and/or sizes.

In one example, one or more rotating devices may be used. Such rotating means may include screwing the tip onto the pipette nozzle. Such threaded means may employ external and/or internal threads. Fig. 59 includes an example of a threaded arrangement. A pipette nozzle 5900 may be provided. The tip 5910 may be configured for connection to a pipette nozzle. The tip may be connected to the pipette nozzle directly or via the interface 5920. In some cases, the interface may be a nut or other connector. The interface 5920 may be connected to the pipette nozzle 5900 in any manner, including a press fit, screws, or any other connection means described elsewhere herein. Similarly, the interface 5920 may be connected to the cleaner head 5910 by a press fit, screws, or any other connection means described elsewhere herein.

In one example, the pipette tip 5910 may have an external threaded ramp 5930. An interface 5920, such as a nut, may have a complementary internally threaded ramp 5940. In an alternative embodiment, the pipette tip may have an internal threaded ramp and the interface such as a nut may have a complementary external threaded ramp. The pipette tip may be able to be screwed into an interior portion of the interface. A portion of the outer surface of the pipette tip may contact the inner surface of the interface.

In an alternative embodiment, the pipette tip may be capable of being screwed onto an exterior portion of the interface. A portion of the inner surface of the pipette tip may contact the outer surface of the interface. In such embodiments, the interface may have an external thread ramp on its outer surface and/or an internal thread ramp on its outer surface. The pipette tip may accordingly have a complementary internally threaded ramp on its inner surface or a complementary externally threaded ramp on its inner surface.

In additional embodiments, a portion of the surface of the tip may be embedded in the interface, or a portion of the interface may be embedded in the tip.

A portion of the pipette tip may be within the interface or a portion of the pipette tip may be outside the interface. In some embodiments, a portion of the pipette nozzle surface may be embedded within a portion of the interface, or a portion of the interface surface may be embedded within a portion of the pipette nozzle.

The pipette nozzle 5900 may have one or more flanges 5950 or other surface features. Other examples of surface features may include grooves, protrusions, bumps, or channels. The flange may fit into a flange seat of the cleaner head 5910. The flange may fit into the flange seat to prevent rotation. This interface may be configured to prevent rotation of the interface and the tip once the tip is correctly screwed in.

In alternative embodiments, interface 5920 may not be required. The tip can be screwed directly into the pipette nozzle. The suction head can be screwed directly onto the nozzle or into the nozzle. The outer surface of the suction head may contact the inner surface of the nozzle or the inner surface of the suction head may contact the outer surface of the nozzle. In alternative embodiments, a portion of the surface of the tip may be embedded within the pipette nozzle, or a portion of the surface of the pipette nozzle may be embedded within the tip.

The cleaner head may have 1, 2 or more external threaded ramps. Any number of external thread ramps may be provided. 1, 2, 3, 4, 5, 6, 7, 8 or more thread ramps may be provided. The thread ramp may be an external thread ramp, an internal thread ramp, or any combination thereof. The thread ramps may be equally radially spaced apart. The pipette tip may have 1, 2 or more flange seats. 1, 2, 3, 4, 5, 6, 7, 8 or more flange seats may be provided. The flange seats may be radially equally spaced. Alternatively, the spacing between the flange seats may be different. The flange seat may be positioned radially where the threaded ramp touches the tip of the pipette tip. Alternatively, the flange seat may be positioned anywhere about the threaded ramp.

The pipette nozzle may have 1, 2, or more flanges or other surface features described elsewhere herein. 1, 2, 3, 4, 5, 6, 7, 8 or more flanges may be provided. The flanges may be radially equally spaced. Alternatively, the spacing between the flanges may be different. The flange may be configured to fit into the flange seat. In some embodiments, a one-to-one correspondence may be provided between the flange and the flange seat. The first flange may fit into the first flange seat and the second flange may fit into the second flange seat. The flange seat may have a shape complementary to the flange. In some embodiments, the flanges may have the same shape, and the flange seat may fit over any of the flanges. Alternatively, the flanges may have different shapes and/or configurations such that a particular flange seat may correspond to a particular flange.

In alternative embodiments, one or more flanges may be provided within the pipette nozzle. A complementary flange seat may be molded on the pipette nozzle.

The flange may be press-fitted into the flange seat. The connection between the flange and the flange seat may be tight. Alternatively, the connection between the flange and the flange seat may be loose, so that the flange may slide out of the flange seat.

Fig. 60 provides additional examples of nozzle-tip interfaces provided in accordance with the specific examples described herein. The pick-up and interface may use one or more features, characteristics or methods employed in a ball-point pen type configuration. The nozzle 6000 may be arranged to be in contact with the tip 6002. One or more pick-up jaws 6004 may be configured to pick up a tip. The pick-up jaw may have one or more jaw teeth 6006 or other component that may grip or pick up a tip

In some cases, collar 6008 may fit over pickup jaws 6004. The pawl teeth 6006 may extend beyond the collar. The collar may have a jaw compression diameter 6010. The jaws are slidable within the picker collar. Thus, the teeth may extend out from the collar by different amounts. The jaw compression diameter may compress the teeth together. This may enable the teeth to grip an object such as a pipette tip as the collar slides over the teeth.

A ratchet device 6012 may be provided. The ratchet device is slidable over a portion of the pawl. One or more pawl pins 6014 may guide the pawl within the ratchet. For example, the pawl pin may keep the pawl moving longitudinally along the ratchet rather than sliding left and right.

A jaw spring 6016 may be provided, which jaw spring 6016 may assist in providing a force along the jaw in the longitudinal direction. In some cases, a nozzle spring 6018 may be provided that may allow the nozzle to move in the longitudinal direction. Still alternatively, the nozzle spring may have a smaller diameter than the pawl spring. The pawl spring may surround the exterior of a portion of the nozzle. One or more covers 6020 may be provided.

The tip 6002 is accessible to the picker assembly, including nozzle 6000, jaws 6004, collar 6008, lid 6020 and associated parts. The combination may be depressed to pick up engage the tip. One or more teeth 6006 of the pawl may catch on the flange of the tip. The collar may be located partially over the teeth so as to compress the teeth against the cleaner head. During the pickup compression step, the collar may be slid further downwardly to tighten the teeth further around the suction head.

The combination can then be pulled up. The teeth may catch on the flange of the cleaner head during the picker locking step. The nozzle may urge the cleaner head against the teeth to form a seal. The entire combination can be used in the pipetting function. For example, a pipette and attached tip may aspirate, dispense, and/or transfer liquid. During the pipetting function, the claw may be locked in the collar.

To remove the tip, the combination may be pressed down in a discharge engagement step. During the discharge pull-off step, the combination can be lifted and the collar slid upwardly relative to the jaws, thereby allowing the teeth to loosen around the cleaner head. The entire combination can be lifted while the suction head is still lowered, thereby separating the suction head from the picking combination.

Fig. 61 shows an example of an internal thread pick-up interface. The tip 6100 can be screwed into the threaded portion 6110 of the pipette. The part may be a pipette nozzle or an interface between a tip and a pipette nozzle. The tip can include one or more flanges 6120 or other surface features. Any number or configuration of flanges may be provided, as described elsewhere herein. The flange may be engaged by one or more means for rotating the cleaner head about the threaded portion. Alternatively, the threaded portion may be rotated while the cleaner head remains stationary, or it may be secured in place using a flange. The threaded portion can include one or more screws 6130 that can be threaded into the tip. Alternatively, the suction head may comprise one or more screws on its outer surface and may be screwed into the threaded portion. The threaded portion can include one or more fluid passages 6140. The liquid passageway can be brought into liquid communication with the interior 6150 of the tip.

FIG. 62 illustrates an example of an O-ring tip picker. The suction head 6200 can be picked up by a pipette nozzle 6210. A portion of the suction head can fit into a portion of the nozzle. For example, a portion of the outer surface of the cleaner head may contact the inner surface of the nozzle. Alternatively, a portion of the nozzle may fit within a portion of the cleaner head. For example, a portion of the internal surface of the cleaner head may contact the external surface of the nozzle.

The nozzle may have one or more O-rings 6220 that may contact the suction head 6200. The O-ring may be formed of an elastomeric material. An O-ring may be provided around the circumference of the pipette nozzle. Alternatively, the resilient material may be provided and need not be provided around the entire circumference of the pipette nozzle. For example, one or more rubber balls or similar resilient projections may be provided at one or more gaps within the pipette nozzle. The pipette nozzle may have one or more grooves into which one or more O-rings may fit. Alternatively, the cleaner head may have one or more grooves on its outer surface into which one or more O-rings or other material may fit.

A high friction and/or soft material may be provided between a part of the nozzle and/or tip. This may enable the nozzle to be press-fitted into the nozzle or the nozzle to be press-fitted into the nozzle. In some cases, both the nozzle and tip may have an O-ring or type of material. An O-ring ensures a liquid seal between the tip and the nozzle.

The pipette nozzle may have an internal shelf or flat back plate 6230. The flat back plate may provide a physical stop to seat the cleaner head in place.

Fig. 63 provides an example of an expanding/contracting smart material tip picker. The tip 6300 can be picked up by the pipette nozzle 6310. A portion of the suction head is fittable into a portion of the nozzle. For example, a portion of the outer surface of the cleaner head may contact the inner surface of the nozzle. Alternatively, a portion of the nozzle may fit within a portion of the cleaner head. For example, a portion of the internal surface of the cleaner head may contact the external surface of the nozzle.

The nozzle may comprise a collar made of magnetostrictive or electrostrictive smart material that is shrinkable when subjected to a magnetic or electric field, respectively. An electromagnetic coil, a magnetic field, or a power source that generates an electric current may be incorporated to control the contraction and expansion of the material.

To pick up the tip, the nozzle may be lowered around the tip and the collar may be activated, causing the collar to contract and grip the tip. The collar may firmly grip the cleaner head. The contraction of the collar holds the pipette tip sufficiently firmly to ensure a tight liquid seal. To release the tip, the collar may be deactivated to allow it to expand and release the tip.

The pipette nozzle may have an internal shelf or flat backup plate 6320. The flat backup plate may provide a physical barrier to engage the pipette in place.

In an alternative embodiment, the smart material of the nozzle may be inserted into a portion of the tip. The material may be activated to cause the material to expand and grip the tip from within. The material may be deactivated to cause the material to contract and release the tip.

Fig. 64 provides an example of an expanding/contracting elastomeric deflecting tip picker. The tip 6400 can be picked up by the pipette nozzle 6410. A portion of the suction head is fittable into a portion of the nozzle. For example, a portion of the outer surface of the cleaner head may contact the inner surface of the nozzle. Alternatively, a portion of the nozzle may fit within a portion of the cleaner head. For example, a portion of the internal surface of the cleaner head may contact the external surface of the nozzle.

The nozzle may include a hard material 6420 and an elastic material 6430. The hard material may be a hard block or a solid material. The suction head may be surrounded by a resilient material. The rigid mass may reside on a resilient material surrounding the cleaner head.

The driver may provide a force 6440, which 6440 may compress the hard mass 6420. The rigid block may be pressed towards the suction head. Squeezing the slugs may compress the elastomer 6430, causing a bulging effect that may deflate the inner chamber of the elastomer. Contracting the interior chamber may cause the elastomer to firmly grip the tip 6400. Compressing the elastomer in a first direction (e.g., toward the tip) can cause the elastomer to expand in a second direction (e.g., perpendicular to the tip), which can cause compression of the elastomer around the tip.

To unload the tip, the force 6440 may be removed, which may cause the slug to move away from the tip and may release the elastomer from its compressed state.

Fig. 65 provides an example of a vacuum gripper tip picker. A suction head 6500 having a large head 6502 may be provided. The large head may have a large flat surface area.

The suction head is engageable with the nozzle 6510. The nozzle may have one or more holes 6520 therein. In some cases, 1, 2, 3, 4, 5, 6, 7, 8, or more tunnels may be provided through the nozzle. The tunnels may be equally radially spaced, or radially spaced at different intervals. The tunnels may be of the same or different diameters. A first port of the tunnel may be coupled to a pressure source and a second port of the channel may face the head 6502 of the tip. The pressure source may be a negative pressure source. The tunnel may be connected to a region of lower pressure, thereby creating a suction force that may act on the flat head of the tip. The suction force may provide a pulling force which may be applied upwardly to secure the cleaner head to the nozzle.

In some embodiments, an O-ring 6530 may be provided. An O-ring or other resilient member may be located between the nozzle and the head of the cleaner head. One or more recesses or shelves may be provided in the nozzle and/or the cleaner head to accommodate the O-rings. An O-ring may allow a seal to be formed between the nozzle and the cleaner head. This may provide a liquid-tight seal between the liquid path 6540 in the nozzle and the liquid path 6550 in the tip.

To discharge the tip from the nozzle, the tunnel may be disconnected from the source of negative suction pressure. Alternatively, the pressure source itself may be turned off.

Such nozzle-tip connections and interfaces are provided by way of example only. Additional tip-nozzle interfaces and/or variations or combinations of the tip-nozzle interfaces described herein may be implemented.

Modular liquid treatment

In some embodiments, one or more of the liquid treatment device configurations described elsewhere herein can be implemented in a modular fashion. For example, one or more pipette tips may be provided in a modular format. In some embodiments, a single pipette module may have a single pipette tip and/or nozzle thereon. Alternatively, a single pipette module may have 2, 3, 4, 5, 6 or more pipette tips and/or nozzles thereon. Pipette modules may be stacked adjacent to one another to form a multi-head configuration. Individual pipette modules may be removable, replaceable and/or swappable. The individual pipette modules may each have the same configuration or may have different configurations. In some cases, different pipette modules may be swapped out with other pipette modules to provide different functionality.

Fig. 66 provides an example of a pipette module according to specific examples described herein. The pipette module may include a pipette body 6600 mounted on a mount 6610. The mount may include one or more guides 6612, rails, screws, or similar features. The pipette body may be able to slide along a guide rod or similar feature. Any description herein of the guide rod may be applicable to any other feature that can guide the movement of the pipette body. In some cases, the pipette body may be able to move up and/or down along the guide rod relative to the mount.

In some cases, the mount may also include a lead screw 6614. The lead screw may interact with the drive interface 6602 of the pipette body. The drive interface may contact the lead screw so that as the lead screw may be rotated, the drive means may engage with the teeth of the screw and may cause the pipette body to move up or down accordingly. In some embodiments, the drive interface may be a spring-loaded flexure. The spring-loaded flexure may be biased against the screw to provide a firm, flexible contact with the screw. The spring-loaded flexure may be configured for precise motion constraint. The screw is rotatable in response to the drive means. In some embodiments, the drive interface may be connected to the pipette piston by means of a magnet, providing sufficient freedom to limit wear and extend the life of the device. In some embodiments, the drive device may be a motor, which may include any type of motor described elsewhere herein. The motor may be directly connected to the screw or may be connected via a coupling. The drive device may be movable in response to one or more instructions from the controller. The controller may be external to the pipette module or may be provided locally on the pipette module.

The pipette body 6600 can include a casing. Still alternatively, the housing may be a shuttle type clamshell housing. The nozzle 6620 can be attached to a pipette body. The nozzle may extend from the pipette body. In some embodiments, the nozzle may extend downwardly from the pipette body. The nozzle may have a fixed position relative to the pipette body. Alternatively, the nozzle may be extended and/or retracted from the pipette body. The nozzle may have a liquid passageway located therein. The liquid passage may be connected to the pipette piston. Any of the descriptions of the plunger, pressure source, or liquid pathway described elsewhere herein can be used in a modular pipette. In some specific examples, the pipette body may support a motor 6630, a gear train, a valve 6632, a lead screw, a magnetic piston mounting block, a piston chamber block, and a valve mount 6634, and/or other components. One or more of the components described herein may be provided within the casing of the pipette body.

The pipette body may also include a guide rail 6640. The guide rail may allow a portion of the pipette to move relative to the pipette body. In one example, the pipette nozzle may be moved up or down relative to the pipette body. The pipette nozzle may be connected to an inner assembly movable along a guide rail. In some embodiments, the guide 6640 can be configured to interface with another device that can prevent rotation of the pipette body. The guide rail may be constrained by the outer housing, which may constrain rotation about the guide bar.

Fig. 67A shows an example of a modular pipette with a retracted shuttle in a full dispense position. The pipette body 6700 can be in an upward position relative to the seat 6710. The pipette body may include a drive interface 6702 engageable with the lead screw 6714. When the shuttle is retracted, the drive interface may be at the top of the lead screw. The mount may have a guide rod 6712, which guide rod 6712 may assist in guiding the pipette body relative to the mount.

Fig. 67B shows an example of a modular pipette with a lowered shuttle in a full dispense position. The pipette body 6700 can be in a downward position relative to the seat 6710. The pipette body may include a drive interface 6702 engageable with the lead screw 6714. The drive interface may be at the bottom of the lead screw when the shuttle is lowered. The mount may have a guide rod 6712, which guide rod 6712 may assist in guiding the pipette body relative to the mount.

The mounts may be fully retracted, fully lowered, or have any intervening position. The screw can be turned to cause the pipette body to be raised or lowered relative to the mounting. The screw is rotatable in a first direction to cause the pipette body to rise and rotatable in a second direction to cause the pipette body to fall. The screw can stop turning at any point to provide the position of the pipette body. The pipette body may be lowered with the nozzle, which may allow greater complexity with less relative movement.

A plurality of pipette modules may be provided in the liquid handling system. The pipette module may have a fin configuration. A thin fin form factor may be provided so that any number of fins may be stacked side-by-side in a modular fashion to form a pipetting system in which each nozzle may be independently operated or moved. A single fin may be composed of multiple tools (nozzles, end effectors, etc.) that may be selected for a particular operation, thereby minimizing the space required for the overall assembly. In some embodiments, the fins may also function as a freezer, refrigerator, humidifier, and/or incubator for samples and/or reagents held in the containers and/or cassettes.

The plurality of pipette modules may or may not be located adjacent to each other. In some specific examples, pipette modules may be narrow and may be stacked next to each other to form a multi-headed pipette configuration. In some specific examples, the pipette module can have a width of less than or equal to 1 μm, 5 μm, 10 μm, 50 μm, 100 μm, 300 μm, 500 μm, 750 μm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 1cm, 1.5cm, 2cm, 3cm, or 5 cm. Any number of pipette modules can be placed together. For example, 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 12 or more, 15 or more, 20 or more, 25 or more, 30 or more, 50 or more, 70 or more, 100 or more pipette modules may be placed together. Additional pipette modules may be placed individually or together and, in turn, may have different nozzles with different sizes and capacities.

The individual pipette modules may be placed adjacent to each other and may or may not be in contact with each other. The pipette modules placed together may or may not share a common support. The pipette bodies of the pipette module may be capable of moving up or down independently of each other relative to the pipette mount. The nozzle of the pipette module may be capable of being independently extended and/or retracted relative to other pipette modules.

Each pipette module may have the same or different configuration. The pipette nozzles of the pipette nozzles may be identical or may be different. The pipette module may be capable of interfacing with multiple types of tips or with dedicated tips. The pipette modules may have the same or different degrees of sensitivity or coefficient of variation. The pipette modules may have the same or different means for controlling liquid aspiration and/or dispensing (e.g., vented, positive displacement, internal plunger, vertical plunger, horizontal plunger, pressure source). The pipette modules may have the same or different means for picking up or removing tips (e.g., press fit, screw in, smart material, elastomeric material, press fit, or any other interface described elsewhere herein or otherwise).

Modular pipettes may have a motion that can be broken down into multiple functions. For example, the motion can be decomposed into (1) motion of the piston and piston block in the (z) direction to aspirate and dispense liquid, and (2) motion of the shuttle combination in the (z) direction to allow the pipette module to engage with the object at various heights and to provide clearance when moving in the (xy) direction. In some specific examples, the (z) direction may be a vertical direction and the (xy) direction may be a horizontal direction. The movement of the piston and the piston block may be parallel to the movement of the shuttle assembly. Alternatively, the movement of the piston and piston block may be non-parallel and/or perpendicular. In other embodiments, the movement of the piston and piston block and/or the movement of the shuttle combination may be horizontal, or may have any other orientation.

For example, as shown in fig. 66, piston motion can be achieved in a very compact flat package through the use of a horizontal stack of gear trains and lead screws. Constant force, compression or wave springs can be used to eliminate gaps in the combination and thus can provide significantly improved accuracy/precision for aspiration and dispensing. The system may use accurate or very accurate motion constraints with various springs in order to allow the combination to operate accurately even in the presence of errors in the position or size of each individual component.

All components that directly act on the tip, nozzle or piston can be mounted to a single "shuttle assembly" and this entire assembly can move as one piece. The shuttle assembly may include a pipette body 6600 shown in fig. 66. Each component can move with the shuttle assembly, which is distinguishable from conventional pipettes in which only the nozzle moves. This design may allow simple rigid connection of these components to critical piston/nozzle areas without complex linkages or relative movement between several components. It may also provide an extensible "platform" on which future components and functionality may be integrated.

The piston may be enclosed in the cavity. The chamber in which the piston is enclosed may be cut from a single piece of metal and any valves or nozzles may be mounted directly to this piece. This may simplify the installation of components that may be directly involved in pipetting activities and may provide a reliable airtight seal with a small unused volume. This can help to reduce the coefficient of variation of the pipetting. Any coefficient of variation value described elsewhere herein can be achieved by pipette.

The shuttle combination may be intentionally under constrained in rotation about the shuttle guide rod. This can help to tolerate misalignment in the device, as the shuttle can have sufficient freedom to pivot from side to side (e.g., xy-plane) into any position required to engage with the tip or other interface object.

The components of the shuttle assembly may be enclosed in two "clamshell components". Some, more than half, or all of the components of the shuttle assembly may be housed within the clamshell member. The clamshell member may comprise two symmetrical halves leading to a shuttle housing that may hold the assembly in place. It may also include a single half with a deep slot for assembly installation and a flat second half that completes the process of holding the assembly in place. The portions of the clamshell member may or may not be symmetrical, or may not have the same thickness. These designs may allow combinations to include a large number of small components without requiring complex mounting methods for each component. The design of the clamshell member may also allow for the following assembly methods: where the assemblies can simply be discharged to their correct position and then the second halves of the clamshells can be brought into position and fastened, locking everything in place. Furthermore, this geometry lends itself to a method of integrating a PCB wiring board directly into a clamshell housing assembly to facilitate wiring of the components within the device.

Any description of the clamshell can be applied to the multi-part housing or shell of the shuttle assembly. The housing of the shuttle assembly may be formed from 1, 2, 3, 4, 5, 6, 7, 8 or more parts joined together to form the housing. A clamshell member may be an example of a two-part shuttle housing. The portions of the clamshell member may or may not be connected by hinges. Portions of the clamshell member can be separated from one another.

In some embodiments, each nozzle/tip/piston/shuttle may be combined into a single module (or fin) that is very thin and flat. This may allow several tabs to be stacked on top of each other at a set distance to create any size pipette. As desired, a desired number of tabs may be stacked together, which may allow the pipette to be increased or decreased as desired. This modular approach may provide great flexibility in mechanical design, as it breaks down functionality and components into interchangeable parts. It also enables the modular assembly in this design to be quickly adapted and integrated into new pipette systems; thus, the same basic modular components may be able to accomplish a wide variety of tasks with different requirements. The modularity of functionality also enables more efficient device protocols due to the rapid and independent nozzle and piston controls carried on each pipette fin. This design may provide an advantage in servicing the device, as having a defective tab that can be independently exchanged without having to require an entire new pipette. One or more of the flaps may be independently movable and/or removable relative to the other positions.

Container/tip

The system may comprise one, two or more vessels and/or tips or may comprise a device that may comprise one, two or more vessels and/or tips. One or more modules of the apparatus may comprise one, two or more vessels and/or tips.

The container may have an inner surface and an outer surface. The container may have a first port and a second port. In some specific examples, the first port and the second port may be opposite to each other. The first port or the second port may be open. In some embodiments, the container may have an open first port and a closed second port. In some embodiments, the container may have one or more additional ends or projections, which may be open or closed. In some embodiments, the container may be used to house a substrate plate for an assay or reaction. In other embodiments, the base plate itself may function as a container, thereby eliminating the need for a separate container.

The container may have any cross-sectional shape. For example, the container may have a circular cross-sectional shape, an elliptical cross-sectional shape, a triangular cross-sectional shape, a square cross-sectional shape, a rectangular cross-sectional shape, a trapezoidal cross-sectional shape, a pentagonal cross-sectional shape, a hexagonal cross-sectional shape, or an octagonal cross-sectional shape. The cross-sectional shape may remain constant along the entire length of the container or may vary.

The container can have any cross-sectional dimension (e.g., diameter, width, or length). For example, the cross-sectional dimension can be less than or equal to about 0.1mm, 0.5mm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm, 4.5mm, 5mm, 6mm, 7mm, 8mm, 9mm, 1cm, 1.2cm, 1.5cm, 2cm, or 3 cm. The cross-sectional dimension may refer to the internal or external dimension of the container. The cross-sectional dimension may remain constant along the entire length of the container or may vary. For example, an open first port may have a larger cross-sectional dimension than a closed second port, or vice versa.

The container can have any height (where height can be a dimension in a direction orthogonal to the cross-sectional dimension). For example, the height can be less than or equal to about 0.1mm, 0.5mm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm, 4.5mm, 5mm, 6mm, 7mm, 8mm, 9mm, 1cm, 1.2cm, 1.5cm, 2cm, 3cm, 4cm, 5cm, 6cm, 7cm, 8cm, 9cm, or 10 cm. In some embodiments, the height may be measured between the first port and the second port of the container.

The interior of the container can have a volume of about 1000 μ L or less, 500 μ L or less, 250 μ L or less, 200 μ L or less, 175 μ L or less, 150 μ L or less, 100 μ L or less, 80 μ L or less, 70 μ L or less, 60 μ L or less, 50 μ L or less, 30 μ L or less, 20 μ L or less, 15 μ L or less, 10 μ L or less, 8 μ L or less, 5 μ L or less, 1 μ L or less, 500nL or less, 300nL or less, 100nL or less, 50nL or less, 10nL or less, 1nL or less, 500pL or less, 250pL or less, 100pL or less, 50pL or less, 10pL or less, 5pL or less, or 1L or less.

One or more walls of the container may have the same thickness or a thickness that varies along the height of the container. In some cases, the thickness of the wall may be less than and/or equal to about 1 μm, 3 μm, 5 μm, 10 μm, 20 μm, 30 μm, 50 μm, 75 μm, 100 μm, 200 μm, 300 μm, 400 μm, 500 μm, 600 μm, 700 μm, 800 μm, 900 μm, 1mm, 1.5mm, 2mm, or 3 mm.

One or more containers may be provided that may have the same shape and/or size or different shapes and/or sizes.

The container may be formed from a single unitary piece. Alternatively, the container may be formed from two or more container parts. The two or more container parts may be permanently attached to each other or may be selectively detachable from each other. The container may include a body and a lid. Alternatively, some containers may include only a body.

The container can be configured to contain and/or confine the sample. The container may be configured to engage with a liquid handling system. Any liquid handling system known in the art, such as a pipette, or the specific examples described elsewhere herein may be used. In some specific examples, the container may be configured to engage with a tip connectable to a liquid handling device (such as a pipette). The container may be configured to receive at least a portion of the tip in the interior of the container. The tip may be at least partially inserted into the vessel. In some embodiments, the tip may be configured to enter the container directly against the bottom of the container. Alternatively, the tip may be configured not to be inserted more than partially into the vessel.

The container material may be of different types depending on the properties required for the respective process. Materials may include, but are not limited to: polymers, semiconductor materials, metals, organic molecules, ceramics, composites, laminates, and the like. The material may be rigid or soft, or capable of being transformed between the two. The container material may include, but is not limited to, polystyrene, polycarbonate, glass, metal, acrylic, semiconductor materials, etc., and may include one of several types of coatings. By introducing functionalized pores in the vessel wall, the vessel material is permeable to the selective species. This allows certain molecular species to pass through the material. The container material may also be coated to prevent absorption of substances such as water. Other coatings may be used to achieve specific optical properties, such as transmission, reflection, fluorescence, and the like.

The containers may have different geometries including, but not limited to, rectangular, cylindrical, hexagonal, and may include, depending on the application, properties such as, but not limited to, perforations, permeable membranes, particulates, or gels. The container may contain micro-liquid channels or circuits, which in turn are on a silicon substrate plate.

The container may also be active and perform a set of tasks. The container may comprise an active conveyor for pumping the liquid/suspension through the membrane/barrier.

The container may be designed to have specific optical properties-transparent, opaque, fluorescent, or other properties associated with any portion of the electromagnetic spectrum. By designing the material to absorb strongly in the infrared portion of the electromagnetic spectrum, the vessel can be designed to act as a locally heated reactor.

The container walls may be designed to respond to different electromagnetic radiation by absorption, scattering, interference, etc. The combination of optical properties and embedded sensors may result in the container being able to act as a self-contained analyzer-for example, a light sensitive material on the container wall and embedded sensors may transform the container into a spectrophotometer capable of measuring changes in the optical signal.

In some embodiments, the container may be considered a smart container that can change its properties by "sampling" the surrounding liquid. The container may allow preferential ion transfer between cells-similar to cells, signaling through electrical and/or chemical triggers. They may also affect the containment of the liquid within in response to external and/or internal stimuli. The change in size/shape of the container may also be caused in response to the stimulus. The container may be adaptive in response to external or internal stimuli and may support reflex detection by altering assay dynamic range, signal strength, etc.

The container may also be embedded with or have embedded therein different sensors, such as environmental (temperature, humidity, etc.), optical, acoustic or electromagnetic sensors. The container may be fitted with a tiny wireless camera to transmit information in real time about its contents, or alternatively about the process taking place therein. Alternatively, the container may contain one or more probes of another type that wirelessly transmit data to the central processor.

The containers can be designed in a range of different volumes, ranging from a few microliters to a few milliliters. Processing liquids across different lengths and time scales involves manipulating and/or utilizing various forces — hydrodynamic, inertial, gravitational, surface tension, electromagnetic, and the like. The container may be designed to utilize certain forces rather than others in order to manipulate the liquid in a particular manner. Examples include the use of surface tension in a capillary to transfer liquid. Operations such as mixing and separation require different strategies depending on the volume-the container can be designed to specifically utilize certain forces. Mixing is particularly important when dealing with small volumes because of the absence of inertial forces. Novel mixing strategies, such as the use of magnetic particles under external forces, shear induced mixing, etc., can be employed to achieve efficient mixing.

The container provides flexibility over microfluidic chips due to its inherent flexibility in handling small and large volumes of liquid. The intelligent design of these containers allows a wider range of volumes/sizes to be handled than microfluidic devices. Additionally, the container may utilize forces not available with microfluidic devices — thereby providing greater flexibility in processing. The container may also provide the ability to dynamically change dimensions by switching to different sizes. In the concept of "smart containers", the same container can vary in volume and other physical properties to handle liquids with different forces. Such actuation may be programmed and actuated externally, or initiated by a change in the internal liquid.

The functionality of the container may exceed liquid containment-different containers may communicate via surface features or external drives and participate in liquid/species transport across container boundaries. The container thus becomes a carrier for liquid containment, handling and transport-similar to a cell. The container may be fused in response to an external drive and/or internal liquid composition change. In this specific example, the container can be regarded as a functional unit, which is capable of performing one or several specialized functions — separation, such as isoelectric focusing, dialysis, etc. The container may be used to sample certain liquids and generate information regarding conversion, endpoint, etc.

The container can act as a self-contained analysis unit with built-in detectors and information exchange means (by sensors and transmitters embedded inside the container wall). The container walls may be made of conventional materials and/or organic semiconductor materials. The container may be integrated with other sensors/actuators and interfaced with other containers. In this particular example, the container may be considered a system capable of housing, processing, measuring, and communicating.

The container may also have sample extraction, collection and liquid transfer functionality. In this embodiment, the container will behave like a pipette stored in the cartridge and be able to transfer liquid to a specific location. Examples include virus transport media for nucleic acid amplification assays, where a container is used to both collect and transport the virus transport media. Another example is a cuvette protruding from the device for the purpose of collecting a finger prick sample.

The container may be designed to hold/process a variety of sample types including, but not limited to, blood, urine, feces, and the like. Different sample types may require changes in container characteristics-material, shape, size, etc. In some embodiments, the container performs sample collection, processing, and analysis of the contained sample.

The container or sub-container may be sealed or otherwise contain reagents therein. The pipette may take action when needed, such as by breaking a seal containing the reagent, to release the reagent from the container for a chemical reaction or other process. The container may be composed of glass or other materials. Reagents that would otherwise be absorbed into a conventional polymer tip or degrade when exposed to the environment may require such separation or sealing in the container.

The container (e.g., a pipette tip) may have an inner surface and an outer surface. A container (e.g., a pipette tip) may have a first port and a second port. In some specific examples, the first port and the second port may be opposite to each other. The first port and/or the second port may be open. The container (e.g., a pipette tip) may include a passageway connecting the first port and the second port. In some embodiments, a vessel (e.g., a pipette tip) may include one or more additional ends or projections. For example, a vessel (e.g., a pipette tip) may have a third end, a fourth end, or a fifth end. In some embodiments, one or more additional ends may be open or closed, or any combination thereof.

The container (e.g., tip) can have any cross-sectional shape. For example, the container may have a circular cross-sectional shape, an elliptical cross-sectional shape, a triangular cross-sectional shape, a square cross-sectional shape, a rectangular cross-sectional shape, a trapezoidal cross-sectional shape, a pentagonal cross-sectional shape, a hexagonal cross-sectional shape, or an octagonal cross-sectional shape. The cross-sectional shape may remain constant along the entire length of the vessel (e.g., tip) or may vary.

The vessel (e.g., tip) can have any cross-sectional dimension (e.g., diameter, width, or length). For example, the cross-sectional dimension can be less than or equal to about 0.1mm, 0.5mm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm, 4.5mm, 5mm, 6mm, 7mm, 8mm, 9mm, 1cm, 1.2cm, 1.5cm, 2cm, or 3 cm. The cross-sectional dimension may refer to an internal dimension or an external dimension of a vessel (e.g., a pipette tip). The cross-sectional dimension may remain constant along the entire length of the vessel (e.g., tip) or may vary. For example, the open first port may have a larger cross-sectional dimension than the open second port, or vice versa. The ratio of the cross-sectional dimensions of the first port to the second port may be less than and/or equal to about 100:1, 50:1, 20:1, 10:1, 5:1, 4:1, 3:1, 2:1, 1:2, 1:3, 1:4, 1:5, 1:10, 1:20, 1:50, or 1: 100. In some embodiments, the change in cross-sectional dimension may change at different rates.

The vessel (e.g., tip) can have any height (where the height can be a dimension in a direction orthogonal to the cross-sectional dimension). For example, the height can be less than or equal to about 0.1mm, 0.5mm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm, 4.5mm, 5mm, 6mm, 7mm, 8mm, 9mm, 1cm, 1.2cm, 1.5cm, 2cm, 3cm, 4cm, 5cm, 6cm, 7cm, 8cm, 9cm, or 10 cm. In some embodiments, the height may be measured between the first port and the second port of the tip.

The interior of the vessel (e.g., tip) can have a volume of about 1000. mu.L or less, 500. mu.L or less, 250. mu.L or less, 200. mu.L or less, 175. mu.L or less, 150. mu.L or less, 100. mu.L or less, 80. mu.L or less, 70. mu.L or less, 60. mu.L or less, 50. mu.L or less, 30. mu.L or less, 20. mu.L or less, 15. mu.L or less, 10. mu.L or less, 8. mu.L or less, 5. mu.L or less, 1. mu.L or less, 500. mu.L or less, 300. mu.L or less, 100. nL or less, 50. mu.L or less, 50. nL or less, 10. nL or less, 1. nL or less, 500. pL or less, 250pL or less, 100pL or less, 50pL or less, 10pL or less, 5pL or less, or 1pL or less.

One or more walls of the vessel (e.g., the tip) may have the same thickness or a thickness that varies along the height of the vessel (e.g., the tip). In some cases, the thickness of the wall may be less than and/or equal to about 1 μm, 3 μm, 5 μm, 10 μm, 20 μm, 30 μm, 50 μm, 75 μm, 100 μm, 200 μm, 300 μm, 400 μm, 500 μm, 600 μm, 700 μm, 800 μm, 900 μm, 1mm, 1.5mm, 2mm, or 3 mm.

One or more containers (e.g., tips) may be provided that may be of the same shape and/or size or of different shapes and/or sizes. Any of the embodiments described herein can have one or more features of a container and/or tip as described elsewhere herein.

The cleaner head may be formed from a single integral piece. Alternatively, the tip may be formed from two or more tip pieces. The two or more tip parts may be permanently attached to each other or may be selectively detachable from each other. It is also possible to physically integrate chemical components or sensors into the tip, effectively enabling complete laboratory detection on a vessel (e.g., a tip). The vessels (e.g., tips) may each individually provide different preparation, assay, or detection functions. A vessel (e.g., a tip) may provide multiple functions or all functions within a single vessel or tip.

The container (e.g., a tip) may be formed of a material that may be rigid, semi-rigid, or soft. The vessel (e.g., tip) may be formed of a material that is electrically conductive, insulative, or contains embedded materials/chemical components/etc. The containers (e.g., tips) can be formed of the same material or different materials. In some embodiments, the container (e.g., tip) may be formed from a transparent, translucent, or opaque material. The internal surfaces of the pipette tip may be coated with reagents that are released into the liquid; such reactants may be plate coated, lyophilized, and the like. The vessel (e.g., tip) may be formed of a material that allows the detection unit to detect one or more signals associated with a sample or other liquid within the vessel (e.g., tip). For example, the vessel (e.g., tip) may be formed of a material that allows one or more electromagnetic wavelengths to pass therethrough. Examples of such electromagnetic wavelengths may include visible light, IR, far IR, UV, or any other wavelength along the electromagnetic spectrum. The material may allow a selected wavelength or one or more ranges of wavelengths to pass through. Examples of wavelengths are provided elsewhere herein. The vessel (e.g., tip) may be transparent to allow optical detection of the sample or other liquid contained therein.

The vessel (e.g., a tip) may form a waveguide. The vessel (e.g., a pipette tip) may allow light to pass vertically through. The vessel (e.g., a tip) may allow light to pass along the length of the vessel. The vessel (e.g., a tip) may allow light to enter and/or travel at any angle. In some embodiments, a vessel (e.g., a tip) may allow light to enter and/or travel at a selected angle or range of angles. The container and/or tip may form one or more optical instruments that may focus, collimate and/or disperse light.

The material may be chosen to be impermeable to one or more liquids. For example, the material may be impermeable to the sample and/or the reagent. The material may be selectively permeable. For example, the material may allow air or other selected liquids to pass through.

Examples of materials used to form the container and/or tip may include: functionalized glass, Si、Ge、GaAs、GaP、SiO₂、SiN₄Modified silicon, or any of a wide range of gels or polymers, such as (poly) tetrafluoroethylene, (poly) vinylidene fluoride, polystyrene, polycarbonate, polypropylene, polymethyl methacrylate (PMMA), ABS, or combinations thereof. In one embodiment, the assay unit can comprise polystyrene. The material may comprise any form of plastic or acrylic. The material may be silicon-based. Other suitable materials may be used in accordance with the present invention. Any of the materials described herein, such as those suitable for use in tips and/or vessels, can be used to form the assay unit. Transparent reaction sites may be advantageous. Further, in the case where there is a light transmissive window allowing light to reach the light detector, the surface may advantageously be opaque and/or preferably light scattering.

The container and/or tip may have the ability to sense the level of liquid therein. For example, the vessel and/or tip may have a capacitive sensor or manometer. The container may employ any other technique known in the art to detect the level of liquid within the container. The container and/or the tip may be able to sense the liquid level with high accuracy. For example, the container and/or tip may be capable of detecting a liquid level with an accuracy of about 1nm, 5nm, 10nm, 50nm, 100nm, 150nm, 300nm, 500nm, 750nm, 1 μm, 3 μm, 5 μm, 10 μm, 50 μm, 75 μm, 100 μm, 150 μm, 200 μm, 250 μm, 300 μm, 400 μm, 500 μm, 600 μm, 700 μm, 800 μm, 900 μm or within 1 mm.

The tip may assist in the dispensing and/or aspiration of the sample. The tip can be configured to selectively contain and/or confine a sample. The tip may be configured to engage with a liquid handling device. Any liquid handling system known in the art, such as a pipette, or the specific examples described elsewhere herein may be used. The tip is connectable to a liquid handling device to form a liquid tight seal. In some embodiments, the tip is insertable into a vessel. The tip may be at least partially inserted into the vessel. The tip may include a surface shape or characteristic that may determine how far the tip may be inserted into the vessel.

The container and/or tip may be formed separately and may be separable from each other. The vessel and/or the tip may be independently movable relative to each other. Alternatively, two or more vessels and/or tips may be connected to each other. They may share a common support. For example, the two or more containers and/or tips may be cut from the same material — e.g., into a common base plate. In another example, two or more containers and/or tips may be directly coupled adjacent to each other such that they are in direct contact with each other. In yet another example, one or more coupling assemblies may couple two or more containers and/or tips together. Examples of coupling assemblies may include rods, straps, chains, rings, springs, plates, or blocks. The coupled containers and/or tips may form a strip, an array, a curve, a circle, a honeycomb, staggered rows, or any other configuration. The container and/or the connection may be formed of an optically transparent, translucent, and/or opaque material. In some cases, the material may prevent light from entering the container and/or the space within the cavity. Any discussion herein of containers and/or tips may be applicable to cuvettes, and vice versa. The cuvette may be one type of container.

Fig. 69 provides an example of a container strip. The container strip provides an example of a plurality of containers that may be commonly coupled. The container strip 6900 can have one or more cavities 6910. The cavity may receive a sample, liquid, or other substance directly therein, or may receive a container and/or tip that may be configured to confine or receive a sample, liquid, or other substance therein. The cavities may form rows, arrays, or any other arrangement as described elsewhere herein. The cavities may be connected to each other via the container strip body.

The container strip may include one or more pick-up interfaces 6920. The pick-up interface may engage a sample processing device, such as a liquid processing device. The pick-up interface may interface with one or more pipette nozzles. Any of the interface configurations described elsewhere herein may be used. For example, the pipette nozzle may be press fit into the pick-up interface. Alternatively, the pick-up interface may interface with one or more other components of the pipette.

The container strip may be useful for colorimetric analysis or cell counting. The container strip may be useful for any other analysis described elsewhere herein.

Fig. 70A and 70B provide another example of a cuvette 7000. The cuvette provides an example of a plurality of channels that may be coupled together. The cuvette holder may have a body formed from one, two or more parts. In one example, the cuvette may have a top body portion 7002a and a bottom body portion 7002 b. The top body portion may have one or more surface features thereon, such as cavities, channels, grooves, passages, voids, pits, or any other surface features. The bottom body portion need not include any surface features. The bottom body portion may be a solid portion without a cavity. The top and bottom body portions may be joined together to form a cuvette body. The top and bottom body portions may have the same footprint or may have different footprints. In some cases, the top body portion may be thicker than the bottom body portion. Alternatively, the bottom body portion may be thicker than or equal to the top body portion.

The cuvette 7000 may have one or more cavities 7004. The cavity may receive a sample, liquid or other substance directly therein. The cavities may form rows, arrays, or any other arrangement as described elsewhere herein. The cavities may be connected to each other via the cuvette body. In some cases, the bottom of the cavity can be formed by bottom body portion 7002 b. The walls of the cavity may be formed by the top body portion 7002 a.

The cuvette may also include one or more fluidly connected cavities 7006. The cavity may be configured to receive a sample, liquid, or other substance therein, or may receive a container and/or tip (e.g., a cuvette) that may be configured to confine or receive a sample, liquid, or other substance therein. The cavities may form rows, arrays, or any other arrangement as described elsewhere herein. The cavities can be in fluid connection with each other via a passage 7008 through the cuvette body.

The passageway 7008 may connect two cavities, three cavities, four cavities, five cavities, six cavities, seven cavities, eight cavities, or more cavities. In some embodiments, multiple vias may be provided. In some cases, a portion of the passageway can be formed by the top body portion 7002a and a portion of the passageway can be formed by the bottom body portion 7002 b. The passageways may be oriented in a non-parallel (e.g., parallel) direction to the orientation of the cavity 7006 to which they are connected. For example, the passageways may be horizontally oriented and the cavities may be vertically oriented. Alternatively still, the passageway may allow liquid to flow from one chamber to another chamber in fluid connection.

The cuvette may include one or more pickup interfaces. Still alternatively, the pickup interface may be one or more cavities 7004, 7006 of the cuvette. The pick-up interface may engage a sample processing device, such as a liquid processing device. The pick-up interface may interface with one or more pipette nozzles. Any interface configuration described elsewhere herein may be used. For example, the pipette nozzle may be press fit into the pick-up interface. Alternatively, the pick-up interface may interface with one or more other components of the pipette.

Cuvettes may be useful for colorimetric analysis or cell counting. The cuvette may be useful for any other analysis described elsewhere herein.

The cuvette may be formed of any material, including those described elsewhere herein. Still alternatively, the cuvette may be formed of a transparent, translucent, opaque material, or any combination thereof. The cuvette may prevent the chemicals contained therein from passing through from one cavity to another.

Figure 71 shows an example of a cleaner head according to one embodiment described herein. The tip 7100 may be capable of interfacing with a miniature card, cuvette holder, and/or tape, including any of the examples described herein.

The tip may include a narrow section 7102 in which a sample may be stored, a sample volume region 7104, and/or a nozzle insertion region 7106. In some cases, the tip may comprise one or more of said zones. The sample storage area may have a smaller diameter than the sample volume area. The sample volume region may have a smaller volume than the nozzle insertion region. The sample storage area may have a smaller volume than the nozzle insertion area.

In some embodiments, a flange 7108 or surface may be provided at the end of the nozzle insertion region 7106. The flange may protrude from a surface of the nozzle insertion region.

The cleaner head may include one or more attachment regions such as a funnel-shaped region 7110 or a stepped region 7112 which may be provided between various types of regions. For example, a funnel-shaped region may be provided between the sample storage region 7102 and the sample volume region 7104. A stepped region 7112 may be provided between the sample volume region 7104 and the nozzle insertion region. Any type of connection region may or may not be provided between the connection regions.

The sample storage area may comprise an opening through which liquid may be drawn and/or dispensed. The nozzle insertion region may comprise an opening into which the pipette nozzle may be inserted in turn or alternatively. Any type of nozzle-tip interface as described elsewhere herein may be used. The opening of the nozzle insertion region may have a larger diameter than the opening of the sample storage region.

The pipette tip may be formed of a transparent, translucent and/or opaque material. The cleaner head may be formed from a stiff or semi-stiff material. The tip may be formed from any of the materials described elsewhere herein. The tip may or may not be coated with one or more reagents.

The tip may be used for nucleic acid detection or any other detection, assay and/or process described elsewhere herein.

FIG. 72 provides an example of detecting a strip. The detection strip may include a detection strip body 7200. The detection strip body may be formed of a solid material, or may be formed of a hollow shell or any other configuration.

The detection strip may include one or more cavities 7210. In some embodiments, the cavities may be provided as rows in the body. The cavities may in turn be provided in rows, in arrays (e.g., m x n arrays, where m, n are integers greater than zero, including but not limited to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or more). The cavities may be positioned in staggered rows, concentric circles, or any other arrangement.

The cavity may receive a sample, liquid, or other substance directly therein, or may receive a container and/or tip that may be configured to confine or receive a sample, liquid, or other substance therein. The cavity can be configured to receive a tip, such as the tip illustrated in fig. 71, or any other tip and/or container described elsewhere herein. The detection strip may in turn be a nucleic acid detection strip, which may be configured to receive and support a nucleic acid tip.

The cavity may have a tapered opening. In one example, the cavity can include a top portion 7210a and a bottom portion 7210 b. The top portion may be tapered and may have a larger opening than the bottom portion.

In some specific examples, the cavity may be configured to receive a pipette nozzle for drawing. One or more pipette nozzles may engage with one or more cavities of the detection strip. 1, 2, 3, 4, 5, 6 or more pipette nozzles may simultaneously engage with corresponding cavities of the detection strip. The tapered opening of the cavity may be useful for nozzle extraction. The pipette nozzle may be press fit into the cavity or may interface with the cavity in any other manner described herein.

One or more samples and/or reagents may be provided in the detection strip. The detection strip may have a narrow profile. Multiple detection strips may be positioned adjacent to each other. In some cases, a plurality of detection strips adjacent to each other may form an array of cavities. The detection strips may be swapped out for the modular configuration. The detection strips and/or reagents may be movable independently of each other. The detection strip may have different samples therein that may need to be maintained under different conditions and/or delivered to different parts of the facility on different schedules.

Fig. 73 shows another example of detecting a strip. The detection strip may have a body 7300. The body may be formed from a single unitary piece or multiple pieces. The body may have a molded shape. The body may be formed of a plurality of circular parts 7310a, 7310b connected to each other or various shapes connected to each other. The bodies of the circular elements may be directly connected to each other or one or more strips or spaces may be provided between the bodies.

The detection strip may include one or more cavities 7330. In some embodiments, the cavities may be provided as rows in the body. The cavities may in turn be provided in rows, in arrays (e.g., m x n arrays, where m, n are integers greater than zero, including but not limited to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, or more). The cavities may be positioned in staggered rows, concentric circles, or any other arrangement.

The cavity may receive a sample, liquid, or other substance directly therein, or may receive a container and/or tip that may be configured to confine or receive a sample, liquid, or other substance therein. The cavity can be configured to receive a tip, such as the tip illustrated in fig. 71, or any other tip and/or container described elsewhere herein. The detection strip may additionally or alternatively be a nucleic acid detection strip which may be configured to receive and support a nucleic acid tip.

Sensing strip body 7330 may be molded around cavity 7330. For example, if the cavity has a circular cross-section, the detection strip body portions 7310a, 7310b around the cavity may have a circular cross-section. Alternatively, the detection strip body need not match the cavity shape.

In some embodiments, the detection strip may include an external pick-up socket 7320. One or more pipette nozzles may engage one or more external pick-up receptacles of the detection strip. 1, 2, 3, 4, 5, 6 or more pipette nozzles may simultaneously engage with corresponding pick-up receptacles of the detection strip. The pick-up socket may have one or more cavities 7340 or through-holes that may be capable of interfacing with a pipette nozzle. The pipette nozzle may be press fit into the cavity or may interface with the receptacle in any other manner described herein.

One or more samples and/or reagents may be provided in the detection strip. The one or more samples may be directly within the cavity or may be provided in a tip and/or container that may be placed in the cavity of the detection strip. The detection strip may have a narrow profile. Multiple detection strips may be positioned adjacent to each other. In some cases, a plurality of detection strips adjacent to each other may form an array of cavities. The detection strips may be swapped out for the modular configuration. The detection strips may be movable independently of each other. The detection strip and/or reagents may have different samples therein that may need to be maintained under different conditions and/or transported to different parts of the apparatus on different schedules.

Nucleic acid container/tip

Fig. 24 illustrates an example of a container provided in accordance with one specific example described herein. In some cases, the container may be useful for isothermal and non-isothermal nucleic acid assays (such as, but not limited to, LAMP, PCR, real-time PCR) or other nucleic acid assays. Alternatively, the container may be used for other purposes.

The container can include a body 2400 configured to receive and confine a sample, wherein the body includes an inner surface, an outer surface, an open end 2410, and a closed end 2420. The container may be configured to engage with a pipette. The container may include a soft material 2430 extending across a cross-section of the container. The flexible material may extend across the open end of the container.

The soft material may or may not have slits, holes or other forms of openings. The flexible membrane may be configured to prevent liquid from passing through the flexible membrane when there is no object inserted through the slit. In some embodiments, the soft material may be a film. The soft material may be a spacer formed of a silicon-based material or any elastic or deformable material. In some embodiments, the soft material may be a self-healing material. An object such as a suction head may be inserted through the soft material. The tip may be inserted through a slit or opening in the soft material or may penetrate the soft material. Figure 24 shows an example of a tip inserted through a flexible material into a vessel from an external view and a cross-sectional view. Insertion of the tip may allow a sample to be dispensed to and/or aspirated from the container through the tip. When the tip is removed, the flexible membrane may be re-sealed, or the slit may be sufficiently closed to prevent liquid from passing through the flexible membrane.

The body of the container may have a first open end 2410 and a second closed end 2420. The first port may have a larger cross-sectional dimension, such as a diameter, than the cross-sectional dimension of the second port. The closed end may have a tapered shape, a circular shape, or a flat shape.

In some specific examples, the body of the container can have a cylindrical portion 2440 of a first diameter having an open end 2442 and a closed end 2444, and a funnel portion 2450 contacting the open end, wherein one end of the funnel portion can contact the open end and can have a first diameter, and a second port 2452 of the funnel portion can have a second diameter. In some embodiments, the second port of the funnel portion can contact another cylindrical portion 2460 having two open ends and can have a second diameter. In some embodiments, the second diameter may be larger than the first diameter. Alternatively, the first diameter may be larger than the second diameter. In some embodiments, the open end of the container body can be configured to engage with the removable cap 2470. In some embodiments, the end of the additional cylindrical portion or the second port of the funnel portion may be configured to engage with the cap.

In some embodiments, the container can also include a cap 2470. The cover may be configured to contact the body at the open end of the body. In some embodiments, at least a portion of the cover may extend into the interior of the body, or may surround a portion of the body. Alternatively, a portion of the body may extend into the interior of the cover, or may surround a portion of the cover. The cover may have two or more ends. In some embodiments, one, two, or more ends may be open. For example, the cap may have a first port 2472 and a second port 2474. The passageway may extend through the cover. The diameter of the cap may remain constant along the entire length of the cap. Alternatively, the diameter of the cap may vary. For example, the end of the cap further from the body may have a smaller diameter than the end of the cap to be engaged with the body.

A soft membrane 2430 may be provided within the body of the container. Alternatively, the flexible membrane may be provided within the lid of the container. The flexible membrane may be sandwiched between the body and the lid of the container. In some cases, the flexible membrane may be provided within both the body and the lid of the container, or a plurality of flexible membranes may be provided, which may be distributed in any manner between the body and the lid of the container. In some embodiments, the body may include an inner portion through which the soft material extends, or the cover may include a passage through which the soft material extends.

One or more tips may be inserted into the vessel. In some embodiments, the tip may be specifically designed for insertion into a nucleic acid container. Alternatively, any of the tips described elsewhere herein can be inserted into a nucleic acid container. In some cases, a pipette tip may be inserted into a nucleic acid container.

The suction head 2480 can have a lower portion 2482 and an upper portion 2484. The lower portion may have an elongated shape. The lower portion may have a smaller diameter than the upper portion. One or more connection features 2486 can be provided between the lower and upper portions.

The lower portion of the pipette tip may be at least partially inserted into the container. The tip may be inserted through the lid of the vessel and/or through the flexible material of the vessel. The pipette tip is accessible inside the container body. The tip may pass through a slit or opening in the flexible material. Alternatively, the tip may pierce through the soft material.

In some embodiments, the tip and/or the container may have any other type of barrier that reduces contamination. The barrier may comprise a soft material or film, a film, an oil (e.g., mineral oil), a wax, a gel, or any other material that may prevent a sample, liquid, or other substance contained within the tip and/or container from passing through the barrier. The barrier may prevent contamination of the environment, atomisation and/or evaporation of material from the tip and/or the container, and/or contamination of other parts of the apparatus. The barrier may allow a sample, liquid, or other substance to pass through the barrier only under desired conditions and/or times.

Fig. 25 illustrates an example of a container provided in accordance with another specific example described herein. In some cases, the container can be used for isothermal and non-isothermal nucleic acid assays (e.g., LAMP, PCR, real-time PCR) or other nucleic acid assays. Alternatively, the container may be used for other purposes. The container may or may not include the features or characteristics of the container described elsewhere herein.

The container can include a body 2500 configured to receive and confine a sample, where the body includes an inner surface, an outer surface, a first port 2510, and a second port 2520. In some embodiments, one or more of the ends may be open. One or more of the ends may be closed. In some embodiments, the first port may be open and the second port may be closed. A passageway may extend between the first port and the second port.

The container can include a material 2530 extending across the passageway, the material capable of having (1) a first state configured to prevent liquid from passing through the material when no object is inserted into the material, and (2) a second state configured to prevent liquid and objects from passing through the material. The first state may be a molten state and the second state may be a solid state. For example, when in a molten state, the material may allow the tip to pass through while preventing liquid from passing through. The liquid may be dispensed and/or aspirated through the tip through the material. When the material is in a molten state, the tip may be capable of being inserted through and removed from the material. When in the solid state, the material may be sufficiently firm to prevent passage of the tip therethrough, and may prevent passage of liquid therethrough.

In some embodiments, the material may be formed from wax. The material may have a selected melting point. For example, the material has a melting point less than and/or equal to about 30 ℃, 35 ℃, 40 ℃, 45 ℃, 50 ℃, 55 ℃, 60 ℃, 65 ℃, 70 ℃, or 75 ℃. The material may have a melting point between 50 and 60 ℃. When the temperature of the material is sufficiently high, the material may enter a molten state. When the temperature of the material is reduced sufficiently, the material may solidify into a solid state.

When an object, such as a tip, is removed from a vessel through a material, a portion of the object may be coated with the material. For example, if the tip is inserted into molten wax and then removed from the wax, the portion of the tip inserted into the wax may be wax coated upon removal. This advantageously seals the pipette tip and reduces or prevents contamination. Additionally, the seal may prevent biohazardous or chemically hazardous materials from escaping the container.

Fig. 25A shows an example of a nucleic acid amplification/wax combination container. The container may have a wax barrier 2530 and an aqueous or lyophilized reagent 2550. The barrier may comprise melted wax placed over the reagent where it solidifies at the transport/storage temperature.

Fig. 25B shows a second step of heating the container to melt the wax and prepare the sample. A pipette/nozzle 2540 may be used to place the container on the heating block. Other means known in the art may be used to deliver heat to the wax. A wax barrier 2530 may be provided in which the wax melts during the heating step. An aqueous or lyophilized reagent 2550 may be provided under the wax barrier.

Fig. 25C shows the step of introducing a sample to the container. A tip 2560 (such as a pipette tip) can penetrate the melted wax barrier 2530. An aqueous or lyophilized reagent 2550 may be provided below the barrier. The pipette tip may contain a DNA sample 2570 that can be deposited under a wax layer. The wax layer is stored under the wax layer to prevent pollution. The sample containing DNA may be deposited in a reagent layer. Alternatively still, the tip may have a portion coated with wax when the tip is removed from the vessel.

Fig. 25D shows the amplification step. A wax barrier 2530 may be provided over reagent and sample layer 2550. The wax may remain as a molten barrier during amplification. Amplification may be performed under a wax layer during the assay. Turbidity or other readings may be taken during or after amplification to indicate the level of product.

Fig. 25E illustrates the wax solidification step after amplification. A wax barrier 2530 may be provided over reagent and sample layer 2550. After taking the assay reading, the container can be cooled and the wax can resolidify, thereby providing an containment barrier for DNA generated by nucleic acid amplification (e.g., PCR, real-time PCR, LAMP).

Fig. 25F shows the step of removing the container. A pipette/nozzle 2540 may be used to remove a fully contained used container. The container may contain a solidified wax barrier 2530. The container may also contain nucleic acid amplification products 2550 ready for disposal. The pipette/nozzle may remove the container from the heating block or may move the container to another part of the apparatus.

The pipette/nozzle may engage the container through the open end of the container. In some embodiments, the pipette/nozzle may form a seal with the container. The pipette/nozzle may be press fit into the container. Alternatively, additional means may be used to allow the pipette/nozzle to be selectively engaged and/or disengaged from the container.

Centrifugal vessel/tip

Fig. 26 illustrates an example of a container provided in accordance with one particular example described herein. In some cases, the container may be used for centrifugation. The container may be configured for insertion into a centrifuge. Any centrifuge known in the art may be used. Examples of centrifuges are described in more detail elsewhere herein. The container may be a centrifuge container. Alternatively, the container may be used for other purposes.

The container can comprise a body 2600 configured to receive and confine a sample, wherein the body comprises an inner surface, an outer surface, a first port 2608, and a second port 2610. In some embodiments, one or more of the ends may be open. One or more of the ends may be closed. In some embodiments, the first port may be open and the second port may be closed. A passageway may extend between the first port and the second port.

One or more ends 2610 of the container may be rounded, tapered, flat, or have any other geometry. In some embodiments, the cross-sectional dimension of the container, such as the diameter, may vary across the length of the container. In some cases, the lower portion 2620 of a container having a closed end can have a smaller diameter than the other upper portion 2630 of the container closer to the open end. In some embodiments, one or more additional portions 2640 of the container can be provided, which additional portions 2640 can be located between the lower and upper portions. In some embodiments, the one or more additional portions may have a diameter intermediate the diameter of the lower portion and the upper portion. One or more funnel-shaped regions 2650, stepped regions or ridges 2660 may connect portions of different diameters. Alternatively, the portions may gradually transition to have different diameters. In some embodiments, the open end of the container may have a larger cross-sectional dimension than the closed end of the container.

The container that interfaces with the centrifuge can be used for several purposes beyond conventional separation. The container that interfaces with the centrifuge may be designed for separation or for a particular assay. Examples of assays that can be performed using a centrifuge include erythrocyte sedimentation rate, erythrocyte antibody screening, and the like. Containers for these applications may be specialized with embedded sensors/detectors and the ability to transmit data. Examples include tips with built-in cameras that can transfer images during red blood cell stacking. The centrifuge vessel may also be designed to be optimized for centrifugal mixing through the use of magnetic and/or non-magnetic beads. Centrifugation of the cuvette allows for forced flow inside the small channel, which may be useful for applications such as liquid focusing and size-based separation. The container may also be designed to handle volumes much smaller than conventional centrifuges, where the container design is critical to avoid destroying delicate biological species such as cells. The centrifuge container may also be equipped with features to prevent fogging without the need to cap the entire centrifuge.

In one specific example, the container may be considered a two-piece component having a top feature that acts as a closure for preventing any liquid loss from the container in aerosol form. Alternatively, the container may be equipped with a duck-nozzle septum valve to prevent aerosol leakage.

Figure 26 also illustrates a cleaning head provided in accordance with one embodiment described herein. The tip may be used to dispense and/or aspirate a sample or other liquid from the container. The tip may be configured to be at least partially inserted into a vessel. In some embodiments, the tip may be a centrifuge extraction tip.

The tip can be configured to receive and confine a sample, where the tip comprises an inner surface, an outer surface, a first port 2666, and a second port 2668. In some embodiments, one or more of the ends may be open. In some embodiments, the first port and the second port may be open. A passageway may extend between the first port and the second port.

One or more of the tips 2668 may be rounded, tapered, flat, or have any other geometry. In some embodiments, the cross-sectional dimension of the tip, such as the diameter, may vary across the length of the tip. In some cases, the lower portion 2670 of the cleaner head at the second port may have a smaller diameter than the other upper portion 2675 of the cleaner head closer to the first port. In some embodiments, one or more additional portions 2680 of the tip may be provided, and the additional portions 2680 may be located between the lower portion and the upper portion. In some embodiments, the one or more additional portions may have a diameter between the diameter sizes of the lower and upper portions. One or more funnel-shaped regions 2690, stepped regions or ridges 2695 may connect portions of different diameters. Alternatively, the portions may gradually transition to have different diameters. In some embodiments, the first port of the cleaner head may have a larger cross-sectional dimension than the second port of the cleaner head. In some embodiments, the lower portion of the cleaner head may be narrow and may have a substantially similar diameter along the entire length of the cleaner head.

The tip may be configured to extend into the vessel through the open end of the vessel. The second port of the pipette tip is insertable into the container. The tip of a tip having a smaller diameter may be inserted through the open end of the container. In some embodiments, the tip may be fully inserted into the container. Alternatively, the pipette tip may be only partially inserted into the container. The tip may have a greater height than the container. A portion of the tip may project beyond the container.

The container or the tip may include a raised surface feature that prevents the second port of the tip from contacting the bottom of the interior surface of the closed end of the container. In some embodiments, the raised surface features may be at or near the closed end of the container. In some embodiments, the raised surface features may be located along the bottom half of the container, the bottom 1/3 of the container, the bottom 1/4 of the container, the bottom 1/5 of the container, the bottom 1/10 of the container, the bottom 1/20 of the container, or the bottom 1/50 of the container. The raised surface features may be located on an inner surface of the container. Alternatively, the raised surface features may be located on the outer surface of the cleaner head. In some cases, the raised surface features may be located on both the interior surface of the vessel and the exterior surface of the tip.

In some embodiments, the raised surface features may include one or more bumps, ridges, or steps. For example, the container may include surface features integrally formed on the bottom interior surface of the container. The surface features may include 1, 2, 3, 4, 5, 6, or more bumps on the bottom interior surface of the container. The surface features may be evenly spaced apart from each other. For example, the protuberances or other surface features may be provided in a radial pattern. The bumps or other surface features may be continuous or intermittent around the interior surface of the container or other surface of the tip.

Alternatively, the raised surface features may be part of the shape of the container or tip. For example, the containers may be formed with different inner diameters and the tips may be formed with different outer diameters. In some embodiments, the interior surface of the vessel may form a step on which the tip may be placed. The profile of the vessel and/or tip may be shaped such that: so that the tip is prevented from contacting the bottom of the vessel based on the internal and external cross-sectional dimensions of the vessel and tip.

The container and/or the tip may be shaped to prevent rocking of the tip within the container when the tip has been inserted to its furthest reach. Alternatively, the vessel and tip may be moulded to allow some oscillation. In some embodiments, the tip can form a seal with the container when the tip is fully inserted into the container. Alternatively, there is no need to form a seal between the tip and the vessel.

In some embodiments, the tip can be prevented from contacting the bottom of the vessel by a desired amount. This gap allows free flow of liquid between the tip and the container. This gap prevents liquid blockage between the tip and the container. In some embodiments, the tip may be prevented from contacting the bottom of the vessel to provide the tip at a desired height along the vessel. In some embodiments, one or more components of a liquid or sample within a container may be separated, and a tip may be positioned to dispense and/or aspirate a desired component of the liquid or sample. For example, a portion of the container where the liquid or sample has a higher density may be provided to the bottom of the container, and a portion having a lower density may be provided to the upper portion of the container. Depending on whether the tip is to draw or deliver liquid or sample to the higher density portion or the lower density portion, the tip may be positioned accordingly closer to the bottom and/or upper portion of the vessel.

In some embodiments, the centrifugation vessel and/or the tip may be provided with other features that may allow for liquid flow between the tip and the vessel at a desired height along the vessel. For example, the cleaner head may comprise one or more openings, passages, slots, channels or ducts connecting an outer surface of the cleaner head with the passage of the cleaner head between the first and second ports. The opening may allow liquid to flow even if the tip of the tip contacts the bottom of the container. In some embodiments, a plurality of openings may be provided along the height of the cleaner head. One or more openings may be provided along the height of the tip to allow liquid to flow over a desired height within the vessel.

The tip may be configured to perform chromatography. In this process, the mixture is dissolved in a liquid called the "mobile phase" which carries the mixture through a structure that holds another material called the "stationary phase". The various components of the mixture travel at different speeds, causing them to separate. Separation is based on differential partitioning between the mobile and stationary phases. Slight differences in the partition coefficients of the compounds lead to differential retention on the stationary phase and thus to variations in separation. The tip may be configured to perform size exclusion chromatography, in which molecules in solution are separated by their size rather than by molecular weight. This may include gel filtration chromatography, gel permeation chromatography. The tip may be configured to enable measurement of the mass-to-charge ratio of charged particles to perform mass spectrometry. That is, the process ionizes chemicals to generate charged molecules, and the ions are then separated according to their mass-to-charge ratio, possibly by an analyzer using an electromagnetic field. The tip may act as an electrode.

Systems and devices provided herein, such as POINT OF service systems (including modules), are configured for use with containers and tips provided in U.S. patent publication No. 2009/0088336 ("MODULAR POINT-OF-CARE DEVICES, SYSTEMS, AND USES theof"), which is incorporated herein by reference in its entirety.

Positive displacement suction head

FIG. 27 also illustrates a suction head 2700 provided in accordance with one embodiment described herein. The tip may be used to dispense and/or aspirate a sample or other liquid from the container. The tip may be capable of providing and/or drawing an accurate and precise amount of liquid, with high sensitivity. The tip may be configured to be at least partially inserted into a vessel. In some embodiments, the tip may be a positive displacement tip.

The tip can be configured to receive and confine a sample, where the tip comprises an inner surface, an outer surface, a first port 2702, and a second port 2704. In some embodiments, one or more of the ends may be open. In some embodiments, the first port and the second port may be open. A passageway may extend between the first port and the second port.

The one or more ends 2704 of the tip may be rounded, tapered, flattened, or have any other geometry. In some embodiments, the cross-sectional dimension of the tip, such as the diameter, may vary across the length of the tip. In some cases, the lower portion 2710 of the tip at the second port may have a smaller diameter than the other upper portion 2720 of the tip that is closer to the first port. In some embodiments, one or more additional portions 2730 of the tip may be provided, and the additional portions 2730 may be located between the lower portion and the upper portion. In some embodiments, the one or more additional portions may have a diameter intermediate the diameter of the lower portion and the upper portion. One or more funnel-shaped regions 2740, stepped regions, or ridges 2750 may connect various portions of different diameters. Alternatively, the portions may gradually transition to have different diameters. In some embodiments, the first port of the cleaner head may have a larger cross-sectional dimension than the second port of the cleaner head. In some embodiments, the lower portion of the cleaner head may be narrow and may have a substantially similar diameter along the entire length of the cleaner head.

In some embodiments, a plunger 2760 can be provided, and the plunger 2760 can be at least partially insertable into a positive displacement pipette tip. In some embodiments, the size and/or shape of the tip may be shaped such that: so that the plunger can be blocked from reaching all the way to the second port of the cleaner head. In some embodiments, the pipette tip may be blocked by the interior shelf 2770. The suction head is prevented from entering the lower part 2710 of the suction head. The tip 2765 of the plunger may be rounded, tapered, flat, or have any other geometry.

The plunger may be configured to be moveable within the tip. The plunger is movable along the height of the pipette tip. In some specific examples, the plunger may be movable to dispense and/or aspirate a desired volume of sample or other liquid.

Positive displacement pipette tips may have an internal volume that may be capable of receiving any volume of liquid. For example, a positive displacement tip can have an internal volume that can comprise less than and/or equal to about 1nL, 5nL, 10nL, 50nL, 100nL, 500nL, 1 μ L, 5 μ L, 8 μ L, 10 μ L, 15 μ L, 20 μ L, 30 μ L, 40 μ L, 50 μ L, 60 μ L, 70 μ L, 80 μ L, 100 μ L, 120 μ L, 150 μ L, 200 μ L, 500 μ L, or any other volume described elsewhere herein.

The tip may incorporate one or more features of a positive displacement tip as described elsewhere herein.

Additional vessel/tip

Figure 28 illustrates an example of a cavity provided in accordance with one embodiment described herein. The cavity may be an example of a container. In some cases, the chamber may be used for various assays. The chamber may be configured to contain and/or confine one or more reagents. In some embodiments, one or more reactions may occur within the chamber. Alternatively, the cavity may be used for other purposes. In some embodiments, a plurality of cavities may be provided. In some embodiments, 384 chambers may be provided. For example, the cavities may be provided in one or more rows, one or more columns, or an array. The cavities may have a diameter of 4.5 μm and may be provided with 384 intervals. Alternatively, the pockets may have any other spacing or size.

The chamber can comprise a body configured to receive and confine a sample, wherein the body comprises an inner surface, an outer surface, a first port 2806, and a second port 2808. In some embodiments, one or more of the ends may be open. One or more of the ends may be closed. In some embodiments, the first port may be open and the second port may be closed. A passageway may extend between the first port and the second port.

One or more of the ends 2808 of the pockets may be rounded, tapered, flattened, or have any other geometry. In some embodiments, the cross-sectional dimension of the container, such as the diameter, may vary across the length of the container. Alternatively, the cross-sectional dimensions of the vessel need not vary greatly. The container size may gradually transition to have a different diameter. In some embodiments, the open end of the container may have a larger cross-sectional dimension than the closed end of the container. Alternatively, the open end and the closed end of the container may have substantially similar or identical cross-sectional dimensions.

In some embodiments, one or more ends of the cavity may have a flange 2810, a ridge, or similar surface features. In some embodiments, a flange may be provided at or near the open end of the cavity. A flange may be provided on the outer surface of the cavity. In some embodiments, the flange may engage a shelf that may support the pocket. In some embodiments, the flange may engage a lid that may cover the cavity. Capillaries and cuvettes are special cases of liquid containment/processing units, as they are designed for specific tasks. Capillaries in the systems provided herein (e.g., blood-metering capillaries) can utilize only capillary forces to transfer liquid to a particular location. The cuvettes use a combination of capillary and/or external forces to transport the liquid in specially designed channels. The cuvettes and capillaries may be surface treated or processed to enhance certain properties such as optical clarity, surface tension, or for addition or coating of other substances such as anticoagulants, proteins, and the like. Different types of beads may be used in conjunction with a particular container to further expand and/or enhance processing in the container. Examples include the following: a) beads may be used to enhance mixing; b) magnetic beads with coated antibodies can be used. Bead separation is achieved by an external EM field; c) non-magnetic beads can be used as affinity columns; d) ordinary beads, such as polystyrene beads, can be functionalized to capture specific targets; and e) long-chain PEG beads can be used to make the wirelike structure.

FIG. 29 also illustrates a cleaner head 2900 provided in accordance with one embodiment described herein. The tip may be a bulk handling tip that may be used to dispense and/or aspirate a sample or other liquid. The tip may be configured for at least partial insertion into a vessel. Alternatively, the tip may be configured to dispense and/or aspirate a sample or other liquid sample without being inserted into the container.

The tip can be configured to receive and confine a sample, wherein the tip comprises an inner surface, an outer surface, a first port, and a second port. In some embodiments, one or more of the ends may be open. In some embodiments, the first port and the second port may be open. A passageway may extend between the first port and the second port.

One or more of the ends of the cleaner head may be rounded, tapered, flattened, or have any other geometry. In some embodiments, the cross-sectional dimension of the tip, such as the diameter, may vary across the length of the tip. In some cases, the lower portion 2910 of the tip at the second port may have a smaller diameter than the other upper portion 2920 of the tip closer to the first port. In some embodiments, one or more additional portions 2930 of the cleaner head may be provided, said additional portions 2930 being positionable between said lower and upper portions. In some embodiments, the one or more additional portions may have a diameter intermediate the diameter of the lower portion and the upper portion. One or more funnel-shaped regions, stepped regions or ridges 2940 may connect the various portions of different diameters. Alternatively, the portions may gradually transition to have different diameters. In some embodiments, the first port of the cleaner head may have a larger cross-sectional dimension than the second port of the cleaner head. In some embodiments, the lower portion of the cleaner head may have a gradually changing diameter. In some embodiments, a large difference in diameter may be provided along the length of the lower portion of the tip. Bulk handling tips can have a larger internal volume than one or more of the other types of tips described herein.

Figure 30 shows another example of a suction head 3000 provided according to one embodiment described herein. The tip may be an assay tip (i.e., a chromogenic tip) configured to provide a colorimetric reading that may be used to dispense and/or aspirate a sample or other liquid. The chromogenic tip can be read using a detection system. The detection system may be incorporated from any of the specific examples described in more detail elsewhere herein. The tip may be configured for at least partial insertion into a vessel.

The tip can be configured to receive and confine a sample, wherein the tip comprises an inner surface, an outer surface, a first port, and a second port. In some embodiments, one or more of the ends may be open. In some embodiments, the first port and the second port may be open. A passageway may extend between the first port and the second port.

One or more of the ends of the cleaner head may be rounded, tapered, flattened, or have any other geometry. In some embodiments, the cross-sectional dimension of the tip, such as the diameter, may vary across the length of the tip. In some cases, the lower portion 3010 of the tip at the second port may have a smaller diameter than the other upper portion 3020 of the tip closer to the first port. In some embodiments, one or more additional portions 3030 of the cleaner head may be provided, said additional portions 3030 being located between said lower and upper portions. In some embodiments, the one or more additional portions may have a diameter intermediate the diameter of the lower portion and the upper portion. One or more funnel shaped regions 3040, stepped regions, or ridges 3050 may connect portions of different diameters.

Alternatively, the portions may gradually transition to have different diameters. In some embodiments, the first port of the cleaner head may have a larger cross-sectional dimension than the second port of the cleaner head. In some embodiments, a relatively narrow lower portion of the cleaner head may be provided. The cross-sectional diameter of the lower portion need not be substantially changed or varied. The lower part of the tip may be readable using a detection system. The detection system may be capable of detecting one or more signals relating to the sample or other liquid in the tip.

Fig. 31 provides a suction head 3100 provided in accordance with another specific example described herein. The tip may be a blood tip that may be used to dispense and/or aspirate a sample or other liquid. The tip may be configured for at least partial insertion into a vessel. The tip can be configured as a "dip stick" that can be used to rapidly probe multiple targets, such as by using a thin-tipped probe functionalized with reagents. In some embodiments, the liquid contained within the blood tip may be blood.

The tip can be configured to receive and confine a sample, wherein the tip comprises an inner surface, an outer surface, a first port, and a second port. In some embodiments, one or more of the ends may be open. In some embodiments, the first port and the second port may be open. A passageway may extend between the first port and the second port.

One or more of the ends of the cleaner head may be rounded, tapered, flattened, or have any other geometry. In some embodiments, the cross-sectional dimension of the tip, such as the diameter, may vary across the length of the tip. In some cases, the lower portion 3110 of the nozzle at the second port may have a smaller diameter than the other upper portion 3120 of the nozzle closer to the first port. In some embodiments, one or more additional portions 3130 of the cleaner head may be provided, which additional portion 3130 may be located between the lower and upper portions. In some embodiments, the one or more additional portions may have a diameter intermediate the diameter of the lower portion and the upper portion. One or more funnel-shaped regions 3140, stepped regions or ridges 3150 may connect portions of different diameters. Alternatively, the portions may gradually transition to have different diameters. In some embodiments, the first port of the cleaner head may have a larger cross-sectional dimension than the second port of the cleaner head. In some embodiments, the lower portion of the cleaner head may have a gradually changing diameter. In some embodiments, a large difference in diameter may be provided along the length of the lower portion of the tip.

FIG. 32 provides a pipette tip 3200 according to yet another embodiment described herein. The tip may be a current reaction tip that may be used to dispense and/or aspirate a sample or other liquid. The tip may be configured for at least partial insertion into a vessel. In some embodiments, one or more reactions may occur within the tip.

The tip can be configured to receive and confine a sample, wherein the tip comprises an inner surface, an outer surface, a first port, and a second port. In some embodiments, one or more of the ends may be open. In some embodiments, the tip may not completely close the passageway. For example, a slot pin array may pick up liquid and deliver it to a pipette by a dipping method. In some embodiments, the first port and the second port may be open. A passageway may extend between the first port and the second port.

One or more of the ends of the cleaner head may be rounded, tapered, flattened, or have any other geometry. In some embodiments, the cross-sectional dimension of the nozzle, such as the diameter, may vary across the length of the nozzle. In some examples, the lower portion 3210 of the tip exiting the second port may have a smaller diameter than the other upper portion 3220 of the tip closer to the first port. In some embodiments, one or more additional portions 3230 of the tip may be provided, and the additional portion 3230 may be located between the lower portion and the upper portion. In some embodiments, the one or more additional portions may have a diameter intermediate the diameter of the lower portion and the upper portion. One or more funnel-shaped regions, stepped regions or ridges 3240 may connect the various portions of different diameters. Alternatively, the portions may gradually transition to have different diameters. In some embodiments, the first port of the cleaner head may have a larger cross-sectional dimension than the second port of the cleaner head. In some embodiments, the lower portion of the cleaner head may have a gradually changing diameter, or may have substantially the same diameter.

For example, additional tips are provided in U.S. patent publication No. 2009/0088336 ("MODULAR POINT-OF-CAREDEVICES, SYSTEMS, AND USES THEREOF"), which is incorporated herein by reference in its entirety.

Mini suction head

FIG. 33 illustrates an example of a mini-tip nozzle 3300 and mini-tip 3310 provided in accordance with one specific example described herein.

The mini-tip nozzle 3300 may be configured to interface with the mini-tip 3310. In some embodiments, a mini-tip nozzle may be connected to the mini-tip. The mini-tip may be attachable and detachable from the mini-tip nozzle. The mini-tip nozzle may be at least partially inserted into the mini-tip. The mini-tip nozzle may form a liquid-tight seal with the mini-tip. In some embodiments, the mini-tip nozzle may include a sealing O-ring 3320 or other sealing feature on its outer surface. In other embodiments, the mini-tip may include a sealing O-ring or other sealing feature within its interior surface.

The mini-tip nozzle may be configured for interfacing with a liquid handling device such as a pipette. In some embodiments, the mini-tip nozzle may be directly connected to a liquid handling device nozzle or orifice. The mini-tip nozzle may form a fluid tight seal with the fluid handling device. In other embodiments, the mini-tip nozzle may be attached to a tip or other intermediate structure that may be connected to a liquid handling device.

FIG. 34 illustrates an example of a mini-tip provided in accordance with one embodiment described herein. For example, according to one specific example described herein, a single mini-tip can be used to contain, dispense, and/or aspirate volumes less than and/or equal to about 1pL, 5pL, 10pL, 50pL, 100pL, 300pL, 500pL, 750pL, 1nL, 5nL, 10nL, 50nL, 75nL, 100nL, 125nL, 150nL, 200nL, 250nL, 300nL, 400nL, 500nL, 750nL, 1 μ L, 3 μ L, 5 μ L, 10 μ L, or 15 μ L. The mini-tip may also be used for any other volume as described elsewhere herein.

The mini-tip can be configured to receive and confine a sample, wherein the mini-tip comprises an inner surface 3402, an outer surface 3404, a first port 3406, and a second port 3408. In some embodiments, one or more of the ends may be open. In some embodiments, the first port and the second port may be open. A passageway may extend between the first port and the second port.

The one or more ends 3408 of the mini-tip may be rounded, tapered, flat, or have any other geometry. In some embodiments, the cross-sectional dimension, such as the diameter, of the mini-tip may vary across the length of the tip. In some examples, the lower portion 3410 of the tip at the second port can have a smaller diameter than the other upper portion 3420 of the tip closer to the first port. In some embodiments, one or more additional portions of the cleaner head may be provided, which additional portions may be located between the lower portion and the upper portion. In some embodiments, the one or more additional portions may have a diameter intermediate the diameter of the lower portion and the upper portion. Alternatively, no intermediate additional portion is provided between the lower and upper portions. One or more funnel-shaped regions, stepped regions, or ridges 3430 may connect the various portions of different diameters. Alternatively, the portions may gradually transition to have different diameters. In some embodiments, the first port of the cleaner head may have a larger cross-sectional dimension than the second port of the cleaner head. In some embodiments, the lower portion of the cleaner head may have a gradually changing diameter, or may have substantially the same diameter. The container may be covered by a rigid and/or porous and/or semi-permeable barrier in order to prevent atomization, evaporation, etc. of the liquid, thereby preventing any contamination of the device. The container can be designed with the ability to handle small volumes (less than 10uL) of liquid in the POS device, thereby reducing sample requirements. The container may be designed not only to contain liquids, but also to serve as a place to perform unit operations involving small volumes of liquids, including, but not limited to: separation, mixing, reaction, and the like. The container may be designed with specific surface properties and/or characteristics to enable the performance of a particular process. Dispersing unit operations among individual containers will result in reduced sample waste, lower resources/lower consumption, and more efficient execution of chemical processes.

Miniature card

FIG. 35 provides an example of a miniature card according to one embodiment described herein. The microcard may include one or more substrate plates 3500 configured to support one or more tips, which in turn may alternatively be mini-tips or containers, used interchangeably herein. The tip or container may have the characteristics or specifications of any other tip or container described elsewhere herein.

The miniature card may in turn either form a cassette or be included within a cassette. The cartridge may be insertable into and/or removable from the sample processing device. The microcard may be insertable into and/or removable from the sample processing device.

The base plate may have a substantially planar configuration. In some embodiments, the base plate may have an upper surface and a lower surface. The upper and lower surfaces may have a planar configuration. Alternatively, the upper and/or lower surfaces may have a curved surface, a ridged surface, or other surface features. The upper surface and the opposing lower surface may be parallel to each other. Alternatively, the upper and lower surfaces may have a configuration in which they are not parallel to each other. In some embodiments, the planar base plate may have a plurality of wells or cavities.

The base plate may have any shape known in the art. For example, the base plate may have a substantially square or rectangular shape. Alternatively, the base plate may have a circular, elliptical, triangular, trapezoidal, parallelogram, pentagonal, hexagonal, octagonal or any other shape.

The base plate can have any lateral dimension (e.g., diameter, width, length). In some specific examples, the one or more transverse dimensions can be about 0.1mm, 0.5mm, 1mm, 5mm, 7mm, 1cm, 1.5cm, 2cm, 2.5cm, 3cm, 3.5cm, 4cm, 4.5cm, 5cm, 5.5cm, 6cm, 6.5cm, 7cm, 7.5cm, 8cm, 9cm, 10cm, 11cm, 12cm, 13cm, 15cm, or 20 cm. The lateral dimensions may be the same or may be different.

The base plate may have any height (where height may be a dimension in a direction orthogonal to the lateral dimension). For example, the height may be less than or equal to about 0.1mm, 0.5mm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm, 4.5mm, 5mm, 6mm, 7mm, 8mm, 9mm, 1cm, 1.2cm, 1.5cm, 2cm, 2.5cm, 3cm, 4cm, or 5 cm.

The base plate may be formed of any material. The base plate may be formed of a hard, semi-hard or soft material. In some specific examples, the base plate comprises a metal such as aluminum, steel, copper, brass, gold, silver, iron, titanium, nickel, or any alloy or combination thereof, or any other metal described elsewhere herein. In other specific examples, the base plate may comprise silicon, plastic, rubber, wood, graphite, diamond, resin, or any other material, including but not limited to those materials described elsewhere herein. One or more surfaces of the base plate may or may not be coated with a material. For example, one or more portions of the chamber may be coated with a rubber material which can grip the container and/or tip and prevent them from slipping.

The base plate may be substantially solid or hollow. The base plate may be formed from a solid material having one or more cavities provided therein. Alternatively, the base plate may have a shell-like structure. The base plate may comprise a cage or mesh structure. The base plate may include one or more components that may couple the cavities together. The linkage assembly may include a rod, chain, spring, plate, block, or any other assembly.

The base plate may be configured to support one or more tips or vessels. The base plate 3500 may include one or more cavities 3510, the cavities 3510 configured to receive one or more tips or containers. The cavities may have any arrangement on the base plate. For example, the cavities may form one or more rows and/or one or more columns. In some embodiments, the cavities may form an array of m x n, where m, n are integers. Alternatively, the cavities may form staggered rows and/or columns. The cavities may form straight lines, bend lines, concentric patterns, random patterns, or have any other configuration known in the art.

Any number of cavities may be provided on the base plate. For example, greater than and/or equal to about 1 cavity, 4 cavities, 6 cavities, 10 cavities, 12 cavities, 24 cavities, 25 cavities, 48 cavities, 50 cavities, 75 cavities, 96 cavities, 100 cavities, 125 cavities, 150 cavities, 200 cavities, 250 cavities, 300 cavities, 384 cavities, 400 cavities, 500 cavities, 750 cavities, 1000 cavities, 1500 cavities, 1536 cavities, 2000 cavities, 3000 cavities, 3456 cavities, 5000 cavities, 9600 cavities, 10000 cavities, 20000 cavities, 30000 cavities, or 50000 cavities may be provided on a single substrate board of a microcard.

The cavities may all be the same size and/or shape, or may be different. In some embodiments, the cavity may extend partially into the base plate without breaching the base plate. The cavity may have an inner wall and a bottom surface. Alternatively, the cavity may extend through the base plate. The cavity may or may not have a bottom surface or a partial bottom surface or shelf.

The cavity may have any geometry. For example, the cross-sectional shape of the cavity can include a circle, an ellipse, a triangle, a quadrilateral (e.g., square, rectangle, trapezoid, parallelogram), a pentagon, a hexagon, an octagon, or any other shape. The cross-sectional shape of the cavity may remain constant or vary along the height of the cavity. The cross-sectional shape of the cavities may be the same for all cavities on the base plate or may vary between cavities on the base plate. The cross-sectional shape of the cavity may or may not be complementary to the external shape of the vessel and/or tip. The cavity may be formed as a receptacle or may be formed by a cuvette or may have a format similar to a microtiter plate.

The cavity can have any cross-sectional dimension (e.g., diameter, width, or length). For example, the cross-sectional dimension can be greater than or equal to about 0.1mm, 0.5mm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm, 4.5mm, 5mm, 6mm, 7mm, 8mm, 9mm, 1cm, 1.2cm, 1.5cm, 2cm, or 3 cm. The cross-sectional dimension may refer to the internal dimension of the cavity. The cross-sectional dimension may remain constant along the entire height of the cavity or may vary. For example, the open upper portion of the cavity may have a larger cross-sectional dimension than the closed bottom portion.

The cavity can have any height (where height can be a dimension in a direction orthogonal to the cross-sectional dimension). For example, the height may be less than or equal to about 0.1mm, 0.5mm, 1mm, 1.5mm, 2mm, 2.5mm, 3mm, 3.5mm, 4mm, 4.5mm, 5mm, 6mm, 7mm, 8mm, 9mm, 1cm, 1.2cm, 1.5cm, 2cm, 3cm, 4cm, or 5 cm. The height of the cavity may be less than the thickness of the base plate. Alternatively, the height of the cavity may be equal to the thickness of the base plate when the cavity extends all the way through.

The bottom of the cavity may have any shape. For example, the bottom of the cavity may be rounded, flat or tapered. The bottom of the cavity may be complementary to a portion of one or more of the containers and/or tips. The bottom of the cavity may be complementary to the lower part of one or more of the containers and/or tips. In some embodiments, the cavity can contain one or more surface features that can allow the cavity to engage with a plurality of containers and/or mini-tips. Different containers and/or tips may engage different surfaces or portions of the cavity. Alternatively, the cavity may be shaped to receive a particular container and/or tip.

The interior of the cavity can have a volume of about 1000 μ L or less, 500 μ L or less, 250 μ L or less, 200 μ L or less, 175 μ L or less, 150 μ L or less, 100 μ L or less, 80 μ L or less, 70 μ L or less, 60 μ L or less, 50 μ L or less, 30 μ L or less, 20 μ L or less, 15 μ L or less, 10 μ L or less, 8 μ L or less, 5 μ L or less, 1 μ L or less, 500nL or less, 300nL or less, 100nL or less, 50nL or less, 10nL or less, or 1nL or less.

The cavity may be shaped to accommodate a particular tip or container. In some embodiments, the cavity is shapeable for accommodating a plurality of different types of tips and/or containers. The cavity may have an inner surface. At least a portion of the interior surface may contact the container and/or the tip. In one example, the cavity may have one or more shelves or internal surface features that may allow a first container/tip having a first configuration to fit within the cavity and a second container/tip having a second configuration to fit within the cavity. The first and second container/tips, which have different configurations, may contact different portions of the interior surface of the cavity.

In some embodiments, the cavity can receive one or more containers and/or mini-tips. The container and/or the tip may be snap-fitted into the cavity. Alternatively, the container and/or mini-tip may slide smoothly into and out of the cavity, may be press fit into the cavity, may twist into the cavity, or may have any other interaction with the cavity.

Alternatively, the cavity need not receive a container and/or a tip. The chamber itself may form a container that may contain and/or confine one or more liquids. For example, the chamber itself may be a sample container, or may contain any other liquid, including reagents. The cavity may be designed such that light does not pass through the cavity. In some cases, the liquid or selected chemical does not pass through the chamber walls.

The cavities may all have openings on the same side of the base plate. In some embodiments, the cavities may all be open to the upper surface of the base plate. Alternatively, some of the cavities may be open to the lower surface of the base plate and/or the side surfaces of the base plate.

In some embodiments, the cavities may be formed using photolithography, etching, laser etching, drilling, machining, or any other technique known in the art. The cavities may be cut into the base plate.

One or more containers and/or mini-tips may be inserted into the cavity. A single cavity may be configured to receive a single container and/or tip. Alternatively, a single cavity may be configured to receive multiple containers and/or mini-tips simultaneously. The cavities may all be filled with containers and/or mini-tips, or some cavities may be empty.

The container and/or the tip may be at least partially inserted into the cavity. The containers and/or tips may extend beyond the surface of the base plate. For example, if the cavity of the base plate has an opening on the upper surface of the base plate, the container and/or the tip may extend beyond the upper surface of the base plate. At least a portion of the container and/or mini-tip may protrude from the base plate. Alternatively, a portion of the vessel and/or tip does not protrude from the base plate. The extent to which the container and/or tip protrudes from the base plate may depend on the type of container and/or tip or the cavity configuration.

In some alternative embodiments, the containers and/or mini-tips may extend all the way through the base plate. The containers and/or mini-tips may extend over two or more surfaces of the base plate. In some embodiments, the vessel and/or the tip may extend at least partially beyond the lower surface of the base plate.

The containers and/or mini-tips may be supported by the base plate such that they are parallel to each other. For example, the container and/or tip may all have a vertical alignment. The containers and/or mini-tips may be aligned orthogonal to the plane of the base plate. The containers and/or tips may be orthogonal to the top and/or bottom surfaces of the base plate. Alternatively, the containers and/or tips need not be parallel to each other.

In some embodiments, each cavity may have a container and/or a tip provided therein. Alternatively, some cavities may be intentionally left open. One or more controllers may track whether the cavity is occupied or empty. One or more sensors may determine whether the cavity is occupied or empty.

The containers and/or tips may be selectively placed on and/or removed from the base plate. The container and/or mini-tip may be moved from the cavity of the base plate to another part of the apparatus or to another cavity of the base plate. The container and/or mini-tip may be placed into the cavity of the base plate from another part of the apparatus or from another cavity of the base plate. The position of the containers and/or mini-tips on the base plate can be changed or swapped. In some specific examples, each cavity may be individually addressable. Each container and/or tip may be individually addressable and/or individually movable. The containers and/or mini-tips may be addressed and/or moved independently of each other. For example, a single container and/or mini-tip may be addressed and/or moved relative to other containers and/or mini-tips. Multiple containers and/or mini-tips may be moved simultaneously. In some cases, a single container and/or mini-tip may be moved seriatim. The individual containers and/or mini-tips may be movable relative to each other and/or the cavity.

The containers and/or tips may be removed from and/or placed on the substrate plate using the liquid handling apparatus. The containers and/or tips may be removed and/or placed using another automated process that does not require human interaction. Alternatively, the container and/or tip may be removed and/or placed manually. The containers and/or tips may be individually moved in an automated process or a manual process.

The microcard may include a plurality of different types of containers and/or tips. The microcard may comprise at least 2, at least 3, at least 4, at least 5, or at least 6 or more different types of containers and/or tips. Alternatively, the mini-card may comprise all of the same type of containers and/or tips. The microcard may comprise one or more containers and/or tips selected from the group consisting of: a nucleic acid container, a nucleic acid tip, a centrifugal container, a centrifugal tip, a positive displacement tip, a chamber, a bulk handling tip, a chromogenic tip, a blood tip, a current reaction tip, a 3 μ L mini-tip, a 5 μ L mini-tip, a 10 μ L mini-tip or a 15 μ L mini-tip, or any other tip/container, or a combination thereof. The microcard may comprise one or more vessels and/or tips configured to perform one or more of the following assays: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscometric assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and/or other types of assays or combinations thereof. The vessels and/or tips supported by the base plate can support 1, 2, 3, 4, 5, 6, or more assays.

Measurement unit

According to one specific example described herein, an assay or any other portion of a module or device may include one or more assay units. The assay unit may be configured to perform a biological or chemical reaction that produces a detectable signal indicative of the presence or absence of one or more analytes and/or the concentration of one or more analytes. The assay unit may be configured to run an assay, which may include any type of assay as described elsewhere herein. The assay may take place within an assay unit.

The detectable signal may include an optical signal, a visual signal, an electrical signal, a magnetic signal, an infrared signal, a thermal signal, motion, weight, or sound.

In some embodiments, a plurality of assay units may be provided. In some embodiments, one or more rows of assay cells and/or one or more columns of assay cells may be provided. In some embodiments, an m x n array of assay units may be provided, where m, n are integers. The assay units may be provided in rows or columns that are staggered with respect to each other. In some embodiments, they may have any other configuration.

Any number of assay units may be provided. For example, there can be greater than and/or equal to about 1, 2, 3, 4, 5, 8, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, 175, 200, 250, 300, 400, 500, or 1000 assay units.

The assay unit may be provided in a cartridge, card, or have any other support structure. The assay units may have the same orientation. Alternatively, the assay unit may have a different orientation. In some examples, the assay unit may be held in a vertical orientation. In other examples, the assay unit may have a horizontal or vertical orientation, or any other angular orientation. The assay unit may remain unchanged over time or may change.

The assay units may be fluidly isolated or hydraulically independent from each other. The assay unit may contain and/or confine samples or other liquids that may be in liquid isolation from each other. The sample and/or other liquids contained within the assay unit may be the same or may differ between units. The system may be able to track what each assay unit contains. The system may be able to track the location and history of each assay unit.

The assay units may be independently movable relative to each other or another part of the device or module. Thus, the liquids and/or samples contained therein may be independently movable relative to each other or other portions of the device or module. The assay units may be individually addressable. The position of each assay unit can be tracked. The assay units may be individually selected for containing and/or providing a liquid. The assay units may be individually selected for carrying the liquid. The liquid may be supplied to or removed from the assay unit separately. The liquid may be dispensed and/or aspirated separately using the assay unit. The assay units may be independently detectable.

Any description herein of a single assay unit may also apply to groups of assay units. A set of assay units may comprise one, two or more assay units. In some embodiments, the assay units within a group may be moved simultaneously. The position of each set of assay units can be tracked. The liquid may be delivered and/or aspirated simultaneously from one or more sets of assay units. Probing may occur simultaneously for assay units within one or more sets of assay units.

The assay unit may have any tip or vessel form or characteristics as described elsewhere herein. For example, the assay unit may be any tip or vessel described herein. Any description herein of an assay unit may also apply to a tip or a vessel, or any description of a tip or a vessel may also apply to an assay unit.

In some embodiments, the assay unit may be an assay tip. The assay tip may have a first port and a second port. The first port and the second port may be opposite to each other. The first port and/or the second port may be open or closed. In some embodiments, both the first port and the second port may be open. In alternative embodiments, the assay unit may have three, four or more ends.

The assay tip may have an inner surface and an outer surface. The pathway may connect the first port and the second port of the assay tip. The passageway may be a pipe or a channel. The first port and the second port of the assay tip may be in fluid communication with each other. The diameter of the first port of the assay tip may be greater than the diameter of the second port of the assay tip. In some embodiments, the first port of the assay tip can have an outer diameter that is greater than an outer diameter of the second port of the assay tip. The internal diameter of the first port of the assay tip may be greater than the internal diameter of the second port of the assay tip. Alternatively, the diameter of the assay tip may be the same at the first and second ports. In some embodiments, the second port of the assay tip may be maintained below the first port. Alternatively, the relative positions of the first and second ports may be varied.

As previously described with respect to tips and/or vessels, the assay unit may be picked up using a liquid handling device. For example, a pipette or other liquid handling device may be connected to the assay unit. The pipette nozzle or orifice may be attached to one end of the assay unit. In some embodiments, a liquid-tight seal may be formed between the liquid handling apparatus and the assay unit. The assay unit may be attached to and/or detached from the liquid handling device. Any other automated device or process may be used to move or manipulate the assay unit. The assay unit may be moved or manipulated without human intervention.

The liquid handling device or any other automated device may be capable of picking up or discharging individual assay units. A liquid handling device or other automated device may be capable of picking up or discharging multiple assay units simultaneously. A liquid handling device or other automated device may be capable of selectively picking up or discharging multiple assay units. In some embodiments, the liquid handling device may be capable of selectively aspirating and/or dispensing a sample using one, two, or more assay units. Any of the descriptions for the liquid handling system as previously described herein may be applicable to the assay unit.

In one particular example, the assay unit may be formed from molded plastic. The assay unit may be commercially available or may be made to have a precise shape and size by custom manufacturing. The units may be coated with capture reagents-the coating is performed in a similar manner to those used to coat microtiter plates, but has the advantage that: they can be processed in batches by placing them in large containers, adding coating reagents, treating with sieves, holders, etc. to recover the parts and washing them as needed. In some embodiments, the capture reagent may be provided on an inner surface of the assay unit.

The assay unit may provide a rigid support on which the reagents may be immobilized. The assay unit may also be selected to provide appropriate characteristics with respect to interaction with light. For example, the assay unit may be made of materials such as: functionalized glass, Si, Ge, GaAs, GaP, SiO₂、SiN₄Modified silicon, or any of a wide range of gels or polymers, such as (poly) tetrafluoroethylene, (poly) vinylidene fluoride, polystyrene, polycarbonate, polypropylene, polymethyl methacrylate (PMMA), ABS, or combinations thereof. In one embodiment, the assay unit can comprise polystyrene. Other suitable materials may be used in accordance with the present invention. Any of the materials described herein, such as those suitable for use in tips and/or vessels, can be used to form the assay unit. Transparent reaction sites may be advantageous. In addition, in the case where there is a light transmission window that allows light to reach the photodetectorThe surface may advantageously be opaque and/or preferably light scattering.

The reagents may be immobilized on the capture surface of the assay unit. In some embodiments, the capture surface is provided on an inner surface of the assay unit. In one example, the capture surface may be provided on a lower portion of the assay tip. The reagent may be any substance useful for detecting a target analyte in a bodily fluid sample. For example, such reactants include, but are not limited to: nucleic acid probes, antibodies, cell membrane receptors, monoclonal antibodies, and antisera reactive with a particular analyte. A variety of commercially available reagents may be used, such as a number of polyclonal and monoclonal antibodies specifically developed for a particular analyte.

Those skilled in the art will appreciate that there are many ways to secure the various reactants to the support where the reaction can occur. Immobilization may be covalent or non-covalent, via a linker moiety, or by tethering it to an immobilization moiety. Non-limiting exemplary binding moieties for attaching nucleic acid or protein molecules, such as antibodies, to a solid support include streptavidin or avidin/biotin linkages, carbamate linkages, ester linkages, amides, thiol esters, (N) -functionalized thioureas, functionalized maleimides, amino, disulfides, amides, hydrazone linkages, and the like. Alternatively, the silyl moiety can attach the nucleic acid directly to a substrate plate (e.g., glass) using methods known in the art. Surface immobilization may also be achieved by poly-L-lysine tethers, which provide charge-to-charge coupling to the surface.

After the final step of incorporating the capture surface, the assay unit may be dried. For example, drying may be performed by passive exposure to a drying atmosphere, or by using a vacuum manifold and/or by applying clean dry air through the manifold.

In some embodiments, instead of using a capture surface on an assay unit, beads or other base plates may be provided to the assay unit on which the capture surface is provided. One or more free-flow substrate plates with capture surfaces may be provided. In some embodiments, a free-flow substrate plate with a capture surface may be provided within the liquid. In some embodiments, the beads may be magnetic. The beads may be coated with one or more reagents known in the art. The magnetic beads can be kept in a desired position within the assay unit. The magnetic beads may be positioned using one or more magnets.

The beads may be used to perform one or more assays, including but not limited to immunoassays, nucleic acid assays, or any other assay described elsewhere herein. The beads may be used during a reaction (e.g., chemical, physical, biological). The beads may be used during one or more sample preparation steps. The beads may be coated with one or more reagents. The beads themselves may be formed from reagents. The beads may be used for purification, mixing, filtration, or any other process. The beads may be formed of a transparent material, a translucent material, and/or an opaque material. The beads may be formed of a thermally conductive material or a thermally insulating material. The beads may be formed of a conductive material or an electrically insulating material. The beads may accelerate sample preparation and/or assay steps. The beads may provide an increased surface area that may react with one or more samples or liquids.

In alternative embodiments, beads or other solid materials may be provided to the assay unit. The beads may be configured to dissolve under certain conditions. For example, the beads may dissolve upon contact with a liquid or upon contact with an analyte or other reagent. The beads may be dissolved at a specific temperature.

The beads may be of any size or shape. The beads may be spherical. The beads can have a diameter of less than or equal to about 1nm, 5nm, 10nm, 50nm, 100nm, 200nm, 300nm, 500nm, 750nm, 1 μm, 2 μm, 3 μm, 5 μm, 10 μm, 20 μm, 50 μm, 100 μm, 200 μm, 300 μm, 400 μm, 500 μm, 600 μm, 700 μm, 800 μm, 900 μm, 1mm, 1.2mm, 1.5mm, 2mm, 2.5mm, 3mm, 4mm, or 5 mm. The beads may be of the same size or of different sizes. The beads may comprise microparticles or nanoparticles.

Any description of beads in the assay unit, processing unit and/or reagent unit may be applicable to beads at any location in the device. The beads can be stored and/or used in any tip/container (including those tips/containers described herein), cuvette, capillary, channel, reservoir, chamber, conduit, tube, conduit, surface, or any other location. The beads may be provided in the liquid or may be separated from the liquid.

Reaction sites may be provided within the assay unit. In some embodiments, the reaction sites may be provided on a surface (such as an inner surface) of the assay unit. The reaction site may be provided within a liquid contained by the assay unit. The reaction site may be on a substrate plate within the assay unit. The reaction sites may be on the surface of a substrate plate that is free floating within the assay cell. The reaction site may be a substrate plate within the assay unit.

The assay unit may be of any size, including those dimensions described elsewhere herein for tips and/or vessels. The assay unit may be capable of containing and/or confining a small volume of sample and/or other liquid, including the volumes mentioned elsewhere herein.

The assay unit may be picked up and/or removed from the liquid handling device. For example, an assay tip or other assay unit may be picked up by the pipette nozzle. The assay tip or other assay unit can be discharged by the pipette nozzle. In some embodiments, assay units may be selectively individually picked and/or discharged. One or more sets of assay units can be selectively picked and/or discharged. Automation may be used to pick up and/or discharge the assay units. The assay unit can be picked up and/or discharged without human intervention. The pipette may pick up and/or unload the assay unit according to the description provided elsewhere herein.

The liquid handling device may be used to move the assay unit within the apparatus and/or module. For example, a pipette tip may be used to transport an assay tip or other assay unit. The assay tip or other assay unit may be transported in a horizontal direction and/or a vertical direction. The assay tip and/or the assay unit may be transported in any orientation. The liquid handling device may be used to move the assay units individually. One or more sets of assay units may be moved simultaneously using the liquid handling device.

The shape and/or size of the measuring unit may be arranged to allow detection by the detection unit. The detection unit may be provided outside or inside the assay unit, or integrated with the assay unit. In one example, the assay unit may be transparent. The determination unit may allow detection of an optical signal, an audio signal, a visual signal, an electrical signal, a magnetic signal, a motion, an acceleration, a weight or any other signal by the detection unit.

The detector may be capable of detecting signals from a single assay unit. The detector can distinguish the signals received from each individual measuring cell. The detector can track and/or track the signal from each individual measuring cell individually. The detector may be capable of detecting signals from one or more sets of assay units simultaneously. The detector may track and/or track signals from one or more sets of assay units.

The assay unit may be formed of any material. The assay unit may be composed of any material including those described elsewhere herein for tips and/or vessels. The assay unit may be composed of a transparent material.

Processing unit

According to one specific example described herein, the preparation meter and/or the assay meter or any other part of the module or device may comprise one or more processing units. The processing unit may be configured for preparing a sample for the performance of a biological or chemical reaction and/or for performing the biological or chemical reaction, which produces a detectable signal indicative of the presence or absence of one or more analytes and/or the concentration of one or more analytes. The processing unit may be used to prepare an assay sample, or to perform any other process on a sample or associated reagent as provided in one or more sample preparation or processing steps as described elsewhere herein. The processing unit may have one or more characteristics of the assay unit as described elsewhere herein. The processing unit may function as the assay unit as described elsewhere herein.

The detectable signal may include an optical signal, a visual signal, an electrical signal, a magnetic signal, an infrared signal, a thermal signal, motion, weight, or sound.

In some embodiments, multiple processing units may be provided. In some embodiments, one or more rows of processing elements and/or one or more columns of processing elements may be provided. In some embodiments, an m x n array of processing units may be provided, where m, n are integers. The processing units may be provided in rows or columns that are interleaved with one another. In some embodiments, they may have any other configuration.

Any number of processing units may be provided. For example, there may be greater than and/or equal to about 1, 2, 3, 4, 5, 8, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, 175, 200, 250, 300, 400, 500, or 1000 processing units.

The processing unit may be provided in a cassette, card, or have any other support structure. The processing units may have the same orientation. Alternatively, the processing units may have different orientations. In some examples, the processing unit may be held in a vertical orientation. In other examples, the processing unit may have a horizontal or vertical orientation, or any other angular orientation. The processing unit may remain unchanged over time or may change.

In some cases, the pipette, tip, or both may be integrated with the cartridge or card. In some cases, the tip or pipette, or a component of the tip or pipette, is integrated with the cartridge or card.

The processing units may be fluidly isolated from each other or hydraulically independent. The processing unit may contain and/or confine samples or other liquids that may be in liquid isolation from each other. The sample and/or other liquids contained within the processing cells may be the same or may differ between cells. The system may be able to track what each processing unit contains. The system may be able to track the location and history of each processing unit.

The processing units may be independently movable relative to each other or another portion of the device or module. Thus, the liquids and/or samples contained therein may be independently movable relative to each other or other portions of the device or module. The processing units may be individually addressable. The location of each processing unit can be tracked. The treatment units may be individually selected for receiving and/or providing liquid. The treatment units may be individually selected for carrying the liquid. The liquid may be supplied separately to the treatment unit or removed from the treatment unit. The liquid may be dispensed and/or aspirated separately using the processing unit. The processing units may be independently detectable.

Any description herein of a single processing unit may also apply to groups of processing units. A group of processing units may comprise one, two or more processing units. In some embodiments, the processing units within a group may move simultaneously. The location of each set of processing units may be tracked. The liquid may be delivered and/or aspirated simultaneously from one or more sets of processing units. Probing may occur simultaneously for processing units within one or more groups of processing units.

The processing unit may have any of the tip or container forms or characteristics as described elsewhere herein. For example, the processing unit may be any of the tips or vessels described herein. Any description herein of a processing unit may also apply to a tip or a vessel, or any description of a tip or a vessel may also apply to a processing unit.

In some embodiments, the processing unit may be a processing tip. The processing tip may have a first port and a second port. The first port and the second port may be opposite to each other. The first port and/or the second port may be open or closed. In some embodiments, the first port and the second port may all be open. In alternative embodiments, the processing unit may have three, four, or more ends.

The processing tip may have an inner surface and an outer surface. The passageway may connect the first port and the second port of the processing tip. The passageway may be a conduit or channel. The first and second ports of the processing tip may be in fluid communication with each other. The diameter of the first port of the processing tip may be greater than the diameter of the second port of the processing tip. In some embodiments, the first port of the processing tip may have an outer diameter that is greater than an outer diameter of the second port of the processing tip. The internal diameter of the first port of the processing tip may be greater than the internal diameter of the second port of the processing tip. Alternatively, the diameter of the processing tip may be the same at the first and second ports. In some embodiments, the second port of the processing tip may be maintained lower than the first port. Alternatively, the relative positions of the first and second ports may be varied.

In some embodiments, the processing unit may be a container. The processing unit may have a first port and a second port. The first port and the second port may be opposite to each other. The first port and/or the second port may be open or closed. In some embodiments, the second port of the processing unit may be kept lower than the first port. Alternatively, the relative positions of the first and second ports may be varied. The open end of the treatment unit may be oriented upward or may remain higher than the closed end.

In some embodiments, the processing unit may have a lid or closure. The lid or closure may be capable of blocking the open end of the processing unit. A lid or closure may be selectively applied to close or open the open end of the processing unit. The lid or closure may have one or more configurations as described elsewhere herein or as known in the art. The lid or closure may form a hermetic seal that may separate the contents of the reagent unit from the surrounding environment. The cap or closure may comprise a film, oil (e.g. mineral oil), wax or gel.

The liquid handling device may be used to pick up a processing unit as previously described in relation to tips and/or containers. For example, a pipette or other liquid handling device may be connected to the processing unit. The pipette nozzle or orifice may be attached to one end of the processing unit. In some embodiments, a liquid-tight seal may be formed between the liquid treatment apparatus and the treatment unit. The treatment unit may be attached to and/or detached from the liquid treatment apparatus. Any other automated device or process may be used to move or manipulate the processing unit. The processing unit may be moved or manipulated without human intervention.

The liquid handling device or any other automated device may be capable of picking up or discharging individual handling units. A liquid handling device or other automated device may be capable of picking up or discharging multiple processing units simultaneously. A liquid handling device or other automated device may be capable of selectively picking up or discharging a plurality of processing units. In some embodiments, the liquid handling device may be capable of selectively aspirating and/or dispensing a sample using one, two, or more processing units. Any of the descriptions for the liquid treatment system as previously described herein may be applicable to the treatment unit.

In one particular example, the processing unit may be formed of molded plastic. The processing unit may be commercially available or may be made with precise shape and size by injection molding. The units may be coated with capture reagents-the coating is performed in a similar manner to those used to coat microtiter plates, but has the advantage that: they can be batched by placing them in a large container, adding coating reagents and treating with screens, holders, etc. to recover the parts and wash them as needed. In some embodiments, the capture reagent may be provided on an interior surface of the processing unit.

The processing unit may provide a rigid support upon which the reactants may be immobilized. The processing unit may also be selected to provide appropriate characteristics with respect to interaction with the light. For example, the processing unit may be made of materials such as: functionalized glass, Si, Ge, GaAs, GaP, SiO₂、SiN₄Modified silicon, or any of a wide range of gels or polymers, such as (poly) tetrafluoroethylene, (poly) vinylidene fluoride, polystyrene, polycarbonate, polypropylene, polymethyl methacrylate (PMMA), ABS, or combinations thereof. In one embodiment, the processing unit may comprise polystyrene. Other suitable materials may be used in accordance with the present invention. Any of the materials described herein, such as those suitable for use in tips and/or vessels, may be used to form the processing unit. Transparent reaction sites may be advantageous. Further, in case there is a light transmissive window allowing light to reach the light detector, the surface may advantageously be opaque and/or preferably light scattering.

The reactants may be immobilized on a capture surface of the processing unit. In some embodiments, the capture surface is provided on an interior surface of the processing unit. In one example, the capture surface may be provided in a lower portion of the processing tip or vessel.

After the final step of incorporating the capture surface, the processing unit may be dried. For example, drying may be performed by passive exposure to a drying atmosphere, or by using a vacuum manifold and/or by applying clean dry air through the manifold.

In some embodiments, instead of using a capture surface on a processing unit, beads or other substrate plates may be provided to the processing unit on which the capture surface is provided. One or more free-flow substrate plates with capture surfaces may be provided. In some embodiments, a free-flow substrate plate with a capture surface may be provided within the liquid. In some embodiments, the beads may be magnetic. The beads may be coated with one or more reagents known in the art. The magnetic beads may be kept in a desired position within the processing unit. The magnetic beads may be positioned using one or more magnets.

The beads may be used to perform one or more assays, including but not limited to immunoassays, nucleic acid assays, or any other assay described elsewhere herein. The beads may be used during a reaction (e.g., chemical, physical, biological). The beads may be used during one or more sample preparation steps. The beads may be coated with one or more reagents. The beads themselves may be formed from reagents. The beads may be used for purification, mixing, filtration, or any other process. The beads may be formed of a transparent material, a translucent material, and/or an opaque material. The beads may be formed of a thermally conductive material or a thermally insulating material. The beads may be formed of a conductive material or an electrically insulating material. The beads may accelerate sample preparation and/or assay steps. The beads may provide an increased surface area that may react with one or more samples or liquids.

In alternative embodiments, beads or other solid materials may be provided to the assay unit. The beads may be configured to dissolve under certain conditions. For example, the beads may dissolve upon contact with a liquid or upon contact with an analyte or other reagent. The beads may be dissolved at a specific temperature.

The beads may be of any size or shape. The beads may be spherical. The beads can have a diameter of less than or equal to about 1nm, 5nm, 10nm, 50nm, 100nm, 200nm, 300nm, 500nm, 750nm, 1 μm, 2 μm, 3 μm, 5 μm, 10 μm, 20 μm, 50 μm, 100 μm, 200 μm, 300 μm, 400 μm, 500 μm, 600 μm, 700 μm, 800 μm, 900 μm, 1mm, 1.2mm, 1.5mm, 2mm, 2.5mm, 3mm, 4mm, or 5 mm. The beads may be of the same size or of different sizes. The beads may comprise microparticles or nanoparticles.

The processing unit can be of any size, including those described elsewhere herein with respect to tips and/or containers. The processing unit may be capable of containing and/or confining a small volume of sample and/or other liquid, including the volumes mentioned elsewhere herein.

The processing unit may be picked up and/or removed from the liquid treatment device. For example, a processing tip or other processing unit may be picked up by a pipette nozzle. The processing tips or other processing units can be discharged by pipette nozzles. In some embodiments, a single pick and/or drop processing unit may be selectively provided. One or more groups of processing units may be selectively picked and/or discharged. Automation may be used to pick up and/or discharge the processing units. The processing units may be picked and/or discharged without human intervention. The pipette may pick up and/or discharge the processing unit according to the description provided elsewhere herein.

The liquid treatment device may be used to move the treatment unit within the apparatus and/or the module. For example, a pipette head may be used to transport processing tips/containers or other processing units. The processing tips/containers or other processing units may be transported in a horizontal direction and/or a vertical direction. The processing tip/vessel and/or the assay unit may be transported in any orientation. The liquid treatment device may be used to move the treatment units individually. One or more groups of treatment units may be moved simultaneously using the liquid treatment apparatus.

The processing unit may be shaped and/or sized to allow detection by the detection unit. The detection unit may be provided external or internal to the processing unit, or integrated with the processing unit. In one example, the processing unit may be transparent. The processing unit may allow detection of optical, audio, visual, electrical, magnetic, chemical, biological, motion, acceleration, weight or any other signal by the detection unit.

The detector may be capable of detecting signals from a single processing unit. The detector can distinguish between the signals received from each individual processing unit. The detector may track and/or track the signals from each individual processing unit individually. The detector may be capable of detecting signals from one or more sets of processing units simultaneously. The detector may track and/or track signals from one or more sets of processing units.

In some embodiments, magnetic particles or superparamagnetic nanoparticles may be used in conjunction with the container and miniaturized magnetic resonance to achieve specific unit operations. The magnetic particles or superparamagnetic nanoparticles may be manipulated by an external magnetic field or by a pipette/liquid transfer device. Magnetic beads can be used for separation (when coated with antibodies/antigens/other capture molecules), mixing (by stirring from an external magnetic field), concentrating analytes (by selectively separating analytes, or by separating impurities), and the like. All these unit operations can be performed efficiently in a small volume with high efficiency.

Reagent unit

According to one specific example described herein, an assay or module or any other portion of a device may include one or more reagent units. The reagent unit may be configured to contain and/or confine reagents that may be used in the assay. The reagents in the reagent unit may be used for biological or chemical reactions. The reagent unit may store one or more reagents before, after or simultaneously with the reaction that may take place with the reagents. The biological and/or chemical reaction may or may not occur outside the reagent unit.

The agent may include any agent described in more detail elsewhere herein. For example, reagents may include a sample diluent, a detector conjugate (e.g., an enzyme-labeled antibody), a wash solution, and an enzyme substrate. Additional reagents may be provided as desired.

In some embodiments, a plurality of reagent units may be provided. In some embodiments, one or more rows of reagent cells and/or one or more columns of reagent cells may be provided. In some embodiments, an m x n array of reagent units may be provided, where m, n are integers. The reagent units may be provided in rows or columns that are staggered with respect to each other. In some embodiments, they may have any other configuration.

Any number of reagent units may be provided. For example, greater than and/or equal to about 1, 2, 3, 4, 5, 8, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, 175, 200, 250, 300, 400, 500, or 1000 reagent units may be present.

Alternatively, the same number of reagent units and assay units may be provided. One or more reagent units may correspond to one assay unit. One or more assay units may correspond to one reagent unit. One or more of the reagent units may be movable relative to the assay unit. Alternatively, one or more of the assay units may be movable relative to the reagent unit. The assay unit may be individually movable relative to the reagent unit.

The reagent units may be provided in a cartridge, card, or with any other support structure. The reagent units may have the same orientation. For example, the reagent unit may have one or more open ends that may face in the same direction. Alternatively, the reagent units may have different orientations. In some examples, the reagent unit may remain vertically oriented. In other examples, the reagent unit may have a horizontal or vertical orientation, or any other angular orientation. The reagent units may remain unchanged over time or may change. The reagent unit may be provided on a support structure together with the assay unit. Alternatively, the reagent unit may be provided on a separate support structure than the assay unit. The reagent unit and the assay unit may be supported in separate parts of the support structure. Alternatively, they may be blended on the support structure.

The reagent units may be liquid isolated or hydraulically independent from each other. The reagent unit may contain and/or confine samples or other liquids that may be in liquid isolation from each other. The sample and/or other liquids contained within the reagent units may be the same or may differ between units. The system may be able to track what each assay unit contains. The system may be able to track the location and history of each assay unit.

The reagent units may be independently movable relative to each other or another part of the device or module. Thus, the liquids and/or samples contained therein may be independently movable relative to each other or other portions of the device or module. The reagent units may be individually addressable. The location of each reagent unit can be tracked. The reagent units may be individually selected for containing and/or providing a liquid. The reagent units may be individually selected for carrying the liquid. The liquid may be supplied to or removed from the reagent unit separately. The reagent units may be independently detectable.

Any description herein of individual reagent units may also apply to groups of reagent units. A set of reagent units may comprise one, two or more reagent units. In some embodiments, the reagent units within a group may be moved simultaneously. The location of each set of reagent units can be tracked. The liquid may be delivered and/or aspirated simultaneously from one or more sets of reagent units. Probing may occur simultaneously for assay units within one or more sets of assay units.

The reagent unit may have any tip or vessel form or characteristics as described elsewhere herein. For example, the reagent unit may be any tip or vessel described herein. Any description herein of a reagent unit may also apply to a tip or a vessel, or any description of a tip or a vessel may also apply to a reagent unit.

In some embodiments, the reagent unit may be a container. The reagent unit may have a first port and a second port. The first port and the second port may be opposite to each other. The first port and/or the second port may be open or closed. In some embodiments, the first port may be open and the second port may be closed. In alternative embodiments, the assay unit may have three, four or more ends. The container may be covered by a septum and/or barrier to prevent evaporation and/or nebulization, thereby preventing loss of reagents and contamination of the device. The container may be disposable. This eliminates the need to fill the reagent externally from a common source. This also allows for better quality control and reagent handling. Furthermore, this reduces contamination of the equipment and surroundings.

The reagent unit may have an inner surface and an outer surface. The pathway may connect the first port and the second port of the reagent unit. The passageway may be a conduit or channel. The first port and the second port of the assay tip may be in fluid communication with each other. The diameter of the first port of the reagent unit may be larger than the diameter of the second port of the reagent unit. In some specific examples, the outer diameter of the first port of the reagent unit may be greater than the outer diameter of the second port of the reagent unit. Alternatively, the diameters may be the same, or the outer diameter of the second port may be greater than the outer diameter of the first port. The inner diameter of the first port of the reagent unit may be larger than the inner diameter of the second port of the reagent unit. Alternatively, the diameter and/or inner diameter of the reagent unit may be the same at the first port and the second port. In some embodiments, the second port of the reagent unit may be kept lower than the first port. Alternatively, the relative positions of the first and second ports may be varied. The open end of the reagent unit may be oriented upwards or may remain higher than the closed end.

In some embodiments, the reagent unit may have a lid or closure. The lid or closure may be capable of blocking the open end of the reagent unit. A lid or closure may be selectively applied to close or open the open end of the reagent unit. The lid or closure may have one or more configurations as described elsewhere herein or as known in the art. The lid or closure may form a hermetic seal that may separate the contents of the reagent unit from the surrounding environment.

As previously described with respect to tips and/or containers, liquid handling equipment may be used to pick up reagent units. For example, a pipette or other liquid handling device may be connected to the reagent unit. The pipette nozzle or orifice may interface with one end of the reagent unit. In some embodiments, a liquid-tight seal may be formed between the liquid handling apparatus and the reagent unit. The reagent unit may be attached to and/or detached from the liquid handling device. The liquid handling device may move the reagent unit from one location to another. Alternatively, the reagent unit is not connected to the liquid handling device. Any other automated device or process may be used to move or manipulate the assay unit. The reagent unit can be moved or manipulated without human intervention.

The reagent unit may be configured to receive the assay unit. In some embodiments, the reagent unit may comprise an open end through which at least a portion of the assay unit may be inserted. In some embodiments, the assay unit may be fully inserted within the reagent unit. The open end of the reagent unit may have a larger diameter than at least one open end of the assay unit. In some cases, the inner diameter of the open end of the reagent unit may be larger than the outer diameter of at least one open end of the assay unit. In some embodiments, the reagent unit may be shaped or may include one or more features that may allow the assay unit to insert a desired amount within the reagent unit. The assay unit may or may not be able to be fully inserted into the reagent unit.

The assay unit may dispense liquid to and/or aspirate liquid from the reagent unit. The reagent unit may provide a liquid, such as a reagent, which may be drawn by the assay unit. The assay unit may in turn or provide a liquid to the reagent unit. The liquid can be transferred through the open end of the reagent unit and the open end of the assay unit. The open ends of the assay unit and the reagent unit may allow the interior portions of the assay unit and the reagent unit to be in fluid communication with each other. In some embodiments, the assay unit may be located above the reagent unit during said dispensing and/or aspirating.

Alternatively, the liquid transfer between the reagent unit and the assay unit may be accomplished by a liquid handling device. One or several such liquid transfers may occur simultaneously. The liquid handling device may in a specific example be a pipette.

In one example, reagents for a chemical reaction may be provided in a reagent unit. The assay unit can be placed into the reagent unit and can aspirate reagent from the reagent unit. The chemical reaction may take place within the assay unit. Excess liquid from the reaction may be dispensed from the assay unit. The assay unit may draw a wash solution. The wash solution may be drained from the assay unit. The washing step may occur 1, 2, 3, 4, 5 or more times. Still alternatively, the wash solution may be drawn up and/or dispensed to the reagent unit. This may reduce background signal interference. The detector may detect one or more signals from the measurement unit. Reduced background signal interference may allow for increased sensitivity of the signal detected from the assay unit. Assay tip specifications may be employed which advantageously provide for convenient liquid drainage to improve wash conditions.

The liquid handling device or any other automated device may be capable of picking up or discharging individual assay units. A liquid handling device or other automated device may be capable of picking up or discharging multiple assay units simultaneously. A liquid handling device or other automated device may be capable of selectively picking up or discharging multiple assay units. In some embodiments, the liquid handling device may be capable of selectively aspirating and/or dispensing a sample using one, two, or more assay units. Any of the descriptions for the liquid handling system as previously described herein may be applicable to the assay unit.

In one particular example, the reagent unit may be formed from molded plastic. The processing unit may be commercially available or may be made with precise shape and size by injection molding. The units may be coated with capture reagents-the coating is performed in a similar manner to those used to coat microtiter plates, but has the advantage that: they can be batched by placing them in a large container, adding coating reagents and treating with screens, holders, etc. to recover the parts and wash them as needed. In some embodiments, the capture reagent may be provided on an inner surface of the reagent unit. Alternatively, the reagent unit may be uncoated or may be coated with other substances.

The reagent unit may provide a rigid support. The reagent unit may be selected to provide appropriate characteristics with respect to interaction with light. For example, the reagent unit may be made of materials such as: functionalized glass, Si, Ge, GaAs, GaP, SiO₂、SiN₄Modified silicon, or any of a wide range of gels or polymers, such as (poly) tetrafluoroethylene, (poly) vinylidene fluoride, polystyrene, polycarbonate, polypropylene, polymethyl methacrylate (PMMA), ABS, or combinations thereof. In one embodiment, the assay unit can comprise polystyrene. Can be used according to the inventionOther suitable materials. Any of the materials described herein, such as those suitable for use in tips and/or vessels, may be used to form reagent units. Transparent reaction sites may be advantageous. Further, in case there is a light transmissive window allowing light to reach the light detector, the surface may advantageously be opaque and/or preferably light scattering.

The reagent unit may or may not be provided with capture surfaces, such as those described for the assay unit. Similarly, the reagent unit may or may not employ beads or other substrate plates to provide a capture surface. Alternatively, any description of beads or other capture surfaces with respect to the assay unit or processing unit may also apply to the reagent unit.

The reagent unit may or may not have a reaction site. Any description herein of the reaction sites of the assay unit may also apply to the reagent unit.

The reagent units may be of any size, including those sizes described elsewhere herein for tips and/or vessels. The reagent unit may be capable of containing and/or confining a small volume of sample and/or other liquid, including the volumes mentioned elsewhere herein.

The reagent unit may be fixed within the device and/or the module. Alternatively, the reagent unit may be movable relative to the device and/or the module. The reagent units may be picked up and/or moved using a liquid handling device or any other automated process. For example, the reagent unit may be picked up by a pipette nozzle in a manner such as described elsewhere for the assay unit.

The measurement unit and the reagent unit can be moved relatively to each other. The assay unit and/or the reagent unit are movable relative to each other. The assay units are movable relative to each other. The reagent units are movable relative to each other. The assay unit and/or the reagent unit may be individually movable relative to the device and/or the module.

The reagent unit may be shaped and/or sized to allow detection by the detection unit. The detection unit may be provided externally or internally to the reagent unit, or integrated with the reagent unit. In one example, the reagent unit may be transparent. The reagent unit may allow detection of an optical signal, an audio signal, a visual signal, an electrical signal, a magnetic signal, a motion, an acceleration, a weight or any other signal by the detection unit.

The detector may be capable of detecting a signal from a single reagent unit. The detector can distinguish the signal received from each individual reagent unit. The detector may track and/or track the signal from each individual reagent unit individually. The detector may be capable of detecting signals from one or more sets of reagent units simultaneously. The detector may track and/or track signals from one or more sets of reagent units. Alternatively, the detector need not detect a signal from a single reagent. In some embodiments, the device and/or system may keep track of the identity of, or information associated with, the reagents or other liquids provided within the reagent unit.

As previously mentioned, the reagent unit may include one or more reagents therein. The reagent may comprise a wash buffer, an enzyme substrate, a dilution buffer or a conjugate (such as an enzyme-labeled conjugate). Examples of enzyme-labeled conjugates may include polyclonal antibodies, monoclonal antibodies, or may be labeled with an enzyme that produces a detectable signal upon reaction with an appropriate substrate. The reagents may also include DNA amplification reagents, sample diluents, wash solutions, sample pretreatment reagents (including additives such as detergents), polymers, chelating agents, albumin binding reagents, enzyme inhibitors, enzymes (e.g., alkaline phosphatase, horseradish peroxidase), anticoagulants, red blood cell agglutinating agents, or antibodies. Any other examples of reagents described elsewhere herein can also be contained and/or confined within the reagent unit.

Dilution of

According to one specific example described herein, an apparatus and/or module may allow for the use of one or more diluents. The diluent may be contained in one or more reagent units, or in any other unit that may contain and/or confine the diluent. The diluent may be provided in a tip, a container, a chamber, a vessel, a channel, a tube, a reservoir, or any other component of the device and/or module. The diluent may be stored in a liquid-tight or hydraulically independent assembly. The fluid-isolated or hydraulically-independent components may be fixed or may be configured to move relative to one or more portions of the device and/or module.

In some embodiments, the diluent may be stored in a diluent unit, which may have any of the characteristics of the reagent unit as described elsewhere herein. The diluent unit may be stored in the same location as the remaining reagent units or may be stored remotely from the remaining reagent units.

Any diluent known in the art may be used for example. The diluent may be capable of diluting or thinning the sample. In most cases, the diluent does not cause a chemical reaction with the sample. The apparatus may employ one type of diluent. Alternatively, the apparatus may have multiple types of diluents available or employ multiple types of diluents. The system may be capable of tracking diluent and/or diluents of various types. Thus, the system may be able to take up a desired type of diluent. For example, the tip may draw the desired diluent.

In some embodiments, a diluent may be provided to the sample. The diluent may dilute the sample. As the diluent is added, the concentration of the sample may become reduced. The degree of dilution may be controlled according to one or more protocols or instructions. In some cases, the procedures or instructions may be provided from an external device, such as a server. Alternatively, the protocol or instructions may be provided onboard the device or the cassette or container. Thus, the server and/or the device may be capable of variable dilution control. By controlling the degree of dilution, the system may be able to detect the presence of one or more analytes or concentrations thereof that may vary over a wide range. For example, the sample may have a first analyte with a concentration detectable in a first range; and a second analyte having a concentration detectable in a second range. The sample may be divided and different amounts of diluent may or may not be applied thereto in order to bring portions of the sample into detectable range of the first and second analytes. Similarly, the sample may or may not be subjected to different degrees of enrichment in order to bring the analyte to the concentration desired for detection.

Dilution and/or enrichment may allow detection of one, two, three, or more analytes with a wide range of concentrations. For example, analytes that differ by an order of magnitude of 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, or 10 or more may be detected from the sample.

In some embodiments, the sample may be combined with a diluent in an assay tip or other types of tips described elsewhere herein. The assay tip can draw diluent. The assay tip may draw diluent from the reagent unit. The diluent may or may not be bound to the sample within the assay tip.

In another example, the diluent and/or sample may be combined in a reagent unit or other type of container described elsewhere herein. For example, a diluent may be added to the sample in the reagent unit, or the sample may be added to the diluent in the reagent unit.

In some embodiments, one or more mixing devices may be provided. Alternatively, no separate mixing device is required. The assay unit, the reagent unit or any other tip, container or compartment that binds the sample to the diluent may be able to move so that mixing is achieved.

Different amounts of diluent and/or sample may be combined to achieve the desired level of dilution. The protocol may determine the relative proportions of diluent and sample to be combined. In some embodiments, the ratio of sample to diluent may be less than and/or equal to about 1:1000000, 1:100000, 1:10000, 1:1000, 1:500, 1:100, 1:50, 1:10, 1:5, 1:3, 1:2, 1:1, or greater than and/or equal to 2:1, 3:1, 5:1, 10:1, 50:1, 100:1, 500:1, 1000:1, 10000:1, 100000:1, or 1000000: 1. The diluted sample may be drawn from the reagent unit using an assay tip where one or more chemical reactions may take place.

The desired amount of diluent may be provided according to one or more sets of instructions. In some embodiments, the amount of dilution provided may be controlled by the liquid handling system. For example, it is determined that the tip can draw a desired amount of diluent and dispense it to a desired location. The volume of diluent drawn up by the assay tip can be controlled with high sensitivity. For example, the amount of diluent drawn may have any volume of liquid or sample discussed elsewhere herein. In some embodiments, it is determined that the tip can draw a desired amount of diluent in a round. Alternatively, the assay tip may draw and dispense diluent multiple times in order to achieve the desired degree of dilution.

Dilution of the sample may occur during a sample pre-processing step. The sample may be diluted before undergoing the chemical reaction. Alternatively, the dilution may occur during and/or after the chemical reaction. In one example, all dilution processes are performed on a cassette plate. In another example, all dilution processes are performed at different locations of the cartridge after the cartridge is inserted into the module. Alternatively, all dilution processes are performed at different locations of the cartridge before the cartridge is inserted into the module. Alternatively still, some dilution processes may be performed at different locations of the cartridge prior to insertion of the cartridge into the module.

Depending on assay requirements, the dilution factor can be optimized in real time for each assay. In one particular example, the real-time determination of the dilution protocol may be performed by knowledge of all assays to be performed. Such optimization can be utilized for multiple assays using the same dilution. The foregoing dilution protocol can result in greater accuracy of the final diluted sample.

Washing machine

According to one specific example described herein, the apparatus and/or module may allow for washing. The wash solution may be contained in one or more reagent units, or in any other unit that may contain and/or confine the wash solution. The wash solution may be provided in a tip, a vessel, a chamber, a vessel, a channel, a tube, a reservoir, or any other component of the device and/or module. The wash solution may be stored in a liquid-isolated or hydraulically-independent assembly. The fluid-isolated or hydraulically-independent components may be fixed or may be configured to move relative to one or more portions of the device and/or module.

In some embodiments, the wash solution may be stored in a wash unit, which may have any of the characteristics of the reagent unit as described elsewhere herein. The wash unit may be stored in the same location as the remaining reagent units or may be stored remotely from the remaining reagent units.

Any washing solution example known in the art may be used. The wash solution may be capable of removing unbound and/or unreacted reactants. For example, a chemical reaction may occur between a sample containing an analyte and an immobilized reactant, which may result in the analyte binding to a surface. Unbound analyte can be washed away. In some embodiments, the reaction may result in the emission of a light signal, light, or any other kind of signal. If unreacted reactants remain nearby, they may cause interfering background signals. It may be desirable to purge unreacted reactants in order to reduce interfering background signals and to allow reading of bound analytes. In some cases, the wash solution does not cause a chemical reaction to occur between the wash solution and the sample.

The apparatus may employ one type of wash solution. Alternatively, the apparatus may have multiple types of wash solutions available or employed. The system may be capable of tracking wash solutions and/or various types of wash solutions. Thus, the system may be able to take up a desired type of wash solution. For example, the tip may draw the desired wash solution.

In some embodiments, a wash solution may be provided to the sample. The wash solution may dilute the sample. As the wash solution is added, the concentration of the sample may become lower. The extent of washing may be controlled according to one or more protocols or instructions. By controlling the extent of washing, the system may be able to detect the presence or concentration of one or more analytes with a desired sensitivity. For example, an increased wash volume may clear undesired reagents or samples that may cause disturbing background noise.

In some embodiments, the wash solution may be provided to an assay tip or other type of tip described elsewhere herein. The assay tip can draw up the wash solution. The assay tip may draw wash solution from the wash unit. The wash solution may or may not be dispensed back through the assay tip. The same opening of the assay tip can aspirate and dispense wash solution. For example, the assay tip may have a bottom opening that can be used to draw and drain wash solution. The assay tip may have both a bottom opening and a top opening, wherein the bottom opening may have a smaller diameter than the top opening. Draining the wash solution through the bottom opening may allow for a more efficient draining of the wash solution than when the bottom of the assay tip is closed.

In another example, the wash solution and/or sample may be combined in a reagent unit or other type of container described elsewhere herein. For example, a wash solution may be added to the sample in the reagent unit, or a sample may be added to the wash solution in the reagent unit. The wash solution may be drained in any manner. In some embodiments, the wash solution and/or sample conjugate may be drawn up by the assay tip.

The desired amount of wash solution may be provided according to one or more sets of instructions. In some embodiments, the amount of wash solution provided may be controlled by the liquid handling system. For example, the assay tip may draw a desired amount of wash solution and dispense it. The volume of wash solution drawn by the assay tip can be controlled with high sensitivity. For example, the amount of wash solution drawn may have any volume of liquid or sample discussed elsewhere herein. In some embodiments, the assay tip may draw a desired amount of wash solution in a round. Alternatively, the assay tip may draw and dispense wash solution multiple times in order to achieve the desired degree of washing.

Different numbers of wash cycles may occur in order to provide the desired detection sensitivity. The protocol may determine the number of wash cycles. For example, greater than and/or equal to about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 wash cycles may occur. The wash solution can be drawn from the wash unit using the assay tip and can be drained from the assay tip.

The washing may occur after undergoing a chemical reaction. Alternatively, the washing may occur during and/or before the chemical reaction.

Pollution abatement

According to one particular example described herein, a device and/or module may allow for prevention and/or reduction of contamination. For example, a touch pad may be provided. The touch pad can be formed of an absorbent material. For example, the absorbent pad may be a sponge, fabric, gel, porous material, capillary tube, or have any characteristic that absorbs or absorbs liquid that may come into contact with the pad. The assay tip may contact the touchup pad, which may result in liquid being absorbed by the touchup pad from the assay tip in proximity to the pad. In some embodiments, the measurement tip may be brought to the contact pad in such a way that it does not contact a previously contacted portion of the pad. In some cases, the liquid is not placed in the same location as the liquid that has been previously blotted. The measurement pipette may be brought to the pad in such a way: the contact points are spaced apart so that a different contact point is used each time the assay tip contacts the pad. One or more controllers may determine the position of the touchdown pads that the tip may contact next. The controller may keep track of which points on the mat have been determined to be contacted by the pipette tip. The assay pad may be absorbent.

The assay tip can be wiped by the pad. Excess liquid or undesired liquid from the assay tip may be removed from the assay tip. For example, an open end (such as a bottom end) of the assay tip may be contacted to the touchdown pad. The pad may be formed of an absorbent material that can wick liquid away from the assay tip. Thus, since the assay tip or other components of the device can be moved throughout the module and/or device, the likelihood of excess or undesirable liquid contaminating other parts of the module and/or device can be reduced.

Another example of a contamination prevention and/or reduction device may include applying a coating or covering to an assay tip or other component of the apparatus. For example, the assay tip may be contacted with a molten wax, oil (such as mineral oil) or gel. In some embodiments, the wax, oil, or gel may harden. Hardening can occur when the material cools and/or is exposed to air. Alternatively, they do not need to be hardened. The coated surface, such as a wax, oil, or gel, may be sufficiently tacky to remain on the assay tip or other component of the device. In one example, the open end of the assay tip may be contacted with a coating material that may cover the open end of the assay tip, thereby sealing the contents of the assay tip.

Additional examples of contamination prevention and/or reduction can be a waste chamber to receive used assay tips, a component that can place one or more lids on used portions of assay tips, a heater or fan, or ultraviolet light emitted onto one or more components or subsystems, or any other component that can reduce the likelihood of contamination. In some embodiments, the liquid handling components of the apparatus do not require periodic decontamination because the stationary components of the apparatus typically do not directly contact the sample. The liquid handling device may be capable of being periodically self-cleaned, for example by using a pipette to aspirate a cleaning agent (e.g. ethanol) from a reservoir. Liquid handling equipment and other equipment resources may also be decontaminated, sterilized or disinfected by a variety of other methods including UV irradiation.

FiltrationDevice for cleaning the skin

The devices and/or modules may include other components that may allow for one or more functions as described elsewhere herein. For example, the device and/or module may have a filter that may allow the sample to be separated by particle size, density, or any other characteristic. For example, particles or liquid having a particle size smaller than a threshold size may pass through the filter, while other particles having a size larger than the threshold size may not. In some embodiments, multiple filters may be provided. The multiple filters may be of the same size or of different sizes, which may allow for sorting of different sized particles into any number of groups.

Centrifugal machine

According to some specific examples described herein, a system may include one or more centrifuges. The apparatus may include one or more centrifuges therein. For example, one or more centrifuges may be provided within the device housing. The module may have one or more centrifuges. One, two or more modules of the apparatus may have a centrifuge therein. The centrifuge may be supported by the module support structure or may be contained within the module housing. The centrifuge may have a form factor that is compact, flat, and requires only a small footprint. In some embodiments, the centrifuge may be miniaturized for point-of-service applications, yet be capable of rotating at high rates, equal to or exceeding about 10000rpm, and be capable of withstanding up to about 1200m/s²Or a greater gravitational force.

The centrifuge may be configured to receive one or more samples. Centrifuges may be used to separate and/or purify materials of different densities. Examples of such materials may include viruses, bacteria, cells, proteins, environmental components, or other components. The centrifuge may be used to concentrate cells and/or particles for subsequent measurement.

The centrifuge may have one or more cavities that may be configured to receive a sample. The cavity may be configured to receive the sample directly within the cavity such that the sample may contact the cavity walls. Alternatively, the cavity may be configured to receive a sample container in which a sample may be contained. Any description of a cavity herein is applicable to any configuration that can receive and/or contain a sample or sample container. For example, the cavity may include a notch in the material, a bucket size, a protrusion with a hollow interior, a member configured to interconnect with a sample container. Any description of a cavity may also include configurations that may or may not have a concave or inner surface. Examples of sample vessels may include any of the vessel or tip designs described elsewhere herein. The sample container may have an inner surface and an outer surface. The sample container may have at least one open end configured to receive a sample. The open end may be closable or sealable. The sample container may have a closed end. The sample container may be a nozzle of a liquid handling device, which may act as a centrifuge to spin liquid among the nozzle, a tip, or another container attached to such a nozzle.

The centrifuge may have 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 8 or more, 10 or more, 12 or more, 15 or more, 20 or more, 30 or more, or 50 or more cavities configured to receive a sample or sample container.

In some embodiments, the centrifuge may be configured to receive a small volume of sample. In some specific examples, the cavity and/or sample container can be configured to receive a sample volume of 1000 μ L or less, 500 μ L or less, 250 μ L or less, 200 μ L or less, 175 μ L or less, 150 μ L or less, 100 μ L or less, 80 μ L or less, 70 μ L or less, 60 μ L or less, 50 μ L or less, 30 μ L or less, 20 μ L or less, 15 μ L or less, 10 μ L or less, 8 μ L or less, 5 μ L or less, 1 μ L or less, 500nL or less, 300nL or less, 100nL or less, 50nL or less, 10nL or less, 5pL or less, or 1pL or less.

In some embodiments, the centrifuge may have a lid that may contain the sample within the centrifuge. The cover may prevent sample fogging and/or evaporation. The centrifuge may alternatively have a film, oil (e.g., mineral oil), wax, or gel that may contain the sample within the centrifuge and/or prevent atomization and/or evaporation thereof. A film, oil, wax or gel may be provided as a layer over the sample that may be contained within the chamber and/or sample container of the centrifuge.

The centrifuge may be configured to rotate about a rotational axis. The centrifuge may be capable of rotating at any number of revolutions per minute. For example, the rotational speed of the centrifuge may be up to 100rpm, 1000rpm, 2000rpm, 3000rpm, 5000rpm, 7000rpm, 10000rpm, 12000rpm, 15000rpm, 17000rpm, 20000rpm, 25000rpm, 30000rpm, 40000rpm, 50000rpm, 70000rpm or 100000 rpm. At some points in time, the centrifuge may remain stationary while at other points in time, the centrifuge may rotate. The stationary centrifuge does not rotate. The centrifuge may be configured to rotate at a variable rate. In some embodiments, the centrifuge may be controlled to rotate at a desired rate. In some specific examples, the rate of change of the rotational speed may be variable and/or controllable.

In some embodiments, the axis of rotation may be vertical. Alternatively, the axis of rotation may be horizontal, or may have any angle between vertical and horizontal (e.g., about 15, 30, 45, 60, or 75 degrees). In some embodiments, the axis of rotation may be in a fixed direction. Alternatively, the axis of rotation may be varied during use of the device. The rotation axis angle may or may not vary when the centrifuge is rotating.

The centrifuge may include a base. The base may have a top surface and a bottom surface. The base may be configured to rotate about an axis of rotation. The axis of rotation may be orthogonal to the top and/or bottom surfaces of the base. In some embodiments, the top surface and/or the bottom surface of the base may be flat or curved. The top and bottom surfaces may or may not be substantially parallel to each other.

In some embodiments, the base may have a circular shape. The base may have any other shape including, but not limited to, an oval, triangular, quadrilateral, pentagonal, hexagonal, or octagonal shape.

The base may have a height and one or more lateral dimensions (e.g., diameter, width, or length). The height of the base may be parallel to the axis of rotation. The transverse dimension may be perpendicular to the axis of rotation. The base may have a lateral dimension greater than the height. The lateral dimension of the base may be 2 times or more, 3 times or more, 4 times or more, 5 times or more, 6 times or more, 8 times or more, 10 times or more, 15 times or more, or 20 times or more greater than the height.

The centrifuge may be of any size. For example, the centrifuge may have about 200cm²Or smaller, 150cm²Or smaller, 100cm²Or smaller, 90cm²Or smaller, 80cm²Or smaller, 70cm²Or smaller, 60cm²Or smaller, 50cm²Or smaller, 40cm²Or smaller, 30cm²Or smaller, 20cm²Or smaller, 10cm²Or less, 5cm²Or less, or 1cm²Or a smaller footprint. The centrifuge can have a height of about 5cm or less, 4cm or less, 3cm or less, 2.5cm or less, 2cm or less, 1.75cm or less, 1.5cm or less, 1cm or less, 0.75cm or less, 0.5cm or less, or 0.1cm or less. In some specific examples, the maximum dimension of the centrifuge can be about 15cm or less, 10cm or less, 9cm or less, 8cm or less, 7cm or less, 6cm or less, 5cm or less, 4cm or less, 3cm or less, 2cm or less, or 1cm or less.

The centrifuge base may be configured to receive a drive device. The drive means may be a motor or any other means that enables the centrifuge to rotate about a rotational axis. The drive device may be a brushless motor, which may comprise a brushless motor rotor and a brushless motor stator. The brushless motor may be an induction motor. The brushless motor rotor may surround the brushless motor stator. The rotor may be configured to rotate about an axis of rotation with respect to the stator.

The base may be connected to or may incorporate a brushless motor rotor, which may cause the base to rotate about the stator. The base may be attached to the rotor or may be formed integrally with the rotor. The base may be rotatable about the stator, and a plane orthogonal to a rotation axis of the motor may be coplanar with a plane orthogonal to the rotation axis of the base. For example, the susceptor may have a plane orthogonal to the axis of rotation of the susceptor that passes substantially between the upper and lower surfaces of the susceptor. The motor may have a plane orthogonal to the motor rotation axis, the plane passing substantially through the motor center. The base plane and the motor plane may be substantially coplanar. The motor plane may pass between the upper and lower surfaces of the base.

The brushless motor assembly may include a rotor and a stator. The motor assembly may include an electronic component. The integration of the brushless motor into the rotor assembly may reduce the overall size of the centrifuge assembly. In some embodiments, the motor assembly does not extend beyond the base height. In other embodiments, the height of the motor assembly is no greater than 1.5 times the base height, 2 times the base height, 2.5 times the base height, 3 times the base height, 4 times the base height, or 5 times the base height. The rotor may be surrounded by the base such that the rotor is not exposed outside the base.

The motor combination enables rotation of the centrifuge without the need for a spindle/shaft combination. The rotor may surround the stator, and the stator may be electrically connected to a controller and/or a power source.

In some embodiments, the cavity may be configured to have a first orientation when the susceptor is stationary and a second orientation when the susceptor is rotated. The first orientation may be a vertical orientation and the second orientation may be a horizontal orientation. The cavity can have any orientation, wherein the cavity can be greater than and/or equal to about 0 degrees, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, 75 degrees, 80 degrees, 85 degrees, or 90 degrees from the vertical and/or axis of rotation. In some specific examples, the first orientation may be closer to vertical than the second orientation. The first orientation may be closer to being parallel to the axis of rotation than the second orientation. Alternatively, the cavity may have the same orientation whether the base is stationary or rotating. The orientation of the cavity may or may not depend on the speed at which the susceptor is rotated.

The centrifuge may be configured to receive a sample container and may be configured to have the sample container in a first orientation when the base is stationary and to have the sample container in a second orientation when the base is rotated. The first orientation may be a vertical orientation and the second orientation may be a horizontal orientation. The sample container can have any orientation, wherein the sample container can be greater than and/or equal to about 0 degrees, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, 75 degrees, 80 degrees, 85 degrees, or 90 degrees from vertical. In some specific examples, the first orientation may be closer to vertical than the second orientation. Alternatively, the sample container may have the same orientation whether the base is stationary or rotating. The orientation of the container may or may not depend on the speed at which the base is rotated.

Fig. 36 illustrates an example of a centrifuge provided according to one specific example described herein. The centrifuge may include a base 3600 having a bottom surface 3602 and/or a top surface 3604. The base may include one, two, or more wings 3610a, 3610 b.

The wing may be configured to fold over a shaft extending through the base. In some embodiments, the shaft may form a cut through the base. The shaft extending through the base may be a folding shaft, which may be formed by one or more pivot points 3620. The wing may comprise the entire portion of the base on one side of the shaft. The entire portion of the base may be folded to form the wing. In some embodiments, the center portion 3606 of the base can intersect the axis of rotation, while the wings do not. The central portion of the base may be closer to the axis of rotation than the wings. A central portion of the base may be configured to receive a drive 3630. The drive means may be a motor, or any other device that can cause the base to rotate, and may be discussed in further detail elsewhere herein. In some specific examples, the wings can have a footprint that is up to about 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% or more of the footprint of the base.

In some embodiments, a plurality of folding axes may be provided through the base. The folding axes may be parallel to each other. Alternatively, some of the fold axes may be orthogonal to each other, or at any other angle relative to each other. The folding axis may extend through the lower surface of the base, the upper surface of the base, or between the lower surface and the upper surface of the base. In some embodiments, the folding axis may extend through the base closer to the lower surface of the base or closer to the upper surface of the base. In some embodiments, the pivot point may be at or closer to the lower surface of the base or the upper surface of the base.

1, 2, 3, 4, 5, 6 or more cavities may be provided in the wings. For example, the wings may be configured to receive one, two or more samples or sample containers. Each wing may be capable of receiving the same number of containers or a different number of containers. The wings may include cavities configured to receive sample containers, wherein the sample containers are oriented in a first orientation when the base is stationary and configured to be oriented in a second orientation when the base is rotated.

In some embodiments, the wings can be configured to be angled relative to the central portion of the base. For example, the wings may be between 90 and 180 degrees of the central portion of the base. For example, the wings may be vertically oriented when the base is stationary. The wing portions may be oriented vertically at 90 degrees to the central portion of the base. The wings may be horizontally oriented when the base is rotated. The wing portions may be oriented 180 degrees from the central portion of the base when oriented horizontally. The wings may extend from the base to form a substantially uninterrupted surface as the base is rotated. For example, the wings may extend to form a substantially continuous surface of the bottom surface and/or the top surface of the base as the base rotates. The wing portion may be configured to fold downwardly relative to the central portion of the base.

The pivot point of the wings may include one or more pivot pins 3622. The pivot pin may extend through a portion of the wing and a portion of the central portion of the base. In some specific examples, the wings and the central portion of the base can have interlocking features 3624, 3626 that can prevent the wings from sliding laterally relative to the central portion of the base.

The wings may have a center of gravity 3680 that is positioned below the fold axis and/or pivot point 3620. When the base is stationary, the center of gravity of the wing may be positioned lower than the shaft extending through the base. The center of gravity of the wing may be positioned lower than the shaft extending through the base as the base rotates.

The wing portions may be formed of two or more different materials having different densities. Alternatively, the wing portion may be formed of a single material. In one example, the wing sections may have a lightweight wing cover 3640 and a heavy wing base 3645. In some embodiments, the wing cover may be formed of a material having a lower density than the wing base. For example, the wing cover may be formed of plastic, while the wing base is formed of metal, e.g., steel, tungsten, aluminum, copper, brass, iron, gold, silver, titanium, or any combination or alloy thereof. The heavier wing base may help provide a wing centroid below the fold axis and/or pivot point.

The wing cover and wing base may be connected by any means known in the art. For example, the fasteners 3650 may be removably provided, or adhesives, welding, interlocking features, clamps, hook and loop fasteners, or any other means may be employed. The wings may alternatively include inserts 3655. The insert may be formed of a heavier material than the flap cover. The insert may help provide the wing centroid below the fold axis and/or pivot point.

One or more cavities 3670 may be provided in the wing cover or wing base, or any combination thereof. In some embodiments, the cavity may be configured to receive a plurality of sample container configurations. The cavity may have an inner surface. At least a portion of the inner surface may contact the sample container. In one example, the cavity may have one or more of the following shelves or interior surface features: it may allow a first sample container having a first configuration to fit within the cavity and a second sample container having a second configuration to fit within the cavity. The first and second sample containers having different configurations may contact different portions of the inner surface of the cavity.

The centrifuge may be configured to engage a liquid handling device. For example, the centrifuge may be configured for connection to a pipette or other liquid handling device. In some embodiments, a water-tight seal may be formed between the centrifuge and the liquid handling apparatus. The centrifuge may be engaged with a liquid handling device and configured to receive a sample dispensed from the liquid handling device. The centrifuge may be engaged with a liquid handling device and configured to receive a sample container from the liquid handling device. The centrifuge may be engaged with a liquid handling device and allow the liquid handling device to draw or aspirate a sample from the centrifuge. The centrifuge may be engaged with a liquid handling device and allow the liquid handling device to pick up the sample container.

The sample container may be configured to engage a liquid handling device. For example, the sample container may be configured for connection to a pipette or other liquid handling device. In some embodiments, a water-tight seal may be formed between the sample container and the liquid handling apparatus. The sample container is engageable with a liquid handling apparatus and is configured to receive a sample dispensed from the liquid handling apparatus. The sample container may engage with the liquid handling device and allow the liquid handling device to draw or aspirate a sample from the sample container.

The sample container may be configured to extend out of the centrifuge wing. In some embodiments, the centrifuge base may be configured to allow the sample container to extend beyond the centrifuge wings when the wings are folded and to allow the wings to pivot between a folded state and an extended state.

Fig. 37 illustrates an example of a centrifuge provided in accordance with another specific example described herein. The centrifuge may include a base 3700 having a bottom surface 3702 and/or a top surface 3704. The base may include one, two, or more buckets 3710a, 3710 b.

The bucket may be configured to pivot about a bucket pivot extending through the base. In some embodiments, the shaft may form a cut through the base. The bucket may be configured to pivot about the rotation point 3720. The base may be configured to receive a drive device. In one example, the drive device may be a motor, such as a brushless motor. The drive device may include a rotor 3730 and a stator 3735. The rotor may alternatively be a brushless motor rotor and the stator may alternatively be a brushless motor stator. The drive means may be any other means that can cause the base to rotate, and may be discussed in further detail elsewhere herein.

In some embodiments, multiple axes of rotation may be provided through the bucket portion of the base. The axes may be parallel to each other. Alternatively, some axes may be orthogonal to each other or at any other angle relative to each other. The bucket axis of rotation may extend through the lower surface of the base, the upper surface of the base, or between the lower and upper surfaces of the base. In some embodiments, the bucket axis of rotation may extend through the base closer to the lower surface of the base or closer to the upper surface of the base. In some embodiments, the point of rotation may be at or closer to the lower surface of the base or the upper surface of the base.

1, 2, 3, 4 or more cavities may be provided in the bucket. For example, the bucket may be configured to receive one, two, or more samples or sample containers 3740. Each bucket may be capable of receiving the same number of containers or a different number of containers. The bucket may include a cavity configured to receive a sample container, wherein the sample container is oriented in a first orientation when the base is stationary and configured to be oriented in a second orientation when the base is rotated.

In some embodiments, the bucket may be configured to be angled with respect to the base. For example, the bucket may be between 0 and 90 degrees of the base. For example, the bucket may be vertically oriented when the base is stationary. When the base is stationary, the bucket may be positioned upwardly over the top surface of the centrifuge base. At least a portion of the sample container may extend beyond the top surface of the base when the base is stationary. The wing portions may be oriented vertically at 90 degrees to the central portion of the base. The bucket may be horizontally oriented when the base is rotated. The bucket portion may be at an angle of 0 degrees to the base when oriented horizontally. As the base rotates, the bucket may retract into the base, thereby forming a substantially uninterrupted top and/or bottom surface. For example, as the base rotates, the bucket may retract, thereby forming a substantially continuous surface of the bottom and/or top surface of the base. The bucket may be configured to pivot upward relative to the base. The bucket may be configured such that at least a portion of the bucket may pivot upward past the top surface of the base.

The point of rotation of the bucket may include one or more pivot pins. The pivot pin may extend through the bucket and the base. In some embodiments, the bucket may be positioned between portions of the base that may prevent the bucket from sliding laterally relative to the base.

The bucket may have a center of mass 3750 that is positioned below the rotation point 3720. When the base is stationary, the center of mass of the bucket may be positioned below the point of rotation. When the base is rotated, the center of mass of the bucket may be positioned below the point of rotation.

The bucket may be formed from two or more different materials having different densities. Alternatively, the bucket may be formed from a single material. In one example, the bucket may have a body 3715 and an internal insert 3717. In some embodiments, the body may be formed of a material having a lower density than the insert. For example, the body may be formed of plastic and the insert formed of metal, such as tungsten, steel, aluminum, copper, brass, iron, gold, silver, titanium, or any combination or alloy thereof. A heavier insert may help provide the bucket center of mass below the point of rotation. The bucket material may include a higher density material and a lower density material, wherein the higher density material is positioned below the point of rotation. The center of mass of the bucket may be located such that: so that when the centrifuge is at rest the bucket naturally swings with the open end up and the heavier end down. The center of mass of the bucket may be located such that: so that the bucket naturally retracts when the centrifuge is rotated at a certain speed. The bucket may be retracted when the speed is at a predetermined speed, which may include any speed or any of the speeds mentioned elsewhere.

One or more cavities may be provided in the bucket. In some embodiments, the cavity may be configured to receive a plurality of sample container configurations. The cavity may have an inner surface. At least a portion of the inner surface may contact the sample container. In one example, the cavity may have one or more of the following shelves or interior surface features: it may allow a first sample container having a first configuration to fit within the cavity and a second sample container having a second configuration to fit within the cavity. The first and second sample containers having different configurations may contact different portions of the inner surface of the cavity.

As previously mentioned, the centrifuge may be configured to engage a liquid handling device. For example, the centrifuge may be configured for connection to a pipette or other liquid handling device. The centrifuge may be configured to receive a sample dispensed by the liquid handling device or to provide a sample to be aspirated by the liquid handling device. The centrifuge may be configured to receive or provide a sample container.

As previously mentioned, the sample container may be configured to engage a liquid handling device. For example, the sample container may be configured for connection to a pipette or other liquid handling device.

The sample container may be configured to extend out of the bucket. In some embodiments, the centrifuge base may be configured to allow the sample container to extend out of the bucket when the bucket is provided in the retracted state, and to allow the bucket to pivot between the retracted and extended states. A sample container extending out of the top surface of the centrifuge may allow for easier transfer of a sample or sample container to and/or from the centrifuge. In some embodiments, the bucket may be configured to retract into the rotor, creating a compact combination and reducing drag during operation, with additional benefits such as reduced noise and heat generation and lower power requirements.

In some embodiments, the centrifuge base may include one or more channels or other similar structures, such as grooves, conduits, or passageways. Any description of the channels may also be applicable to any similar structure. The channel may contain one or more ball bearings. The ball bearing is slidable through the channel. The channels may be open, closed or partially open. The channel may be configured to prevent the ball bearing from falling out of the channel.

In some embodiments, ball bearings may be placed in a sealed/closed track within the rotor. Such a configuration is useful for dynamically balancing the centrifuge rotor, particularly when simultaneously centrifuging different volumes of sample. In some embodiments, the ball bearings may be external to the motor, making the overall system more robust and compact.

The channel may surround the centrifuge base. In some embodiments, the channel may surround the base along a perimeter of the centrifuge base. In some embodiments, the channel may be at or near an upper surface of the centrifuge base or a lower surface of the centrifuge base. In some cases, the channels may be equidistant from the upper and lower surfaces of the centrifuge base. The ball bearings are slidable along the perimeter of the centrifuge base. In some embodiments, the channel may surround the base at a distance from the axis of rotation. The channel may form a circle with the axis of rotation at substantially the center of the circle.

Fig. 38 illustrates an additional example of a centrifuge provided in accordance with another specific example described herein. The centrifuge may include a base 3800 having a bottom surface 3802 and/or a top surface 3804. The base may include one, two, or more buckets 3810a, 3810 b. The bucket may be connected to a module frame 3820, which may be connected to a base. Alternatively, the bucket may be directly connected to the base. The bucket may also be attached to a counterweight 3830.

The module frame may be connected to the base. The module frame may be connected to the base at a boundary, which may form a continuous or substantially continuous surface with the base. A portion of the top, bottom and/or side surfaces of the base may form a continuous or substantially continuous surface with the module frame.

The bucket may be configured to pivot about a bucket pivot extending through the base and/or the module frame. In some embodiments, the shaft may form a cut through the base. The bucket may be configured to pivot about a bucket pivot 3840. The base may be configured to receive a drive device. In one example, the drive device may be a motor, such as a brushless motor. The drive device may include a rotor 3850 and a stator 3855. In some embodiments, the rotor may be a brushless motor rotor and the stator may be a brushless motor stator. The drive means may be any other means that can cause the base to rotate, and may be discussed in further detail elsewhere herein.

In some embodiments, multiple axes of rotation may be provided through the bucket portion of the base. The axes may be parallel to each other. Alternatively, some axes may be orthogonal to each other or at any other angle relative to each other. The bucket axis of rotation may extend through the lower surface of the base, the upper surface of the base, or between the lower and upper surfaces of the base. In some embodiments, the bucket axis of rotation may extend through the base closer to the lower surface of the base or closer to the upper surface of the base. In some embodiments, the bucket pivot may be at or closer to the lower surface of the base or the upper surface of the base. The bucket pivot may be at or closer to the lower surface of the module frame or the upper surface of the module frame.

1, 2, 3, 4 or more cavities may be provided in the bucket. For example, the bucket may be configured to receive one, two or more samples or sample containers. Each bucket may be capable of receiving the same number of containers or a different number of containers. The bucket may include a cavity configured to receive a sample container, wherein the sample container is oriented in a first orientation when the base is stationary and configured to be oriented in a second orientation when the base is rotated.

In some embodiments, the bucket may be configured to be angled with respect to the base. For example, the bucket may be between 0 and 90 degrees of the base. For example, the bucket may be vertically oriented when the base is stationary. The bucket may be positioned upwardly over a top surface of the centrifuge base when the base is stationary. At least a portion of the sample container may extend beyond the top surface of the base when the base is stationary. The wings may be oriented 90 degrees from the central portion of the base when oriented vertically. The bucket may be horizontally oriented when the base is rotated. The bucket may be at 0 degrees to the base when oriented horizontally. As the base rotates, the bucket may retract into the base and/or frame module, thereby forming a substantially uninterrupted top and/or bottom surface. For example, as the base rotates, the bucket may retract, forming a substantially continuous surface with the base and/or the bottom and/or top surfaces of the frame module. The bucket may be configured to pivot upwardly relative to the base and/or frame module. The bucket may be configured such that: such that at least a portion of the bucket may pivot upwardly over the top surface of the base and/or frame module.

The bucket may be locked in a plurality of positions to support the discharge and pick up of centrifuge tubes, as well as to draw and dispense liquid into and out of the centrifuge container when the centrifuge container is in the centrifuge bucket. One means of achieving this is one or more motors that drive a wheel in contact with the centrifuge rotor to finely position and/or lock the rotor. Another approach may be to use a CAM (CAM) shape formed on the rotor without the need for an additional motor or wheel. An accessory from the pipette, such as a centrifuge tip attached to a pipette nozzle, may be pressed down onto the cam shape on the rotor. This force on the cam surface may cause the rotor to rotate to a desired locked position. The continued application of this force may enable the rotor to be held rigidly in the desired position. A plurality of such cam shapes may be added to the rotor to support a plurality of locking positions. While the rotor is held by one pipette nozzle/tip, another pipette nozzle/tip may interface with the centrifuge bucket to discharge or pick up centrifuge containers or perform other functions, such as aspirating or dispensing from centrifuge containers in the centrifuge bucket.

The bucket pivot may include one or more pivot pins. Pivot pins may extend through the bucket and the base and/or frame module. In some embodiments, the bucket may be positioned between the base and/or frame module: the parts prevent the bucket from sliding transversely relative to the base.

The bucket may be attached to a counterweight. The counterweight may be configured to move as the base begins to rotate, causing the bucket to pivot. When the base begins to rotate, the weight may be caused to move by centrifugal force exerted on the weight. The counterweight may be configured to move away from the axis of rotation when the base begins to rotate at the threshold speed. In some embodiments, the counterweight may move in a linear direction or path. Alternatively, the counterweight may move along a curved path or any other path. The bucket may be attached to the counterweight at counterweight pivot point 3860. One or more pivot pins or projections may be used which may allow the bucket to rotate relative to the counterweight. In some embodiments, the counterweight may move along a horizontal linear path, causing the bucket to pivot up or down. The weight may be moved in a linear direction orthogonal to the rotation axis of the centrifuge.

Counterweights may be located between portions of the module frame and/or base. The module frame and/or the base may be configured to prevent the counterweight from sliding off the base. The module and/or the base may limit the path of the counterweight. The path of the counterweight may be restricted to a straight direction. One or more guide pins 3870 may be provided that may limit the weight path. In some embodiments, the guide pins may pass through the frame module and/or the base and the counterweight.

A biasing force may be provided to the counterweight. The biasing force may be provided by a spring 3880, a resilient structure, a pneumatic device, a hydraulic device, or any other device. The biasing force may maintain the weight in the first position when the base is stationary, while centrifugal force from rotation of the centrifuge may cause the weight to move to the second position when the centrifuge rotates at a threshold speed. The counterweight may return to the first position when the centrifuge is back at rest or the speed drops below a predetermined rotational speed. When the counterweight is in the first position, the bucket portion can have a first shape; and the bucket portion may have a second orientation when the counterweight is in the second position. For example, when the counterweight is in the first position, the bucket may have a vertical orientation; and when the counterweight is in the second position, the bucket portion can have a horizontal orientation. The first position of the counterweight may be closer to the axis of rotation than the second position of the counterweight.

One or more cavities may be provided in the bucket. In some embodiments, the cavity may be configured to receive a plurality of sample container configurations. The cavity may have an inner surface. At least a portion of the inner surface may contact the sample container. In one example, the cavity may have one or more shelves or interior surface features that may allow a first sample container having a first configuration to fit within the cavity and a second sample container having a second configuration to fit within the cavity. The first and second sample containers having different configurations may contact different portions of the inner surface of the cavity.

As previously mentioned, the centrifuge may be configured to engage a liquid handling device. For example, the centrifuge may be configured for connection to a pipette or other liquid handling device. The centrifuge may be configured to receive a sample dispensed by the liquid handling device or to provide a sample to be aspirated by the liquid handling device. The centrifuge may be configured to receive or provide a sample container.

As previously mentioned, the sample container may be configured to engage a liquid handling device. For example, the sample container may be configured for connection to a pipette or other liquid handling device.

The sample container may be configured to extend out of the bucket. In some embodiments, the centrifuge base and/or the module frame may be configured to allow the sample container to extend out of the bucket when the bucket is provided in the retracted state, and to allow the bucket to pivot between the retracted state and the extended state. A sample container extending out of the top surface of the centrifuge may allow for easier transfer of a sample or sample container to and/or from the centrifuge.

In some embodiments, the centrifuge base may include one or more channels or other similar structures, such as grooves, conduits, or passageways. Any description of the channels may also be applicable to any similar structure. The channel may contain one or more ball bearings. The ball bearing is slidable through the channel. The channels may be open, closed or partially open. The channel may be configured to prevent the ball bearing from falling out of the channel.

The channel may surround the centrifuge base. In some embodiments, the channel may surround the base along a perimeter of the centrifuge base. In some embodiments, the channel may be at or near an upper surface of the centrifuge base or a lower surface of the centrifuge base. In some cases, the channels may be equidistant from the upper and lower surfaces of the centrifuge base. The ball bearings are slidable along the perimeter of the centrifuge base. In some embodiments, the channel may surround the susceptor at a distance rotated off-axis. The channel may form a circle with the axis of rotation at substantially the center of the circle.

Other examples of centrifuge configurations known in the art may be used, including various oscillating bucket configurations. See, for example, U.S. patent No. 7,422,554, which is hereby incorporated by reference in its entirety. For example, the bucket may swing downward rather than upward. The bucket may swing to project sideways rather than upwards or downwards.

The centrifuge may be enclosed within a housing or shell. In some embodiments, the centrifuge may be completely enclosed within the housing. Alternatively, the centrifuge may have one or more open sections. The housing may include movable portions that may allow liquid handling equipment or other automated equipment to access the centrifuge. The liquid handling apparatus and/or other automated apparatus may provide samples, take samples, provide sample containers, or take sample containers in a centrifuge. Such access may be permitted at the top, sides, and/or bottom of the centrifuge.

The sample may be dispensed and/or drawn from the cavity. The sample may be dispensed and/or drawn using a liquid handling system. The liquid handling system may be a pipette as described elsewhere herein, or any other liquid handling system known in the art. The sample may be dispensed and/or drawn using a tip having any of the configurations described elsewhere herein. The dispensing and/or aspirating of the sample can be automated.

In some embodiments, the sample container may be provided to or removed from a centrifuge. The sample container may be inserted into or removed from the centrifuge using the apparatus in an automated process. The sample container may extend from the surface of the centrifuge, which may simplify automated picking and/or retrieval. The sample may already be provided within the sample container. Alternatively, the sample may be dispensed and/or drawn from a sample container. The sample may be dispensed and/or drawn from the sample container using the liquid handling system.

In some embodiments, a tip from a liquid handling system may be at least partially inserted into a sample vessel and/or cavity. The tip may be insertable and removable from the sample container and/or the cavity. In some embodiments, the sample vessels and tips may be centrifugal vessels and centrifugal tips as previously described, or have any other vessel or tip configuration. In some specific examples, a cuvette (such as the cuvette described in fig. 70A and 70B) may be placed in a centrifuge rotor. Such an arrangement may provide certain advantages over conventional tips and/or containers. In some embodiments, the cuvettes may be patterned with one or more channels having a specialized geometry to allow the products of the centrifugation process to be automatically separated into individual compartments. One such specific example may be a cuvette with a tapered channel terminating in a compartment separated by a narrow opening. Supernatant (e.g., plasma from blood) may be forced into the compartment by centrifugal force while red blood cells remain in the main channel. The cuvette may be more complex, with several channels and/or compartments. The channels may be isolated or connected.

In some embodiments, one or more cameras may be placed in the centrifuge rotor such that they can image the contents of the centrifuge container as the rotor rotates. The camera images may be analyzed and/or communicated in real-time, for example, by using wireless communication methods. This method can be used to track sedimentation rate/cell packing-for example for ESR (erythrocyte sedimentation rate) measurements, where the RBC (erythrocyte) sedimentation rate is measured. In some embodiments, one or more cameras may be positioned outside the rotor that can image the contents of the centrifuge vessel as the rotor rotates. This can be achieved by using a stroboscopic light source that is timed synchronously with the camera and the rotating rotor. Real-time imaging of the centrifuge vessel contents as the rotor is rotated may allow for stopping the rotation of the rotor after the centrifugation process is complete, saving time and possibly preventing excessive stacking and/or excessive separation of the contents.

Thermal control unit

According to some specific examples described herein, a system may include one or more thermal control units. The apparatus may include one or more thermal control units therein. For example, one or more thermal control units may be provided within the device housing. The module may have one or more thermal control units. One, two or more modules of the apparatus may have a thermal control unit therein. The thermal control unit may be supported by the module support structure or may be contained within the module housing. Thermal control units may be provided at the equipment level (e.g., the entirety of all modules in the equipment), the rack level (e.g., the entirety of all modules in the rack), the module level (e.g., within a module), and/or the component level (e.g., within one or more components of a module).

The thermal control unit may be configured to heat and/or cool the sample or other liquid or module temperature or the temperature of the entire apparatus. Any discussion of controlling the temperature of the sample may also refer to any other liquid herein, including but not limited to reagents, diluents, dyes, or wash liquids. In some embodiments, separate thermal control unit assemblies may be provided to heat and cool the sample. Alternatively, the same thermal control unit assembly can both heat and cool the sample.

The thermal control unit may be used to vary and/or maintain the temperature of the sample to maintain the sample at a desired temperature or within a desired temperature range. In some embodiments, the thermal control unit may be capable of maintaining the sample within 1 ℃ of the target temperature. In other embodiments, the thermal control unit may be capable of maintaining the sample within 5 ℃,4 ℃, 3 ℃, 2 ℃, 1.5 ℃, 0.75 ℃, 0.5 ℃, 0.3 ℃, 0.2 ℃, 0.1 ℃, 0.05 ℃ or 0.01 ℃ of the target temperature. The desired target temperature may be programmed. The desired target temperature may be changed or maintained over time. The target temperature profile may account for the change in the desired target temperature over time. The target temperature profile may be dynamically provided from an external device (such as a server), may be provided on-board from the device, or may be input by an operator of the device.

The thermal control unit may be able to account for the temperature outside the device. For example, one or more temperature sensors may determine an ambient temperature external to the device. The thermal control unit may be operable to reach the target temperature to compensate for the different external temperatures.

The target temperature may remain constant or may change over time. In some embodiments, the target temperature may be varied in a cyclical manner. In some embodiments, the target temperature may be temporarily changed and then maintained constant. In some embodiments, the target temperature may follow a curve known in the art for nucleic acid amplification. The thermal control unit may control the sample temperature such that it follows a known curve for nucleic acid amplification. In some embodiments, the temperature may be in the range of 30-40 degrees Celsius. In some cases, the temperature range may be 0-100 degrees Celsius. For example, for nucleic acid assays, temperatures up to 100 degrees celsius may be achieved. In one specific example, the temperature range is about 15-50 degrees Celsius. In some embodiments, the temperature can be used to incubate one or more samples.

The thermal control unit may be capable of rapidly changing the temperature of one or more samples. For example, the thermal control unit may ramp up or down the temperature of the sample at a rate greater than and/or equal to 1, 5, 10, 15, 30, 45, 1, 2, 3, 4, 5, 7, or 10 ℃/sec.

The thermal control unit of the system may comprise a thermoelectric device. In some embodiments, the thermal control unit may be a heater. The heater may provide active heating. In some embodiments, the voltage and/or current provided to the heater may be varied or maintained to provide a desired amount of heating. The thermal control unit may be a resistive heater. The heater may be a thermoblock.

The thermal block may have one or many openings to support the incorporation of the detector and/or light source. The thermal block may have an opening for imaging the contents. The openings in the thermal block may be filled and/or covered to improve thermal performance of the block.

The heater may or may not have components that provide active cooling. In some embodiments, the heater may be in thermal communication with a heat sink. The heat sink may be passively cooled and may allow heat to dissipate to the ambient environment. In some embodiments, the heat sink or heater may be actively cooled, such as with forced liquid flow. The heat sink may or may not include one or more surface features such as fins, ridges, bumps, protrusions, grooves, channels, holes, fins, or any other feature that may increase the surface area of the heat sink. In some embodiments, one or more fans or pumps may be used to provide forced liquid cooling.

In some embodiments, the thermal control unit may be a Peltier Device (Peltier Device), or may be incorporated into a Peltier Device.

The thermal control unit may alternatively incorporate a fluid flow to provide temperature control. For example, one or more heated or cooled liquids may be provided to the thermal control unit. In some embodiments, the heated liquid and/or the cooled liquid may be contained within, or may flow through, a thermal control unit. By the use of heat pipes, air temperature control can be enhanced to rapidly warm up to a desired level. By using forced convection, the heat transfer can be made faster. Forced convection heat transfer can also be used to thermally cycle a particular area by alternately blowing hot air and cold air. Reactions requiring specific temperatures and temperature cycles can be performed on the tip and/or the vessel, with the heating and cooling of the tip being carefully controlled, such as by an IR heater.

In some specific examples, the thermal control unit may use conduction, convection, and/or radiation to provide heat to or remove heat from the sample. In some embodiments, the thermal control unit may be in direct physical contact with the sample or sample holder. The thermal control unit may be in direct physical contact with the vessel, tip, minicard or housing of the vessel, tip or minicard. The thermal control unit may contact a conductive material that may be in direct physical contact with the sample or sample holder. For example, the thermal control unit may contact a conductive material that may be in direct physical contact with the vessel, tip, microcard, or a housing used to support the vessel, tip, or microcard. In some embodiments, the thermal control unit may be formed of, or include, a high thermal conductivity material. For example, the thermal control unit may include a metal, such as copper, aluminum, silver, gold, steel, brass, iron, titanium, nickel, or any combination or alloy thereof. For example, the thermal control unit may comprise a metal block. In some embodiments, the thermal control unit may comprise a plastic or ceramic material.

One or more samples may be brought to and/or removed from the thermal control unit. In some embodiments, the sample may be brought to and/or removed from the thermal control unit using a liquid handling system. Any other automated process may be used to bring and/or remove the sample to and/or from the thermal control unit. The sample may be delivered to and from the thermal control unit without human intervention. In some embodiments, the sample may be transferred to and from the thermal control unit manually.

The thermal control unit may be configured to be in thermal communication with the small volume of the sample. For example, the thermal control unit may be configured to be in thermal communication with a sample having a volume as described elsewhere herein.

The thermal control unit may be in thermal communication with the plurality of samples. In some cases, the thermal control unit may maintain each identical sample at the same temperature relative to each other. In some cases, the thermal control unit may be thermally coupled to a heat sink, which may provide heat uniformly to the plurality of samples.

In other embodiments, the thermal control unit may provide different amounts of heat to the plurality of samples. For example, the first sample may be maintained at a first target temperature and the second sample may be maintained at a second target temperature. The thermal control unit may form a temperature gradient. In some cases, separate thermal control units may maintain different samples at different temperatures, or operate along separate target temperature profiles. The plurality of thermal control units may be independently operable.

One or more sensors may be provided at or near the thermal control unit. One or more sensors may be provided at or near the sample in thermal communication with the thermal control unit. In some embodiments, the sensor may be a temperature sensor. Any temperature sensor known in the art may be used, including but not limited to a thermometer, thermocouple, or IR sensor. The sensor may provide one or more signals to the controller. Based on the signal, the controller may send a signal to the thermal control unit to alter (e.g., increase or decrease) or alter the temperature of the sample. In some embodiments, the controller may directly control the thermal control unit to alter or maintain the sample temperature. The controller may be separate from the thermal control unit or may be part of the thermal control unit.

In some embodiments, the sensor may provide a signal to the controller periodically. In some embodiments, the sensor may provide real-time feedback to the controller. The controller may adjust the thermal control unit periodically or in real time in response to feedback.

As previously described, the thermal control unit may be used for nucleic acid amplification (e.g., isothermal and non-isothermal nucleic acid amplification, such as PCR), incubation, evaporation control, condensation control, obtaining a desired viscosity, separation, or any other use known in the art.

Cell counter

According to some embodiments described herein, the system may include one or more cell counters. The device may include one or more cell counters therein. For example, one or more cell counters may be provided within the device housing. The module may have one or more cell counters. One, two or more modules of the apparatus may have a cell counter therein. The cell counter may be supported by the module support structure or may be contained within the module housing. Alternatively, the cell counter may be provided outside the module. In some cases, the cell counter may be provided within the device and may be shared by multiple modules. The cell counter may have any configuration known in the art or later developed.

In some embodiments, the cytometer may have a small volume. For example, the cell counter can have a size of less than or equal to about 0.1mm³、0.5mm³、1mm³、3mm³、5mm³、7mm³、10mm³、15mm³、20mm³、25mm³、30mm³、40mm³、50mm³、60mm³、70mm³、80mm³、90mm³,100mm³、125mm³、150mm³、200mm³、250mm³、300mm³、500mm³、750mm³Or 1m³The volume of (a).

The cell counter may have a size less than or equal to about 0.1mm²、0.5mm²、1mm²、3mm²、5mm²、7mm²、10mm²、15mm²、20mm²、25mm²、30mm²、40mm²、50mm²、60mm²、70mm²、80mm²、90mm²,100mm²、125mm²、150mm²、200mm²、250mm²、300mm²、500mm²、750mm²Or 1m²The footprint of (2). The cell counter may have one or more dimensions (e.g., width, length, height) less than or equal to 0.05mm, 0.1mm, 0.5mm, 0.7mm, 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 15mm, 17mm, 20mm, 25mm, 30mm, 40mm, 50mm, 60mm, 70mm, 80mm, 100mm, 150mm, 200mm, 300mm, 500mm, or 750 mm.

The cytometer may receive a small volume of sample or other liquid. For example, the cell counter can receive a sample volume of about 500 μ L or less, 250 μ L or less, 200 μ L or less, 175 μ L or less, 150 μ L or less, 100 μ L or less, 80 μ L or less, 70 μ L or less, 60 μ L or less, 50 μ L or less, 30 μ L or less, 20 μ L or less, 15 μ L or less, 10 μ L or less, 8 μ L or less, 5 μ L or less, 1 μ L or less, 500nL or less, 300nL or less, 100nL or less, 50nL or less, 10nL or less, 1nL or less, 500pL or less, 250pL or less, 100pL or less, 50pL or less, 10pL or less, 5pL or less, or 1pL or less.

The cytometer may utilize one or more illumination techniques including, but not limited to, bright field, dark field, forward illumination, oblique illumination, backward illumination, phase contrast, and differential interference microscopy. Focusing can be achieved using any illumination source, including but not limited to dark field imaging. Dark field imaging may be performed with various illumination sources of different wavelength bands. Dark field imaging may be performed using an optical waveguide outside the objective lens. The image produced by the imaging system may be monochromatic and/or color. The imaging system can be configured without optics, thereby reducing cost and size.

The cell counter (and other modules) may be configured to incorporate image processing algorithms to extract quantitative information from images of cells and other elements in the sample, thereby supporting the calculation of reported value. Upon rejection, image processing and analysis may include, but is not limited to: a) image acquisition, compression/decompression and quality improvement, b) image segmentation, c) image stitching, and d) quantitative information extraction.

Detection unit

According to some specific examples described herein, a system may include one or more detection units. The device may comprise one or more detection units therein. For example, one or more detection units may be provided within the device housing. The module may have one or more detection units. One, two or more modules of the device may have a detection unit therein. The detection unit may be supported by the module support structure or may be contained within the module housing. Alternatively, the detection unit may be provided outside the module.

The detection unit may be adapted to detect a signal generated by at least one assay on the device. The detection unit may be used to detect signals generated by one or more sample prep instruments in the apparatus. The detection unit may be capable of detecting signals generated at any stage in the sample preparation or assay of the device.

In some embodiments, a plurality of detection units may be provided. Multiple detection units may operate simultaneously and/or sequentially. The plurality of detection units may comprise detection units of the same type and/or detection units of different types. The multiple probing units may operate according to a synchronized scheduling arrangement or independently of each other.

The detection unit may be above, below, to the side of, or integrated into the component from which the signal is detected, or may have a different orientation relative to the component from which the signal is detected. For example, the detection unit may be in communication with the assay unit. The detection unit may be close to the component from which the signal is detected or may be remote from the component from which the signal is detected. The detection unit may be located within 1mm or more, 1cm or more, 10cm or more from the component from which the signal is detected.

The detection unit may have a fixed position or may be movable. The detection unit may be movable relative to the component from which the signal is to be detected. For example, the detection unit may be moved into communication with the assay unit, or the assay unit may be moved into communication with the detection unit. In one example, a sensor is provided for positioning the assay unit relative to the detector when an assay is detected.

The detection unit may comprise one or more optical or visual or acoustic or magnetic or radioactive sensors or some combination of these sensors. For example, the detection unit may include microscopy, visual inspection, via photographic film, or may include the use of an electronic detector such as a digital camera, a Charge Coupled Device (CCD), a super cooled CCD array, a photodetector, or other detection instrument. The light detector may also include the following non-limiting examples: including photodiodes, photomultiplier tubes (PMTs), photon counting detectors or avalanche photodiodes, avalanche photodiode arrays. In some embodiments, a PIN diode may be used. In some embodiments, a PIN diode may be coupled to the amplifier to create a detection instrument with sensitivity comparable to a PMT. Some assays may generate luminescence as described herein. In some embodiments, fluorescence or chemiluminescence is detected. In some embodiments, the detection assembly may include a plurality of optical cables connected in bundles to the CCD detector or to the PMT array. The fiber optic bundle may be constructed from discrete optical fibers or a number of small optical fibers fused together to form a dense bundle. Such a dense beam is commercially available and is easily coupled to a CCD detector. In some embodiments, the fiber optic cable may be incorporated directly into the assay unit or the reagent unit. For example, the sample or tip described elsewhere herein may comprise a fiber optic cable. In some embodiments, an electronic sensor for detection or analysis (such as image processing) may be built into the pipette or other component of the liquid handling system.

The one or more detection units may be configured to detect a detectable signal, which may be an optical signal including, but not limited to, photoluminescence, electroluminescence, sonoluminescence, chemiluminescence, fluorescence, phosphorescence, polarization, absorbance, turbidity or scattering. In some embodiments, one or more labels may be employed during the chemical reaction. The label may allow the generation of a detectable signal. Methods for detecting labels are well known to those skilled in the art. Thus, for example, where the marker is a radioactive marker, the means for detecting may comprise a scintillation counter or photographic film as in autoradiography. In the case where the label is a fluorescent label, the fluorescent label may be detected by exciting a fluorescent dye with light of an appropriate wavelength and detecting the resulting fluorescence, for example, by microscopy, visual inspection, via photographic film, by using an electronic detector such as a digital camera, Charge Coupled Device (CCD), or photomultiplier and photocell, or other detection means. In some specific examples, an imaging instrument, such as a camera, may be used. In some cases, the camera may use a CCD, CMOS, may be a lensless camera (e.g., a frankencera camera), a microlens array camera, an open source camera, or may use any other visual detection technique known in the art or later developed. The camera may acquire an irregular image, e.g. a holographic image, tomographic or interferometric imaging, fourier transform spectroscopy, which may then be interpreted with or without the aid of computational methods. The camera may include one or more of the following features: which may focus the camera during use or may take an image that may be focused at a later time. In some embodiments, the imaging modality may employ 2-D imaging, 3-D imaging, and/or 4-D imaging (including changes over time). The imaging modality may take still images. The optical protocols used to achieve 3-D and 4-D imaging may be one or more of several protocols known to those skilled in the art, such as structured illumination microscopy (SLM), Digital Holographic Microscopy (DHM), confocal microscopy, light field microscopy, and the like. Still images may be taken at one or more points in time. The imaging modality may also take video images and/or dynamic images. Video images may be taken continuously over one or more time periods. The imaging device may acquire signals from an optical system that scans the sample in an arbitrary scanning pattern (e.g., raster scan). In some specific examples, an imaging modality may use one or more components of a device in the capture of an image. For example, the imaging instrument may use a tip and/or a container to assist in capturing images. The tip and/or the container may function as an optical instrument to aid in the capture of images.

The detection unit may also be able to take an audio signal. One or more image capture audio signals may be communicated. An audio signal may be captured with and/or associated with one or more still images or video images. Alternatively, the audio signal may be taken independently of the image.

In one example, a PMT may be used as the detector. In some cases, count rates as low as 100 counts per second and up to 10000000 count rates are measurable. The linear response range of the PMT (e.g., the range where the count rate is proportional to the number of photons per unit time) may be about 1000-3000000 counts per second. In one example, the assay has detectable signals of about 200-1000 counts/second at the low end and about 10000-2000000 counts/second at the high end. In some cases, for protein biomarkers, the count rate is directly proportional to the alkaline phosphatase bound to the capture surface, and also directly proportional to the analyte concentration.

In another example, the detector may include a camera, which may image in real time. Alternatively, the camera may take snapshots at selected time intervals or when triggered by an event. Similarly, the camera may take a video at selected time intervals or when triggered by an event. In some embodiments, the camera may image multiple samples simultaneously. Alternatively, the camera may image a selected view and then move to the next location to image a different selected view.

The detection unit may have an output such that: it is in digital form and is typically a one-to-one or one-to-many transformation of the detected signal, e.g. the image intensity values are integers proportional to the positive power of the number of photons reaching the camera sensor in the exposure time. Alternatively, the detection unit may output an analog signal. The detectable range of an exemplary detector may be adapted to the detector used.

The detection unit may be capable of capturing and/or imaging signals from anywhere along the electromagnetic spectrum. For example, the detection unit may be capable of capturing and/or imaging visible signals, infrared signals, near infrared signals, far infrared signals, ultraviolet signals, gamma rays, microwaves, and/or other signals. The detection unit may be capable of taking sound waves over a large frequency range, e.g. audio, ultrasound. The detection unit may be capable of measuring magnetic fields having a wide range of magnitudes.

The light detector may also include a light source such as a light bulb, incandescent bulb, electroluminescent lamp, laser diode, Light Emitting Diode (LED), gas discharge lamp, high intensity discharge lamp, natural daylight, chemiluminescent light source. Examples of other light sources are provided elsewhere herein. The light source may illuminate the assembly to assist in the detection results. For example, the light source may illuminate the assay to detect the results. For example, the assay may be a fluorescence assay or an absorbance assay as is commonly used for nucleic acid assays. The detector may also contain optics to deliver the light source to the assay, such as lenses, mirrors, scanning or galvo mirrors, prisms, fiber optic optics or liquid light guides. The detector may further comprise an optical instrument to deliver light from the assay unit to the detection unit.

The optical detection unit may be adapted to detect one or more optical signals. For example, the detection unit may be used to detect a reaction providing luminescence. The detection unit may be used to detect reactions that provide fluorescence, chemiluminescence, photoluminescence, electroluminescence, sonoluminescence, absorbance, turbidity or polarization. The detection unit may be capable of detecting light signals related to color intensity and phase or spatial or temporal gradients thereof. For example, the detection unit may be configured to detect a selected wavelength or wavelength range. The optical detection unit may be configured to move over the sample and the mirrors may be used to scan the sample simultaneously.

In some embodiments, the detection system may comprise an optical or non-optical detector or sensor for detecting a particular parameter of the subject. Such sensors may beIncluding sensors for temperature, electrical signal, for oxidized or reduced compounds (e.g. O)₂、H₂O₂And I₂) Or sensors that can oxidize/reduce organic compounds. The detection system may include sensors that measure sound waves, sound pressure variations, and sound speed.

Examples of temperature sensors may include thermometers, thermocouples, or IR sensors. The temperature sensor may or may not use thermal imaging. The temperature sensor may or may not contact the object whose temperature is to be sensed.

Examples of sensors for electrical properties may include sensors that can detect or measure voltage levels, current levels, conductivity, impedance, or resistance. The electrical property sensor may also comprise a potentiometer or an amperometric sensor.

In some embodiments, the marker may be selected to be detectable by the detection unit. The marker may optionally be selectively detected by a detection unit. Examples of markers are discussed in more detail elsewhere herein.

Any sensor may be triggered based on one or more schedules or detected events. In some embodiments, the sensors may be triggered when they receive instructions from one or more controllers. The sensor may continuously sense and may indicate when a certain condition is sensed.

One or more sensors may provide signals indicative of the measured property to the controller. One or more sensors may provide signals to the same controller or to different controllers. In some embodiments, the controller may have a hardware module and/or a software module that may process the sensor signal to interpret the signal for the controller. In some embodiments, the signal may be provided to the controller via a wired connection, or may be provided wirelessly. The controller may be provided on a system-wide level, a device group level, a device level, a module level, or a component level of a module, or any other level as described elsewhere herein.

Based on the signals from the sensors, the controller may effect changes in the components or maintain the state of the cell. For example, the controller may change the temperature of the thermal control unit, alter the rotational speed of the centrifuge, determine protocols to run on a particular assay sample, move the vessel and/or tip, or dispense a sample and/or aspirate a sample. In some embodiments, the controller may maintain one or more conditions of the device based on the signals from the sensors. The one or more signals from the sensors may also allow the controller to determine the current state of the device and track what actions have occurred or are being taken. This may or may not affect future actions to be performed by the device. In some cases, sensors (e.g., cameras) may be useful for detecting conditions that may include equipment errors or malfunctions. The sensors may detect conditions that may lead to errors or malfunctions in the data collection. The sensors are useful in providing feedback in an attempt to correct a detected error or fault.

In some specific examples, one or more signals from a single sensor may be considered for a particular action or condition of a device. Alternatively, one or more signals from multiple sensors may be considered for a particular action or condition of the device. One or more signals may be evaluated based on the time at which they were provided. Alternatively, one or more signals may be evaluated based on information collected over time. In some embodiments, the controller may have hardware modules and/or software modules that may process one or more sensor signals in an interdependent or independent manner to interpret the signals for the controller.

In some embodiments, multiple types of sensors or detection units may be useful for measuring the same property. In some cases, multiple types of sensors or detection units may be used to measure the same property, and may provide a way to verify the measured property, or as a coarse first measurement, which may in turn be used to refine the second measurement. For example, a camera and a spectroscope or other type of sensor may be used together to provide colorimetric readings. Nucleic acid assays can be observed via fluorescence and another type of sensor. The cell concentration can be measured with low sensitivity using absorbance or fluorescence, with the aim of configuring the same or another detector before performing high sensitivity cell counting.

The controller may also provide information to an external device. For example, the controller may provide the assay readings to an external device, which may further analyze the results. The controller may provide the signal provided by the sensor to an external device. The controller may pass such data as raw data collected from the sensors. Alternatively, the controller may process and/or pre-process the signals from the sensors before providing them to the external device. The controller may or may not perform any analysis of the signals received from the sensors. In one example, the controller may convert the signal to a desired specification without performing any analysis.

In some embodiments, the detection unit may be provided inside a housing of the device. In some cases, one or more detection units, such as sensors, may be provided outside the housing of the device. In some embodiments, the device may be capable of external imaging. For example, the apparatus may be capable of performing MRI, ultrasound or other scans. This may or may not utilize sensors outside the device. In some cases, it may utilize a peripheral, which may communicate with the device. In one example, the peripheral may be an ultrasound scanner. The peripheral may communicate with the device through a wireless connection and/or a wired connection. The device and/or peripheral may be brought into close proximity (e.g., within 1m, 0.5m, 0.3m, 0.2m, 0.1cm, 8cm, 6cm, 5cm, 4cm, 3cm, 2cm, 1cm, 0.5 cm) or contact with the area to be scanned.

Camera with a camera module

The camera described herein may be a Charge Coupled Device (CCD) camera, a super cooled CCD camera, or other optical camera. Such cameras may be formed on a chip with one or more cameras, such as part of a camera array. Such cameras may include one or more optical components, for example, to take light, focus light, polarize light, filter out unwanted light, minimize scattering, improve image quality, improve signal-to-noise ratio. In one example, the camera may include one or more lenses and mirrors. Such cameras may have a color sensor or a monochrome sensor. Such cameras may also include electronic components, such as microprocessors and digital signal processors, for one or more of the following tasks: image compression, dynamic range enhancement using computational methods, automatic exposure, automatic determination of optimal camera parameters, image processing, triggering of a flash in synchronization with the camera, and enabling an on-line controller to compensate for the effects of temperature changes on the performance of the camera sensor. Such cameras may also include on-board memory to buffer images acquired at high frame rates. Such cameras may include mechanical features for image quality improvement, such as a cooling system or an anti-vibration system.

The cameras may be provided at various locations on the point of service systems, devices, and modules described herein. In one particular example, a camera may be provided in the module for imaging various processing conventions including sample preparation and assay. This may enable the system to detect faults, perform quality control assessments, perform longitudinal analyses, perform process optimization, and synchronize operations with other modules and/or systems.

In some cases, the camera includes one or more optical components selected from the group consisting of: lenses, mirrors, diffraction gratings, prisms, and other components for directing and/or manipulating light. In other cases, the camera is a lensless camera configured to operate without one or more lenses. One example of a lensless camera is a Franken camera. In one particular example, a lensless camera uses (or collects) reflected or scattered light and performs computer processing to infer the structure of the object.

In a specific example, the lens-free camera has a diameter of at most about 10 nanometers ("nm"), at most about 100nm, at most about 1 μm, at most about 10 μm, at most about 100 μm, at most about 1mm, at most about 10mm, at most about 100mm, or at most about 500 mm. In another embodiment, the object lens camera has a diameter between about 10nm and 1mm or between about 50nm and 500 μm.

The camera configurations provided herein are for fast image capture. Systems employing such cameras may provide images in a delayed manner, where there is a delay from the point in time when an image is captured to the point in time when it is displayed to the user, or in a real-time manner, where there is little or no delay from the point in time when an image is captured to the point in time when it is displayed to the user. In some cases, the cameras provided herein are configured to operate in low lighting conditions or substantially low lighting conditions.

In some cases, the cameras provided herein are formed from an optical waveguide configured to guide electromagnetic waves in the optical spectrum. Such optical waveguides may be formed in an array of optical waveguides. The optical waveguide may be a planar waveguide, which may include one or more gratings for guiding light. In some cases, the camera may have a fiber optic image bundle, image conduit, or panel that carries light to the camera sensor.

The camera may be used as a detection unit. The camera may also be useful for imaging one or more samples or portions of samples. The camera may be useful for pathology. The camera may also be useful for detecting the concentration of one or more analytes in a sample. The camera may be useful for imaging motion or changes in the sample and/or analytes in the sample over time. The camera may comprise a video camera that can continuously take images. The camera may also take images again or one or more times (e.g., periodically, at predetermined intervals (regular or irregular), in response to one or more detected events). For example, the camera may be useful for taking up cell morphology, changes in concentration and spatial distribution of entities in cells labeled with contrast agents (e.g., fluorescent dyes, gold nanoparticles), and/or motion. Cellular imaging may include images taken over time that may be useful for analyzing cellular movement and morphological changes and associated disease states or other conditions. The camera may be useful for capturing sample kinematics, dynamics, morphology or histology. Such images may be useful for diagnosis, prognosis, and/or treatment of a subject. The imaging modality may be a camera or sensor that detects and/or records electromagnetic radiation and associated spatial and/or temporal dimensions.

The camera may be useful for device operator interaction with the device. The camera may be used for communication between the device operator and another person. The camera may allow for teleconferencing and/or video conferencing. The camera may allow for simulation of face-to-face communication between individuals who may be in different locations. Images of the sample or components thereof or assays or reactions involving the sample or components thereof may be stored to support subsequent reflectance detection, analysis and/or review. Image processing algorithms may be used to analyze images acquired within the device or remotely.

The camera may also be useful for biometric measurements of the subject (e.g., waist circumference, neck circumference, arm circumference, leg circumference, height, weight, body fat, BMI) and/or identifying the subject or device operator who may in turn be characterized by imaging (e.g., facial recognition, retinal scan, fingerprint, handprint, gait, motion). The embedded imaging system may also take ultrasound or MRI (magnetic resonance imaging) of the subject through the system. As described elsewhere herein, cameras may also be useful for security applications. The camera may also be useful for imaging one or more parts of the device and for detecting errors within the device. The camera may image and/or detect mechanical failure and/or proper functioning of one or more components of the device. The camera may be used to capture problems, correct problems, or learn from detected conditions. For example, the camera may detect the presence of a bubble in the tip-the presence of which may cause a deviation in the reading or may cause an error. The camera may also be used to detect whether the tip is not properly coupled to the pipette. The camera may take an image of the component and determine whether the component is positioned correctly or where the component is positioned. The camera may be used as part of a feedback loop with the controller to determine component positions with sub-micron resolution and adjust the system configuration to account for the precise position.

Dynamic resource sharing

One or more resources of the device may be shared. Resource sharing may occur at any level of the device. For example, one or more resources of a module may be shared within the module. In another example, one or more resources of a device may be shared between modules. One or more resources of the rack may be shared within the rack. One or more resources of the device may be shared between the racks.

The resources may include any component of the device, reagents provided within the device, samples within the device, or any other liquid within the device. Examples of components may include, but are not limited to, liquid handling devices, tips, vessels, assay units, reagent units, dilution units, wash units, contamination abatement devices, filters, centrifuges, magnetic separators, incubators, heaters, thermal blocks, cell counters, light sources, detectors, housings, controllers, displays, power supplies, communication units, identifiers, or any other component known in the art or described elsewhere herein. Other examples of components may include reagents, detergents, diluents, samples, markers, or any liquid or substance that may be useful for carrying out a chemical reaction. A module may include 1, 2, 3, 4, 5, or more of the resources listed herein. A device may include 1, 2, 3, 4, 5, or more of the resources listed herein. Modules may include different resources or may include the same resources. The device may include one or more modules not provided within the module.

It may be desirable to use resources that may not be readily available. A resource may not be readily available when the resource is being used, scheduled for use, absent, or otherwise inoperable. For example, it may be desirable to centrifuge a sample within a module, however the module may not have a centrifuge, the centrifuge may be in use, and/or the centrifuge may be subject to error. The device may determine whether additional centrifuges are available within the module. If additional centrifuges are available within the module, the device may use the available centrifuges. This may apply to any resource within the module. In some embodiments, resources within one module may be able to make up for deficiencies in another module. For example, if two centrifuges are required, but one cannot be used, another centrifuge may be used to accommodate two centrifuges simultaneously or sequentially.

In some cases, the desired resource may not be available within the selected module, but may be available in another module. The resources in the other module may be used. For example, if a centrifuge in a first module is damaged, in use, or is not present, a centrifuge in a second module may be used. In some embodiments, a sample and/or other liquid may be transferred from a first module to a second module in order to use a resource. For example, a sample may be transferred from a first module to a second module for use with a centrifuge. Once the resources have been used, the sample and/or other liquid may be transferred back to the first module, may remain in the second module, or may be transferred to the third module. For example, the sample may be transferred back to the first module for further processing using the resources available in the first module. In another example, if the required resources are available in the second module, the same sample may remain in the second module for further processing. In yet another example, if the required resources are not available in both the first and second modules, or the scheduling arrangement is improved in some way by using the resources of the third module, the sample and/or other liquid may be transferred to the third module.

Samples and/or other liquids may be transferred between modules. In some embodiments, a robotic arm may shuttle samples, reagents, and/or other liquids between modules, as described in more detail elsewhere herein. Samples and/or other liquids may be transferred using a liquid handling system. Samples and/or other liquids may be transferred between modules within a tip, vessel, unit, compartment, chamber, tube, conduit, or any other liquid containing and/or transferring device. In some embodiments, the liquid may be contained within a liquid-isolated or hydraulically-independent container as it is transferred between modules. Alternatively, they may flow through conduits between modules. The conduits may provide fluid communication between the modules. Each module may have a liquid handling system or device that may be capable of controlling movement of samples and/or liquids within the module. A first liquid handling device in a first module may provide liquid to the inter-module liquid transport system. A second liquid handling device at the second module may draw liquid from the inter-module liquid delivery system and may transfer the liquid to support use of resources in the second module.

In alternative embodiments, one or more resources may be transferred between modules. For example, a robotic arm may shuttle resources between modules. Other means may be used to transfer resources from the first module to the second module. In one example, the first module may contain a reagent within the reagent unit. The reagent and reagent unit may be transferred to a second module where the reagent and reagent unit may be used.

The resources may be provided within a device that may be external to all modules. The sample and/or other liquid may be transferred to the resource and the resource may be used. The sample and/or liquid may be transferred to a resource external to the cartridge using a robotic arm or any other transfer device described elsewhere herein. Alternatively, external resources may be transferred to one or more modules. In one example, a cell counter may be provided within the device but outside all modules. To access the cytometer, the sample may be transported back and forth from the module to the cytometer.

Such resource allocation within a module, between modules, or within a device external to a module may occur dynamically. The device may be able to track which resources are available. Based on one or more procedures, the device may be able to determine in real-time whether a resource is available or unavailable. The device may also be able to determine whether another resource is available within the same module, within a different module, or elsewhere within the device. The device may determine whether to wait to use a currently unavailable resource or use another available resource according to one or more sets of procedures. The device may be able to track whether the resource will become unavailable in the future. For example, the centrifuge may be scheduled to be used after the sample has been incubated for a predetermined length of time. The centrifuge may not be usable from the beginning of the predetermined time of use to the end of the intended use. The procedures may account for resources that are not available in the future.

In some embodiments, signals from one or more sensors may facilitate real-time determination of resource status and/or resource availability. One or more sensors and/or detectors may be capable of providing real-time feedback or updates regarding the status of the resource and/or process. The system may determine whether adjustments to the scheduling need to be made and/or whether another resource is used.

A procedure may include one or more sets of instructions that may determine what resources to use at what time. A procedure may include instructions to use resources within the same module, within different modules, or external to a module. In some specific examples, a procedure may include one or more sets of priorities or criteria. For example, if a resource within the same module is available, the resource may be used rather than a module provided within another module. Resources that are closer to the sample using the resource may have a higher priority. For example, if one or more steps are being performed on a sample within a first module and a resource is available within the first module, the resource may be used. If multiple copies of the resource are available within the first module, the copy of the resource closest to the sample may be used. If a resource is not available within the first module, the available resource in the module closest to the first module may be used. In another example, current and future availability may also be considered for determining usage of the module. This information may come from the cloud, the controller, the device, or from the module itself. In some specific examples, completion speeds may have priority over proximity (e.g., attempting to keep samples within the same module). Alternatively, proximity may have priority over speed. Other criteria may include, but are not limited to, proximity, speed, completion time, fewer steps, or less energy consumption. The criteria may have any level of prioritization or any other set of instructions or procedures may determine the use of resources and/or scheduling.

Shell body

According to some specific examples described herein, a system may include one or more devices. The device may have a housing and/or a support structure.

In some embodiments, the device housing may completely enclose the device. In other embodiments, the device housing may partially enclose the device. The device housing may comprise 1, 2, 3, 4, 5, 6 or more walls, which may at least partially enclose the device. The device housing may include a bottom and/or a top. The device housing may contain one or more modules of the device within the housing. The device housing may contain electronic and/or mechanical components within the housing. The apparatus housing may contain the liquid treatment system within the housing. The device housing may contain one or more communication units within the housing. The device housing may contain one or more controller units. The device user interface and/or display may be contained within the housing or may be disposed on a surface of the housing. The device may or may not contain a power source or an interface to a power source. The power source may be provided or incorporated within the housing, external to the housing, or incorporated within the housing.

The device may or may not be air-tight or liquid-tight. The device may or may not prevent light or other electromagnetic waves from entering the housing from outside the device or escaping the housing from within the device. In some cases, individual modules may or may not be air-tight or liquid-tight, and/or may not block light or other electromagnetic waves from entering the module.

In some embodiments, the apparatus may be supported by a support structure. In some embodiments, the support structure may be an equipment enclosure. In other embodiments, the support structure may support the apparatus from below the apparatus. Alternatively, the support structure may support the apparatus from one or more sides or from the top. The support structure may be integrated within the device or between portions of the device. The support structure may connect portions of the device. Any description herein of the device housing may also apply to any other support structure, or vice versa.

The device housing may completely or partially enclose the entire device. The device housing can enclose less than or equal to about 4m³、3m³、2.5m³、2m³、1.5m³、1m³、0.75m³、0.5m³、0.3m³、0.2m³、0.1m³、0.08m³、0.05m³、0.03m³、0.01m³、0.005m³、0.001m³、500cm³、100cm³、50cm³、10cm³、5cm³、1cm³、0.5cm³、0.1cm³、0.05cm³Or 0.01cm³Total volume of (c). The device may have any volume described elsewhere herein.

The device and/or the device housing may have a footprint that covers a lateral area of the device. In some embodiments, the device footprint may be less than or equal to about 4m²、3m²、2.5m²、2m²、1.5m²、1m²、0.75m²、0.5m²、0.3m²、0.2m²、0.1m²、0.08m²、0.05m²、0.03m²、100cm²、80cm²、70cm²、60cm²、50cm²、40cm²、30cm²、20cm²、15cm²、10cm²、7cm²、5cm²、1cm²、0.5cm²、0.1cm²、0.05cm²Or 0.01cm²。

The device and/or device housing may have a transverse dimension (e.g., width, length, or diameter) or height of less than or equal to about 4m, 3m, 2.5m, 2m, 1.5m, 1.2m, 1m, 80cm, 70cm, 60cm, 50cm, 40cm, 30cm, 25cm, 20cm, 15cm, 12cm, 10cm, 8cm, 5cm, 3cm, 2cm, 1cm, 0.5cm, 0.1cm, 0.05cm, or 0.01 cm. The lateral dimensions and/or heights may be different from each other. Alternatively, they may be the same. In some cases, the device may be a tall, thin device, or may be a short, wide device. The ratio of height to transverse dimension may be greater than or equal to 100:1, 50:1, 30:1, 20:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:30, 1:50, or 1: 100.

The device and/or the device housing may have any shape. In some embodiments, the device may have a rectangular or square transverse cross-sectional shape. In other specific examples, the device may have a transverse cross-sectional shape that is circular, elliptical, triangular, trapezoidal, parallelogram, pentagonal, hexagonal, octagonal, or any other shape. The device may have a longitudinal cross-sectional shape that is circular, oval, triangular, rectangular, square, trapezoidal, parallelogram, pentagonal, hexagonal, octagonal, or any other shape. The device may or may not have a box shape. The device may or may not have a flat planar shape and/or a circular shape.

The device housing and/or support structure may be formed of rigid, semi-rigid or soft materials. The device housing may be formed from one or more materials. In some embodiments, the device housing may comprise polystyrene, plastic, or machinable plastic. The device housing may comprise a polymeric material. Non-limiting examples of polymeric materials include polystyrene, polycarbonate, polypropylene, Polydimethylsiloxane (PDMS), polyurethane, polyvinyl chloride (PVC), polysulfone, Polymethylmethacrylate (PMMA), acrylonitrile-butadiene-styrene (ABS), and glass. The device housing may be an opaque material, a translucent material, a transparent material, or may include portions that are any combination thereof.

The device housing may be formed from a single unitary piece or multiple pieces. The device housing may contain multiple pieces that may be permanently affixed to one another or removably attached to one another. In some cases, one or more connection features of a housing may be contained solely within the housing. Alternatively, one or more connection features of the device housing may be external to the device housing. The device housing may be opaque. The device housing may prevent uncontrolled light from entering the device. The device housing may include one or more transparent portions. The device housing may allow controlled light to enter selected areas of the device.

The device housing may contain one or more movable portions that may be used to receive a sample into the device. Alternatively, the device housing may be static when providing the sample to the device. For example, the device housing may include an opening. The device opening may remain open or may be closable. The device may include one or more removable trays that may receive one or more samples or other components of the device. The tray may be translatable in a horizontal and/or vertical direction. The opening may be in fluid communication with one or more portions of the fluid treatment system therein. The opening may be selectively opened and/or closed. One or more portions of the device housing may be selectively opened and/or closed.

In some embodiments, the device housing may be configured to receive a cartridge or sample acquisition unit. In some embodiments, the device housing may be configured to receive or collect a sample. The device housing may be configured for collecting a sample directly from a subject or environment. The device housing may be in contact with a subject or an environment. Additional details regarding sample collection may be described elsewhere herein.

In some embodiments, the housing may enclose one or more racks, modules, and/or components as described elsewhere herein. Alternatively, the housing may integrally form one or more of the brackets, modules, and/or assemblies described elsewhere herein. For example, the housing may provide power and/or energy to the device. The housing may power the device from an energy storage unit, an energy generation unit and/or an energy delivery unit of the housing. The housing may provide communication between the device and/or an external device.

Controller

The controller may be provided at any level of the system described herein. For example, one or more controllers can be provided for a system, a group of devices, a single device, a module, a component of a device, and/or a portion of a component.

The system may include one or more controllers. The controller may provide instructions to one or more devices, modules of devices, components of devices, and/or portions of components. The controller may receive signals detectable from one or more sensors. The controller may receive a signal provided by the detection unit. The controller may contain local memory or may access remote memory. The memory may include a tangible computer readable medium having code, instructions, language to perform one or more steps as described elsewhere herein. The controller may be a processor or use a processor.

The system-wide controller may be provided external to one, two, or more devices, and may provide instructions to or receive signals from the one, two, or more devices. In some embodiments, the controller may communicate with a selected group of devices. In some embodiments, the controller may communicate with one or more devices at the same geographic location or at different geographic locations. In some embodiments, the system-wide controller may be provided on a server or another network device. Fig. 39 shows an example of a plurality of devices communicating with an external device through a network. In some cases, the external device may contain a controller, or may be a controller that communicates with other devices. In some embodiments, a system-wide controller may be provided on a device, which may have a master-slave relationship with other devices.

According to another specific example described herein, an apparatus may include one or more controllers. The controller may provide instructions to one or more modules of the device, components of the device, and/or portions of the components. The device level controller may receive signals detectable from one or more sensors and/or detection units.

The controller may contain local memory or may access remote memory on the device. The memory may include a tangible computer readable medium having code, instructions, language to perform one or more of the steps described elsewhere herein. The device may have local memory that may store one or more procedures. In some embodiments, the controller may be provided on a cloud computing infrastructure. The controller may be distributed throughout one or more of the hardware devices. The memory for the controller may be provided on one or more hardware devices. The protocol may be generated onboard and/or stored on the device. Alternatively, the protocol may be received from an external source, such as an external device or controller. The procedures may be stored on a cloud computing infrastructure or a peer-to-peer infrastructure. The memory may also store data collected from the detection unit of the device. Data may be stored for analysis of the detected signals. Some signal processing and/or data analysis may or may not occur at the device level. Alternatively, the signal processing and/or data analysis may occur on an external device, such as a server. Signal processing and/or data analysis may occur using a cloud computing infrastructure. The signal processing and/or data analysis may occur at a different location than where the device is located, or at the same geographic location.

A device level controller may be provided within a device and may provide instructions to or receive signals from one, two or more racks, modules, components of modules, or portions of components. In some embodiments, the controller may communicate with a selected group, component, or portion of modules. In some cases, the device level controller may be provided within a module that communicates with other modules. In some embodiments, the device level controller may be provided on a module, which may have a master-slave relationship with other modules. The module controller may be insertable into and/or removable from the device.

The device level controller may receive instructions from a system-wide controller or from a controller that provides instructions to one or more devices. The instructions may be procedures that may be stored on a local memory of the device. Alternatively, the instructions may be executed by the device in response to the received instructions without the need to store the instructions on the device or only temporarily store them on the device. In some embodiments, the device may store only the most recently received procedure. Alternatively, the device may store a plurality of protocols and be able to refer to these at a later time.

The device may provide information about the detected signal from the detection unit to an external source. The external source of the received information may or may not be the same as the source of the procedure. The device may provide raw information about the signal detected from the detection unit. Such information may include assay result information. The device may provide some processing of the collected sensor information. The device may or may not perform analysis of the collected sensor information locally. The information sent to the external source may or may not include processed data and/or analyzed data.

The device level controller may instruct the device to execute as a point of service device. The point of service device may perform one or more actions at a location remote from another location. The device level controller may command the device to interact directly with the subject or environment. The device level controller may allow the device to be operated by an operator of the device, which may or may not be a healthcare professional. The device level controller may instruct the device to receive the sample directly, where some additional analysis may occur remotely.

According to additional specific examples described herein, a module may include one or more controllers. The controller may provide instructions to one or more components and/or portions of components of the module. The module level controller may receive signals detectable from one or more sensors and/or detection units. In some examples, each module may have one or more controllers. Each module may have one or more microcontrollers. Each module may have a different operating system that can independently control each module. The modules may be capable of operating independently of each other. One or more modules may have one or more microcontrollers that control different peripherals, detection systems, robots, movements, work platforms, liquid drives, sample drives, or any other action within the module. In some cases, each module may have built-in graphics capabilities for high performance processing of images. In additional specific examples, each module may have their own controller and/or processor that may allow parallel processing using multiple modules.

The controller may contain local memory or may access remote memory on the module. The memory may include a tangible computer readable medium having code, instructions, language to perform one or more of the steps described elsewhere herein. The module may have local memory that may store one or more procedures. The protocol may be generated onboard and/or stored on the module. Alternatively, the protocol may be received from an external source, such as an external module, device, or controller. The memory may also store data collected from the detection units of the modules. Data may be stored for analysis of the detected signals. Some signal processing and/or data analysis may or may not occur at the module level. Alternatively, the signal processing and/or data analysis may occur at the device level or at an external device such as a server. Signal processing and/or data analysis may occur at a different location or the same geographical location as where the module is located.

A module level controller may be provided within a module and may provide instructions to or receive signals from one, two or more components or portions of components of the module. In some embodiments, the controller may communicate with selected groups of components or partial groups. In some cases, the module level controller may be provided within a component that communicates with other components. In some embodiments, a module level controller may be provided on a component that may have a master-slave relationship with other components. The module controller may be insertable into and/or removable from the module.

The module level controller may receive instructions from a full device controller, a full system controller, or from a controller that provides instructions to one or more devices. The instructions may be procedures that may be stored on the module's local memory. Alternatively, instructions may be executed by the modules in response to received instructions, without the need to store the instructions on the modules or only store them temporarily on the modules. In some embodiments, the module may store only the most recently received protocol. Alternatively, the module may store a plurality of procedures and be able to refer to these at a later time.

The module may provide information about the detected signal from the detection unit to the device or to an external source. The device or external source receiving this information may be the same as the source of the protocol or may be different. The module may provide raw information about the signal detected from the detection unit. Such information may include assay result information. The module may provide some processing of the collected sensor information. The module may or may not perform the analysis of the collected sensor information locally. The information sent to the device or external source may or may not include processed data and/or analyzed data.

The module level controller may instruct the modules to execute as service point modules. The module level controller may command the module to interact directly with the subject or environment. The module level controller may allow the module to be operated by an operator of the device, who may or may not be a healthcare professional.

The controller may be provided at any level of the system as described herein (e.g., a high-level system, group of devices, device, rack, module, component, portion of a component). The controller may or may not have memory at its level. Alternatively, it may access and/or use memory at any other level. The controllers may or may not communicate with additional controllers on the same or different levels. The controllers may communicate with additional controllers on levels immediately below or above them, or on levels above or below them. The controllers may communicate to receive and/or provide instructions/procedures. The controllers may communicate to receive and/or provide collected data or information based thereon.

User interface

The device may have a display and/or a user interface. In some cases, a user interface is provided to the subject by way of a display, such as through a Graphical User Interface (GUI), which may enable the subject to interact with the device. Examples of displays and/or user interfaces may include touch screens, video displays, LCD screens, CRT screens, plasma screens, light sources (e.g., LEDs, OLEDs), IR LED-based surfaces throughout or across a device, module, or other component, pixel sensing (pixelsense) based surfaces, infrared camera or other camera-based surfaces, projectors, projection screens, holograms, buttons, mice, buttons, knobs, sliders, joysticks, audio components, voice activation, speakers, microphones, cameras (e.g., 2D, 3D cameras), multiple cameras (e.g., may be useful for taking gestures and motions), glasses/contact lenses with built-in screens, video capture, tactile interfaces, temperature sensors, body mass index sensors, motion sensors, and/or pressure sensors. Any description herein of a display and/or user interface may be applicable to any type of display and/or user interface. The display may provide information to an operator of the device. The user interface may provide information to and/or receive information from an operator. In some specific examples, such information may include visual information, audio information, sensory information, thermal information, pressure information, motion information, or any other type of information. In providing feedback to a user using a point of service system or information system or communicating with the system by touch or other means, audio, video and color coded information (such as a red LED indicating that the module is in use) may be used. In some embodiments, a user interface or other sensor of the device may be able to detect whether a person is approaching the device and wake up.

Fig. 56 illustrates a service point device 5600 having a display 5601. The display is configured to provide a Graphical User Interface (GUI)5602 to the subject. The display 5601 may be a touch display, such as a resistive touch display or a capacitive touch display. The device 5600 is configured to communicate with a remote device 5603, such as a personal computer, smart phone, tablet computer, or server, for example. The device 5600 has a Central Processing Unit (CPU)5604, a memory 5605, a communication module (or interface) 5606, and a hard disk drive 5607. In some specific examples, the device 5600 includes a camera 5608 (or in some cases multiple cameras, such as for three-dimensional imaging) for image and video capture. Device 5600 may include an audio recorder for capturing sound. Images and/or video may be provided to the subject by way of the display 5601. In other specific examples, camera 5608 may be a motion-aware input device (e.g.,)。

one or more sensors may be incorporated into the device and/or user interface. The sensor may be provided on, external to or within the device housing. Any of the sensor types described elsewhere herein may be incorporated. Some examples of sensors may include optical sensors, temperature sensors, motion sensors, depth sensors, pressure sensors, electrical property sensors, gyroscopes, or acceleration sensors (e.g., accelerometers).

In one example, the device includes an accelerometer that detects when the device is not mounted on a desired surface (e.g., a horizontal surface), such as when the device is tipped over. In another example, an accelerometer detects when the device is moved. In such cases, the device may be shut down to prevent damage to the various components of the device. In some cases, a particular instance of the device takes a picture of a predetermined area on or around the device prior to closing by means of a camera on the device (see fig. 56).

The user interface and/or the sensor may be provided on a housing of the device. They may be integrated into the housing of the device. In some embodiments, the user interface may form an outer layer of a housing of the device. The user interface may be visible when viewing the device. The user interface may be selectively visible when operating the device.

The user interface may display information related to the operation of the device and/or data collected from the device. The user interface may display information related to protocols that may be run on the device. The user interface may include information related to a protocol provided from a source external to the device or provided from the device. The user interface may display information related to the subject and/or the subject's healthcare accessibility. For example, the user interface may display information related to the identity of the subject and the medical insurance of the subject. The user interface may display information related to scheduling and/or processing operations of the device.

The user interface may be capable of receiving one or more inputs from a user of the device. For example, the user interface may be capable of receiving instructions regarding one or more assays or programs to be performed by the device. The user interface may receive instructions from a user regarding one or more sample processing steps to occur within the device. The user interface may receive instructions regarding one or more analytes to be detected.

The user interface may be capable of receiving information regarding the identity of the subject. The subject identity information may be entered by the subject or another operator of the device, or imaged or otherwise ingested by the user interface itself. Such identification may include biometric information, issued identification cards, or other uniquely identifiable biological or identifying features, materials, or data. The user interface may include one or more sensors that may assist in receiving identifying information about the subject. The user interface may have one or more questions or instructions regarding the identity of the subject to which the subject may respond.

In some cases, the user interface is configured to display a questionnaire to the subject, the questionnaire comprising questions regarding the subject's dietary intake, exercise, health status, and/or mental status (see above). The questionnaire may be a guided questionnaire with a plurality of questions regarding the subject's dietary intake, exercise, health status, and/or mental status. The questionnaire may be presented to the subject by means of a user interface, such as a Graphical User Interface (GUI), on a display of the device.

The user interface may be capable of receiving additional information related to the subject's condition, habits, lifestyle, diet, exercise, sleep patterns, or any other information. This additional information may be directly input by the subject or another operator of the device. The subject may be prompted by one or more questions or instructions from the user interface, and may enter information in response. The questions or instructions may relate to a qualitative manifestation of the subject's life (e.g., how the patient feels). In some embodiments, the information provided by the subject is not quantitative. In some cases, the subject may also provide quantitative information. The information provided by the subject may or may not relate to one or more analyte levels within a sample from the subject. The survey may also gather information about treatments and/or medications experienced by the subject or currently taken. The user interface may prompt the subject for a survey or similar technique. The survey may include graphics, images, video, audio, or other media features. The survey may or may not have a fixed set of questions and/or instructions. The survey (e.g., the order and/or content of the questions) may be dynamically changed according to the subject's answers.

The identification information about the subject and/or additional information about the subject may be stored in the device and/or transmitted to an external device or cloud computing infrastructure. Such information may be useful in the analysis of data about a sample collected from a subject. Such information may also be useful for determining whether to proceed with sample processing.

The user interface and/or sensors may be capable of collecting information about the subject or the environment. For example, the device may collect information via a screen, thermal sensor, optical sensor, motion sensor, depth sensor, pressure sensor, electrical property sensor, acceleration sensor, any other type of sensor described herein or known in the art. In one example, the optical sensor may be a multi-aperture camera capable of acquiring multiple images and calculating depth from this point. The optical sensor may be any type of camera or imaging device as described elsewhere herein. The optical sensor may capture one or more still images of the subject and/or video images of the subject.

The device may acquire an image of the subject. The image may be a 2D image of the subject. The device may acquire a plurality of images of the subject, which may be used to determine a 3D representation of the subject. The device may acquire a one-time image of the subject. The device may acquire images of the subject over time. The device may acquire images at any frequency. In some embodiments, the device may continuously acquire images in real time. The device may capture video of the subject. The device may acquire images of any portion of the subject including, but not limited to, the subject's eye or retina, the subject's face, the subject's hand, the subject's fingertip, the subject's torso, and/or the subject's whole body. The acquired images of the subject may be useful for identifying the subject and/or for diagnosis, treatment, monitoring, or prevention of a disease in the subject. In some cases, the images may be useful for determining a height, chest circumference, weight, or body mass index of the subject. The device may also capture an image of the subject's identification card, insurance card, or any other object associated with the subject.

The device may also capture audio information of the subject. Such audio information may include the voice of the subject or the sounds of one or more biological processes of the subject. For example, the audio information may include the sound of the subject's heartbeat.

The device may collect biometric information about the subject. For example, the device may collect information about the body temperature of the subject. In another example, the device may collect information about the pulse rate of the subject. In some cases, the device may scan a portion of the subject, such as the retina, fingerprint, or handprint of the subject. The device may determine a weight of the subject. The device may also collect a sample from a subject and sequence the subject's DNA, or a portion thereof. The device may also collect a sample from a subject and perform proteomic analysis thereon. Such information may be used for operation of the device. Such information may relate to the diagnosis or identity of the subject. In some embodiments, the device may collect information about an operator of the device, which may be different from or the same as the subject. Such information may be useful for verifying the identity of the device operator.

In some cases, such information collected by the device may be used to identify the subject. The identity of the subject may be verified for insurance or therapeutic purposes. The subject identification may be tied to the subject's medical record. In some cases, data collected by the device from the subject and/or sample may be associated with a record of the subject. The subject identity may also be tied to the subject's medical insurance (or other payer) record.

Power supply

The device may have a power source or be connected to a power source. In some embodiments, the power source may be provided external to the device. For example, the power may be provided from a grid/utility. Power may be provided from an external energy storage system or reservoir. The power may be provided by an external power generation system. In some embodiments, the device may include a plug or other connector capable of electrically connecting the device to an external power source. In another example, the device may use the body's natural electrical pulses to power the device. For example, the device may contact, be worn by, and/or swallowed by a subject, who may or may not provide some power to the device. In some specific examples, a device may include one or more piezoelectric components, which may be movable and capable of providing power to the device. For example, the device may have a patch configuration configured for placement on the subject, such that power is generated and provided to the device as the subject moves and/or the patch flexes.

The device may additionally or alternatively have an internal power source. For example, local energy storage may be provided on the device. In one particular example, the local energy storage may be one or more batteries or super capacitors. Any battery chemistry known in the art or later developed may be used as a power source. The battery may be a primary battery or a secondary (rechargeable) battery. Examples of batteries include, but are not limited to: zinc-carbon, zinc-chlorine, alkaline, oxy-nickel hydroxide, lithium, mercury oxide, zinc-air, silver oxide, NiCd, lead-acid, NiMH, NiZn, or lithium ions. The internal power source may be independent or may be coupled to an external power source. In some specific examples, the device may include an energy generator. The energy generator may be provided separately or may be coupled to an external power source and/or an internal power source. The energy generator may be a conventional generator as known in the art. In some specific examples, the energy generator may use renewable energy sources, including but not limited to: solar photovoltaic, solar thermal, wind, water or geothermal energy. In some specific examples, the electricity can be generated by nuclear energy or by nuclear fusion.

Each device may be connected to or have a power source. Each module may be connected to a power source or have its own local power source. In some cases, the module may be connected to a power source of the device. In some cases, each module may have its own local power supply and may be capable of operating independently of other modules and/or devices. In some cases, modules may be able to share resources. For example, if a power source in one module is damaged or compromised, that module may be able to access the power source of another module or device. In another example, if a particular module is consuming a relatively large amount of power, that module may be able to access the power supply of another module or device.

Still alternatively, the device assembly may have a power source. Any discussion herein of power supplies for modules and/or devices may also refer to power supplies at other levels, such as systems, groups of devices, racks, device components, or portions of device components.

Communication unit

The device may have a communication unit. The device may be able to communicate with an external device using the communication unit. In some cases, the external device may be one or more of the same type of device. The external device may be part of, or may interact with the cloud computing infrastructure. In some cases, the external device with which the device may communicate may be a server or other device as described elsewhere herein.

The communication unit may allow wireless communication between the device and an external device. Alternatively, the communication unit may provide wired communication between the device and an external device. The communication unit may be capable of wirelessly transmitting and/or receiving information to/from an external device. The communication unit may allow one-way communication and/or two-way communication between the device and one or more external devices. In some embodiments, the communication unit may transmit information collected or determined by the device to an external device. In some embodiments, the communication unit may receive a procedure or one or more instructions from an external device. The device may be able to communicate with a selected external device or may be able to freely communicate with a wide variety of external devices.

In some embodiments, the communication unit may allow the devices to communicate over a network, such as a Local Area Network (LAN) or a Wide Area Network (WAN), such as the internet. In some embodiments, the devices may communicate via a telecommunications network, such as a cellular network or a satellite network. It should be appreciated that the communication unit may implement the network connectivity techniques described herein using any network connectivity hardware and/or software. This includes network connectivity techniques as described herein and in the icons associated with fig. 83-88.

Some examples of technologies that may be used by the communication unit may include bluetooth or RTM technologies. Alternatively, various communication methods may be used, such as a dial-up wired network using a modem, a direct link such as TI, ISDN, or cable lines. In some embodiments, the wireless connection may use an exemplary wireless network such as a cellular network, a satellite network or pager network, GPRS, or a local data transfer system such as an Ethernet network or a beacon ring over a LAN. In some embodiments, the communication unit may include a wireless infrared communication component for sending and receiving information.

In some embodiments, information may be encrypted prior to transmission over a network, such as a wireless network. In some embodiments, the encryption may be hardware-based encryption. In some cases, the information may be encrypted on hardware. Any or all of the information, which may include user data, subject data, test results, identifier information, diagnostic information, or any other type of information, may be encrypted according to hardware-based and/or software-based encryption. Encryption may also be based in turn or on subject specific information. For example, a subject may have a certain sample being processed by the device, and the subject's password may be used to encrypt data about the subject sample. By encrypting the data of the subject with the subject-specific information, only the subject can retrieve the data. For example, decryption can only occur when the subject enters a password on the web tablet. In another example, information transmitted by the device may be encrypted with information specific to the operator of the device at the time and retrieved only when the operator enters the operator's password or provides operator-specific information.

Each device may have a communication unit. Each module may have its own local communication unit. In some cases, the modules may share a communication unit with the device. In some cases, each module may have its own local communication unit and may be able to communicate independently of other modules and/or devices. The module may communicate with external devices, or other modules using its communication unit. In some cases, modules may be able to share resources. For example, if a communication unit is damaged or compromised in one module, that module may be able to access a communication unit of another module or device. In some cases, a device, a shelf, a module, a component, or a portion of a device component may be capable of sharing one or more routers. The various levels and/or components in the hierarchy may be capable of communicating with each other.

Still alternatively, the device component may have a communication unit. Any discussion herein of communication units of modules and/or devices may also refer to communication units at other levels, such as systems, groups of devices, racks, device components, or portions of device components.

Device, module and component identifiers

The device may have a device identifier. The device identifier may identify the device. In some embodiments, the device identifier may be unique to each device. In other specific examples, the device identifier may identify the type of device or module/component provided within the device. The device identifier may indicate a function that the device is capable of performing. In such a case, the device identifier may or may not be unique.

The device identifier may be a physical object formed on the device. For example, the device identifier may be read by an optical scanner or an imaging device (such as a camera). The device identifier may be read by one or more types of sensors as described elsewhere herein. In one example, the device identifier may be a barcode. The barcode may be a 1D or 2D barcode. In some embodiments, the device identifier may transmit one or more signals that may identify the device. For example, the device identifier may provide an infrared signal, a thermal signal, an ultrasonic signal, an optical signal, an audio signal, an electrical signal, a chemical signal, a biological signal, or other signal indicative of the identity of the device. The device identifier may use a Radio Frequency Identification (RFID) tag.

The device identifier may be stored in a memory of the device. In one example, the device identifier may be a computer readable medium. The device identifiers may communicate wirelessly or via a wired connection.

The device identifier may be static or changeable. The device identifier may change with possible changes to one or more modules provided for the device. The device identifier may vary based on the available components of the device. The device identifier may change when commanded by an operator of the device.

A device identifier may be provided to allow integration of the device into system wide communications. For example, an external device may communicate with multiple devices. The external device may distinguish one diagnostic device from another via a device identifier. The external device may provide it with special instructions based on the identifier of the diagnostic device. The external devices may include memory or may be in communication with memory that may maintain records of information about the devices. The device identifier of a device may be linked in memory with information gathered from or associated with the device.

In some embodiments, an identifier may be provided on the module or component level to uniquely identify each component in the device on the system level. For example, each module may have a module identifier. The module identifier may or may not be unique to each module. The module identifier may have one or more characteristics of a device identifier.

The module identifier may allow a device or system (e.g., external device, server) to identify the module provided therein. For example, a module identifier may identify the type of module and may allow a device to automatically probe the components and capabilities provided by the module. In some cases, the module identifier may uniquely identify the module, and the device may be able to track particular information associated with a particular module. For example, the device may be able to track the age of the module and estimate when certain components may need to be updated or replaced. The module may communicate with the processor of the device of which it is a part.

Alternatively, the module may communicate with a processor of an external device. The module identifier may provide the same information at a system-wide level. In some embodiments, the system, rather than the device, may track information associated with the module identifier.

The module identifier may be communicated to the device or system when the module identifier is connected to or interfaced with the device. For example, the module identifier may be communicated to the device or system after the module has been installed on the support structure. Alternatively, the module identifier may be transmitted remotely when the module is not already connected to the device.

The identifier may be provided at any other level described herein (e.g., external device, group of devices, rack, device component, component part). Any of the characteristics of the identifiers provided herein may also be applicable to such identifiers.

System for controlling a power supply

FIG. 39 provides an illustration of a diagnostic system according to one specific example described herein. One, two, or more devices 3900a, 3900b can communicate with an external device 3910 over a network 3920. The device may be a diagnostic device. The device may have any of the features or characteristics as described elsewhere herein. In some examples, the device may be a desktop device, a handheld device, a patch, and/or a pill. The device may be configured to receive a sample and perform one or more of a sample preparation step, an assay step, or a probing step. An apparatus may include one or more modules as described elsewhere herein.

In some embodiments, the patch or pill is configured to be operatively coupled (or linked) to a mobile device, such as a network device, that is configured to communicate with another device and/or network (e.g., an intranet or the internet). In some cases, the patch is configured to communicate with a pill that is circulated through the body of the subject or disposed within the body of the subject (such as within the tissue of the subject). In other cases, the pellets are particles having a size on the order of nanometers, micrometers, or larger. In one example, the pill is a nanoparticle. The patch and/or pill may include on-board electronics to allow the patch and/or pill to communicate with another device.

The system may include any number of devices 3900a, 3900 b. For example, a system may include 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 10 or more, 20 or more, 50 or more, 100 or more, 500 or more, 1000 or more, 5000 or more, 10000 or more, 100000 or more, or 1000000 or more devices.

The devices may or may not be connected into device groups. The devices may be associated with 1, 2,3, 10 or any number of groups. The devices may be part of a group, subgroup, sub-subgroup, and no restrictions are placed on the sub-groups in the system. In some embodiments, a device group may include devices that are in a particular geographic location. For example, a group of devices may refer to devices in the same room or in the same building. The device group may include devices within the same retailer location, laboratory, clinic, healthcare facility, or any other location. A group of devices may refer to devices within the same town or city. A device group may include devices within a particular radius. In some cases, a device group may include devices that use the same communication port. For example, a group of devices may include devices that use the same router, internetwork hub, telecommunications tower, satellite, or other communications port.

Alternatively, a device group may include devices associated with the same entity or department of an entity. For example, the device group may be associated with a laboratory, healthcare provider, medical facility, retailer, company, or other entity.

Any description herein regarding a system-wide hierarchy may refer to an overall global system, which may include or communicate with any device. Alternatively, any description of the system herein may also relate to a group of devices.

As described elsewhere herein, a network 3920 may be provided. For example, the network may include a Local Area Network (LAN) or a Wide Area Network (WAN) such as the Internet. In some specific examples, the device may communicate via a telecommunications network, such as a cellular network or a satellite network.

The device may communicate with the network using wireless technology, such as bluetooth or RTM technology. Alternatively, various communication methods may be used, such as a dial-up wired connection using a modem, a direct connection such as TI, ISDN, or a cable line. In some specific examples, the wireless connection may use an exemplary wireless network such as cellular, WIMAX, WIFI, satellite or pager network, GPRS, or a local data transfer system such as ethernet or beacon ring over LAN. In some embodiments, the device may communicate wirelessly using an infrared communication component.

According to one specific example described herein, an external device 3910 may be provided. The external device may be any network device described elsewhere herein or known in the art. For example, the external device may be a server, personal computer, notebook computer, tablet computer, mobile device, mobile phone, satellite phone, smart phone (e.g., iPhone, Android, Blackberry, Palm, Symbian, Windows), Personal Digital Assistant (PDA), pager, or any other device. In some cases, the external device may be another diagnostic device. A master-slave, point-to-point, or distributed relationship may be provided between the diagnostic devices. It should be appreciated that the device 3910 may implement the network connectivity techniques described herein using any network connectivity hardware and/or software. This includes network connectivity techniques as described herein and in the icons associated with fig. 83-88.

The external device may have a processor and memory. The external device may access local memory or communicate with memory. The memory may include one or more databases.

Any description of the external devices may also be applicable to any cloud computing infrastructure. An external device may refer to one or more devices that may include a processor and/or memory. The one or more devices may or may not communicate with each other.

In some embodiments, the external device may perform the functions of the controller or may comprise the controller and perform one or more of the functions of the controller as described elsewhere herein. The external devices may function as a system-wide controller, may control groups of devices, or may control individual devices.

In one example, the external device may store data in memory. Such data may include analyte threshold data. Such data may include curves or other information that may be useful for performing analysis and/or calibration. The external device may also receive and/or store data received from the sample processing device. Such data may include data related to one or more signals detected by the sample processing device. In some embodiments, one or more diagnostics and/or calibrations may be performed on the sample processing device. Such diagnostics and/or calibration may use and/or access curves or other data stored onboard the device or stored on an external device, such as a server.

Fig. 1 shows an example of a device 100 in communication with a controller 110 according to one specific example described herein.

The device may have any particular, structure, or function as described elsewhere herein. For example, the apparatus 100 may include one or more support structures 120. In some embodiments, the support structure may be a stent or any other support as described elsewhere herein. In some cases, the apparatus may include a single support structure. Alternatively, the apparatus may comprise a plurality of support structures. The plurality of support structures may or may not be connected to each other.

The apparatus 100 may include one or more modules 130. In some cases, the support structure 120 may include one or more modules. In one example, the modules may have a fin specification that is mountable on a rack support structure. Each device or support structure may be provided with any number of modules. Different support structures may have different numbers or types of modules.

The apparatus 100 may include one or more components 140. In some cases, module 130 may include one or more components of the module. The support 120 may contain one or more components of a module. Each device, rack, or module may be provided with any number of components. Different modules may have different numbers or types of components.

In some examples, the device may be a desktop device, a handheld device, a wearable device, a swallowable device, an implantable device, a patch, and/or a pill. The device may be portable. The device may be placed on a surface such as a counter, table, floor, or any other surface. The apparatus may be mounted or attached to a wall, ceiling, floor, and/or any other structure. The device may be worn directly by the subject, or may be incorporated into the subject's clothing.

The device may be self-contained. For example, a device may include local memory. The local memory may be provided to the overall device, or may be provided to one or more modules, or may be distributed across one or more modules. The local memory may be contained within the housing of the device. The local memory may be provided on a support of the module or within the housing of the module. Alternatively, the local memory of the device may be provided outside the module but inside the device housing. The local memory of the device may or may not be supported by the support structure of the device. The local memory may be provided outside the support structure of the device or may be integrated within the support structure of the device.

One or more procedures may be stored in local memory. One or more procedures may be delivered to the local memory. The local memory may include a database of information for on-board analysis of the detected signals. Alternatively, the local memory may store information related to the detected signals, which may be provided to an external device for remote analysis. The local memory may include some signal processing of the detected signal, but the signal may be transmitted to an external device for analysis. The external device may or may not be the same device controller.

The local memory may be capable of storing a non-transitory computer-readable medium that may include code, logic, or instructions capable of performing the steps described herein.

The apparatus may include a local processor. The processor may be capable of receiving instructions and providing signals to execute the instructions. The processor may be a Central Processing Unit (CPU) that may execute instructions of a tangible computer-readable medium. In some embodiments, the processor may include one or more microprocessors. The processor may be capable of communicating with one or more components of the device and carrying out operations of the device.

The processor may be provided to an overall device, or may be provided to one or more modules, or may be distributed across one or more modules. The processor may be contained within the housing of the device. The processor may be provided on a support of the module or within the housing of the module. Alternatively, the processor of the device may be provided outside the module, but inside the device housing. The processor of the device may or may not be supported by the support structure of the device. The processor may be provided outside the support structure of the device or may be integrated within the support structure of the device.

The controller 110 may be in communication with the device 100. In some embodiments, the controller may be a system-wide controller. The controller may communicate with any device. The controller may selectively communicate with a group of devices. For example, a system may include one, two, or more controllers, where one controller may be dedicated to a group of devices. The controller may be able to communicate with each device individually. In some cases, the controller may associate with a group of devices without distinguishing between devices within the group. The controller may communicate with any combination of devices or groups of devices.

The controller may be provided outside the device. The controller may be an external device in communication with the device. As described elsewhere herein, the external device may be any kind of network device. For example, the controller may be a server, a mobile device, or another diagnostic device that may have a master-slave relationship with the device.

In alternative implementation embodiments, the controller may be provided locally to the device. In this case, the device may be completely self-contained, requiring no external communication.

The controller may include or may be in communication with a memory. One or more protocols may be stored on the controller memory. These protocols may be stored outside the device. The procedures may be stored in memory and/or in a cloud computing infrastructure. The procedure can be updated on the controller side without the need to change the equipment. The controller memory may include a database of information related to the device, the sample, the subject, and/or information collected from the device. The information collected from the device may include raw data of the signals detected within the device. The information collected from the device may include some signal processing of the detected signals. Alternatively, the information gathered from the device may include analysis that may have been performed on-board the device.

The controller memory may be capable of storing a non-transitory computer readable medium that may include code, logic, or instructions capable of performing the steps described herein.

The controller may include a processor. A processor may be capable of receiving instructions and providing signals to execute the instructions. The processor may be a Central Processing Unit (CPU) that may execute instructions of a tangible computer-readable medium. In some embodiments, the processor may include one or more microprocessors. The processor of the controller may be capable of analyzing data received from the device. The processor of the controller may also be capable of selecting one or more protocols to provide to the device.

In some embodiments, the controller may be provided on a single external device. The single external device may be capable of providing a protocol to the diagnostic device and/or receiving information collected from the diagnostic device. In some cases, the controller may be provided on multiple devices. In one example, a single external device or multiple external devices may be able to provide a protocol to a diagnostic device. A single external device or multiple external devices may be able to receive the information collected from the diagnostic device. A single external device or multiple external devices may be able to analyze the information collected from the diagnostic device.

Alternatively, the system may use cloud computing. One or more of the functions of the controller may be provided by a computer network, rather than being limited to a single external device. In some embodiments, a network or a plurality of external devices may communicate with the diagnostic device and provide instructions to or receive information from the diagnostic device. Multiple processors and storage devices may be used to perform the functions of the controller. The controller may be provided in an environment in which: the environment supports convenient on-demand access to a shared pool of configurable computing resources (e.g., networks, servers, storage, applications, and services) that can be quickly provisioned and released with minimal management workload or service provider interaction.

Communication may be provided between the diagnostic device and the controller. The communication may be a one-way communication. For example, the controller may push the protocol down to the device. In another example, the device may initiate a request for a procedure from the controller. Alternatively, the device may only provide information to the controller, without requiring a procedure from the controller.

Preferably, two-way communication is provided between the diagnostic device and the controller. For example, the protocol may be provided from a source external to the device. The procedure may or may not be based on information provided by the device. For example, the protocol may or may not be based on input provided to the device, which may determine in some way the information provided by the device to the controller. The input may be determined manually by an operator of the apparatus. For example, the operator may specify one or more probes that the operator wishes the device to perform. In some cases, the input may be determined automatically. For example, the tests to be run may be automatically determined based on characteristics of the sample, which modules are available or have been used, past records about the subject, a schedule of expected tests, or any other information.

In some embodiments, the device may request a particular protocol from the controller. In some other specific examples, the device may provide information to the controller, and the controller may select one or more protocols to provide to the device based on the information.

The device may provide information collected at the device based on one or more detected signals from one or more sensors. The sensed information may be provided to a controller. The sensed information may or may not be collected during operation of the protocol. In some embodiments, the controller may provide additional protocols based on information collected during the first protocol. Based on the collected information, the first protocol may be completed before the additional protocol is initiated, or the additional protocol may be initiated before the first protocol is completed.

A feedback system may be provided in which the protocol may be provided or changed based on information collected during the protocol or after the protocol is completed. One or more agreements may be run in parallel, in sequence, or in any combination thereof. The device may perform an iterative process that may use the instructions, the actions performed based on the instructions, data collected from the performed actions, which may in turn or may affect subsequent instructions, and so forth. The protocol may cause the device to perform one or more actions including, but not limited to, a sample acquisition step, a sample preparation step, an assay step, and/or a detection step.

Within the system, a device may be able to communicate with one or more entities. For example, the device may communicate with a laboratory benefits manager, which may collect information from the device. A laboratory welfare manager may analyze information collected from the device. The device may communicate with an agreement provider, which may provide one or more instructions to the device. The protocol provider and the laboratory benefit manager may be the same entity or may be different entities. The device may in turn or otherwise communicate with a payer (such as an insurance company). The device may in turn or otherwise communicate with a healthcare provider. A device may communicate directly with one or more of these entities or may communicate indirectly with them through another party. In one example, the device may communicate with a laboratory benefit manager, which may communicate with payers and healthcare providers.

In some specific examples, the device may enable the subject to communicate with a healthcare provider. In one example, the device may allow one or more images of the subject to be taken by the device and provided to the subject's physician. The subject may or may not see the doctor on the device. The images of the subject may be used for identification or diagnostic purposes. As described elsewhere herein, other information regarding subject identification may be used. The subject may communicate with the physician in real time. Alternatively, the subject may view a record provided by a physician. The subject may advantageously communicate with the subject's own physician, which may provide the subject with additional sensations of comfort and/or interpersonal interaction. Alternatively, the subject may communicate with other healthcare providers, such as a specialist.

In some embodiments, diagnostic devices within a system may share resources. For example, devices within the system may communicate with each other. The devices may be directly linked to each other or may communicate over a network. The device may be directly linked to the shared resource or may communicate with the shared resource over a network. An example of a shared resource may be a printer. For example, multiple devices may communicate with a single printer. Another example of a shared resource is a router.

Multiple devices may share additional peripherals. For example, a plurality of devices within the system may communicate with a peripheral device that may ingest one or more physiological parameters of the subject. For example, the device may communicate with a blood pressure measurement device, a weighing appliance, a pulse rate measurement device, and an ultrasound image capture device, or any other peripheral device. In some cases, multiple devices and/or systems may communicate with a computer, mobile device, tablet computer, or any other device that may be useful for interacting with a subject. Such external devices may be useful for collecting information from a subject via a survey. In some specific examples, one or more controllers of the system may determine which device may use which peripheral at any given time.

The system may be capable of dynamic resource allocation. In some embodiments, the dynamic resource allocation may be system-wide or within a group of devices. For example, multiple devices may be connected to multiple shared resources. In one example, device a and device B may be connected to printer X, while device C and device D may be connected to printer Y. If a problem occurs with printer X, device A and device B may be able to use printer Y. Device a and device B may be able to communicate directly with printer Y. Alternatively, device a and device B may not be able to communicate directly with printer Y, but may be able to communicate with printer Y through device C and device D. This may also be the case for routers or other shared resources.

Method of producing a composite material

Method for processing a sample

In some embodiments, a single device, such as a module or a system having one or more modules, is configured to perform one or more routines selected from the group consisting of sample preparation, sample assay, and sample probing. Sample preparation may include physical and chemical treatments. In some cases, a single device is a single module. In other cases, a single device is a system with multiple modules as described above.

FIG. 40 shows an example of one or more steps that may be performed in a method. The method may or may not be performed by a single device.

The method may include the steps of sample acquisition 4000, sample preparation 4010, sample assay 4020, probing 4030, and/or output 4040. Any of these steps are optional. Further, these steps may occur in any order. One or more of the steps may be repeated one or more times.

In one example, after a sample is collected, it may undergo one or more sample preparation steps. Alternatively, after the sample is collected, it may be directly subjected to a sample measurement step. In another example, the detecting step may occur directly after the sample is collected. In one example, the detecting step may include taking an image of the sample. The image may be a digital image and/or video.

In another example, after a sample has undergone one or more sample preparation steps, it may proceed to a sample assay step. Alternatively, it may go directly to the detection step.

After the sample has undergone one or more assay steps, the sample may proceed to a probing step. Alternatively, the sample may be returned to one or more sample preparation steps.

After the sample has undergone the probing step, it may be output. The outputting may include displaying and/or transmitting data acquired during the detecting step. After probing, the sample may undergo one or more sample preparation steps or sample assay steps. In some cases, additional samples may be taken after probing.

After the sample has been displayed and/or transmitted, additional sample preparation steps, sample assay steps, and/or detection steps may be performed. In some cases, a protocol may be sent to the device in response to the transmitted data, which may implement additional steps. In some cases, the agreement may be generated on-board in response to the detected signal. The analysis may occur onboard the device or may occur remotely based on the transmitted data.

A single device may be capable of performing one or more sample processing steps. In some embodiments, the term "processing" includes one or more of preparing a sample, assaying the sample, and probing the sample to generate data for subsequent off-board (i.e., off-tool) or on-board (i.e., on-tool) analysis. The sample processing step can include a sample preparation procedure and/or assay, including any of the sample preparation procedures and/or assays described elsewhere herein. Sample processing may include one or more of the chemical reaction and/or physical processing steps described herein. Sample processing may include assessment of the histology, morphology, kinematics, kinetics, and/or status of the sample, which may include such assessment for cells or other assessments described herein. In one embodiment, the single device is configured for one or more sample preparation procedures selected from the group consisting of: weighing or volumetric measurement of the sample, centrifugation, sample processing, separation (e.g., magnetic separation), other processing with magnetic beads and/or nanoparticles, reagent processing, chemical separation, physical separation, chemical separation, incubation, anticoagulation, agglutination, removal of portions of the sample (e.g., physical removal of plasma, cells, lysate), dispersion/solubilization of solid matter, concentration of selected cells, dilution, heating, cooling, mixing, addition of one or more reagents, removal of interfering factors, preparation of cell smears, pulverization, grinding, activation, sonication, microcolumn processing, and/or any other type of sample preparation step known in the art, including but not limited to those listed in figure 57. In one example, a single module is configured to execute multiple sample preparation procedures. In another example, a single system, such as system 700, is configured to perform multiple sample preparation procedures. In another embodiment, a single device is configured to perform 1 or more, or 2 or more, or 3 or more, or 4 or more, or 5 or more, or 10 or more assays selected from the group consisting of: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscometric assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and/or other types of assays, or combinations thereof. In some cases, a single device is configured to perform multiple types of assays, wherein at least one assay is a cell count or agglutination. In other cases, a single device is configured to perform multiple types of assays, including cell counting and agglutination. In one example, the system 700 is configured to perform cell counting with the aid of a cell counter 707. A single device may be configured to perform any number of assays, including the numbers described elsewhere herein, involving in the field chemo-conventional chemistry, hematology (including cell-based assays, coagulation, and male morbidities), microbiology-bacteriology (including "molecular biology"), chemo-endocrinology, microbiology-virology, diagnostic immunology-general immunology, chemo-urinalysis, immunohematology-ABO blood group and Rh type, diagnostic immunology-syphilis serology, chemo-toxicology, immunohematology-antibody detection (transfusion), immunohematology-antibody detection (non-transfusion), histocompatibility, microbiology-mycobacteria, microbiology-mycology, microbiology-parasitology, hemo, Immunohematology-antibody recognition, immunohematology-compatibility testing, pathology-histopathology, pathology-oral pathology, pathology-cytology, radiobiological assay, or clinical cytogenetics. A single device may be configured for measurement of one or more, two or more, three or more, or any number (including the numbers described elsewhere herein) of: proteins, nucleic acids (DNA, RNA, hybrids thereof, microRNA, RNAi, EGS, antisense strands), metabolites, gases, ions, particles (which may include crystals), small molecules and metabolites thereof, elements, toxins, enzymes, lipids, carbohydrates, prions, tangible elements (e.g., cellular entities (e.g., whole cells, cellular debris, cell surface markers)). A single device may be capable of performing various types of measurements including, but not limited to, imaging, spectrometry/spectroscopy, electrophoresis, chromatography, sedimentation, centrifugation, or any other measurement mentioned in fig. 58.

Systems or devices provided herein that are capable of performing two or more sample preparation procedures or assay types described herein may provide various advantages over using two or more separate systems or devices to perform two or more sample preparation procedures or assay types of the same sample preparation procedure or assay type.

In one example, the performance of two or more sample preparation procedures or assay types in a device provided herein may allow for the use of a smaller amount of sample than is required to perform the same sample preparation procedure or assay type in two or more systems or devices. For example, in the systems or devices provided herein, samples can be efficiently transported between different modules, units, or other components of a system for performing different assays or preparation procedures on the samples, resulting in little to no sample mechanical loss. If the same assay or sample preparation procedure is performed in one or more separate devices, a larger amount of sample will be required.

In another example, a system or device provided herein capable of performing two or more sample preparation procedures or assay types can perform the two or more sample preparation procedures on a single sample obtained from a subject. Thus, by providing a single sample from a subject to a system or device provided herein, information from multiple assays or sample preparation steps associated with a sample can be readily provided from a single device. Thus, a large amount of information relating to a single subject can be provided quickly and efficiently by a single device provided herein. Conversely, if two or more separate systems or devices are used to perform the same two or more sample preparation procedures or assay types, it will typically take a much longer time to perform the same sample preparation procedures or assay types. With conventional laboratory equipment, sample preparation procedures or assay types are typically performed only when multiple samples from multiple subjects are available to load the equipment. Because it takes time to accumulate multiple samples from multiple subjects, performing two or more sample preparation procedures or assay types on separate systems or devices can typically take much longer than employing the systems or devices provided herein.

In other examples, a system or device provided herein that is capable of performing two or more sample preparation procedures or assay types may perform a sample processing procedure or assay type more accurately and/or more precisely than would be performed if the same sample preparation procedure or assay type were performed on two or more different devices. The use of the systems or devices provided herein may increase accuracy and/or precision for the following reasons: a reduction in human operator involvement in performing sample preparation or assays, a reduction in complexity of human operator involvement in performing sample preparation or assays, a reduction in manual processing of samples, a reduction in manual supervision of sample preparation or assays, and so forth. Thus, in some embodiments, two or more sample preparation procedures and/or assays performed on a system or device provided herein have a lower coefficient of variation than the same sample preparation procedure and/or assay performed on two or more separate systems.

In yet another example, a system or device provided herein capable of performing two or more sample preparation procedures or assay types can process one or more substrate type samples (e.g., blood, urine, saliva). This may be advantageous, for example, to analyze multiple sample types from a single subject on a single device, in order to obtain various types of information about the subject from a single device. Thus, a system or device provided herein that is capable of performing two or more sample preparation procedures or assay types allows for more rapid, convenient, accurate, and/or precise analysis of multiple types of samples from a single subject than if two or more different devices were used to process samples of two or more substrate types.

In another example, a system or device provided herein capable of performing two or more sample preparation procedures or assay types may perform two or more sample preparation procedures or assay types at a lower cost than if the same sample preparation procedures or assay types were performed using two or more separate devices or systems.

In some cases, the histology of the sample contains static information of the sample as well as the change in the sample over time. In one example, the collected sample contains cells that proliferate (or divide) or metastasize after the sample is collected.

In another specific example, a single apparatus is configured to perform one or more types of sample detection routines, such as those described elsewhere herein.

In some embodiments, the multi-purpose or multi-function device is configured to prepare and process a sample. Such devices may include 1 or more, or 2 or more, or 3 or more, or 4 or more, or 5 or more, or 6 or more, or 7 or more, or 8 or more, or 9 or more, or 10 or more, or 20 or more, or 30 or more, or 40 or more, or 50 or more, or 100 or more modules as a single system or as part of multiple systems in communication with one another. The modules may be in fluid communication with each other. Alternatively, the modules may be fluidly isolated or hydraulically independent from each other. In such a case, the sample transfer device may enable the transfer of the sample to and from the cartridge. Such a device may receive 1 or more, or 2 or more, or 3 or more, or 4 or more, or 5 or more, or 6 or more, or 7 or more, or 8 or more, or 9 or more, or 10 or more, or 20 or more, or 30 or more, or 40 or more, or 50 or more, or 100 or more samples. In one specific example, the device receives samples in a batch fashion (e.g., 5 samples are provided to the device at a time). In another embodiment, the apparatus receives the samples in a continuous manner. In some embodiments, the hydraulically isolated or hydraulically independent modules are hydraulically isolated from each other.

In one specific example, samples are processed in parallel. In another embodiment, the samples are processed sequentially (or one after the other). The devices provided herein can prepare and analyze the same sample or a plurality of different samples. In one example, the apparatus provided herein processes the same blood, urine, and/or tissue samples. In another example, the devices provided herein process different blood, urine, and/or tissue samples.

In some embodiments, the apparatus for processing a sample receives a sample in a volume of at least about 1 nanoliter (nL), or 10nL, or 100nL, or 1 microliter (μ L), or 10 μ L, or 100 μ L, or 1 milliliter (mL), or 10mL, or 100mL, or 1 liter (L), or 2L, or 3L, or 4L, or 5L, or 6L, or 7L, or 8L, or 9L, or 10L, or 100L, or 1000L. In another specific example, an apparatus for processing a sample receives a sample having a mass of at least about 1 nanogram (ng), or 10ng, or 100ng, or 1 microgram (μ g), or 10 μ g, or 100 μ g, or 1 milligram (mg), or 10mg, or 100mg, or 1 gram (g), or 2g, or 3g, or 4g, or 5g, or 6g, or 7g, or 8g, or 9g, or 10g, or 100g, or 1000 g.

The apparatus may perform sample preparation, processing and/or detection by means of a module or modules. For example, the device may prepare a sample in a first module (e.g., first module 701 of fig. 7) and run (or perform) an assay in a second module (e.g., second module 702 of fig. 7) separate from the first module.

The apparatus may receive a sample or multiple samples. In one embodiment, the system receives a single sample and prepares, processes, and/or probes the single sample. In another embodiment, the system receives a plurality of samples and prepares, processes, and/or probes one or more of the plurality of samples simultaneously.

In some embodiments, one or more modules of the apparatus are fluidly isolated or hydraulically independent from each other. In one particular example, the plurality of modules 701-706 of the system 700 are fluidly isolated with respect to one another. In one example, the liquid isolation is provided by a sealing means (such as a liquid seal or a pressure seal). In some cases, such a seal is a hermetic seal. In other embodiments, one or more modules of the system are fluidly coupled to each other.

In some cases, devices having multiple modules are configured to communicate with each other. For example, a first device having multiple modules (such as device 1000) communicates with another device (such as the same or similar device having multiple modules). In this manner, two or more devices may communicate with each other, for example, to facilitate resource sharing.

In one example, two stand-type devices like the system 700 of fig. 7 are provided. The devices are configured to communicate with each other, such as by way of a direct link (e.g., wired network) or a wireless link (e.g., bluetooth, WiFi). While a first of the two rack-type devices processes a portion of a sample (e.g., a blood aliquot), a second of the two rack-type devices performs sample probing of another portion of the same sample. The first rack-type device then transmits its results to a second rack-type device, which uploads the information to a server that is in network communication with the second rack-type device but not the first rack-type device.

The apparatus and methods provided herein are configured for use with a point of service system. In one example, the device may be deployed at a healthcare provider's site (e.g., pharmacy, doctor's office, clinic, hospital) for sample preparation, processing, and/or probing. In some cases, the devices provided herein are configured only for sample acquisition and preparation, while processing (e.g., probing) and/or diagnosis is performed at a remote location authenticated by an authentication and authorization entity (e.g., government authentication).

In some embodiments, a user provides a sample to a system having one or more modules, such as system 700 of fig. 7. The user provides the sample to a sample acquisition module of the system. In one particular example, the sample acquisition module comprises one or more scalpels, needles, microneedles, phlebotomists, scalpels, cups, swabs, detergents, buckets, baskets, kits, permeable matrices, or any other sample acquisition device or method described elsewhere herein. Next, the system directs the sample from the sample acquisition module to one or more processing modules (e.g., modules 701-706) for sample preparation, assaying, and/or probing. In a specific example, the sample is guided from the acquisition module to the one or more processing modules by means of a sample processing system, such as a pipette. Next, the sample is processed in the one or more modules. In some cases, a sample is assayed in one or more modules and then subjected to one or more detection protocols.

In some embodiments, after processing in one or more modules, the system communicates the results to a user or system (e.g., a server) in communication with the system. Other systems or users may then take the results to assist in treating or diagnosing the subject.

In one particular example, the system is configured for bidirectional communication with other systems, such as similar or identical systems (e.g., a rack, such as the rack described in the context of fig. 7) or other computer systems, including servers.

The apparatus and methods provided herein may advantageously reduce the energy or carbon footprint of a point of service system by supporting parallel processing. In some cases, a system, such as system 700 of fig. 7, has a footprint that is at most 10%, or 15%, or 20%, or 25%, or 30%, or 35%, or 40%, or 45%, or 50%, or 55%, or 60%, or 65%, or 70%, or 75%, or 80%, or 85%, or 90%, or 95%, or 99% of other point of service systems.

In some embodiments, methods for detecting an analyte are provided. In one particular example, processing the routine includes detecting the presence or absence of the analyte. This processing is conventionally facilitated by the systems and apparatus provided herein. In some cases, the analyte is associated with a biological process, a physiological process, an environmental condition, a sample condition, a disorder, or a stage of a disorder, such as one or more of an autoimmune disease, obesity, hypertension, diabetes, a neuronal and/or muscle degenerative disease, a cardiac disease, and an endocrine disease.

In some cases, the device processes one sample at a time. However, the system provided herein is configured for multiple sample processing. In one embodiment, the device processes multiple samples at once or at overlapping times. In one example, a user provides a sample to a device having a plurality of modules, such as the system 700 of fig. 7. The device then processes the sample by means of one or more modules of the device. In another example, a user provides a plurality of samples to a device having a plurality of modules. The apparatus then processes the sample simultaneously with the plurality of modules by processing a first sample in a first module while processing a second sample in a second module.

The system may process samples of the same type or samples of different types. In one embodiment, the system processes one or more portions of the same sample simultaneously. This may be useful if various assays and/or detection protocols for the same sample are desired. In another embodiment, the system processes different types of samples simultaneously. In one example, the system processes blood and urine samples simultaneously in different modules of the system, or in a single module having a processor for processing blood and urine samples.

In some embodiments, a method for processing a sample with a point of service system (such as system 700 of fig. 7) includes: the probing criteria or parameters are admitted and a probing order or scheduling is determined based on the criteria. The probing criteria are received from a user, system or server in communication with the service point system. The criteria may be selected based on desired or predetermined effects, such as: minimal time, cost, component usage, steps, and/or energy. The point of service system processes the samples in a probing order or schedule. In some cases, a feedback loop (coupled with the sensor) enables the point of service system to monitor the progress of the sample processing and maintain or change the detection order or schedule. In one example, if the system detects that processing has taken longer than a predetermined amount of time set forth in the schedule, the system speeds up the processing or adjusts for any parallel processing, such as sample processing in another module of the system. The feedback loop allows real-time or pseudo real-time (e.g., buffered) monitoring. In some cases, a feedback loop may provide for allowing reflection detection, which may result in initiation of subsequent detection, determination, preparation steps, and/or other processes after another detection and/or determination or sensing of one or more parameters is initiated or completed. Such subsequent detection, determination, preparation steps and/or other processes may be initiated automatically without any human intervention.

In some embodiments, the service point system may adhere to a predetermined probing order or schedule based on initial parameters and/or desired effects. In other embodiments, the scheduling and/or probing order may be modified in real-time. The scheduling and/or order of detection may be modified based on one or more detected conditions, one or more additional processes to be run, one or more processes that are no longer to be run, one or more processes to be modified, one or more resource/component utilization modifications, one or more detected error or alarm conditions, the unavailability of one or more resources and/or components, one or more subsequent inputs or samples provided by a user, external data, or any other reason.

In some examples, one or more additional samples may be provided to the device after one or more initial samples are provided to the device. The additional samples may be from the same subject or different subjects. The additional sample may be the same type of sample as the initial sample or a different type of sample (e.g., blood, tissue). Additional samples may be provided before, after, and/or concurrently with processing one or more initial samples on the device. The additional samples may be provided with the same and/or different detection or desired criteria relative to each other and/or the initial sample. The additional samples may be processed sequentially and/or in parallel with the initial samples. The additional samples may use one or more of the same components as the initial sample, or may use different components. Additional samples may or may not be needed in view of one or more detected conditions of the initial sample.

In some embodiments, the system receives the sample with a sample collection module, such as a scalpel, or liquid collection container. The system then loads or takes the procedures to execute one or more process recipes from the plurality of potential process recipes. In one example, the system is loaded with a centrifugation protocol and a cell counting protocol. In some embodiments, the protocol may be loaded from an external device to the sample processing device. Alternatively, the protocol may already be on the sample processing device. The protocol may be generated based on one or more desired criteria and/or processing conventions. In one example, generating the procedure may include generating a list of one or more subtasks for each input procedure. In some embodiments, each subtask is to be performed by a single component of one or more devices. The generation procedure may also include the order in which the list is generated, the timing, and/or the allocation of one or more resources.

In one embodiment, the protocol provides details or instructions specific to the sample or components in the sample. For example, the centrifugation protocol may include a rotation rate and processing time suitable for a predetermined sample density that supports density-dependent separation of the sample from other materials that may be present with the desired components of the sample.

The procedures are contained in the system, such as in a procedure repository of the system, or retrieved from another system (such as a database) in communication with the system. In one embodiment, the system is in one-way communication with a database server that provides procedures to the system in accordance with the system's request for one or more treatment procedures. In another embodiment, the system is in two-way communication with the database server, which enables the system to upload the user-specific processing routine to the database server for future use by the user or other users who may use the user-specific processing routine.

In some cases, the treatment protocol may be adjusted by the user. In one particular example, a user may generate a treatment protocol by way of a protocol engine that provides the user with one or more options directed to customizing the protocol for a particular use. The customization may occur prior to the use protocol. In some embodiments, the procedure may be modified and updated while the procedure is being used.

With the aid of the protocol, the system processes the sample, which may include preparing the sample, assaying the sample, and detecting one or more components of interest in the sample. In some cases, the system performs data analysis on the processed sample or samples. In other cases, the system performs data analysis during processing. In some embodiments, the data analysis is performed on-board, i.e., on-board, the system. In other embodiments, the data analysis is performed using a data analysis system other than the system. In such cases, the data is directed to the analysis system while the sample is being processed or after processing.

Accuracy, sensitivity, precision and coefficient of variation

Accuracy is the degree of accuracy. Accuracy is the degree of reproducibility. Accuracy is a measure of the closeness of a measurement to a predetermined target measurement, result, or reference (e.g., a reference value). Accuracy is the closeness of multiple measurements to each other. In some cases, the average degree of reproducibility is used to quantify the accuracy. Accuracy may be quantified using deviation or dispersion from a predetermined value.

In some embodiments, the system has a sensitivity that remains constant regardless of the type of sample being processed. In some cases, a system may be capable of producing a nucleic acid molecule at about 1 molecule (e.g., nucleic acid molecule), 5 molecules, 10 molecules, or at about 1pg/mL, 5pg/mL, 10pg/mL, 50pg/mL, 100pg/mL, 500pg/mL, 1ng/mL, 5ng/mL, 10ng/mL, 50ng/mL, 100ng/mL, 150ng/mL, 200ng/mL, 300ng/mL, 500ng/mL, 750ng/mL, 1 μ g/mL, 5 μ g/mL, 10 μ g/mL, 50 μ g/mL, 100 μ g/mL, 150 μ g/mL, 200 μ g/mL, 300 μ g/mL, 500 μ g/mL, 750 μ g/mL, 1mg/mL, 1.5mg/mL, 2mg/mL, 3mg/mL, or at about 1pg/mL, 4mg/mL, 5mg/mL, 7mg/mL, 10mg/mL, 20mg/mL, or 50mg/mL detects analyte or signal within range. In some specific examples, a system, including one or more modules of the system, has a sensitivity that is sample-specific. That is, the sensitivity of the system detection depends on one or more sample-specific parameters, such as the type of sample.

In some embodiments, the system has an accuracy that remains unchanged regardless of at least one sample-specific sample parameter (such as the type of sample). In a particular example, a system has an accuracy of at least about 20%, or 25%, or 30%, or 35%, or 40%, or 45%, 55%, or 60%, or 65%, or 70%, or 75%, or 80%, or 85%, or 90%, or 91%, or 92%, or 93%, or 94%, or 95%, or 96%, or 97%, or 98%, or 99%, or 99.9%, or 99.99%, or 99.999%. Modules and/or components may have any accuracy, including those described elsewhere herein. In some specific examples, a system, including one or more modules of the system, has a sample-specific accuracy. That is, the accuracy of the system depends on at least one sample-specific sample parameter, such as the type of sample. In such cases, the system may be able to provide more accurate results for one type of sample than another type of sample.

In some embodiments, the system has an accuracy that remains constant regardless of at least one sample-specific sample parameter (such as the type of sample). In other embodiments, the system has an accuracy that is specific to the sample. In such cases, the system processes one type of sample with greater accuracy than another type of sample.

The coefficient of variation is the ratio between the standard deviation and the absolute value of the mean. In one embodiment, the system has a Coefficient of Variation (CV) (also referred to herein as "relative standard deviation") of less than or equal to about 20%, 15%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.3%, or 0.1%. In another specific example, a module in the system has a coefficient of variation of less than or equal to about 20%, 15%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.3%, or 0.1%. In yet another specific example, the treatment routinely has a coefficient of variation of less than or equal to about 20%, 15%, 12%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.3%, or 0.1%.

The system provided herein has a coefficient of variation suitable for longitudinal trend analysis, such as a research study involving repeated observations of the same variable over a predetermined period of time. In one example, results from samples processed with a first system having a CV of less than about 15% and a second system having a CV of less than about 15% can be correlated in order to assess a trend in the health or treatment of the subject.

The systems provided herein have a dynamic range suitable for processing samples having a concentration range in excess of 100 orders of magnitude or more, 50 orders of magnitude or more, 30 orders of magnitude or more, 10 orders of magnitude or more, 7 orders of magnitude or more, 5 orders of magnitude or more, 4 orders of magnitude or more, 3 orders of magnitude or more, 2 orders of magnitude or more, or 1 order of magnitude or more. In one example, the system performs two treatments of the sample, a first treatment of a sample volume of about 0.1mL and a second treatment of a sample volume of about 10 mL. The results for both cases fall within the accuracy, precision and coefficient of variation described above. Further, the system configurations provided herein are used to detect signals over a range of 1, 2,3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more orders of magnitude ("dynamic range"). In some cases, dynamic range is supported by dilution. In one specific example, dynamic feedback is used to determine the level of sample dilution.

Sample processing rate

In a particular example, the point of service system or one or more modules within the system are configured to centrifuge a sample over a period of time of up to about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In another specific example, the point of service system or one or more modules within the system is configured to perform a cell count assay on a sample over a time period of up to about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In yet another specific example, the point of service system or one or more modules within the system are configured to perform an immunoassay on a sample over a period of time of at most about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In another specific example, a point of service system or one or more modules within the system is configured to perform nucleic acid assays on a sample over a time period of up to about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In yet another specific example, a point of service system or one or more modules within the system is configured to perform a receptor assay on a sample over a time period of up to about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In another specific example, the point of service system or one or more modules within the system are configured to perform a colorimetric assay on a sample over a period of time of at most about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In yet another specific example, the point of service system or one or more modules within the system is configured to perform an enzymatic assay on a sample over a time period of up to about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In another specific example, the point of service system or one or more modules within the system is configured to perform mass spectrometry (or mass spectrometry) measurements on the sample over a time period of up to about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In yet another specific example, the point of service system or one or more modules within the system is configured to perform infrared spectrometry on the sample over a period of time of at most about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In another specific example, the point of service system or one or more modules within the system are configured to perform X-ray photoelectron spectroscopy on the sample over a period of time of at most about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In yet another specific example, a point of service system or one or more modules within the system is configured to perform an electrophoretic assay on a sample over a period of time of at most about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In another specific example, a point-of-service system or one or more modules within the system is configured to perform nucleic acid sequencing (e.g., single molecule sequencing) assays on a sample over a time period of up to about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In yet another specific example, the point of service system or one or more modules within the system is configured to perform an agglutination assay on the sample over a period of time of at most about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In another specific example, the point of service system or one or more modules within the system are configured to perform a chromatographic assay on a sample over a period of time of up to about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In yet another specific example, the point of service system or one or more modules within the system is configured to perform a coagulation assay on a sample over a time period of up to about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In another specific example, the point of service system or one or more modules within the system are configured to perform electrochemical measurements on the sample over a time period of up to about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In yet another specific example, the point of service system or one or more modules within the system are configured to perform a histological assay on a sample over a time period of at most about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds. In another specific example, the point of service system or one or more modules within the system is configured to perform a live cell analysis (assay) on the sample over a time period of up to about 4 hours, or 3 hours, or 2 hours, or 1 hour, or 45 minutes, or 30 minutes, or 15 minutes, or 10 minutes, or 9 minutes, or 8 minutes, or 7 minutes, or 6 minutes, or 5 minutes, or 4 minutes, or 3 minutes, or 2 minutes, or 1 minute, or 45 seconds, or 30 seconds, or 20 seconds, or 10 seconds, or 5 seconds, or 3 seconds, or 1 second, or 0.5 seconds, or 0.1 seconds.

In a specific example, a processing system, such as a point of service system, is configured to perform any one of the assays selected from the group consisting of: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and/or other types of assays, or combinations thereof. In another specific example, a processing system, such as a point of service system, is configured to perform any two assays selected from the group consisting of: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and/or other types of assays, or combinations thereof. In yet another specific example, a processing system, such as a point of service system, is configured to perform any three assays selected from the group consisting of: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and/or other types of assays, or combinations thereof.

In a particular example, a point-of-service system, such as system 700 of fig. 7, is configured to process at least 1, 2,3, 4, 5,6, 7, 8, 9, or 10 samples over a period of time of at most about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds. In another specific example, multiple point of service systems operating in parallel are configured to process at least 1, 2,3, 4, 5,6, 7, 8, 9, or 10 samples over a period of time of at most about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds.

In a particular example, a processing system, such as a point of service system, is configured to collect and process samples over a time period of up to about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds. In another specific example, a processing system, such as a point of service system, is configured to collect a sample, process the sample, and provide (or communicate) results of the processing over a time period of up to about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds.

In a particular example, a processing system, such as a point of service system, is configured to collect a plurality of samples and process the samples over a time period of up to about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds. In another specific example, a processing system, such as a point of service system, is configured to collect a plurality of samples, process the samples, and provide (or communicate) results of the processing over a time period of up to about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds.

In a particular example, a processing system, such as a point of service system, is configured to collect and assay samples over a time period of up to about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds. In another specific example, a processing system, such as a point of service system, is configured to collect a sample, assay the sample, and provide (or communicate) results of the assay over a time period of up to about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds.

In a particular example, a processing system, such as a point of service system, is configured to collect, prepare, and assay samples over a time period of up to about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds. In another specific example, a processing system, such as a point of service system, is configured to collect a sample, prepare a sample, assay a sample, and provide (or communicate) results of an assay over a time period of up to about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds.

In a particular example, a processing system, such as a point of service system, is configured to collect and perform a plurality of assays on a sample over a time period of up to about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds. In another specific example, a processing system, such as a point of service system, is configured to collect a sample, perform a plurality of assays on the sample, and provide (or communicate) results of the assays over a time period of up to about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds.

In a particular example, a processing system, such as a point of service system, is configured to collect a plurality of samples and perform a plurality of assays on the samples over a time period of up to about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds. In another specific example, a processing system, such as a point of service system, is configured to collect a plurality of samples, perform a plurality of assays on the samples, and provide (or communicate) results of the assays over a time period of up to about 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds.

A processing system, such as a point of service system, may be configured to collect one or more samples and sequence genetic markers from the samples. The entire genome may be sequenced or selected portions of the genome may be sequenced. The processing system may be configured to collect and sequence samples over a time period of up to about 48 hours, 36 hours, 24 hours, 18 hours, 12 hours, 8 hours, 6 hours, 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds. In another specific example, a processing system, such as a point of service system, is configured to collect, perform various assays on, and provide (or communicate) results of the assays over a time period of up to about 48 hours, 36 hours, 24 hours, 18 hours, 12 hours, 8 hours, 6 hours, 5 hours, or 4 hours, or 3 hours, or 2 hours, or 1 hour, or 30 minutes, or 10 minutes, or 5 minutes, or 1 minute, or 30 seconds.

The systems provided herein are configured to store data with a data storage module of the system or an external storage system coupled to the system. In some cases, data collected and/or generated during or after sample processing is compressed and stored in a physical storage medium such as a hard disk, memory, or cache. In one specific example, the data is compressed by means of lossless compression. This may minimize or eliminate any loss in data fidelity.

The processing system described herein is configured to act as a point of service system. In one particular example, the point of service system is a point of care system. The point-of-care system can be used at a point-of-service location, such as the location of a subject (e.g., a residence or business location or sporting event location or security check-out location or battle location), the location of a healthcare provider (e.g., a doctor), a pharmacy or retailer, a clinic, a hospital, an emergency room, a nursing home, an end-of-care location, or a laboratory. The retailer may be a pharmacy (e.g., retail pharmacy, clinical pharmacy, hospital pharmacy), pharmacy, chain store, supermarket, or grocery store. Examples of retailers include, but are not limited to, Walgreen, CVS Pharmacy, Duane read, Walmart, Target, Rite Aid, Kroger, Costco, Kaiser Permanente, or Sears. In some cases, a point of service system (including but not limited to a point of care system) is deployed at any location designated for use by an authenticating or authorizing entity (e.g., a governmental authentication entity). In other cases, the point-of-service system may be used in or embedded in a vehicle, such as in a car, ship, truck, bus, airplane, motorcycle, van, ambulatory medical vehicle, mobile unit, ambulance, fire truck/truck, emergency care vehicle, or other vehicle configured to transport a subject from one point to another. The sample collector may be at a sample acquisition site and/or a health assessment and/or treatment site (which may include any of the sample collection sites described elsewhere herein, including but not limited to emergency rooms, doctor's offices, emergency treatment facilities, screening booths (which may be at remote locations), healthcare professionals walking into one's home to provide home care).

A system (device) or combination of systems (devices) may be located/placed at strategic service point sites. The location may be selected and optimized based on various goals such as, but not limited to, disease prevalence, disease development rate, predicted morbidity, estimated risk of outbreak, demographics, government policy and regulations, consumer, physician and patient preferences, use of other technologies at the location, security and risk estimation, security threats, and the like. The devices may be relocated periodically to increase overall utility frequently (such as daily, weekly, monthly, yearly, etc.). The system may be updated to improve performance and/or add functionality. The system may be updated on a module by module basis. System updates may occur via hardware and/or via software. The system may be updated with minimal downtime via features that support tab and/or module extraction and insertion.

Further, the point of service location at which the sample may be collected from the subject or provided by the subject may be a location remote from the analysis facility. The sample collector may have a facility independent of the laboratory. The sample may or may not be freshly collected from the subject at the point-of-service location. Alternatively, samples may be taken from subjects at other locations and brought to the point-of-service location. In some embodiments, no sample preparation step is provided for the sample prior to providing the sample to the apparatus. For example, there is no need to prepare the slide before providing the sample to the apparatus. Alternatively, one or more sample preparation steps may be performed on the sample prior to providing the sample to the apparatus.

The sample collection instrument at the point-of-service site may be a blood collection center or any other body fluid collection center. The sample acquiring instrument may be a biological sample acquiring center. In some embodiments, the sample collector may be a retailer. Other examples of sample collectors may include hospitals, clinics, healthcare professional offices, schools, day care centers, health centers, assisted living residences, government agencies, ambulatory medical care units, or residences. For example, the sample collector may be the subject's home. The sample acquiring instrument may be any location where a sample from a subject is received by the device. The acquisition instrument may be a mobile location, such as on or with a patient, or in a mobile unit or vehicle, or with an ambulatory physician. Any location may be designated as a sample collector. The enactment may be made by any subject including, but not limited to, a laboratory, an entity associated with a laboratory, a government device, or a regulatory device. Any description herein regarding a sample capture meter or point of service location may relate to or be applicable to a retailer, hospital, clinic, or any other example provided herein, and vice versa.

The point of service systems described in the embodiments, such as point of care systems, are configured for use in conjunction with various types of samples, such as tissue samples (e.g., skin, organ portions), liquid samples (e.g., breath, blood, urine, saliva, cerebrospinal fluid), and other biological samples (e.g., feces) from a subject.

The point of service system described herein is configured to process samples at locations where the point of service system is accessible to a user. In one example, the point of service system is located at the subject's home and samples are taken and processed from the subject in the subject's home. In another example, the point of service system is located at a pharmacy and samples are taken and processed from subjects at the pharmacy. In yet another example, the point of service system is located at a healthcare provider's site (e.g., a doctor's office), and samples are taken and processed from subjects at the healthcare provider's site. In another example, the point of service system is located onboard a transport system (e.g., a vehicle) and samples are collected and processed from the subject on the transport system.

In some specific examples, the sample processing system can be deployed at a location outside of a central laboratory (e.g., at a school, residence, field hospital, clinic, enterprise, vehicle, etc.). In some specific examples, the sample processing system can be deployed in a location having a primary purpose other than laboratory services (e.g., at a school, home, battlefield hospital, clinic, business, vehicle, etc.). In some embodiments, the sample processing system may be deployed at a location that is not dedicated to processing samples received from multiple sample acquisition locations. In some embodiments, the sample processing system may be located less than about 1 kilometer, 500 meters, 400 meters, 300 meters, 200 meters, 100 meters, 75 meters, 50 meters, 25 meters, 10 meters, 5 meters, 3 meters, 2 meters, or 1 meter from the location at which the sample is obtained from the subject. In some embodiments, the sample processing system may be located in the same room, building, or campus as where the sample was obtained from the subject. In some embodiments, the sample processing system can be on or within a subject. In some embodiments, the sample is provided directly from the subject to a sample processing system. In some specific examples, the sample can be provided to the sample processing system within 48 hours, 36 hours, 24 hours, 12 hours, 8 hours, 6 hours, 4 hours, 3 hours, 2 hours, 1 hour, 45 minutes, 30 minutes, 15 minutes, 10 minutes, 5 minutes, 1 minute, or 30 seconds of the sample being collected from the subject.

In some embodiments, the sample processing system may be portable. In some embodiments, the sample processing system can have a width of less than about 4m³、3m³、2m³、1m³、0.5m³、0.4m³、0.3m³、0.2m³、0.1m³、1cm³、0.5cm³、0.2cm³Or 0.1cm³Total volume of (c). In some embodiments, the sample processing system can have a mass of less than about 1000kg, 900kg,A mass of 800kg, 700kg, 600kg, 500kg, 400kg, 300kg, 200kg, 100kg, 75kg, 50kg, 25kg, 10kg, 5kg, 2kg, 1kg, 0.5kg, 0.1kg, 25g, 10g, 5g or 1 g. In some embodiments, the sample processing system may be configured for flow sample processing.

In some embodiments, post-sample processing analysis, including diagnosis and/or treatment, is performed by the point-of-service system at the location of the point-of-service system. In other embodiments, post-sample processing analysis is performed remotely, remote from the sample collection and processing site. In one example, post-sample processing analysis is performed at the site of the healthcare provider. In another example, post-sample processing analysis is performed at the site of the processing system. In yet another example, post-sample processing analysis is performed on a server (e.g., on the cloud).

Post-sample processing analysis may be performed in a laboratory or by an entity affiliated with the laboratory. A laboratory may be an entity or facility capable of performing clinical exploration or analyzing acquired data. Laboratories may provide controlled conditions under which scientific research, experiments, and measurements may be performed. The laboratory may be a medical laboratory or a clinical laboratory in which detection of clinical samples may be undertaken or analysis may be performed on data collected from clinical samples in order to obtain information about the health of a patient suitable for diagnosis, prognosis, treatment and/or prevention of a disease. The clinical specimen may be a sample collected from a subject. Preferably, as further detailed elsewhere herein, the clinical specimen is collected from the subject at a sample collection instrument located at a facility separate from the laboratory. Clinical specimens may be collected from a subject using a device placed on or in a designated sample collector or subject.

In some embodiments, the laboratory may be a certification laboratory. The certification laboratory may be an authorized analysis facility. Any description herein of a laboratory may apply to an authorized analytical facility, and vice versa. In some cases, the laboratory may be certified by a government device. The laboratory may accept certification or supervision by a supervisory device. In one example, the laboratory may be authenticated by an entity such as a medicare and medicaid service Center (CMS). For example, the authorized analytical facility may be a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory or its equivalent entity in any foreign jurisdiction.

In other embodiments, post-processing analysis is performed on the device. The same device that receives the sample and/or processes the sample may also perform post-processing analysis. Alternatively, the device receiving the sample and/or processing the sample does not perform post-processing analysis. In some cases, post-processing analysis may occur on-site and off-site.

In one embodiment, the post-processing analysis is performed by means of a post-processing module of the service point system. In another embodiment, the post-processing analysis is performed by means of a post-processing system other than the point-of-service system. In one example, such post-processing systems may be located at a healthcare provider or other entity authorized to perform post-processing analysis.

In some cases, the point of service system is installed at the site of the payer or entity. In one example, the point of service system is installed at the site of a healthcare provider that provides (or will provide) payment for use of the point of service system. In another example, the point of service system is installed at a pharmacy that provides (or will provide) payment for use of the point of service system.

In one particular example, the post-processing system supports diagnostics, such as disease diagnostics. In another embodiment, the post-treatment system supports treatment. In yet another embodiment, the post-processing system supports diagnosis and treatment. The post-treatment system may be useful for disease diagnosis, treatment, monitoring and/or prevention.

In one example, the post-processing system supports drug screening. In this case, the point-of-service system collects a sample (e.g., a urine sample) from the subject and processes the sample, such as by performing centrifugation and one or more assays. Next, the point-of-service system generates data for subsequent post-processing analysis, including identifying (or marking) whether the predetermined medication is found in the sample. Post-processing analysis was performed on the system. Alternatively, post-processing analysis is performed at a site remote from the service point system location.

In some cases, the point-of-service system is used for clinical trials, such as for the development of therapies. Such clinical trials include one or more protocols that are intended to allow the collection of safety (or more specifically, information about adverse drug reactions and adverse effects of other treatments) and efficacy data for health interventions (e.g., drugs, diagnostics, devices, treatment regimens). The point of service system and information system provided herein can be used to facilitate registration of patients in clinical trials by probing or by an integrated EMR (electronic medical record) system or both.

In some cases, the point of service systems provided herein are configured for preclinical development (or testing). In one example, a point of service system, such as system 700 of fig. 7, is used to process samples and collect data for use in feasibility detection, iterative detection, and security that can be used for preclinical development. Such assays may include animal detection. The point of service system described herein advantageously supports probing with small sample volumes at a processing rate that supports performing many probes with a given sample. Preclinical testing with the aid of the point of service system provided herein supports the assessment of efficacy and/or toxicity of a therapeutic drug or metabolite thereof or therapeutic regimen.

The point of service system provided herein may in turn or alternatively be used for biotoxin detection. The point-of-service system can process environmental or product samples and can detect one or more toxins. The point of service system described herein advantageously supports probing with small sample volumes at a processing rate that supports performing many probes with a given sample. Toxin detection by way of the point-of-service systems provided herein supports assessment of threats in an environment (e.g., contaminated water, air, soil) or a product (e.g., food and/or beverage products, building materials, and/or any other product).

The point of service systems provided herein, such as system 700 of fig. 7, support phylogenetic classification, paternity testing, forensic testing, compliance or non-compliance monitoring, monitoring Adverse Drug Reactions (ADRs), developing personalized medicine, calibration of therapy or treatment systems and methods, assessing reliability of therapy or treatment systems and methods, and/or trend analysis (e.g., longitudinal trend analysis). Compliance or non-compliance detection by means of the point of service system described above may improve tolerance compliance, which may reduce healthcare costs associated with adherence to a particular therapy.

As part of personalized medicine, the subject uses a point of service system to collect a sample from the subject and process the sample. In one example, a urine sample is collected from a subject and detected for the presence of one or more predetermined drugs. In some cases, the collection of samples, processing of samples, and post-processing analysis provide subject-specific (or individualized) care. In some cases, after a sample is collected from a subject and processed, a point of service system or post-processing system transmits a notification or alert to the subject or healthcare provider. In one example, if the point of service system determines that the monitored concentration of the drug (or metabolite of the drug) is above and/or below a predetermined limit, the system transmits an alert to the physician of the subject.

In one particular example, the point-of-service system is used to process samples and perform post-processing analysis to generate data for use by other systems. In another embodiment, the point of service system is configured to process the sample and direct the post-processing data to another system for post-processing analysis using the post-processing data. In such cases, the results of the analysis are configured to be shared with other systems or individuals, such as if certain access requirements are met. In one example, the post-processing data or results of the post-processing analysis are shared by payers (e.g., insurance companies), healthcare providers, laboratories, clinics, other point-of-service devices or modules, and/or subjects.

The point of service system may be used to receive, process and/or analyze a small volume of sample, which may include the volumes described elsewhere herein. The point of service system may also be used to provide quick results. The point-of-service system may be capable of processing and/or analyzing samples within a short amount of time, which may include the length of time described elsewhere herein.

The system configuration provided herein serves as a point-of-service system. Such systems are configured for collecting and processing one or more samples at various locations, such as the subject's home or the location of a healthcare provider. In some specific examples, a system provided herein, such as system 700 of fig. 7, has a downtime of at most about 2 hours, 1 hour, 30 minutes, 10 minutes, 5 minutes, 1 minute, 30 seconds, 1 second, or 0.5 seconds between sample processing routines. In some cases, the system is reset during the downtime. In other specific examples, a system provided herein, such as system 700 of fig. 7, is configured to transmit data to a post-processing system within a time period of up to about 10 minutes, 9 minutes, 8 minutes, 7 minutes, 6 minutes, 5 minutes, 4 minutes, 3 minutes, 2 minutes, 1 minute, 30 seconds, 10 seconds, 5 seconds, 1 second, 0.5 seconds, 0.1 seconds, or 0.01 seconds, or 0.001 seconds after processing. In one example, the system 700 collects and processes a first sample and transmits the data to a post-processing system. The system 700 can accept a second sample for processing 0.5 seconds after the system 700 transmits the data.

In some cases, a system, such as system 700 of fig. 7, is configured to routinely receive 1, or 2, or 3, or 4, or 5, or 6, or 7, or 8, or 9, or 10 samples per acquisition. In other instances, a system, such as system 700 of fig. 7, is configured to receive 1 sample at a time over a time period of up to about 10 minutes, 9 minutes, 8 minutes, 7 minutes, 6 minutes, 5 minutes, 4 minutes, 3 minutes, 2 minutes, 1 minute, 30 seconds, 10 seconds, 5 seconds, or 1 second between sample collectors.

In some embodiments, the plurality of samples may include a plurality of types of samples. In other cases, the plurality of samples may include samples of the same type. Multiple samples may be taken from the same subject or from different subjects. Multiple samples may be taken at the same time or at different time points. Any combination of these may be provided for multiple samples.

In some embodiments, a point-of-service system, such as system 700 of fig. 7, is configured for teletherapy, such as via audio and/or visual media coupled with a communication system (such as a network or a telephone system). In one example, a subject provides a sample to a point of service system, which processes the sample to generate processed data. Next, the system establishes a communication link with a remote healthcare provider that reviews the subject's data and provides a diagnosis. The healthcare provider then assists the subject in the treatment. In one embodiment, the healthcare provider is selected by the subject.

In some embodiments, at least one component of the system is constructed from a polymeric material. Non-limiting examples of polymeric materials include polystyrene, polycarbonate, polypropylene, Polydimethylsiloxane (PDMS), polyurethane, polyvinyl chloride (PVC), polysulfone, Polymethylmethacrylate (PMMA), acrylic-butadiene-styrene (ABS), and glass.

The system and subassemblies of the system may be manufactured by a variety of methods including, but not limited to, stamping, injection molding, embossing, casting, blow molding, machining, welding, ultrasonic welding, and heat bonding. In one embodiment, the device is manufactured by injection molding, heat bonding, and ultrasonic welding. The subassemblies of the apparatus may be affixed to one another by heat bonding, ultrasonic welding, friction fit (press fit), adhesives, or, in the case of certain substrate sheets such as glass or semi-rigid or non-rigid polymer substrate sheets, natural bonding between the two components.

Device use and identification method

The device may be configured to perform only sample processing and data generation. Alternatively, the device may be configured to perform sample processing, data generation, and subsequent qualitative and/or quantitative evaluation. In other embodiments, the same device may perform sample processing, data generation, and/or qualitative and/or quantitative evaluation on a case-by-case basis. For example, any combination of these device functionalities may be applied on a probe-by-probe basis, a sample-by-sample basis, a patient-by-patient basis, a customer-by-customer basis, an operator-by-operator basis, and/or a location-by-location basis.

The identity of the subject may be verified before, after, and/or concurrently with the device receiving the sample. The sample may have been collected from a subject. The identity of the subject may also be verified before, after, and/or concurrently with the processing of the sample by the device. This may include verifying the identity of the subject before, after, and/or simultaneously with the device preparing the sample and/or the device assaying the sample.

In some embodiments, the subject may be associated with a payer. For example, a payer, such as a medical insurance company, a government payer, or any other payer as described herein, may provide insurance coverage to a subject. The payer may pay some or all of the subject's medical bill. Any description herein of the subject's insurance coverage and/or verification insurance coverage may also apply to any other insurance coverage paid by any payer. The insurance coverage of the subject can be verified. For example, the system may verify that the subject is a member with insurance coverage rights. The system may also verify that the subject qualifies for certain probes and/or items according to insurance. For example, certain subjects are eligible for free diabetes testing or genetic testing. In some cases, different subjects may be eligible for different tests. The availability of such detection may be tailored to individual subjects or to groups of people. Such detection qualification may be based on a set of rules or guidelines generated for the insurance company. Such insurance membership and/or detection qualification verification may be implemented by a software system.

The subject may arrive at the point of service and enroll. In some embodiments, enrolling may include verifying the identity of the subject. Enrollment may also include determining a payer for the subject, such as whether the subject has a medical insurance coverage. These procedures may be automated at the point of service. The service point may include a doctor's office, a retailer point, or any other service point described elsewhere herein. In some embodiments, the device may be used to enroll the subject. Alternatively, the subject may be enrolled using an external device that may or may not communicate with the device. Enrolling the subject may allow the system to access one or more pre-existing records of the subject.

In some embodiments, the identification of the subject may be verified when the subject reaches the point of service. In some embodiments, the sample collected from the subject may or may not arrive at the point of service with the subject. The subject's identification may be verified using the device and/or by personnel at the point of service. For example, a person at the point of service may view the subject's identification card and/or insurance card. The device may or may not capture an image of the subject and/or acquire one or more biometric parameters from the subject. The device may evaluate one or more characteristics associated with the subject to facilitate identifying the subject, including, but not limited to, the subject's appearance, facial recognition, retinal scan, fingerprint scan, handprint scan, weight, height, bust, voice, gait, movement, proportion, proteomic data, genetic data, analyte levels, heart rate, blood pressure, electrophysiological readings, and/or body temperature. The one or more characteristics of the subject that may be evaluated may include one or more physiological parameters of the subject, which may include one or more of the characteristics listed above (e.g., heart rate, blood pressure, electrophysiological readings, body temperature). The device may generate a genetic signature of the subject from a sample collected from the subject and compare the genetic signature to a pre-stored genetic signature of the subject. The device may also generate a protein signature of the subject from a sample collected from the subject and compare the protein signature to a pre-stored subject protein signature. In some embodiments, the identification of the subject can be verified when the genetic signature matches a pre-stored genetic signature. An exact match or an approximate match may be required. The identity of the subject can be verified when the difference between the protein identity and the pre-stored protein identity falls within an acceptable range. The identity of the subject may be verified using a combination of static and dynamic signature verification of one or more biological samples from the subject. For example, the subject's genetic signature may be static, while the subject's protein signature may be dynamic. Other examples of dynamic signatures may include one or more analyte levels, and/or other physiological characteristics of the subject.

Authentication may include comparing one or more static and/or dynamic signature information with previously stored information relating to the subject. The previously stored information is accessible by the device. The previously stored information may be located on-board the device or off-board the device. Identity verification may also incorporate general knowledge that is not subject-specific. For example, when the subject is a fully grown adult, if the subject's height changes substantially, the verification may be directed to a possible problem with the dynamic signature marking; but when the subject is a growing child or adolescent, the problem may not be flagged if the subject's height changes within an acceptable range. The general knowledge may be on board the device or external to the device. The general knowledge may be stored in one or more memories. In some embodiments, the device and/or the external device may be capable of data mining public information provided on the network.

Verification may occur onboard the device. Alternatively, the subject's identification may be collected at a service point and may be further verified at another entity or location. The other entity or location may automatically verify identity and/or insurance coverage without human intervention, or verify this with or without human intervention. Verification may occur onboard or off-board using a software program. In some examples, a laboratory, medical care professional, or payer may verify the subject's identity. The device, laboratory, medical care professional, and/or payer may be able to access subject information, such as electronic health records. Verification may occur quickly and/or in real time. For example, validation may occur within 1 hour or less, 30 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. The verification may be automated without any manual intervention.

The system may verify the subject's identity for system records, for insurance coverage, to reduce costs, save time, prevent fraud, or any other purpose. The verification may be performed by the device. The authentication may be performed by an entity communicating with the device or by an external device. Verification may occur at any time. In one example, the identity of the subject may be verified before preparing a sample of the subject for probing. The identity of the subject may be verified prior to providing the sample to the device and/or cartridge. Verification of the subject's identity may be provided before, after, or simultaneously with verifying the subject's insurance coverage. Verification of the subject's identity may be provided before, after, or simultaneously with verification that the subject has received a prescription to be subjected to said qualitative and/or quantitative assessment. The verification may be through communication with a healthcare provider, laboratory, payer, laboratory welfare manager, or any other entity. Authentication may occur by accessing one or more data storage units. The data storage unit may include an electronic medical records database and/or a payer database. The electronic medical records database may include any information related to the health, medical records, medical history, or treatment of the subject.

Verification may occur quickly and/or in real time. For example, validation may occur within 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. The verification may be automated without any manual intervention.

The verification may include information provided by the subject. For example, the verification may include scanning the subject's identification card and/or insurance card. Verification may include taking a picture of the subject and/or the subject's face. For example, the verification may include taking a two-dimensional or three-dimensional snapshot of the subject. The following cameras may be used: which may provide a two-dimensional digital image of the subject and/or may be capable of creating a three-or four-dimensional image of the subject. In some embodiments, multiple cameras may be used simultaneously. The four-dimensional image of the subject may include changes over time. Authentication may include taking a picture of the face of the subject for identification. Verification may include taking a picture of another portion of the subject's face for identification purposes, including but not limited to the patient's whole body, arms, hands, legs, torso, feet, or any other part of the body. The verification may employ a video camera and/or microphone that may ingest additional visual and/or audio information. Verification may include comparing the subject's movements (e.g., gait) or speech.

Authentication of the subject may include entering personal information related to the subject, such as the subject's name, insurance policy number, answers to key questions, and/or any other information. Verification may include acquiring one or more biometric readings of the subject. For example, the verification may include a fingerprint, handprint, footprint, retinal scan, temperature reading, weight, height, audio information, electrical reading, or any other information. Biometric information may be collected by the device. For example, the device may have a touch screen on which the subject may place their palm for reading by the device. The touch screen may be capable of scanning one or more body parts of the subject and/or receiving temperature, electrical, and/or pressure readings from the subject.

In some embodiments, the touch screen may be capable of measuring a body mass index of the subject. Such measurements may be based on electrical readings from the subject. In one example, a method for measuring body fat percentage of a subject may be provided that includes providing a touch screen and placing a first finger on a first side of the touch screen and a second finger on a second side of the touch screen. An electrical current may be directed through the body of the subject, wherein the electrical current is directed through the body of the subject via the first finger and the second finger. By measuring the electrical resistance between the first finger and the second finger, the percentage of body fat of the subject can be determined by means of the current directed through the body of the subject. The touch screen may be a capacitive touch screen or a resistive touch screen. In one example, the touch screen may be an at least 60-point touch screen. The first finger may be on a first hand of the subject and the second finger may be on a second hand of the subject.

Alternatively, the device may receive biometric information from other devices. For example, the device may receive the weight of the subject from a weighing apparatus that is separable from the device. This information may be sent directly from the other device (e.g., via a wired or wireless connection), or may be manually entered.

Validation may also include information based on a sample collected from the subject. For example, the validation may include a genetic marker of the subject. When providing a sample to the device, the device can use at least a portion of the sample to determine a genetic signature of the subject. For example, the device may perform one or more nucleic acid amplification steps and may determine key genetic markers of the subject. This may form a genetic marker for the subject. The genetic marker of the subject may be obtained before, after, or simultaneously with processing the sample on the device. The subject's genetic signature may be stored on one or more data storage units. For example, the subject's genetic signature may be stored in the subject's electronic medical record. The collected genetic markers of the subject may be compared to the genetic markers of the subject (if present) that have been stored in the record. Any other uniquely identifying characteristic of the subject may be used to verify the identity of the subject.

Methods for amplification of nucleic acids (including DNA and/or RNA) are known in the art. The amplification method may involve a temperature change, such as a thermal denaturation step; or may be an isothermal process that does not require thermal denaturation. The Polymerase Chain Reaction (PCR) uses multiple cycles of denaturation, adhesion of primer pairs to opposite strands, and primer extension to exponentially increase the copy number of the target sequence. Denaturation of adhered nucleic acid strands can be achieved by application of heat, increasing local metal ion concentration (e.g., US6277605), ultrasonic radiation (e.g., WO/2000/049176), application of a voltage (e.g., US5527670, US6033850, US5939291, and US6333157), and application of an electromagnetic field and incorporation of primers (e.g., US5545540) bound to a magnetically responsive material, which patents and patent applications are hereby incorporated by reference in their entirety. In a variation, referred to as RT-PCR, complementary DNA (cDNA) is generated from RNA using Reverse Transcriptase (RT), and the cDNA is then amplified by PCR to produce multiple copies of the DNA (e.g., US5322770 and US5310652, which are hereby incorporated by reference in their entirety).

An example of an isothermal amplification method is strand displacement amplification, commonly referred to as SDA, which uses the following cycles: primer pair sequences are attached to opposite strands of a target sequence, primer extension in the presence of dntps to produce a hemiphosphorothioated primer extension product duplex, endonuclease-mediated nicking of a hemimodified restriction endonuclease recognition site, and polymerase-mediated primer extension from the 3' end of the nick to displace an existing strand and generate a strand for the next round of primer attachment, nicking production, and strand displacement, resulting in geometric amplification of the product (e.g., US5270184 and US5455166, which are hereby incorporated by reference in their entirety). Thermophilic SDA (tSDA) uses thermophilic endonucleases and polymerases at higher temperatures in essentially the same process (European patent No. 0684315, which is hereby incorporated by reference in its entirety).

other Amplification methods include Rolling Circle Amplification (RCA) (e.g., Lizardi, "Rolling circle replication Reporter Systems", U.S. Pat. No. 5,854,033), Helicase-Dependent Amplification (HDA) (e.g., Kong et al, "Helica Dependent Amplification Nucleic Acids", U.S. patent application publication No. US2004-0058378A 1), and loop-mediated isothermal Amplification (LAMP) (e.g., Notomi et al, "Process for synthesizing Nucleic Acid Acids", U.S. Pat. No. 6,410,278), which is hereby incorporated by reference in its entirety, isothermal Amplification using transcription initiated from promoter sequences by RNA polymerases, e.g., can be incorporated into oligonucleotide primers) in some cases, transcription-based Amplification methods in the field include Nucleic Acid sequence-based Amplification, also referred to as US (e.g., US 5138), Amplification methods based on additional transcription by RNA polymerase, e.g., incorporated by reference into oligonucleotide primers, such as NASES. DNA polymerase, such as NASES. NASES, NASES. DNA replication-DNA replication methods, including the linear Amplification by DNA Amplification methods commonly used in US DNA Amplification methods such as the nucleotide sequences incorporated by NASEQUES. NASEQUENCER-DNA Amplification methods (NASES) and other Amplification methods such as the genomic DNA Amplification methods, such as the genomic DNA Amplification methods (NASES) incorporated by NASES-DNA Amplification methods, such as the genomic DNA polymerase, NASEQUENCER-DNA Amplification methods, NASES, such as the LIZAT DNA Amplification methods, NASES, NASES. DNA Amplification methods, NASES, NASES. DNA, NASES. US PRS, NASES, NA.

Nucleic acid amplification for identification of a subject may include sequential, parallel, or simultaneous amplification of multiple nucleic acid sequences, e.g., about or greater than about 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 50, 100, or more target sequences. In some embodiments, the entire genome or entire transcriptome of the subject is non-specifically amplified, the products of which are probes for one or more recognition sequence features. Identifying sequence features includes any feature of a nucleic acid sequence that can serve as a basis for distinguishing between individuals. In some embodiments, about or more than about 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 50, 100 or more identification sequences are used to uniquely identify an individual with a selected statistical significance. In some embodiments, the statistical significance is about or less than about 10^-2、10^-3、10^-4、10^-5、10^-6、10^-7、10^-8、10^-9、10^-10、10^-11、10^-12、10^-13、10^-14、10^-15Or smaller. Examples of recognition sequences include restriction fragment length polymorphisms (RFLP; Botstein, et al, am. J. hum. Genet.32:314-331, 1980; WO90/13668), single nucleotide polymorphisms (SNPs; Kwok, et al, Genomics31:123-126,1996), randomly amplified polymorphic DNA (RAPD; Williams et al, nucleic acids Res.,18:6531-6535,1990), simple sequence repeats (SSRs; Zhao and Kochert, Plant mol. biol.21:607-614, 1993; Zietkiewicz, et al, Genomics20:176-183,1989), amplified fragment length polymorphisms (LP; Vos, et al, nucleic acids Res., 44021: 4407-4414,1995), Short Tandem Repeats (STRs), variable number of tandem repeats (transposon), micro-transposon-map polymorphisms (SNP), PCR-map-17, PCR-map-9), amplified fragment length polymorphisms (SNP-PCR), PCR-, retrotransposon-based insertion polymorphisms (RBIP), short interspersed elements (SINE), and sequence-specific amplification polymorphisms (SSAP). Further examples of identification sequences are known in the art, for example in US20030170705, which is incorporated herein by reference. A gene signature may consist of multiple recognition sequences of a single type (e.g., SNPs), or may include a combination of two or more different types of recognition sequences in any number or combination.

Genetic markers can be used in any process requiring identification of one or more subjects, such as paternal or maternal paternity testing, immigration and inheritance disputes, animal breeding tests, twins egg type detection, close-relative breeding tests for humans and animals; evaluation of transplant compatibility, such as bone marrow transplantation; identification of human and animal remains; controlling the quality of the cultured cells; forensic investigations such as forensic analysis of semen samples, blood stains and other biological materials; characterization of the genetic makeup of the tumor by detecting loss of heterozygosity; and determining the allele frequency of the specific recognition sequence. Samples used to generate genetic markers include evidence from a crime scene, blood, bloodstain, semen, seminal plaques, bone, teeth, hair, saliva, urine, feces, nails, muscle or other soft tissue, cigarettes, stamps, envelopes, dandruff, fingerprints, items containing any of these materials, and combinations thereof. In some embodiments, two or more gene signatures are generated and compared. In some embodiments, the one or more genetic markers are compared to one or more known genetic markers, such as genetic markers contained in a database.

The genetic marker may be generated by the device receiving the sample. Genetic markers may be generated by the device that prepares the sample and/or runs one or more assays. The data collected from the device may be transmitted to an external device that can generate the genetic marker. The genetic markers may be generated jointly on the device and on an external device.

The system may also verify whether the subject has received instructions from a healthcare professional to undergo a clinical trial. Thus, the system can verify whether the subject has received a prescription from a medical care professional that requires it to perform a qualitative and/or quantitative evaluation of the biological sample. For example, the system may verify whether the subject has received a prescription to be probed from a healthcare professional. The system may verify whether the subject has received instructions from a healthcare professional to provide the sample to the device. The system may also verify that the subject is authorized to go to a particular service point subject to detection. Authentication may occur with the aid of a device. Verification may occur at any time. In one example, the authorization of the subject to perform the testing may be verified prior to preparing a sample of the subject for testing. The authorization of the subject to perform the detection may be verified prior to providing the sample to the device and/or cartridge. Verification of the authorization of the subject may be provided after verifying the identity of the subject. Verification of the authorization of the subject may be provided before or after verifying that the subject has insurance coverage for clinical detection. The system may verify whether the subject is covered by medical insurance for qualitative and/or quantitative evaluation of the sample, wherein the verifying step is performed before, after or simultaneously with processing the biological sample by means of the device or transmitting data from the device. The verification may be through communication with a healthcare provider, laboratory, payer, laboratory welfare manager, or any other entity. Verification may occur quickly and/or in real time. For example, validation may occur within 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. The verification may be automated without any manual intervention.

The system may also verify whether the subject has insurance coverage (and/or insurance coverage provided by any other payer) for the occurrence of one or more sample processing steps. The system can verify whether the subject has insurance coverage and whether the subject has insurance coverage for detection of a particular requirement. The system can verify whether the subject has insurance coverage to provide the sample to the device. The system may also verify whether the subject has insurance coverage for traveling to the service point and undergoing one or more detections. Verification may occur at any time. In one example, the insurance coverage of a subject may be verified before preparing a sample of the subject for detection. The insurance coverage of the subject may be verified prior to providing the sample to the device and/or cartridge. Verification of the insurance coverage of the subject may be provided after verifying the identity of the subject. Verification of the insurance coverage of the subject may be provided before or after verifying that the subject has received a prescription for clinical testing. The verification may be through communication with a medical care provider, laboratory, payer, laboratory welfare manager, or any other entity. Authentication may occur with the aid of a device. Verification may occur quickly and/or in real time. For example, validation may occur within 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. The verification may be automated without any manual intervention.

The system may also verify whether the clinical probe is appropriate for the subject. The system may verify that the prescription for qualitative and/or quantitative evaluation is within a set of rule limits. Such rule limits may form guidelines. Such rule limits may be those of a payer, prescribing doctor or other prescribing medical care professional, laboratory, government or regulatory device, or any other entity. Such verification may depend on one or more known characteristics of the subject, including but not limited to, gender, age, or past medical history. A clinical decision support system may be provided. The system may be capable of accessing one or more medical records, or accessing information associated with the subject. The system may also be able to access general medical data. The system may be able to access records related to the identity of the subject, the insurance coverage of the subject, the past and current medical treatment of the subject, the biological characteristics of the subject, and/or the prescription provided to the subject. The system may be able to access electronic health records and/or recall records and medical histories of the patient. The system may also call out payer records, such as insurance and financial information about the subject. Authentication may occur with the aid of a device.

In determining the appropriateness of the probing, the system may provide additional front-end decision support. For example, if the doctor has scheduled the subject for the same probe as the previous week, and it is not of the type of probe that needs to be repeated within a week, the system may determine that the probe is inappropriate. In another example, if the detection somehow conflicts with a previous detection or would be inappropriate in view of the therapy being experienced by the subject, the system may determine that the detection is inappropriate.

In some specific examples, the system may be capable of accessing one or more records databases and/or payer databases prior to providing qualitative and/or quantitative assessments. In some cases, the system may be able to determine which records databases and/or payer databases to access before providing the qualitative and/or quantitative assessments, and/or before accessing the databases. Further, the system may be able to access general information that may or may not be specific to the subject or an equivalent population of subjects. The system may be capable of network crawling and/or mining common information, which may include information on a network such as the internet. The system may make such a determination based on the identity of the subject, the subject's payer information, information regarding sample collection, qualitative and/or quantitative assessments of the offer, and/or any other information.

In one example, an inappropriate detection may be a pregnancy test for a male subject or a detection of PSA (prostate specific antigen) levels for a female subject. Such detection may be outside the rules limits of the payer or prescribing physician. Such a booking error may be detected by reviewing the detection of the booking and information associated with the subject. Such associated information may include a medical record of the subject or identifying information about the subject. In one example, the appropriateness of the probing is verified before preparing a sample of the subject for probing. The adequacy of detection of the subject may be verified before, after, or simultaneously with providing the sample to the device and/or cartridge. Verification of the adequacy of detection of the subject may be provided after or before verifying the identity and/or insurance coverage of the subject. The verification may be through communication with a medical care provider, laboratory, payer, laboratory welfare manager, or any other entity. The clinical decision support system may run quickly and/or in real-time. For example, validation may occur within 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. The clinical decision support system may be automated without any manual intervention.

In some embodiments, the qualified person may assist in acquiring the identity of the subject and/or providing a sample from the subject to the device. Qualified personnel may be authorized technicians that have been trained in using the equipment. The qualified person may be a designated operator of the apparatus. The qualified person may or may not be a medical care professional. In some embodiments, the identity of qualified personnel may be verified. The identity of the qualified person may be verified before, after, or concurrently with receiving the biological sample, electronically transmitting data from the device, and/or analyzing the transmitted data. The identity of the qualified person may be verified before, after, or simultaneously with verifying the identity of the subject. The identity of the qualified person may be verified using one or more of the techniques described elsewhere herein.

The system may be capable of providing one or more laboratory reports. The laboratory report may be provided to a medical care professional. In some cases, a laboratory report may be provided to the subject. The laboratory report may be provided via a user interface on the sample processing device. Alternatively, the laboratory report may be provided to one or more external devices. The laboratory report may include data viewable in the portrait orientation. The data may include information collected over time. Such information over time may include biochemical data, analyte levels, physiological information, lifestyle information, medical care and treatment information, and/or any other information that may be collected by a device. One or more diagrams or graphs may show the change or stability of information over time. One or more projected trends may also be displayed.

In some cases, laboratory reports (or reports of or relating to the health, condition, or wellness of a subject) are prepared by means of METHODS (e.g., multivariate METHODS) provided in U.S. patent application No. 12/412,334 ("METHODS AND SYSTEMS FOR assisting clinical outcomes"), to Michelson et al, which is incorporated herein by reference in its entirety. In one example, the laboratory report includes details regarding the trajectory, velocity, and/or acceleration of the progression of the subject's condition (e.g., a health condition or a disease condition). The trajectory may indicate a likelihood of progressing to a clinical outcome. Laboratory reports may be prepared by means of asynchronous data management.

In some embodiments, the longitudinal data can be displayed on the sample processing device. The sample processing device may process the sample and transmit data to an external device. The analysis may occur outside the device or onboard the device. The results of the analysis may include one or more laboratory reports, electronic medical records, laboratory analyses, medical consultations, medical references, or any other display, which may be displayed on the sample processing device. Any description herein of a laboratory report and/or any other item on the above list can be applicable to reference to any other item on the above list. Alternatively, the laboratory report, electronic medical record, or any other display may be displayed on a device other than the sample processing device.

The display of data may include longitudinal data that is presented over time. Such longitudinal data may account for a change in value, a rate of change in value, or any further rate of change thereof. Such longitudinal data may include predictive data and/or past estimation data. Such information may include diagrams or charts showing such data over time. Such information includes video showing the image as a function of time. Such data may include assessment information. Such information may include information relating to diagnosis, prognosis, and/or treatment.

Longitudinal analysis may be possible due to the low coefficient of variation of the acquired data. The longitudinal display and/or analysis may be based on data having a coefficient of variation with any of the values described elsewhere herein. In some cases, longitudinal analysis may be possible due to the high frequency of detection. In some cases, the detection of high frequencies may be supported by a convenient point-of-service location such as a pharmacy, a doctor's office, a clinic, a hospital, a supermarket, or the subject's home or office.

The system may include automated clinical decision support. The clinical decision support may comprise a front-end clinical decision support system and/or a back-end clinical decision support system. In one example of a front-end system, when a probe is ordered for a subject, the clinical decision support system may indicate whether the probe is appropriate/inappropriate for the subject, whether the subject has been probed already (e.g., if the probe was recently performed, it may show the results of the probe rather than performing the probe), and/or whether the subject is being subjected to too many probes. Clinical decision support may also recommend additional probes for the subject. In some embodiments, the data may be provided in real-time on a user interface, such as on a touch screen. The data displayed may be customized for the individual viewing the data, or may be customized based on the data. For example, the display and associated clinical decision support may be customized for a medical care professional based on biochemical data. The customized health report or treatment analysis can display customized recommendations based on the best practices of the relevant clinical decision support system, as well as provide better insight into the occurrence, progression, and regression of disease, for example, through treatment analysis, longitudinal analysis, and other multivariate (multivariate) analysis of the data. The treatment analysis report may include information from existing EMR system analysis or any results of any detection described herein for the subject, and/or any prognosis or treatment plan or health advice otherwise tailored specifically for a given subject.

In one example of a backend system, the clinical decision support system may reference one or more guidelines or rules. The guidelines/rules may be customized according to the healthcare professional, according to the subject, according to the medical insurance company or other payer, according to the hospital, clinic or other medical entity, or any other party. In some cases, guidelines/rules may be customized based on biochemical data. The clinical decision support system may take biochemical data and customize recommendations for a subject based on lifestyle information, dietary information, or any other collectable information, including information described elsewhere herein. In some cases, back-end clinical decision support may take data (e.g., including biochemical data) and customize one or more financial matters. Such financial transactions may include reimbursement by an insurance company and/or healthcare professional, or a charge for one or more services.

Clinical decision support may be linked to one or more subject records. Clinical decision support may be linked to medical records and/or payer records for a subject. Clinical decision support may integrate the use of additional general knowledge. The clinical decision support may be updated periodically or continuously to accommodate up-to-date clinical knowledge. Clinical decision support may include best practices or data associated with diagnosis, treatment, monitoring, and/or prevention of one or more diseases. In one example, the clinical decision support system may have one or more instructions associated with diabetes care. By linking the records of the subjects, the clinical decision support system may be able to provide personalized care for the subjects. For example, by linking the medical records of the subject with the clinical decision support system, the clinical decision support system may be able to subscribe to additional exploration or advice for the next steps based on additional information about the subject including, but not limited to, the subject's medical history, the subject's family medical history, demographic information about these subjects (age, gender), lifestyle information about the subject (the subject's diet, exercise, habits), possible environmental considerations (e.g., whether the subject lives in an area exposed to a particular toxin or has a higher risk of certain diseases), and/or any other information about the subject.

The clinical decision support system may also be capable of providing population-based clinical decision support. A clinical decision support system may be able to provide support for one or more peer groups. Such a population may be divided in any manner. For example, the population may be based on age, gender, lifestyle, geography, occupation, medical history, family medical history, or any other factor. The clinical decision support system may use epidemiological models to provide decision support. Information gathered from epidemiological sources can be applied to one or more patient populations.

In one example, individuals may arrive and be qualified for detection to verify whether they are qualified for one or more detections. The individual may then be pre-screened and may answer a questionnaire. The questionnaire can include questions about the subject's lifestyle (e.g., diet, exercise, habits) and/or medical history. The doctor can perform a doctor examination of the individual. In some cases, the questionnaire includes questions about the subject's dietary intake, exercise, health status, and/or mental status. The health condition of the subject may be, or be associated with, a physiological condition of the subject. The mental condition of the subject may be related to the mood of the subject or a depressive disorder, such as depression. The questionnaire can be a guided questionnaire having a plurality of questions directed to or associated with dietary intake, exercise, health status, and/or mental status of the subject. In some cases, the questionnaire is presented to the subject by means of a system (or subsystem) configured to learn the subject's responses and to specifically customize subsequent questions in response to the subject's responses. The questionnaire may be presented to the subject on a display of the device by means of a user interface, such as a Graphical User Interface (GUI).

In some embodiments, a recommendation for a lifestyle may be made by a device and/or system and transmitted back to the customer. Such suggestions may be provided before, after, or simultaneously with the completion of the questionnaire. Such recommendations may be made based on information collected within questionnaires, medical records, biochemical data, and/or probe results.

The device may interpret the subject's response to the question by means of the reference information. In some cases, the reference information includes a pictorial depiction of the food serving taken by the diet, the level of exertion exercised, the present status of health condition, and/or the present status of mental condition. The reference information may be included in a calibration matrix stored in a memory location (e.g., cache, hard drive, flash memory) of the device.

The device and/or healthcare worker may collect biometric information about the individual (e.g., blood pressure, weight, body temperature). This may be combined with the detection of a sample collected from the subject that may be processed by the device. All of the information may be linked and accessible by the clinical decision support system. In some embodiments, all of the information may be linked within a record of a single subject. Such procedures may be useful for annual physical examination or preventive care. Such procedures may also be useful for diagnosing, treating, or monitoring diseases.

Clinical decision support may provide improved patient triage. For example, the clinical decision support system can make a diagnosis or recommendation of the condition of the subject based on the patient's information (e.g., analyte levels, physiological information, additional information, or any combination thereof). By incorporating subject-specific information, such patient conditions may be better narrowed or more accurate/accurate probabilities may be assigned. Clinical decision support may also be able to flag one or more critical situations and may result in providing an alert to the subject and/or the subject's healthcare provider. The clinical decision support system may be capable of flagging one or more conditions that may require accelerated further analysis and enacting one or more processes to assist in the further analysis.

The subject's healthcare provider may be able to access the clinical decision support system and/or additional records associated with the subject. For example, a subject may provide a sample to a device, and the device may run one or more probes. The clinical decision support system may provide the probe results to the subject's basic healthcare practitioner. The base healthcare practitioner may be able to view the subject's findings and/or past findings. The base healthcare practitioner may also be able to view additional information provided by the clinical decision support system. In some embodiments, the clinical decision support system may be capable of providing a base healthcare practitioner with professional information beyond the expertise of the base healthcare practitioner. For example, if a basic healthcare practitioner has a cancer patient, the clinical decision support system may utilize cancer-specific information to assist the basic healthcare practitioner. The clinical decision support system may provide one or more recommendations to the physician. The decision may include a recommendation of one or more interventions by the physician. Such recommendations may be provided to the physician when requested by the physician, when a particular condition is detected, when the clinical decision support completes the analysis, or according to a schedule. In some embodiments, the device may be provided in a doctor's office. The subject may be able to provide the sample to a device in the doctor's office, and the doctor may receive one or more test results while the subject is visiting the doctor's office.

The clinical decision support system can determine the quality of care for a given healthcare professional. In some cases, the quality of care of the doctor may be determined by a clinical decision support system for provision to one or more payers (e.g., medical insurance companies). The quality of care can be determined based on changes in the subject data during the subject's interaction with the healthcare professional. Such changes may include changes in lifestyle, changes in biochemical data, feedback from the patient, or any other information.

A method may be provided that may advantageously accommodate reflection detection. Additional probes may be run on the device based on the one or more probe results. Such detection and subsequent detection may be scheduled in real time. Since the detection results may be provided onboard the device or may be automatically performed off-board and may result in subsequent detections being automatically performed using the device. Subsequent probing may be performed on the same sample that has undergone one or more initial probes. Alternatively, the device may request additional samples from the subject based on the required probing. After the first probe is performed, it can be quickly initiated if a second probe is needed. In some embodiments, the second probe is initiated within 4 hours or less, 3 hours or less, 2 hours or less, 1 hour or less, 30 minutes or less, 15 minutes or less, 10 minutes or less, 5 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 15 seconds or less, 5 seconds or less, 1 second or less, or 0.1 seconds or less from the completion of the first probe. This may advantageously allow multiple detections to occur without requiring the subject to travel to the sample collector multiple times. This may also advantageously allow multiple detections to occur without requiring additional steps to be prescribed by the physician. The amount of time required to effect diagnosis, monitoring, treatment and/or prevention of a disease can be greatly reduced. Such a reflex procedure can be used during a visit by the subject to a doctor. Such a reflex procedure can occur before the subject meets the doctor, while the subject is meeting the doctor, and/or after the subject has met the doctor. The reflex procedure may use clinical decision support.

In some cases, when a probe is ordered, the healthcare professional may perform a reflex and determine additional probes or steps. Alternatively, the device and/or clinical decision support may provide for reflectance detection. For example, if a certain value is out of range (e.g., the analyte level of a sample is outside of an expected range), a healthcare professional can perform a reflectance analysis on the same sample through a touch screen. Alternatively, all tests may be run automatically on the sample and the data may be displayed if the healthcare professional wants to perform another test because something is out of range. In some cases, the displayed data may include only data that is ordered by a healthcare professional. Alternatively, additional data deemed relevant by clinical decision support may be displayed.

In some cases, one or more laboratory reports may be provided to a healthcare professional. In some cases, the laboratory report may be displayed on the sample processing device, or on any external device. The laboratory report and/or laboratory reservation system may be customized for reflectance analysis. In one example, the order may allow the user to subscribe to the probe, and may also show fields for entering and/or displaying what reflection analysis is desired. The report may show the reflection analysis performed on the results. The results of the reflection analysis may also be displayed.

Clinical decision support may be able to do self-learning. In some embodiments, the subject's response to one or more treatments, may be monitored, and such data may be accessed by a clinical decision support system. The self-learning of clinical decision support may be for individual subjects. For example, clinical decision support may be aware that a particular subject is poorly responsive to a particular type of drug. The self-learning of clinical decision support may also be generalized. For example, the clinical decision support system may be aware of patterns in which a particular demographic population or population with particular characteristics may or may not respond well to a particular treatment. Clinical decision support may utilize records of subjects, records of other patients, general health information, public information, medical and statistical data, insurance information, or other information. Some information is publicly available on the internet (e.g., netgraphs, articles, periodicals, databases, medical statistics). The clinical decision support system may in turn either crawl a web instrument or database to update the information. Additional information that may be collected/accessed by the clinical decision support system may include the entity's own trial and information about drug effectiveness and/or toxicity. In some specific examples, self-learning may occur on the cloud. When additional data is collected, it can be uploaded to the cloud and it can be accessed by the clinical decision support system.

The apparatus may be useful for assisting in the prescription of medications and/or medications. For example, the device may be used to check the analyte level in a subject prior to writing a prescription for a drug. The device may determine the drug concentration. The device may be used to periodically probe the subject to gauge how much medication the subject has taken, regardless of when the reformulation of the medication was made. The device may be used to detect the presence or level of a drug in a subject before, after, or simultaneously with providing a prescription for the drug. Such detection to determine drug levels and/or analyte levels may be useful for detecting the efficacy and safety of a drug. After the drug has been prescribed to the subject, the device may be useful for determining whether the drug is safe or effective based on the pharmacodynamic profile. Such detection may also be useful for detecting compliance and/or non-compliance of a subject with taking medication (e.g., if the level of medication is too high, the subject may take an overdose; if the level of medication is too low, the subject may not take medication as often as the subject would otherwise be). The device may be useful for monitoring the level of medication in a subject over time to determine whether the subject is following a dosing schedule. Drug and/or analyte levels may be associated with compliance and/or non-compliance. Components of the device, such as the wings, may store the drug, which may be in tablet or liquid form. These drugs may be distributed to the subject based on the results of the detection, historical data, physician orders, medical instructions, and/or other desired medical records. The drug may be automatically packaged, sealed, and labeled by the device as needed, and then dispensed to the subject.

If certain conditions are detected, one or more alerts may be provided to the healthcare professional and/or the subject. For example, if the device has a toxic or detrimental effect on the subject, and/or if the subject is not in compliance with the regulations, an appropriate alert may be provided.

The sample or a portion thereof may be archived by the device for later detection. This process may be triggered by a probe result, a device error, or other factors, as defined by a set of procedures and/or rules. The samples of the trays may be packaged to maintain the integrity of the samples and may be stored in a refrigerated compartment. The samples of the trays can be automatically sealed in containers and marked by the apparatus as needed. The stocked sample may later be analyzed by the same device, either transferred to another device, or sent to another detection facility. The test results using the inventory sample may be combined with any previous test results from the initial sample test.

The devices described herein may be useful for telemedicine. As described elsewhere herein, the device may be useful for verifying the identity of a subject and/or device operator. The device and/or system may be capable of confirming the identity of the subject, accessing payer information, determining whether the subject has received an order to be probed, determining whether the probe is within a set of rules, accessing a clinical decision support system, dispensing a prescription medication, or performing other steps.

The device may be capable of performing qualitative and/or quantitative analysis of the health condition and/or medical condition of the subject. For example, the device may be capable of processing a sample of a subject, which may be useful for determining one or more analyte levels of the subject. The presence and/or concentration of the analyte may be used to assess the health of the subject and/or to verify the identity of the subject. The device may also be capable of acquiring one or more physiological measurements of the subject. Such information may also be useful for assessing the health of a subject and/or verifying the identity of a subject. In some cases, additional qualitative information about the lifestyle and/or habits of the subject may be collected and used to assess the health of the subject. Any information collected about the subject as described in any of the various places herein may be useful for assessing the health of the subject (e.g., for diagnosis, treatment, and/or disease prevention of the subject).

Any information collected by the device relating to the subject may be accessed by the subject's doctor or other healthcare professional. In some embodiments, the physician of the subject may only have access to a subset of the information collected by the device. Any description of a doctor herein may be applicable to a basic health care doctor or other health care professional of the subject. The subject's doctor may be in a different location than the subject. Alternatively, the subject's doctor may be in the same location as the subject. The subject's doctor may be able to assess the health status of the subject without having to see the subject himself. The device may be provided at a point-of-service location. The device may advantageously enable the subject to travel to a point of service location and conduct a collection of information about the subject that can be relied upon by a physician to assess the health status of the subject. The physician may be a basic health care physician for the subject, which may enable the subject to maintain a personal relationship with a physician who is familiar with the subject and the subject's medical history and condition.

In another embodiment, the device may execute the real-time language interpretation service when the patient speaks a different language than the healthcare provider. For example, a person visiting a country may travel to a facility location (e.g., a retail location) to contact the most medically relevant, qualified, or visible healthcare personnel who may not be able to speak the visitor's language. In such a case, the device may automatically detect such an obstacle, or the device may prompt the patient or healthcare provider for language preferences and automatically provide translation services.

In yet another embodiment, the apparatus may be placed in remote and less developed areas, villages or locations where a large population may never be accessible to high-quality health care personnel. In this example, the device automatically, with the help of an external controller or cloud, associates healthcare professionals from the developed world with patients in remote and rural areas of the body and performs language and other cultural interpretations based on sign language, body language, and limb movements, not only on spoken language, but also using cameras, imaging analysis, and motion detection and other sensors in the device or module.

In another specific example, the device may use external controllers and clouds to overcome cultural barriers established on the basis of local customs that may prevent the provision of medical care to certain populations. For example, in certain regions where a female healthcare professional is only allowed to come into contact with a female patient, the device may detect the gender of the patient and automatically or through manual verification connect the female patient with a female healthcare provider at a remote or local location, thereby enabling a wider range of healthcare services to be obtained where access to such services is otherwise impossible or less likely. The device may use image acquisition, recognition, voice, and other physical cues using cameras and image analysis and facial recognition to provide this capability.

In some embodiments, the physician may interact with the subject in real-time from a remote location or at the same location via the device. In other embodiments, the physician and patient do not need real-time interaction — information relating to the subject can be collected via the device and accessed by the physician at another time. The physician may decide which follow-up actions, if any, need to be taken, or whether real-time on-the-spot or remote access should be scheduled.

One or more cameras may be provided that may capture images of a subject. Any type of camera or combination of cameras as described elsewhere herein may be useful for capturing images. In some embodiments, the camera may capture a still image of the subject or a video image of the subject. In one example, a streaming video of the subject may be ingested by the device, which may be sent to a doctor at a remote location. The camera may or may not take a doctor image at the site where the doctor is located and send the doctor image to the device. The image of the doctor may be taken by a sample processing device at the doctor's site. Alternatively, the image of the doctor may be taken by any other type of device. For example, the subject and the doctor may conduct a video conference via the device. The video conference may show two-dimensional images of the subject and the doctor, or three-dimensional images of the subject and the doctor. In an alternative embodiment, audio information may be used to conduct a teleconference between the subject and the doctor. One or more still and/or video images may be captured and transmitted between the subject and/or the doctor.

In some embodiments, the conference may be provided between any number of parties. For example, a meeting may be allowed between two parties (e.g., a subject and a doctor of the subject, or a basic health care doctor and a specialist of the subject), three parties (e.g., between the subject, the basic health care doctor of the subject, and the specialist), four parties, five parties, six parties, or more. This may be useful when consulting one or more specialist physicians or other healthcare providers of the subject. This may also be useful if the subject wishes to join a family member or friend at a meeting. Each party may be in a different location, or some parties may be in the same location.

The conversation between the subject and/or the doctor (or any party or combination of parties described herein) can occur in real-time via the device. Alternatively, the subject may view a prerecorded video of the subject's physician. The subject may record statements and/or other information from the subject. The videotaped video of the subject may be sent to the subject's doctor, who may view the videotaped video in real time or at a later time. Any description herein of subject-physician interaction may also apply to any other party, parties, or combination of parties described elsewhere herein.

Further, as described elsewhere herein, an image of the subject, a portion of the subject, or a sample taken from the subject can be taken. Such images may be useful for identification purposes.

The captured image may also be useful for other purposes. For example, an image of a subject may be taken and changes or invariance in the height and/or waist circumference of the subject may be analyzed and evaluated for health and/or medical purposes. For example, a sudden increase or decrease in the subject's chest circumference may signal a danger, or be evaluated along with other information collected about the sample to determine if a health problem exists. The gait of the subject can be analyzed to determine whether the subject is lameness or moving in a manner indicative of an injury. The facial expressions of a subject may be stored and analyzed to determine whether the subject is in a particular mental state.

Images of a portion of the body may also be acquired to assess the health status of the subject. For example, a rash or lesion on the subject's skin, a mole on the subject's skin, an image of the subject's throat, or any other type of image may be captured by the device and/or viewable by a physician. The doctor may evaluate the dermatological condition based on the acquired one or more images of the subject's skin. The physician may access one or more images of the orifice of the subject. In some embodiments, the transmitted image may be a two-dimensional image. The transmitted image may also be a three-dimensional image, which may be useful for viewing one or more features (e.g., whether the rash is swollen or not).

In another example, an image of a sample acquired from a subject may be sent to a physician. For example, one or more images of a tissue sample, a body fluid sample, or other sample may be sent to a physician. The image may also include samples at various stages of processing. The apparatus may advantageously be capable of generating images quickly, thereby freeing the physician from having to wait for such images while interacting with the subject. In some embodiments, such images may be accessible by a basic healthcare physician, pathologist, or other healthcare professional of the subject.

Such images may be analyzed relative to earlier images acquired for the subject. Such images may also be analyzed in an independent manner without reviewing historical images acquired for the subject. In some embodiments, trend analysis may be performed on one or more images acquired from a subject. Such trend analysis may extend for a long period of time (e.g., historical data about moles on the subject and how they change over multiple visits), or for a shorter period of time (e.g., how the sample reacts over the course of a visit). Images from multiple visits by the subject or from one visit by the subject may be analyzed.

In some embodiments, a method for diagnosing or treating a subject with a device may be provided. The method may comprise authenticating the subject and obtaining a three-dimensional representation of the subject by means of a three-dimensional imaging device. The three-dimensional imaging device may be any camera or cameras described elsewhere herein. In some embodiments, the three-dimensional imaging device may use multiple lenses. The three-dimensional imaging device may include optical, motion, and/or audio capture techniques. The system may include an image recognition module for analyzing at least a portion of the dynamic three-dimensional spatial representation of the subject for treatment. The image recognition may or may not be onboard the device. The method can include providing the three-dimensional representation to a display of a computer system of a healthcare provider, the computer system communicatively coupled to the three-dimensional imaging device, the healthcare provider in remote communication with the subject. The method may further comprise diagnosing or treating the subject with the aid of the three-dimensional representation on the computer system display.

In some cases, the three-dimensional image displayed to the physician may be an actual three-dimensional image of the imaged portion of the subject. Alternatively, the three-dimensional image may represent the subject being ingested. This may include simplified or altered images. In some embodiments, the three-dimensional representation may include a visual indication of other information acquired from the subject. For example, a three-dimensional image may be generated: which shows a rash on the skin of a subject, and a color indication that may indicate the amount of heat at different areas of the rash or the concentration of an analyte detected at different portions of the rash. The three-dimensional image may include a computer-generated model.

The healthcare provider may have been selected by the subject. In some embodiments, the healthcare provider is the subject's own basic healthcare physician. The diagnosis may be provided in real time. In some embodiments, diagnosing may include combining the three-dimensional representation with subject-specific information. In some embodiments, the subject may be authenticated by verifying the identity of the subject. Such identification verification may use any of the techniques described elsewhere herein. In some cases, the subject may be verified via a fingerprint or genetic marker. The subject may be authenticated by touching the touch screen of the device. The authenticating step may be performed by means of one or more of a biometric scan, an insurance card of the subject, a name of the subject, a driver's license of the subject, an identification card of the subject, an image of the subject taken by means of a camera in the point-of-care system, and a gesture recognition device.

A point of service system may be provided for diagnosing or treating a subject. The system may include: a point of service device having a three-dimensional imaging device for providing a dynamic three-dimensional spatial representation of a subject; and a remote computer system in communication with the three-dimensional imaging device, the remote computer system for authenticating the subject and retrieving a dynamic three-dimensional spatial representation of the subject after the authenticating. The system may include an image recognition module for analyzing at least a portion of the dynamic three-dimensional spatial representation of the subject for treatment.

Other physiological data collected from a subject may be useful for assessing the health of the subject. For example, the subject's blood pressure level, heart rate, and/or body temperature may be assessed by a physician and/or in view of other information related to the subject in order to assess the health of the subject. The weight of the subject can also be used to assess the health of the subject. For example, if the subject suddenly increases or loses weight, this may be considered an indication by the physician.

Physical data associated with a sample of a subject may be useful for assessing the health of the subject. For example, a sample from a subject may be processed and the acquired data may be accessible by a physician of the subject. In some embodiments, one or more analysis steps may be performed on the data collected by the device before the physician views the data.

Furthermore, as described elsewhere herein, information related to the lifestyle and/or habits of the subject may be collected. Such information may be collected from a graphical user interface, as described elsewhere herein. In some cases, such information may be collected in the form of a survey, as described elsewhere herein. In some cases, such information may be collected via an external device that may be able to communicate with the device. The external device may be a computer, server, tablet, mobile device, or any other type of network device described elsewhere herein. Such information may be stored in the device and/or transmitted from the sample processing device. Such information may be accessible by the subject's doctor or other healthcare professional.

Any information collected relating to the subject may be accessed by one or more physicians of the subject, and the health of the subject may be assessed thereby by the physicians. Having the device at a point-of-service location may allow the subject to travel to one of the point-of-service locations that is convenient for the subject. This may widen the accessibility of the subject to various physicians. For example, if a subject lives in a first location and has a basic healthcare practitioner that the subject likes, if the subject moves to a second location, the subject may still primarily interact with the same basic healthcare practitioner. This may also provide flexibility in the timing of the subject and the physician. For example, the subject may provide information to the sample processing device when the subject is available or at a time convenient to the subject. When a doctor has time in his schedule, the doctor may be able to access information about the subject. An on-the-fly and/or real-time meeting or conference between the doctor and the subject can be scheduled if/when necessary, but much of the prior data collection and analysis can occur prior to such a meeting, thereby making such a meeting more efficient.

Asynchronous data management

The systems described herein may additionally or alternatively use asynchronous data management. Asynchronous data management may use the sample processing devices described herein. Alternatively, asynchronous data management may also occur outside of the context of the sample processing devices described herein.

Data about the subject may be stored. Such data may include medical records of the subject. Such medical records may span a length of time (e.g., multiple visits), or may come from a single point in time or a very short time (e.g., a single visit). Such data may be accessed by one or more parties. For example, a physician of the subject may be able to access information related to the subject.

In some embodiments, one or more parties may be able to control who has access to information of the subject, and which information is authorized for access. For example, the subject may decide which doctors or healthcare devices have access to the subject's data. The subject may wish to select a physician and/or specialist for the subject. The subject may specify which data other parties have access to. For example, the subject may decide that certain healthcare professionals only have access to a certain subset of the medical data. The subject may decide that a specialist has access only to data within the field of the specialist or relevant to the specialist's assessment of the subject's health. Different parties may be granted access to different subsets of information. Alternatively, the subject may choose to authorize different parties to access the same information. In some cases, the subject may choose to authorize access to all of the information.

In some embodiments, other parties may decide who may have access to the subject's information. For example, a doctor's office may collect information about the subject. The doctor and/or the entity associated with the subject may decide who has access to the information and which portions of the information other parties have information access. In some cases, a physician may decide which information the subject has access to. In some cases, the information-collecting entity may decide who has access to which information of the subject. Any other party may be the designated party who decides who has access to the subject's information.

The authorizer of the access rights can decide when other parties can access the selected information. For example, the subject, doctor, or any other party may be the designated authorizer of access. The authorizer may provide an expiration time and/or date for the access rights provided to the other party. In some cases, the authorizer may specify a start time and/or an end time at which another party may access the information. In some cases, the authorizer need not specify an expiration time, and may choose to revoke access at any time.

In some cases, a doctor may wish to share information with another healthcare provider, a subject, or an associated party of the subject. In one example, a doctor may wish to obtain a second opinion from another healthcare provider, such as a specialist in a particular field. The doctor may need to obtain approval of the subject for the shared information. Alternatively, the doctor may have the authority to share certain portions of the information. A first party (e.g., a doctor) may provide selected data to a second party (e.g., a specialist) in a first format. In one example, the physician may be able to provide a chart or other visual depiction of the data, while including video and/or audio that records the physician's mind. The shared and/or provided data may relate to access rights that may be granted to the original data.

The second party may view the data in the first format. The second party may be able to change the data from the first format to the second format. The second party may be able to insert or modify some data provided to the second party. For example, the second party may view a chart or other visual depiction of the data that accompanies the recording of the doctor's mind. The second party may be able to stop recording and insert the doctor's own thoughts at any point. For example, a video may be provided showing a visual avatar (e.g., data) and an audio avatar (e.g., physician notes). The second party may be able to stop the video and record the second party's own voice and ideas, which may be inserted into the video. Similarly, the second party may be able to alter and manipulate the data shown. For example, the second party may be able to write the second party's own remarks or opinions in the display of the data.

In addition to adding or inserting additional information, the second party may be able to alter the data provided in the first format. For example, the first party may draw notes about the data. The second party may be able to change the note-e.g., change the shape of the trend line, or change the equation. Data having the second format is accessible to the second party and the first party. In some cases, the second party may send data at the second party back to the first party. Any reference to transmitting data may include providing access to the original data. The raw data may be stored in one or more databases, or in other memory. The raw data may be stored in a cloud computing infrastructure.

Such changes may occur asynchronously. For example, a first party may send information having a first format to a second party. Such changes to the second format may be made by the second party at another time after the information has been sent. The second party may then send information in the second format to the first party. This information may be sent after the changes have been made. Such changes may manipulate the underlying real-time data. The discussion of sending information may involve sending access to the underlying real-time data. In some cases, only one party may access the data at a time to alter the data. Alternatively, multiple parties may access and/or alter data simultaneously.

In some embodiments, data may be collected from the sample processing device. The sample processing device can also include an interface that can allow a user to provide access to one or more other parties. For example, a send key or interface may be provided in which a user may select information to send and/or provide access to one or more designated recipients, and/or a time limit. The device may also include a camera and/or microphone through which the user may record one or more comments and/or notes that may accompany the data. The user may also be able to add comments or notes via a touch screen or other user interface of the device.

The data may be stored on the cloud. The user of the device may be able to select which parties have access to the information. The selected recipients may be able to access data stored on the cloud. The selected recipients may be able to access the data via one or more devices, which may include a sample processing device, a computer, a tablet computer, a mobile device, or any other type of network device described elsewhere herein.

In alternative embodiments, such changes may occur in real time. For example, a video conference may occur in which multiple parties may view the same information at the same time. The meeting may allow one or more of the parties to alter information-e.g., add notes, draw charts, or otherwise manipulate information. The one or more parties may manipulate underlying information, or visual representations of information.

Device calibration and/or maintenance

In some specific examples, the device may be capable of performing onboard calibration and/or control. The device may be capable of performing one or more diagnostic steps (e.g., a preparation step and/or an assay step). If the results are outside of expected ranges, a portion of the equipment may be cleaned and/or replaced. The results may also be useful for calibrating the device. On-board calibration and/or control may occur without human intervention. Calibration and control may occur within the device housing.

The device may also be capable of performing on-board maintenance. If a condition requiring repair and/or maintenance of the equipment is detected during calibration, operation of the equipment, diagnostic testing, or at any other point in time, the equipment may institute one or more automated procedures to perform the maintenance and/or repair. Any description of maintenance may include repair, cleaning, and/or adjustment. For example, the device may detect that a component is loose and may automatically tighten the component. The apparatus may also detect an insufficient level of detergent or diluent in a module and provide an alert to add more detergent or diluent, or to call up detergent or diluent from another module.

The system may be configured to continue to operate after certain modules are removed and/or fail.

Calibration and/or maintenance may occur periodically. In some embodiments, device calibration and/or maintenance may occur automatically at regular or irregular intervals. Device calibration and/or maintenance may occur when one or more conditions are detected from the device. For example, if one component is suspected of failing, the device may run diagnostics on the associated component. Device calibration and/or maintenance may occur as instructed by an operator of the device. Device calibration and/or maintenance may also occur based on automated instructions from an external device. The external device or control may maintain a device calibration schedule and/or a device maintenance schedule for the plurality of devices. Device calibration and/or maintenance may occur on a time-based schedule or a usage-based schedule. For example, devices that are used more frequently than others may be subject to more frequent calibration and/or maintenance, and/or vice versa.

In some embodiments, the apparatus may be calibrated and quality controlled periodically. Each module containing one or more hardware units may be periodically calibrated by utilizing a calibration cassette. The calibration cassette may contain a series of standard liquids to which a properly calibrated system will give a known response. Module results for these criteria can be read, analyzed, and if necessary, module status can be determined and corrected based on their deviation or absence. The calibration standards may be stored in the apparatus or introduced separately as a cassette.

In some embodiments, some modules may be automatically modified for any change in the environment. For example, a temperature sensor on the pipette may automatically trigger an adjustment in the required piston movement to make corrections for temperature fluctuations. In general, a module in which feedback on performance is available may make automatic corrections to any changes over time.

In some embodiments, the output measurements of the cell counter may be calibrated to match results from the decision device or devices utilizing other techniques as desired.

Safety of equipment

One or more security features may be provided on the sample processing device. The device may have one or more motion sensors that can determine when the device changes orientation or movement. The device may be able to detect whether a person is attempting to turn on the device. For example, one or more sensors may detect whether portions of the device are disassembled. The device may be able to detect whether the device has fallen or fallen over. The device may be capable of sensing any motion of the device or any motion in the vicinity of the device. For example, the device may be able to sense whether an object or person is within a certain distance of the device (e.g., using a motion sensor, an optical sensor, a thermal sensor, and/or an audio sensor). The device may be able to determine if the device is unplugged or if an error has occurred on the device. Any description of actions that may occur as a result of device tampering may apply to any other device condition as described herein, and vice versa.

In some embodiments, an alert may be provided if a person attempts to open the device, or if a person comes within the proximity of the device. In some cases, an alarm may be provided if the device housing is breached. Similarly, if the device is dropped, tipped over, or if an error is detected, an alarm may be provided. The apparatus may incorporate a stabilising system which in turn or otherwise possesses shock absorbing and dampening capabilities to prevent it from tipping over, for example when moving on a vehicle travelling at high speed. In some cases, a camera on the device may capture an image of the environment surrounding the device if the device detects that the device is being opened, accessed, or tampered with. The device may capture an image of the person attempting to open the device. Data associated with the device may be sent to the cloud or to an external device. An image of a device associated with device tampering, such as an individual tampering with the device, may be transmitted from the device. Data associated with the device, which may include one or more images, may be stored in the device. In the event that the device is not able to transmit data immediately, the data may be transmitted once the device is able to transmit and/or connect to the network.

The device may include one or more microphones or audio detection devices that may be capable of recording and/or relaying sound. For example, if the device is tampered with, the microphone may capture audio information, and the audio information may be stored on the device or may be transmitted from the device.

The devices may include one or more position sensing devices. For example, the device may have a GPS tracker within the device. The location of the device may be transmitted from the device when any tampering with the device is detected. The location may be transmitted to an external device or cloud. In some cases, the location of the broadcast device may be continued once tampering is detected, or broadcast at one or more intervals or upon detection of other events. The owner or an entity associated with the device may be able to track the location of the device. In some cases, multiple location sensors may be provided, so that even if the device is disassembled, and/or one or more location sensors are discovered and destroyed, it is still possible to track other components of the device. In the event that the device is unable to transmit the device location at a particular time, the device may be able to store the device location and transmit the device location once it is able to transmit.

In some embodiments, the device may be designed such that it can only be opened from the inside, or designed to be opened only from the inside. For example, in some embodiments, the device is free of fasteners or screws on the exterior of the device. Any mechanical fastening and/or opening feature may be internal to the device. The device may be mechanically locked from within the housing. The outer part of the housing may not comprise any external fastening/locking means. The device may be opened from the inside according to one or more instructions from the controller. For example, a device may have one or more touch screens or other user interfaces that may accept instructions from a user to open the device. The device may have one or more communication units that may receive instructions from an external device to open the device. In accordance with the instructions, one or more opening devices within the apparatus may cause the apparatus to open. In some cases, the device may require power to open the device. In some cases, the device may only be turned on when powered on. Alternatively, the device may be turned on when powered by a local energy storage system or energy production system. In some cases, a device may only turn on when it receives an instruction from a user that has been identified or authenticated. For example, only certain users may be granted the right to cause the device to open.

The device may have one or more local energy storage systems. The energy storage system may allow one or more portions of the device to operate even when the device is separate from an external source of energy. For example, if the device is unplugged, the one or more energy storage systems may allow one or more portions of the device to operate. In some cases, the energy storage system may allow all portions of the device to operate. In other examples, the local energy storage system may allow certain information to be transmitted from the device to the cloud. The local energy storage system may be sufficient to power a camera that may take one or more images of the device's surroundings and/or an individual tampering with the device. The local energy storage system may be sufficient to power a GPS or other location sensor that may indicate the location of the device. The local energy storage system may be sufficient to save and/or transmit the state of the device, for example in a record-based logging method, so that the device can restart at its end or know which steps need to be performed. The local energy storage system may be sufficient to power the transmission unit, which may send information about the device to the cloud and/or to an external device.

In one particular example, the device and the external controller maintain a security mechanism by which any unauthorized person physically proximate to the device is unable to retrieve and link the probe information back to the individual, thereby protecting the privacy of the patient health data. One example of this is for the device to take the user's identification information, send it to an external device or cloud, receive the key from the cloud and erase all patient information from the device. In such a scenario, if the device sends any further data about the patient to the external device, it will involve linking by means of a key that has been obtained from the external device.

Spectrophotometer

Fig. 74A-74D illustrate a spectrophotometer 7400 according to specific examples described herein. Spectrophotometer 7400 may be spectrophotometer 714 described in the context of fig. 7. Spectrophotometer 7400 includes a detection block 7401 ("block") having laser diodes, filters, sensors (for detecting electromagnetic radiation), and a printed circuit board. In some cases, spectrophotometer 7400 includes a controller having one or more processors. A light source, such as a xenon lamp light source, is located in the compartment 7402 adjacent the block 7401. The block 7401 includes a sample receptacle (or inlet) port or channel 7403 configured to receive a first consumable 7404 or a second consumable 7405. The first consumable 7404 is a cuvette and the second consumable is a tip. Consumables 7404 and 7405 are configured to be moved, carried, and manipulated by the various sample processing systems (e.g., robots) provided herein. The cuvette includes a sample holder.

Referring to fig. 74C, a first consumable 7404 is configured for installation in the port 7403. The single sample rack 7406 of the first consumable 7404 is configured for placement in direct view or with the aid of optical instruments on the view of a light source 7407 (e.g., a xenon light source). Light passes from the individual sample holders to a detector 7408 (e.g., a CCD sensor) for detection. Referring to fig. 74D, a second consumable 7405 is inserted into the port 7403 for sample detection. Light from the laser diode 7409 is directed to the second consumable 7405. The light then passes to a filter 7410 that is moved into the path of the light emanating from the second consumable 7405. The light is then directed to sensor 7408. Optical instruments may be used to direct light from either the first consumable 7404 or the second consumable 7405 to the sensor 7408.

Consumables 7404 and 7405 are configured to hold the sample for probing. Consumables 7404 and 7405 may be discarded after use. In some cases, spectrophotometer 7400 is configured to hold one consumable at a time, however in some cases spectrophotometer 7400 may hold multiple consumables during processing. In some cases, a non-consumable sample rack may be used.

In one particular example, the liquid handling apparatus may be used to transfer the assay container to a spectrophotometer where the optical properties of the sample are measured. The property may include, but is not limited to, absorbance, fluorescence, turbidity, and the like. The spectrophotometer may include one or more sensors capable of processing one or more samples simultaneously. Similarly, one or more signals (absorbance, turbidity, etc.) may be measured simultaneously.

The spectrophotometer may comprise a PCB board connected to an external computer and/or processing unit. Alternatively, the computer may be part of the PCB board itself. The computer may receive data from the spectrophotometer sensor after it is processed by the plate. The computer is programmed to analyze the data sent from the board in real time. In one embodiment, the results of the computer analysis may provide feedback to the board. The feedback may include a change in acquisition time, the number of acquisitions used to calculate the average, etc. In some embodiments, the feedback can be used to automatically calibrate the spectrophotometer components.

Measurement of

Receptor binding assays

Receptor:

in some embodiments, the analyzer is configured to perform a receptor-based assay. In general, receptor-based assays involve detecting an interaction between two binding partners, an analyte receptor and an analyte. Typically, the analyte receptor and the analyte in a given pair of binding partners are distinguished on the basis that one of the pair is known (analyte receptor) and the other one is detected (analyte). Likewise, in other embodiments, the exemplary analyte receptors described herein can be detected as analytes, and in other embodiments, the exemplary analytes as described herein can be used as analyte receptors for detecting the respective binding partners. In some embodiments, the analyte receptor, the analyte, or both comprise a protein. Analyte receptors include, but are not limited to: natural or synthetic proteins, cellular receptor proteins, antibodies, enzymes, polypeptides, polynucleotides (e.g., nucleic acid probes, primers, and aptamers), lipids, small organic or inorganic molecules, antigens (e.g., for antibody detection), metal binding ligands, and any other natural or synthetic molecule with binding affinity for a target analyte. In some embodiments, the binding affinity of the analyte receptor for the analyte is K_DLess than about 5X 10^-6M、1×10^-6M、5×10^-7M、1×10^-7M、5×10^-8M、1×10^-8M、5×10^-9M、1×10^-9M、5×10^-10M、1×10^-10M、5×10^-11M、1×10^-11M or less.

In some embodiments, the analyte receptor is a peptide comprising a recognition structure that binds to a target structure on an analyte, such as a protein. Various recognition structures are well known in the art and can be prepared using methods known in the art, including by phage display libraries (see, e.g., Gurraja et al (2000) chem. biol.7: 515-27; Houimel et al (2001) Eur. J. Immunol.31: 3535-45; Cochran et al (2001) J. am. chem. Soc.123: 625-32; Houimel et al (2001) int.748. J. cancer92: 55, each incorporated herein by reference). Various recognition structures are known in the art (see, e.g., Cochran et al, (2001) J.Am.chem.Soc.123: 625-32; Boer et al, (2002) Blood100: 467-73; Guallilo et al, (2002) mol.cell Endocrinol.190:83-9, each hereby incorporated by reference), including, e.g., combinatorial chemistry methods for generating recognition structures (e.g., polymers having affinity for target structures on proteins) (see, e.g., Barn et al, (2001) J.Comb.chem.3: 534-41; Ju et al, (1999) Biotechnol.64:232-9, each hereby incorporated by reference).

In some embodiments, the analyte receptor is a peptide, polypeptide, oligopeptide, or protein. The peptide, polypeptide, oligopeptide or protein may be composed of naturally occurring amino acids and peptide bonds or synthetic peptidomimetic structures. Thus, as used herein, "amino acid" or "peptide residue" includes both naturally occurring and synthetic amino acids. For example, homophenylalanine, citrulline, and norleucine are considered amino acids for use in at least some embodiments described herein. The side chain may be in the (S) or (R) configuration. In some embodiments, the amino acid is in the (S) or L-configuration. If non-naturally occurring side chains are used, substituents other than amino acids may be used, for example to prevent or retard in vivo degradation. Proteins containing non-naturally occurring amino acids can be prepared synthetically, or in some cases recombinantly; see, e.g., van Hest et al, FEBS Lett 428: (1-2) 5 months and 22 days 68-701998 and Tang et al, Abstr.Pap AM. chem.S 218: u138 part 2, 1999, 8/22, both of which are hereby incorporated by reference.

In some embodiments, the analyte receptor is a cell signaling molecule that is part of a signaling pathway, such as a receptor protein. Receptor proteinsmay be a membrane-associated protein (e.g., an extracellular membrane protein, an intracellular membrane protein, an integral membrane protein or a transient membrane-associated protein), a cytoplasmic protein, a chaperone protein or a protein associated with one or more organelles (e.g., a nucleoprotein, a nuclear envelope protein, a mitochondrial protein, a Golgi and other transporters, endosomal proteins, lysosomal proteins, etc.) examples of receptor proteins include, but are not limited to, hormone receptors, steroid receptors, cytokine receptors such as IL1- α, IL- β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-15, IL-18, IL-21, CCR5, CCR7, CCR 631-10, CCL20, chemokine receptors such as CXCR4, adhesion receptors and growth factor receptors including, PDGF-R (platelet derived growth factor receptor), estrogen-R (growth factor receptor), VEGF-R (vascular growth factor receptor), chemokine receptor (e.g.5, receptor ligand, receptor ligand of the like CD receptor ligand of the CD3, receptor ligand of the CD receptor of the CD3, receptor of the CD receptor of the CD3, receptor of the CD 14, receptor of the CD8, CD receptor of the CD 14, CD receptor of the CD, CD5, CD receptor of the CD, CD receptor of the CD7, CD receptor of the CD7, CD₁、β₂、β₃、β₄、β₅、β₆、α₁、α₂、α₃、α₄、α₅and alpha₆or is MAC-1 (. beta.)₂and CD11b) or α_Vβ₃. The receptor protein may be a member of one or more cellular signaling pathways, including but not limited to MAP kinase, PI3K/Akt, NFkB, WNT, RAS/RAF/MEK/ERK, JNK/SAPK, p38MARK, Src family kinase, JAK/STAT, and/or PKC signaling pathways.

In some embodiments, the analyte receptor is an antibody, and the receptor-based assay is referred to as an immunoassay with one or more antigens as the analyte. Alternatively, the immunoassay may comprise the use of an antigen as an analyte receptor in order to detect the presence of a target antibody as an analyte. The term "antibody" as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e., molecules that comprise antigen binding units ("Abu" or "Abus") that specifically bind to (are "immunoreactive with") an antigen. Structurally, the simplest naturally occurring antibody (e.g., IgG) comprises 4 polypeptide chains — two heavy (H) chains and two light (L) chains, which are linked by disulfide bonds. Immunoglobulins represent a large family of molecules, which include several types of molecules, such as IGD, IgG, IgA, IgM, and IgE. The term "immunoglobulin molecule" includes, for example, hybrid or altered antibodies, and fragments thereof. Based on the type of their molecular structure, antigen-binding units can be broadly classified into "single-stranded" (Sc) and "non-single-stranded" (Nsc) types.

The terms "antibody" and "antigen binding unit" also include immunoglobulin molecules and fragments thereof, which may be human, non-human (of vertebrate or invertebrate origin), chimeric or humanized. The concept of chimeric and humanized antibodies is described in Clark et al, 2000 and references cited therein (Clark, (2000) Immunol. Today21: 397-402). Chimeric antibodies comprise the variable regions of a non-human antibody operably linked to the constant regions of a human antibody, such as VH and VL domains of mouse or rat origin (see, e.g., U.S. Pat. No. 4,816,567). In some embodiments, the antibodies of the invention are humanized. As used herein, a "humanized" antibody refers to an antibody that comprises human Framework Regions (FRs) and one or more Complementarity Determining Regions (CDRs) from a non-human (usually mouse or rat) antibody. The non-human antibodies that provide the CDRs are referred to as "donors" and the human immunoglobulins that provide the framework are referred to as "acceptors". Humanization relies primarily on grafting donor CDRs onto acceptor (human) VL and VH frameworks (Winter, U.S. Pat. No. 5,225,539). This strategy is called "CDR-grafting". Selected acceptor framework residues are often required to be "back-mutated" to the corresponding donor residues to regain the affinity lost in the original graft construct (U.S. Pat. No. 5,530,101; U.S. Pat. No. 5,585,089; U.S. Pat. No. 5,693,761; U.S. Pat. No. 5,693,762; U.S. Pat. No. 6,180,370; U.S. Pat. No. 5,859,205; U.S. Pat. No. 5,821,337; U.S. Pat. No. 6,054,297; U.S. Pat. No. 6,407,213). The humanized antibody will also preferably comprise at least a portion of an immunoglobulin constant region, typically at least a portion of a human immunoglobulin constant region, and thus will typically comprise a human Fc region. Methods for humanizing non-human antibodies are well known in the art and can be performed essentially as described by Winter and co-workers (Jones et al, 1986, Nature321: 522-525; Riechmann et al, 1988, Nature332: 323-329; Verhoeyen et al, 1988, Science, 239: 1534-1536). Other examples of humanized murine monoclonal antibodies are also known in the art, e.g., antibodies that bind to human Protein C (O' Connor et al, 1998, Protein Eng11:321-8), interleukin 2 receptor (Queen et al, 1989, Proc Natl Acad Sci, USA86:10029-33), and human epidermal growth factor receptor 2(Carter et al, 1992, Proc Natl Acad Sci, USA89: 4285-9). In an alternative embodiment, the antibody of the invention may be a fully human antibody, i.e., the sequence of the antibody is fully or substantially human. Many methods for generating fully human antibodies are known in the art, including the use of transgenic mice (Bruggemann et al, 1997, CurrOpin Biotechnol8:455-458) or human antibody libraries plus selection methods (Griffiths et al, 1998, Curr Opin Biotechnol9: 102-108). In addition, humanized antibodies may comprise residues that are not found in both the recipient antibody and the introduced CDR or framework sequences. These modifications are made to further refine and optimize the performance of the antibody and to minimize immunogenicity when introduced into humans.

A "non-single-chain antigen-binding unit" ("Nsc Abus") is a heteromultimer comprising a light chain polypeptide and a heavy chain polypeptide. Examples of Nsc Abus include, but are not limited to: (i) an ccFv fragment stabilized by a heterodimerization sequence; (ii) any other monovalent and multivalent molecule comprising at least one ccFv fragment; (iii) a Fab fragment consisting of the VL, VH, CL and CH1 domains; (iv) an Fd fragment consisting of the VH and CH1 domains; (v) (ii) an Fv fragment consisting of the VL and VH domains of one arm of an antibody; (vi) a F (ab')2 fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bond at the hinge region; (vii) a diabody; and (viii) Little et al, (2000) Immunology Today or any other Nsc Abus described in U.S. Pat. No. 7429652.

As noted above, Nsc Abus may be "monovalent" or "multivalent". The former has one binding site per antigen binding unit, while the latter contains multiple binding sites capable of binding more than one antigen of the same or different species. Depending on the number of binding sites, Nsc Abus may be bivalent (with two antigen binding sites), trivalent (with three antigen binding sites), tetravalent (with four antigen binding sites), and the like.

although such molecules will normally bind only two different antigens (i.e. bispecific Abus), when used herein, the expression also includes antibodies with additional specificity, such as trispecific antibodies, examples of bispecific antigen binding units include antigen binding units with one arm directed against a tumor cell antigen and the other arm directed against a cytotoxic trigger molecule, such as anti-CD/anti-malignant B-cell (1D), anti-CD/anti-P185 HER, anti-CD/anti-P, anti-CD/anti-renal cell carcinoma, anti-CD/anti-OVCAR-3, anti-CD/L-D (anti-bowel cancer), anti-CD/anti-melanocyte stimulating hormone analogues, anti-gamma/anti-CD, anti-P185/CD/anti-RII (CD II), anti-CD/anti-CD-TNF/anti-TNF-CD-D (anti-CD stimulating hormone analogues, anti-CD-rat, anti-rat.

"Single-chain antigen-binding unit" ("Sc Abu") refers to the monomeric Abu. Although the two domains of the Fv fragment are encoded BY separate genes, a synthetic linker can be made that enables them to be single chain proteins (i.e., single chain Fv ("scFv"), as described in Bird et al (1998) Science242:423-426 and Huston et al, 1988) PNAS85:5879-5883) BY RECOMBINANT ETHODS. Other Sc Abus include antigen binding molecules stabilized by heterodimerization sequences, and dAb fragments (Ward et al, (1989) Nature341:544-546) consisting of a VH domain and an isolated Complementarity Determining Region (CDR). An example of a linker peptide is a sequence of four glycine followed by one serine, the 5 amino acid sequence being repeated twice for a total length of 15 amino acids, the linker peptide bridging between the carboxy terminus of one V-domain and the amino terminus of the other V-domain by about 3.5 nm. Other linking sequences may also be used and they may provide additional functions, such as means for attaching drugs or solid supports. Preferred single-chain antigen-binding units comprise VL and VH regions linked together and stabilized by a pair of heterodimerization sequences. The scFv can be assembled in any order, e.g., VH- (first heterodimerization sequence) - (second heterodimerization sequence) -VL, or VL- (first heterodimerization sequence) - (second heterodimerization sequence) -VH. An antibody or Abu "specifically binds" or "immunoreacts" with an antigen if the affinity or avidity of binding of the antibody or Abu to the antigen is greater than the affinity or avidity of binding to other reference antigens, including polypeptides or other substances.

In some embodiments, the analyte receptor is an enzyme and the analyte of interest is a substrate for the enzyme, or the analyte receptor is a substrate for the enzyme and the analyte is an enzyme that acts on the substrate, such that detection is achieved by activity of the enzyme on the substrate, for example by producing a detectable product. Many enzymes useful in or detectable by detection of the activity of various substrates are known in the art and include, but are not limited to, proteases, phosphatases, peroxidases, sulfatases, peptidases, glycosidases, hydrolases, oxidoreductases, lyases, transferases, isomerases, ligases, and synthases. Of particular interest are a physiologically significant class of enzymes. Such enzymes include, but are not limited to, protein kinases, peptidases, esterases, proteinsThe enzyme is selected from the group consisting of a phosphatase, an isomerase, a glycosylase, a synthetase, a protease, a dehydrogenase, an oxidase, a reductase, a methylase, etc. Enzymes of interest also include enzymes involved in the production or hydrolysis of esters (both organic and inorganic), glycosylation and amide hydrolysis. Any class can be further subdivided, as in kinases, where the kinase may be specific for phosphorylation of serine, threonine and/or tyrosine residues in peptides and proteins. Thus, the enzyme may be, for example, a kinase from a different functional group of kinases including cyclic nucleotide regulated protein kinase, protein kinase C, Ca²⁺The kinases that are regulated by/CaM, cyclin-dependent kinases, ERK/MAP kinases and protein tyrosine kinases. The kinase may be a protein kinase in the signaling pathway that efficiently phosphorylates oligopeptide substrates, such as ERK kinase, S6 kinase, IR kinase, P38 kinase and AbI kinase. For these kinases, the substrate may comprise an oligopeptide substrate. Other kinases of interest can include, for example, Src kinase, JNK, MAP kinase, cyclin-dependent kinase, P53 kinase, platelet-derived growth factor receptor, epidermal growth factor receptor, and MEK.

in particular, the enzymes useful in the present invention include any protein exhibiting enzymatic activity, such as lipases, phospholipases, sulfatases, urease, peptidases, proteases and esterases, including acid phosphatase, glucosidase, glucuronidase, galactosidase, carboxylesterase and luciferase.

In some embodiments, the analyte receptor used to detect the analyte is an aptamer. The aptamer may be located on a bead or other surface, such as a microarray-type surface. The term "aptamer" is used to refer to a peptide, nucleic acid, or combination thereof that is selected for its ability to specifically bind one or more target analytes. Peptide aptamers are affinity reagents, typically comprising one or more variable loop domains displayed on the surface of a scaffold protein. Aptamers are oligonucleotides that bind specifically, being oligonucleotides that are capable of selectively forming complexes with a predetermined target analyte. This complexing is target specific, meaning that other materials, such as other analytes that may accompany the target analyte, do not complex with as great an affinity to the aptamer. It is generally accepted that complexation and affinity are only a matter of degree; however, in this context "target-specific" means that the aptamer binds to the target with a much higher affinity than it binds to the contaminating material. Thus, specificity is used herein in a similar sense to that used for specificity of an antibody, for example. Aptamers can be prepared by any known method, including synthetic, recombinant, and purification methods. In addition, the term "aptamer" also includes "secondary aptamers" that contain a consensus sequence obtained from the comparison of two or more known aptamers to a given target.

Typically, aptamers are about 9 to about 35 nucleotides in length. In some embodiments, the nucleic acid aptamer is at least 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 80, 90, 100 or more nucleic acids in length. While aptamers are typically single-stranded or double-stranded oligonucleotides, it is contemplated that aptamers may sometimes exhibit a three-or four-stranded structure. In some embodiments, the aptamer is circular, as in US 20050176940. The aptamer specific binding oligonucleotide should contain the specificity conferred by the sequence, but may be extended with flanking regions and otherwise derivatized or modified. Aptamers that are found to bind to the target analyte can be isolated, sequenced, and then synthesized as conventional DNA or RNA portions, or oligomers that may be modified. These modifications include, but are not limited to, the introduction of: (1) modified or similar forms of sugars (e.g., ribose and deoxyribose); (2) an alternative linking group; or (3) analogous forms of purine and pyrimidine bases.

nucleic acid aptamers may include DNA, RNA, functionalized or modified nucleobases, nucleic acid analogs, modified or alternative backbone chemical entities or combinations thereof, the oligonucleotides of the aptamers may comprise the conventional bases adenine, guanine, cytosine and thymine or uridine, synthetic aptamers incorporating similar forms of purine and pyrimidine are those commonly known in the art, among which many non-limiting examples of similar forms of purine and pyrimidine (i.e., base analogs) that are used as chemotherapeutic agents include aziridinylcytosine, 4-acetylcytosine, 5-fluorouracil, 5-bromouracil, 5-carboxymethylaminomethyl-2-thiouracil, 5-carboxymethyl-aminomethyluracil, inosine, N6-isopentenyladenine, 1-methyladenine, 1-methylpseudouracil, 1-methylguanine, 1-methylinosine, 2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylguanine, 5-methylguanidine, 5-2-methylguanidine, 5-methylguanidine, 3-methylguanidine, 5-2-methylguanidine, 5-2-methoxyuracil, thymine-2-methylguanidine, thymine-2-methylguanidine, thymine-2-methylguanidine, thymine-2-.

the aptamer oligonucleotides may contain similar forms of ribose or deoxyribose as known in the art, including but not limited to 2' substituted sugars such as 2' -O-methyl-ribose, 2' -O-allyl-ribose, 2' fluoro-ribose or 2' -azido-ribose, carbocyclic sugar analogs, α -anomeric sugars, epimeric sugars such as arabinose, xylose or lyxose, pyranose, furanose, sedoheptulose, Locked Nucleic Acid (LNA), Peptide Nucleic Acid (PNA), acyclic analogs, and abasic nucleoside analogs such as methyl nucleosides.

Aptamers may also include intermediates in their synthesis. For example, any commonly present hydroxyl group may be substituted with a phosphonate group, a phosphate group, protected via a standard protecting group, or activated in preparation for additional attachment to other nucleotides or substrates. The 5' terminal OH is usually free, but can be phosphorylated; the OH substituent at the 3' end may also be phosphorylated. Hydroxyl groups may also be derivatized as standard protecting groups. One or more phosphodiester linkages may be substituted with an alternative linking group. These alternative linking groups include, but are not limited to, specific examples in which P (O) O is replaced with P (O) S ("phosphorothioate"), P (S) S ("phosphorodithioate"), P (O) NR2 ("phosphoramidate"), P (O) R, P (O) OR ', CO, OR CH2 ("formacetal"), wherein each R OR R' is independently H OR substituted OR unsubstituted alkyl (1-20C), OR contains an ether linkage (-O-), aryl, alkenyl, cycloalkyl, cycloalkenyl, OR aralkyl.

One specific example of an aptamer for use in the present invention is based on an RNA aptamer as disclosed in U.S. patent nos. 5,270,163 and 5,475,096, which are incorporated herein by reference. The above patents disclose SELEX methods involving the same general selection scheme, selection from a mixture of candidate oligonucleotides and stepwise repetition of binding, isolation and amplification to achieve almost any desired criteria of binding affinity and selectivity. Starting from a mixture of nucleic acids preferably containing fragments of randomized sequences, the SELEX method comprises the following steps: contacting the mixture with a target, such as a target analyte, under conditions conducive to binding, separating unbound nucleic acids from those nucleic acids that have specifically bound to the target molecule, dissociating the nucleic acid-target complex, amplifying the nucleic acids dissociated from the nucleic acid-target complex to obtain a ligand-enriched mixture of nucleic acids, and then repeating the multiple cycles required for the steps of binding, separating, dissociating, and amplifying to produce nucleic acid ligands with high specificity and high affinity for the target molecule. In some embodiments, a negative screen is employed in which multiple aptamers are exposed to the analyte or other material that may be present in the sample to be analyzed at the same time as the analyte of interest, and only the unbound aptamers remain.

The SELEX method involves the identification of high affinity nucleic acid ligands containing modified nucleotides that confer improved properties on the ligand, such as increased in vivo stability or improved delivery properties. Examples of such modifications include chemical substitutions at ribose and/or phosphate and/or base positions. In some embodiments, two or more aptamers are linked to form a multivalent aptamer molecule. The multivalent aptamer molecule can comprise multiple copies of the aptamer, each copy directed to the same analyte, two or more different aptamers directed to different analytes, or a combination of these.

The analyte receptor may be used to detect the analyte in any of the detection schemes described herein. In one embodiment, the analyte receptor is coupled to the substrate covalently or non-covalently. Non-limiting examples of substrates to which analyte receptors may be coupled include microarrays, microbeads, pipette tips, sample transfer devices, cuvettes, capillary or other tubes, reaction chambers, or any other suitable format compatible with the present detection system. The biochip microarray can be produced using various semiconductor fabrication techniques, such as solid phase chemistry, combinatorial chemistry, molecular biology, and robotics. One commonly used method is a photolithographic fabrication process for producing microarrays containing millions of analyte receptors on a single chip. Alternatively, if the analyte receptors are pre-synthesized, they can be attached to the array surface by using techniques such as microchannel pumping, "ink jet" spotting, template stamping, or photo-crosslinking. An exemplary photolithography process begins with coating a quartz chip with a photosensitive compound to prevent coupling between the quartz chip and the first nucleotide of the resulting DNA probe. Photolithographic masks are used to block or allow light to be transmitted to specific locations on the surface of a chip. The surface is then contacted with a solution that may contain adenine, thymine, cytosine or guanine, and coupling occurs only at those regions on the glass that have been deprotected by illumination. The coupled nucleotides have photosensitive protecting groups, making the cycle repeatable. In this way, by repeating the cycle of deprotection and coupling, a microarray is created while the probe is synthesized. This process can be repeated until the probe reaches its full length. Commercially available arrays are typically manufactured to a density of over 130 million unique features per array. Each chip may be cut into tens or hundreds of individual arrays depending on the requirements of the experiment and the number of probes required for each array.

Other methods may also be used to produce a solid surface with a coating of analyte receptors attached. The solid surface of the coating may be Langmuir-Bodgett film, functionalized glass, germanium, silicon, PTFE, polystyrene, gallium arsenide, gold, silver, film, nylon, PVP, polymeric plastics or any other material known in the art capable of introducing functional groups such as amino, carboxyl, Diels-Alder reactants, thiol or hydroxyl groups on its surface. These groups can then be covalently linked to a cross-linking agent so that subsequent analyte receptor and target analyte binding will occur in solution without hindrance from the biochip. Typical crosslinking groups include ethylene glycol oligomers, diamines, and amino acids. Alternatively, the analyte receptors may be coupled to the array using an enzymatic process, as described in US 20100240544.

In some embodiments, the analyte receptor is coupled to the surface of a microbead. Microbeads for coupling analyte receptors such as oligonucleotides are known in the art and include magnetic and non-magnetic beads. The microbeads may be labeled with 1,2,3, 4,5, 6, 7, 8, 9, 10 or more dyes to facilitate coding of the microbeads and recognition of the analyte receptor to which they are attached. The encoding of the microbeads may be used to distinguish at least 10, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 5000 or more different microbeads in an array, each microbead corresponding to a different analyte receptor specific for a different analyte.

In some embodiments, the analyte receptor is coupled to a surface of a reaction chamber, such as a tip. For example, the interior surface of the tip may be coated with an analyte receptor specific for a single analyte. Alternatively, the interior surface of the tip may be coated with two or more analyte receptors specific for different analytes. When two or more different analyte receptors are coupled to the same internal surface of the tip, each different analyte receptor may be coupled at a different known location, for example forming a different arrangement of rings or bands at different locations along the axis of the tip. In this case, a plurality of different analytes may be analyzed in the same sample by aspirating the sample to the tip and allowing the analytes contained in the sample to bind to analyte receptors at successive locations along the tip coating. The binding event can then be visualized as described herein, with the location of each band in the band pattern corresponding to a particular known analyte.

An analyte:

analyte receptors are useful as diagnostic and prognostic agents, as agents for the discovery of novel therapies, as agents for monitoring drug responses in individuals, and as agents for the discovery of novel therapeutic targets. The analyte receptors may be used to detect one or more target analytes. The term "analyte" refers to any type of biomolecule, including, for example, simple intermediary metabolites, sugars, lipids, and hormones, as well as macromolecules such as complex carbohydrates, phospholipids, nucleic acids (e.g., DNA, RNA, mRNA, miRNA, rRNA, tRNA), polypeptides, and peptides. Further non-limiting examples of analytes include drugs, drug candidates, prodrugs, agents, drug metabolites, biomarkers such as expressed proteins and cell markers, antibodies, serum proteins, cholesterol and other metabolites, electrolytes, metal ions, polysaccharides, genes, eggsWhite matter, glycoproteins, glycolipids, lectins, growth factors, cytokines, vitamins, enzymes, enzyme substrates, enzyme inhibitors, steroids, oxygen, and other gases found in physiological fluids (e.g., CO)₂) Cells, cell components, cell adhesion molecules, plant and animal products, cell surface markers (e.g., cell surface receptors and other molecules identified herein as receptor proteins), and cell signaling molecules. Non-limiting examples of protein analytes include membrane-associated proteins (e.g., outer membrane proteins, inner membrane proteins, or transient membrane-associated proteins), cytoplasmic proteins, chaperones, proteins associated with one or more organelles (e.g., nuclear proteins, nuclear membrane proteins, mitochondrial proteins, golgi and other transporters, endosomal proteins, lysosomal proteins, etc.), secreted proteins, serum proteins, and toxins. Non-limiting examples of analytes to be detected include adiponectin, alanine aminotransferase (ALT/GPT), alpha-fetoprotein (AFP), albumin, alkaline phosphatase (ALP), alpha-fetoprotein, apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), apolipoprotein B/apolipoprotein A-1 ratio (Apo B/A1), aspartate aminotransferase (AST/GOT),(11-dehydro-thromboxane B2), bicarbonate (CO2), Direct Bilirubin (DBIL), Total Bilirubin (TBIL), Blood Urea Nitrogen (BUN), hydroxyl-terminal collagen cross-linking (β -Cross Laps), calcium, cancer antigen 125(CA125), cancer antigen 15-3(CA15-3), cancer antigen 19-9(CA19-9), carcinoembryonic antigen (CEA), chloride (Cl), whole blood cell count and Classification (CBC), C-peptide, C-reactive protein (CRP-hs), Creatine Kinase (CK), creatinine (serum), creatinine (urine), cytochrome P450, cystatin-C, D-dimer, dehydroepiandrosterone sulfate (DHEA-S), estradiol, F2 isoglutamine, factor V Leiden, ferritin, fibrinogen (mass), folate, follicle stimulating hormone (prostaglandin), free fatty acid/non-esterified fatty acid (FFA/NEFA), fructosyl-glutamyl transferase (GGT), glucosaminyl transferase (GGT), HDL-cholesterol density (3891), HDL-cholesterol (HDL-C), high estimated high cholesterol density (HDL-3-cholesterol (HDL-C), high density protein (HDL-C), high density estimate (HDL-64-3, cholesterol (HDL-C), high density estimateLipoprotein particle number (HDL-P), high sensitivity C-reactive protein (hs-CRP), homocysteine, insulin, iron and TIBC, Lactate Dehydrogenase (LDH), leptin, lipoprotein (a) cholesterol (Lp (a) chol), lipoprotein (a) mass (Lp (a) mass), lipoprotein-associated phospholipase A2(Lp-PLA2), direct low density lipoprotein cholesterol (LDL-C), low density lipoprotein particle number (LDL-P), Luteinizing Hormone (LH), magnesium, methylenetetrahydrofolate reductase (MTHFR), microalbumin, Myeloperoxidase (MPO), N-terminal b-type natriuretic peptide precursor (NT-proBNP), non-high density lipoprotein cholesterol, omega-3 fatty acid profile, osteocalcin, parathyroid hormone (PTH), phosphorus, potassium (K +), total prostate specific antigen (total PSA), Prothrombin, resistin, Sex Hormone Binding Globulin (SHBG), small dense low density lipoprotein (sdLDL), small dense low density lipoprotein/low density lipoprotein cholesterol ratio (sd LDL/LDL-C ratio), sodium (NA +), T uptake, testosterone, Thyroid Stimulating Hormone (TSH), thyroxine (T4), Total Cholesterol (TCHOL), total protein, Triglycerides (TRIG), triiodothyronine (T3), T4 (free), uric acid, vitamin B12, 25-hydroxy-vitamin D, blood clotting factors (e.g., factor I (fibrinogen), factor II (prothrombin), factor III (thromboplastin), factor IV (calcium), factor V (thromboplastin), factor VI (no longer considered to have hemostatic activity), factor VII (transition accelerating factor), factor VIII (anti-factor); hemophilin, Factor IX (plasma coagulation hormone component; Christmas factor), factor X (stuart factor), factor XI (plasma coagulation hormone precursor), factor XII (hageman factor), factor XIII (fibrin stabilizing factor)).

in some specific examples, the analyte is a cell signaling molecule, such as a protein, wherein the protein is a protein that can be detected as an analyte, such as a protein-related receptor, including a kinase, phosphatase, lipid signaling molecule, adaptor protein/scaffold protein, GTPase activating protein, isomerase, deacetylase, methylase, demethylase, tumor suppressor gene, caspase, protein involved in apoptosis, cell cycle regulatory factor, chaperone, metabolic enzyme, vacuolar transporter, cytokine regulatory factor, ubiquitinase, adhesion molecule, cytoskeletal/contractile protein, heterotrimeric protein, GTP enzyme, small molecular weight GTPase, guanylate exchange factor, hydroxylase, protease, ion channel, molecular transporter, transcription factor/DNA binding factor, transcription regulator, and translation regulator, such as protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein kinase, protein.

In some embodiments, the analyte of interest may be selected from an endogenous analyte produced by the host or an exogenous analyte that is foreign to the host. Suitable endogenous analytes include, but are not limited to, autoantigens (which are targets of autoimmune reactions) and cancer or tumor antigens. Illustrative examples of autoantigens useful in the treatment or prevention of autoimmune diseases include, but are not limited to, antigens associated with: diabetes, arthritis (including rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, psoriatic arthritis), Crohn's disease, ulcerative colitis, conjunctivitis, keratoconjunctivitis, ulcerative colitis, asthma, allergic asthma, cutaneous lupus erythematosus, scleroderma, vaginitis, proctitis, drug eruptions, leprosy recurrence, leprosy erythema nodosum, autoimmune uveitis, allergic encephalomyelitis, multiple sclerosis, myasthenia gravis, systemic lupus erythematosus, autoimmune thyroiditis, dermatitis (including atopic dermatitis and eczematous dermatitis), Wegener's granulomatosis, chronic active hepatitis, Stevens-Johnson syndrome, idiopathic sprue, lichen planus, Graves's eye disease, sarcoidosis, primary biliary cirrhosis, posterior uveitis,Syndrome (includingKeratoconjunctivitis sicca secondary to the syndrome), alopecia (alopecia greata), allergic reactions due to arthropod bite reactions, acute hemorrhagic necrotizing encephalopathy, idiopathic bilateral progressive sensorineural hearing loss, aplastic anemia, pure red blood cell anemia, idiopathic thrombocytopenia, polychondritis, and pulmonary interstitial fibrosis. Other autoantigens include nucleosomes for treatment of systemic lupus erythematosusfurther non-limiting examples of analytes include U1-RNP, fibrillin (scleroderma), pancreatic β cell antigen, GAD65 (diabetes related), insulin, myelin basic protein, myelin proteolipid protein, histone, PLP, collagen, glucose-6-phosphate isomerase, citrullinated protein and peptides, thyroid antigen, thyroglobulin, Thyroid Stimulating Hormone (TSH) receptor, various tRNA synthetases, components of acetylcholine receptor (AchR), MOG, protease-3, myeloperoxidase, epidermal cadherin, acetylcholine receptor, platelet antigens, nucleic acids, protein complexes, joint antigens, nervous system antigens, salivary gland protein, skin antigens, kidney antigens, heart antigens, lung antigens, eye antigens, erythrocyte antigens, liver antigens, and stomach antigens.

In some embodiments, the analyte is associated with the presence of cancer or other tumor growth examples of cancer and tumor-associated analytes detected by binding to an analyte receptor include but are not limited to gp100, MART, Melan-A/MART-1, TRP-1, Tyros, TRP2, MC1R, MUC1F, MUC1R, BAGE, GAGE-1, gp100In4, MAGE-1, MAGE-3, MAGE4, PRAME, TRP2IN2, NNSO 1A, NNSO 1B, LAGE1, p97 melanoma antigen, p5 protein, gp75, oncofetal antigen, GM2 and GD2 ganglioside, cdc27, p21ras, PMel117, 27, 36733, cyclophilin B (acute lymphoblastic leukemia), EP-1, MURAB-1, MUC-1, CEA-2, CEA-2, CEA-CEA, CEA-2, CEA-2, CEA-CEA, CEA-CEA, CEA-beta-CEA, CEA-beta-glycoprotein, and a (NEE-beta-glycoprotein, and a (CEA-glycoprotein, and beta-glycoprotein, and a (NE.

In some embodiments, the analyte is a foreign antigen. Foreign antigens include, but are not limited to, transplantation antigens, allergens, and antigens from pathogenic organisms. Transplantation antigens can be produced from donor cells or tissues from, for example, heart, lung, liver, pancreas, kidney, nerve graft components, or from donor antigen presenting cells carrying self-antigen loaded MHC in the absence of exogenous antigen. Non-limiting examples of allergens include Fel d1 (i.e., cat skin and salivary gland allergens in domestic cats); der p L Der p II or Der fi (i.e., the major protein allergen from house dust mite); and allergens derived from: grass, tree and weed (including ragweed) pollen; fungi and molds; foods such as fish, shellfish, crabs, lobsters, peanuts, nuts, gluten, eggs, and milk; stinging insects such as bees, wasps and hornets and chimonidae (non-biting gnats); other insects, such as houseflies, fruit flies, lucilia sericata, spiral flies, grain weevils, domestic silkworms, bees, non-biting gnat larvae, wax borer larvae, whiteflies, cockroaches, and larvae of Tenibrio molitor beetles; spiders and mites, including house dust mites; allergens found in dander, urine, saliva, blood or other body fluids of mammals such as cats, dogs, cows, pigs, sheep, horses, rabbits, rats, guinea pigs, mice, and gerbils; particulates normally carried by air; latex; and a protein detergent additive.

In some embodiments, the analyte is a pathogen or a product or fragment thereof. Typical pathogens include, but are not limited to, viruses, bacteria, prions, protozoa, unicellular organisms, algae, eggs of pathogenic organisms, microorganisms, cysts, molds, fungi, worms, amoebas, pathogenic proteins, parasites, algae, and viroids. A number of Pathogens and their markers are known in the art (see, e.g., Foodborne Pathologens: Microbiology and molecular biology, Caister Academic Press, eds. Fratamico, Bhunia, and Smith (2005); maize et al, Parasite antibodies Parasite Genes: A Laboratory Manual for molecular Parasite, Cambridge University Press (1991); National Library of Medicine; US20090215157 and US 207207161). Illustrative examples of viruses include viruses that cause diseases including, but not limited to: measles, mumps, rubella, polio, hepatitis (e.g., hepatitis a, b, c, d, and e), influenza, adenovirus, rabies, yellow fever, epstein barr virus, and other viruses such as papilloma virus, ebola virus, influenza virus, japanese encephalitis, dengue virus, hantavirus, sendai virus, and Human Immunodeficiency Virus (HIV). Any suitable antigen derived from such viruses is useful in the practice of the present invention. For example, exemplary retroviral antigens derived from HIV include, but are not limited to, antigens such as the gene products of the gag, pol, and env genes, the Nef protein, reverse transcriptase, and other HIV components. Illustrative examples of herpes simplex virus antigens include, but are not limited to, antigens such as immediate early protein, glycoprotein D, and other herpes simplex virus antigen components. Non-limiting examples of varicella zoster virus antigens include antigens such as 9PI, gpII and other varicella zoster virus antigen components. Non-limiting examples of Japanese encephalitis virus antigens include antigens such as protein E, M-E, M-E-NS1, NS1, NS1-NS2A, and Japanese encephalitis virus antigen components. Illustrative examples of hepatitis viral antigens include, but are not limited to, antigens such as S, M and L proteins of hepatitis B virus, pre-S antigen of hepatitis B virus, and other hepatitis (e.g., hepatitis A, B, and C), viral components such as viral DNA, and/or viral RNA. Illustrative examples of influenza virus antigens include, but are not limited to, antigens such as hemagglutinin and neuraminidase (neurarnididase), as well as other influenza virus components. Illustrative examples of measles virus antigens include, but are not limited to, antigens such as measles virus fusion proteins and other measles virus components. Illustrative examples of rubella virus antigens include, but are not limited to, antigens such as proteins E1 and E2, as well as other rubella virus components; rotavirus antigens such as VP7sc, and other rotavirus components. Illustrative examples of cytomegalovirus antigens include, but are not limited to, antigens such as envelope glycoprotein B and other cytomegalovirus antigenic components. Non-limiting examples of respiratory syncytial virus antigens include antigens such as the RSV fusion protein, the M2 protein, and other respiratory syncytial virus antigenic components. Representative examples of rabies virus antigens include, but are not limited to, antigens such as rabies glycoprotein, rabies nucleoprotein, and other rabies virus antigen components. Illustrative examples of papillomavirus antigens include, but are not limited to, the L1 and L2 capsid proteins and the E6/E7 antigens associated with cervical cancer. See, e.g., Fundamental Virology, second edition, Fields, b.n. and Knipe, ed.m., 1991, Raven Press, new york.

Illustrative examples of fungi include Acremonium spp, Aspergillus spp, Exophiala johnsonii, Exophiala spp, Pychnum compacta, Pythium pehnsonii, Fusarium oxysporum, Microcoporia farinosa, Microcoporia sp, Bipolar, Blastomyces dermatitidis, Candida, Dosophyllium, Carriera, Cocconidia, Microcoporia, Microcospora, Microcorium, Micro, (Pseudocalliphytia boydii), Pyrenochaeta romalia, Rhizopus arrhizus (Rhizopus arrhizus), Scopulariopsis brevicaulis, Scytalidium dimyrium, Trichophyton schenckii, Trichophyton sp (Trichophyton sp.), Trichophyton sp, Zygocete, Gracilaria grisea (Malaria grisea), Microcorium vulgare (Maurella myces), Microcorium furfuraceum (Malaria furaria furorula), Microcorium vulgare (Malaria furaria furorula furiosu), Microcorium versicolor (Microcoriaria furaria furcificum), Microcorium sp, Rhizopus novaculeatus (Neosporotrichia), Rhizophora pararhizopus (Rhizophora), Rhizophora pararhizopus oryzae (Rhizophora), Rhizophora pararhizopus (Rhizophora), and Rhizophora (Rhizophora), Rhizophora glabra (Rhizophora), Rhizophora (Rhizophora rubrum). Thus, exemplary fungal antigens that can be used in the compositions and methods of the present invention include, but are not limited to, candida antigenic components; cryptococcus fungal antigens such as capsular polysaccharides and other cryptococcus fungal antigen components; histoplasma fungal antigens such as heat shock protein 60(HSP60) and other histoplasma fungal antigenic components; coccidiodes fungal antigens such as endospore antigens and other coccidiodes fungal antigen components; and tinea fungal antigens such as trichophyton and other coccidioidomycosis fungal antigen components.

Illustrative examples of bacteria include bacteria that cause diseases including, but not limited to: diphtheria (e.g. Corynebacterium diphtheriae (Corynebacterium diphtheria)), pertussis (e.g. bordetella pertussis (Bordetella), anthrax (e.g. Bacillus anthracis), typhoid fever, plague, Shigella (e.g. Shigella dysenteriae), botulism (e.g. Clostridium botulinum), tetanus (e.g. Clostridium tetani), tuberculosis (e.g. Mycobacterium tuberculosis), bacterial pneumonia (e.g. Haemophilus influenzae), cholera (e.g. Vibrio cholerae), salmonellosis (e.g. Salmonella typhi (Salmonella typhi)), peptic ulcer (e.g. helicobacter pylori (helicobacter pylori)), Legionella (e.g. Legionella (Borrelia), and other pathogenic bacteria including Legionella (e.g. Borrelia), including Legionella typhi), and Borrelia species such as Borrelia (Borrelia), and other species of the genus Borrelia (e.g. Borrelia), including Legionella (Borrelia), Borrelia species such as Borrelia (bacterium) Clostridium perfringens (Clostridium perfringens), Clostridium difficile (Clostridium difficile), Pseudomonas aeruginosa (Pseudomonas aeruginosa), Staphylococcus aureus (Staphylococcus aureus), and Streptococcus pyogenes (Streptococcus pyogenes). Further examples of bacteria include Staphylococcus epidermidis (Staphylococcus epidermidis), Staphylococcus species (Staphylococcus sp.), Streptococcus pneumoniae (Streptococcus pneumoniae), Streptococcus agalactiae (Streptococcus agalactiae), enterococcus species (enterococcus sp.), Bacillus cereus (Bacillus cereus), Bifidobacterium bifidum (Bifidobacterium bifidum), Lactobacillus species (Lactobacillus sp.), Listeria monocytogenes (Listeria monocytogenes), Nocardia species (Nocardia sp.), Rhodococcus equi (Rhodococcus equi), erysiphe suis (rhodochrous), Streptococcus pyogenes (Streptococcus pneumoniae), Propionibacterium acnes (proteus, Streptococcus sp), Streptococcus sp, Streptococcus pneumoniae (Streptococcus sp), Streptococcus sp, actinomyces actinomycetemcomitans (Actinobacillus actinomyces), Acinetobacter baumannii (Acinetobacter baumannii), Brucella sp, Campylobacter sp, Carboruncatus sp, Corynebacterium parvum (Cardiobacter hominis), Excanicola (Eikeella corridorensis), Francisella tularensis (Francisella tularensis), Haemophilus duchensis (Haemophilus crephyii), Helicobacter pylori (Helicobacter pylori), gold plaque (Kingella kingae), Legionella pneumophila (Leginonella pneumophila), Salmonella multocida (Pasteurella sp), Salmonella typhi (Klebsiella pneumoniae), Escherichia coli (Klebsiella pneumoniae), Salmonella enterica (Klebsiella pneumoniae), Escherichia coli (Escherichia coli), Escherichia coli (Salmonella typhimurium), Escherichia coli (Escherichia coli), Escherichia coli (Klebsiella pneumoniae), Escherichia coli (Escherichia coli), Escherichia coli (Escherichia coli) strains, Escherichia coli (Escherichia coli), Escherichia coli (Escherichia coli ), Escherichia coli (Escherichia coli), Escherichia coli (Escherichia coli, Escherichia coli (Escherichia coli, Shigella species (Shigella sp.), Serratia marcescens (Serratia marcescens), Yersinia enterocolitica (Yersinia enterocolitica), Yersinia pestis (Yersinia pestis), Aeromonas species (Aeromonas sp), Shigella neisseria (Plesiomonas shigelloides), Vibrio cholerae (Vibrio cholerae), Vibrio parahaemolyticus (Vibrio parahaemolyticus), Vibrio vulnificus (Vibrio vulnificus), acinetobacter species (acidetobacter) of acinetobacter, Flavobacterium sp, Burkholderia cepacia (burkhderia), Vibrio parahaemolyticus (fusobacterium sp), clostridium sp, fusobacterium species (fusobacterium sp), clostridium sp. Accordingly, bacterial antigens useful in the compositions and methods described herein include, but are not limited to: pertussis bacterial antigens such as pertussis toxin, filamentous hemagglutinin, pertactin, F M2, FIM3, adenylate cyclase, and other pertussis bacterial antigen components; diphtheria bacterial antigens such as diphtheria toxin or toxoid as well as other diphtheria bacterial antigen components; tetanus bacterial antigens such as tetanus toxin or toxoid and other tetanus bacterial antigen components; streptococcal bacterial antigens, such as the M protein and other streptococcal bacterial antigen components; gram-negative bacilli bacterial antigens, such as lipopolysaccharide and other gram-negative bacterial antigen components; mycobacterium tuberculosis bacterial antigens such as mycolic acid, heat shock protein 65(HSP65), 30kDa major secreted protein, antigen 85A, and other mycobacterial antigenic components; a helicobacter pylori bacterial antigen component; pneumococcal bacterial antigens such as pneumolysin, pneumococcal capsular polysaccharide and other pneumococcal bacterial antigen components; haemophilus influenzae bacterial antigens, such as capsular polysaccharides and other haemophilus influenzae bacterial antigen components; anthrax bacterial antigens, such as anthrax protective antigen and other anthrax bacterial antigen components; rickettsial bacterial antigens such as rompA and other rickettsial bacterial antigen components. Bacterial antigens as described herein also include any other bacterial, mycobacterial, mycoplasma, rickettsia or chlamydia antigens.

Illustrative examples of disease-causing protozoa and other parasites include, but are not limited to, malaria (e.g., Plasmodium falciparum), hookworm, tapeworm, worm, whipworm, tinea, nematode, pinworm, roundworm, filariasis (filariads), onchocerciasis (e.g., Onchocerca volvulus), schistosomiasis (e.g., Schistosoma spp.), toxoplasmosis (e.g., Toxoplasma spp.)), trypanosomiasis (e.g., Trypanosoma spp.)), leishmaniasis (e.g., leishmania spp.)), giardiasis (e.g., Giardia lamblia), proteiasis (e.g., entomorpha histolytica), filariasis (e.g., Brugia malayi), and trichinosis (e.g., Trichinella spira). Accordingly, antigens that may be used in the compositions and methods of some embodiments described herein include, but are not limited to: plasmodium falciparum antigens such as merozoite surface antigens, sporozoite surface antigens, circumsporozoite antigens, gametocyte/gamete surface antigens, blood stage antigens pf155/RESA and other plasmodium antigen components; leishmania major and other leishmanial antigens such as gp63, lipoglucan and its related proteins and other leishmanial antigenic components; toxoplasma antigens such as SAG-1, p30 and other Toxoplasma antigen components; schistosome antigens such as glutathione-S-transferase, paramyosin, and other schistosome antigen components; and trypanosoma cruzi antigens such as 75-77kDa antigen, 56kDa antigen, and other trypanosoma cruzi antigen components.

In some embodiments, the analyte is a drug or a drug metabolite. A feature of the system is the ability to run any type of assay on the same system.

Detection

in some embodiments, one or more detectable labels or tags are used to detect binding of one or more analyte receptors to one or more target analytes, typically labels are molecules that are detectable directly (i.e., primary labels) or indirectly (i.e., secondary labels), e.g., labels that are visible and/or measurable or otherwise recognizable such that their presence or absence may be known, labels that are directly or indirectly coupled to one or more analyte receptors, analytes, or tags (e.g., probes) that interact with one or both of the analytes or analyte receptors, typically labels provide a signal, non-limiting examples of labels useful in the present invention include fluorochromes (e.g., fluorescein isothiocyanate, texas Red, rhodamine, etc.), enzymes (e.g., LacZ, CAT, horseradish peroxidase, alkaline phosphatase, I2-galactosidase, β -galactosidase, and glucose oxidase, acetylcholinesterase and other commonly used enzymes), enzyme labeled with biotin, streptavidin labeled with a chromophore, biotinylated, or labeled with other fluorescent probes such as a biotinylated antigen-fluorescein-labeled-ligand, biotinylated rabbit antigen-ligand, such as a biotinylated antibody, biotinylated epitope, e.g., fluorescein-fluorescein, biotinylated epitope, biotinylated antigen-fluorescein-labeled with a fluorescent probe, fluorescein-labeled with a detectable molecule, such as a fluorescent probe, fluorescein-labeled with a fluorescent dye, a fluorescent dyeA component of a binding pair of (a); magnetic particles; an electronic tag; a thermal marker; a light-emitting molecule; a phosphorescent molecule; a chemiluminescent molecule; fluorophores such as umbelliferone, fluorescein, rhodamine, tetramethylrhodamine, eosin, green fluorescent protein, erythrosine, coumarin, methylcoumarin, pyrene, malachite green, stilbene, fluorescein, cascade blue, dichlorotriazinylamine fluorescein, dansyl chloride, phycoerythrin, lanthanide fluorescent complexes such as those including europium and terbium, molecular beacons and fluorescent derivatives thereof, luminescent materials such as luminol; light scattering or plasmon resonance materials such as gold or silver particles or quantum dots; comprises that¹⁴C、¹²³I、¹²⁴I、¹³¹I、¹²⁵I、Tc99m、³²P、³⁵S or³Radioisotope labels or heavy isotopes including H; or a spherical shell; and Probes labeled with any other signal that produces a label known to those skilled in the art, for example, as described in Principles of fluorescence spectroscopy, Joseph r.lakowicz (eds.), Plenum Pub Corp, second edition (7 months 1999) and the sixth edition of Molecular Probes Handbook, Richard p.hoagland. Two or more different labels may be used simultaneously to detect two or more analytes in a single assay. In some embodiments, about or more than about 1,2,3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more different labels are used in a single assay.

In some embodiments, the label is an enzyme whose activity produces a product with a detectable signal. The substrate for sensitive detection may be colorimetric, radioactive, fluorescent or chemiluminescent. Conventional colorimetric substrates produce a new color (or change in spectral absorption) after the enzyme acts on the chromogenic substrate. Typically, colorimetric substrates produce a change in spectral absorption. In some embodiments, the enzyme is horseradish peroxidase, substrates of which include, but are not limited to, 3' -Diaminobenzidine (DAB), 3-amino-9-ethylcarbazole (AEC), and Bajoran violet. In some embodiments, the enzyme is alkaline phosphatase, substrates of which include, but are not limited to, fast red and Ferangi blue. Various other enzyme labels and associated chromophores are known in the art and are commercially available from commercial suppliers such as Thermo Fisher Scientific. A non-limiting example of an enzymatic assay is an enzyme-linked immunosorbent assay (ELISA). Methods for performing ELISA are known in the art and may be similarly applied in at least some of the methods described herein. The analyte may or may not be bound by the unlabeled first analyte receptor (e.g., a sandwich ELISA) and specifically binds to the analyte or the first analyte receptor prior to exposure to the labeled second analyte receptor. In a typical ELISA assay, the analyte receptor linked to the enzyme is an antibody. A similar assay may be performed when the antibody is replaced with another analyte receptor.

Suitable fluorescent labels include, but are not limited to, fluorescein, rhodamine, tetramethylrhodamine, eosin, erythrosine, coumarin, methylcoumarin, pyrene, malachite green, stilbene, fluorescein, cascade blue^TMsuitable optical dyes are described in Molecular Probes Handbook, 1996 edition of richardp.haugland, which is expressly incorporated by reference herein, suitable fluorescent markers also include, but are not limited to, Green Fluorescent Protein (GFP), Enhanced GFP (EGFP), Blue Fluorescent Protein (BFP), Enhanced Yellow Fluorescent Protein (EYFP), luciferase, β -galactosidase, and renilla fluorescent markers further examples are in WO92/15673, WO95/07463, WO98/14605, WO98/26277, WO99/49019, U.S. patent No. 5,292,658, U.S. patent No. 5,418,155, U.S. patent No. 5,683,888, U.S. patent No. 5,741,668, U.S. patent No. 5,777,079, U.S. patent No. 5,38387, U.S. patent No. 3, U.S. 5,925,558, which is incorporated by reference herein, and U.S. patent 5,925,558.

In some embodiments, the markers used in the present invention include: Alexa-Fluor dyes (AlexaFluor350, Alexa Fluor430, Alexa Fluor488, Alexa Fluor546, Alexa Fluor568, Alexa Fluor594, Alexa Fluor633, Alexa Fluor660, Alexa Fluor680), cascade blue, cascade yellow and R-Phycoerythrin (PE) (Molecular Probes) (Eugene, Oreg.), FITC, rhodamine and Texas Red (Pierce, Rockford, Ill.), Cy5, Cy5.5, Cy7(Amersham Life Science, Pittsburgh, Pa.). Tandem coupling protocols for Cy5PE, cy5.5pe, Cy7PE, cy5.5apc, Cy7APC are known in the art. Quantification of fluorescent probe coupling can be assessed to determine the extent of labeling, and protocols involving the spectral properties of dyes are also well known in the art. In some embodiments, the fluorescent label is conjugated to an aminodextran linker, which is conjugated to the binding member or antibody. Additional markers are listed in and available from the following company's online and hard copy catalogs: BD Biosciences, Beckman Coulter, Anaspec, Invitrogen, Cell Signaling Technology, Millipore, eBioscience, Caltag, Santa Cruz Biotech, Abcam, and Sigma, the contents of which are incorporated herein by reference.

The label may bind to the analyte receptor, the analyte, or both, and their binding may be covalent or non-covalent. Detection may result from an increase or decrease in the detectable signal from the label. In some embodiments, the degree of enhancement or reduction is related to the amount of analyte. In some embodiments, a sample containing an analyte to be analyzed is treated with a labeling compound to conjugate the analyte to a label, such as a fluorescent tag. Binding can then be determined by detecting the label, e.g., by measuring fluorescence, to detect the presence and, in turn, or quantity of one or more analytes, such as binding to analyte receptors coupled to the array or to the encoded beads. In some embodiments, the sample is treated with a labeling compound to couple the analyte to the linker. After binding, the linker is functionalized with a label, such as a fluorescent tag, and positive events, such as an increase in fluorescence, are determined by detecting the tag. In some embodiments, the analyte binding domain of the analyte receptor is bound by a probe comprising a label, such as a fluorescent label; upon binding to the analyte, the probe is released, which results in a measurable decrease in the detectable signal (e.g., decrease in fluorescence) from the label. In some embodiments, the analyte receptor is fluorescently labeled and is bound in part by a probe labeled with a quencher that is proximal to the fluorescent label; upon binding to the analyte, the complementary probe is released, resulting in a measurable increase in fluorescence of the label conjugated to the analyte receptor. In some embodiments, the analyte receptor is bound by a probe, the hybridization of which blocks a domain comprising a secondary structure; upon binding to the analyte, the probe is released and the secondary structure is made available to a label such as an intercalating dye that is used to generate a measurable signal. Labels useful for detecting binding between an analyte receptor and an analyte in a binding pair can include, for example, fluorescein, tetramethylrhodamine, texas red, or any other fluorescent molecule known in the art. The level of the detected label will vary with the amount of the target analyte in the mixture being measured.

In some embodiments, the displacement probe is coupled to a member of an affinity pair, such as biotin. The detectable molecule is then coupled to the other member of the affinity pair, e.g., avidin. After the detection mixture is added to the assay unit containing the analyte receptor, the detectable molecule is added. The amount of detectable molecules will vary inversely with the amount of target molecules present in the detection mixture. In another specific example, the displacement probe will be biotin-labeled and can be detected by the addition of fluorescently labeled avidin; the avidin will then itself be linked to another fluorescently labeled, biotin-coupled compound. The biotin group on the replacement oligonucleotide may also be used to bind an avidin-linked reporter enzyme; the enzyme will then catalyze a reaction that results in the deposition of a detectable compound. Alternatively, the reporter enzyme will catalyze the production of an insoluble product that will locally quench the fluorescence of the inherently fluorescent solid surface. In another embodiment of the displacement assay, the displacement probes will be labeled with an immunodetectable probe such as digoxigenin. The displacement probes will then be bound by a first set of antibodies that specifically recognize the probes. These primary antibodies will then be recognized and bound by a second set of antibodies that are fluorescently labeled or conjugated to a reporter enzyme.

In some embodiments, an analyte receptor, such as an antibody, induces an agglutination reaction in the presence of one or more analytes (e.g., antigens) of interest. A typical agglutination reaction involving the use of antibodies involves (i) mixing a polyclonal antibody with a sample containing an antigen corresponding to the antibody and observing the formation of an immunoagglutinate; (ii) mixing the monoclonal antibody with a sample containing an antigen having at least two antigen functions (bivalent or multivalent antigen), and observing the formation of an immunoagglutinate; (iii) mixing at least two different monoclonal antibodies with a sample comprising a monovalent antigen and observing the immunoagglutination; (iv) any of the reactions described above, but employing antibodies or other suitable analyte receptors as described herein coupled to particles such as latex particles, colloids, and the like; and (v) any of the above reactions, but applied to antigens present on the surface of cells, in which case the number of antigens per physical unit is typically 100 or more, and in which case the cells can be agglutinated by monoclonal antibodies or other suitable analyte receptors as described herein, even though each antigenic molecule is monovalent. Agglutination reactions can be observed on the surface of a solid substrate such as a glass or plastic plate or in a solution such as a microtiter plate, cuvette, tip, capillary or other suitable vessel. The solid surface or container is preferably colored to contrast with the color of the agglutinate. In some embodiments, the solid surface or container is optically transparent, such that agglutination can be measured by detection of a change in color, contrast, absorbance, or any other suitable label as described herein. In some embodiments, agglutination is measured in a liquid stream, wherein the presence of agglutination is determined by interrupting the flow of the liquid. In some embodiments, the agglutination reaction is a hemagglutination reaction. In some embodiments, the agglutination reaction is an agglutination inhibition reaction, wherein the presence of the analyte (e.g., small molecule, drug, or drug metabolite) inhibits or slows the speed of the agglutination reaction, such as by competing for binding to an analyte receptor (e.g., an antibody) in the presence of an agglutination target (e.g., a bead coated with the analyte).

The receptor binding assay as described herein may be combined with one or more other assays, such as different samples or the same sample, for use in at least one embodiment of the system described herein. Different assays may be performed on one or more samples simultaneously or sequentially.

In some embodiments, multiple analytes may be determined simultaneously. Multiple analytes can be analyzed in separate containers or in the same container. Different detectors may be used to determine the same analyte. This may allow the system to maintain high accuracy over a range of different concentrations of the analyte.

Nucleic acid hybridization assay

In some embodiments, the analyte is a target nucleic acid (e.g., DNA, RNA, mRNA, miRNA, rRNA, tRNA, and hybrids thereof) that is detected in a nucleic acid hybridization reaction. The target nucleic acid in the sample may be a nucleic acid from the individual from which the sample was obtained, or from a source in which the individual providing the sample is a host, for example a pathogen as described herein. In general, hybridization refers to a reaction in which one or more polynucleotides react to form a complex that is stabilized by hydrogen bonding between the bases of the nucleotide residues. Hydrogen bonding can occur by Watson Crick base pairing, Hoogstein binding, or in any other sequence specific manner. The compomer may comprise two strands forming a duplex structure, three or more strands forming a multi-stranded compomer, a self-hybridizing strand, or any combination thereof. Hybridization reactions can constitute a step in a broader process, such as the initiation of an amplification process (e.g., PCR, ligase chain reaction, self-sustained sequence replication), or the enzymatic cleavage of a polynucleotide by an endonuclease. Sequences that are capable of hybridizing to a given sequence are referred to as "complementary sequences" of the given sequence. In some embodiments, hybridization occurs between a target nucleic acid (analyte) and a nucleic acid probe. In some embodiments, the target nucleic acid is modified prior to hybridization to the probe, for example by ligating an adapter to one or both ends of the target nucleic acid, thereby generating a modified target nucleic acid. In modified nucleic acids comprising adapters, the probe may hybridize to only the adapter sequence, only the target nucleic acid sequence, or to both the adapter and the target nucleic acid sequence. Non-limiting examples of uses of nucleic acid probes include detecting the presence of viral or bacterial nucleic acid sequences indicative of infection, detecting the presence of variants or alleles of mammalian genes associated with disease and cancer, genotyping one or more loci (e.g., single nucleotide polymorphisms), determining the source of nucleic acids found in forensic samples, and paternity testing.

Nucleic acid probes of the invention can comprise DNA, RNA, modified nucleotides (e.g., methylated or labeled nucleotides), modified backbone chemical entities (e.g., morpholine ring-containing backbones), nucleotide analogs, or combinations of two or more thereof. The probe may be the coding strand or complementary strand of the complete gene or gene fragment or its expression product. The nucleotide sequence of the probe may be any sequence that has sufficient complementarity to a nucleic acid sequence in the biological sample to allow the probe to hybridize to a target nucleic acid in the biological sample under desired hybridization conditions. Ideally, the probe will only hybridize to the nucleic acid target in the sample, and will not non-specifically bind to other non-complementary nucleic acids in the sample or other regions of the target nucleic acid in the sample. Hybridization conditions may vary depending on the degree of stringency required in the hybridization reaction. For example, if the hybridization conditions are directed to high stringency, the probe will only bind to nucleic acid sequences in the sample with which it has a very high degree of complementarity. Low stringency hybridization conditions will allow the probe to hybridize to nucleic acid sequences in the sample that have some complementarity to the probe sequence, but are not as highly complementary to the probe sequence as would be required if hybridization occurred at high stringency. Hybridization conditions will vary depending on the biological sample, probe type, and target. The skilled person will know how to optimise hybridisation conditions for a particular application of the method of the invention, or alternatively how to design nucleic acid probes for optimal use under a given set of conditions.

Nucleic acid probes may be commercially available or may be synthesized according to standard nucleotide synthesis protocols well known in the art. Alternatively, probes can be generated by isolating and purifying nucleic acid sequences from biological material according to standard methods in the field of molecular biology (Sambrook et al 1989.molecular cloning: A Laboratory Manual, second edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.). The nucleic acid probe may be amplified according to a known nucleic acid amplification procedure (e.g., polymerase chain reaction). Furthermore, the probes of the invention can be linked to any of the labels of the invention by standard procedures in the art.

It is further contemplated that the invention also encompasses nucleotide hybridization methods in which the nucleic acid probes are used as primers for enzyme-catalyzed extension reactions such as PCR and primer extension labeling reactions (e.g., in situ and in vitro PCR and other primer extension-based reactions). In addition, in situ hybridization methods are also included.

Labels that may be attached to the nucleic acid probes of the invention include, but are not limited to, haptens, biotin, digoxigenin, Fluorescein Isothiocyanate (FITC), dinitrophenyl, aminomethylcoumarin acetic acid, acetylaminofluorene, and the mercury-thiol-ligand complex, chromophoric dyes, fluorescent dyes, and any other suitable label as described herein, e.g., described in combination with a label for an analyte receptor. In some embodiments, hybridization is detected indirectly by detecting the products of a hybridization reaction, such as PCR. For example, the amplification product can be detected with a dye or stain (e.g., an intercalating or groove binding dye) capable of detecting the amplified nucleic acid, such as ethidium bromide, SYBR green, SYBR blue, DAPI, acriflavine, fluorocoumarin, ellipticine, daunomycin, chloroquine, distamycin D, chromomycin, propidium iodide, Hoest, SYBR gold, acridine, proflavine, acridine orange, cuminium, mithramycin, ruthenium polypyridine, anisidine, and other suitable stains known in the art. In some embodiments, multiple probes, each having a different target nucleic acid and a different label, are hybridized to a sample simultaneously, e.g., about or more than about 1,2,3, 4,5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more different probes.

In one embodiment, the nucleic acid probe is coupled to the substrate covalently or non-covalently. Non-limiting examples of substrates to which nucleic acid probes may be coupled include microarrays, microbeads, pipette tips, sample transfer devices, cuvettes, capillaries or other test tubes, reaction chambers, or any other suitable format compatible with the present detection system. The production of biochip microarrays can use a variety of semiconductor manufacturing techniques, such as solid phase chemistry, combinatorial chemistry, molecular biology, and robotics. One common method is a photolithographic fabrication process for producing microarrays with millions of nucleic acid probes on one chip. Alternatively, if the nucleic acid probes are synthesized beforehand, they can be attached to the array surface using, for example, microchannel pumping, "ink jet" spotting, template stamping, or photocrosslinking techniques. An exemplary photolithography process begins with coating a quartz chip with a photosensitive compound to prevent coupling between the quartz chip and the first nucleotide of the resulting DNA probe. Photolithographic masks are used to block or allow light to be transmitted to specific locations on the surface of a chip. The surface is then contacted with a solution that may contain adenine, thymine, cytosine or guanine, and coupling occurs only at those regions on the glass that have been deprotected by illumination. The coupled nucleotides have photosensitive protecting groups, making the cycle repeatable. In this way, by repeating the cycle of deprotection and coupling, a microarray is created while the probe is synthesized. This process can be repeated until the probe reaches its full length. Commercially available arrays are typically manufactured to a density of over 130 million unique features per array. Each chip may be cut into tens or hundreds of individual arrays depending on the requirements of the experiment and the number of probes required for each array.

Other methods may also be used to produce a coated solid surface with nucleic acid probes attached. The solid surface of the coating may be Langmuir-Bodgett film, functionalized glass, germanium, silicon, PTFE, polystyrene, gallium arsenide, gold, silver, film, nylon, PVP, polymeric plastics or any other material known in the art capable of introducing functional groups such as amino, carboxyl, Diels-Alder reactants, thiol or hydroxyl groups on its surface. These groups can then be covalently linked to a cross-linking agent so that subsequent nucleic acid probe and target nucleic acid analyte binding will occur in solution without hindrance from the biochip. Typical crosslinking groups include ethylene glycol oligomers, diamines, and amino acids. Alternatively, the nucleic acid probes may be coupled to the array using an enzymatic process, as described in US 20100240544.

In some embodiments, the nucleic acid probe is coupled to the surface of a microbead. Microbeads for coupling nucleic acid probes are known in the art and include magnetic and non-magnetic beads. The microbeads may be labeled with 1,2,3, 4,5, 6, 7, 8, 9, 10 or more dyes to facilitate coding of the microbeads and identification of the nucleic acid probes attached thereto. The encoding of the microbeads can be used to distinguish at least 10, 50, 100, 200, 300, 400, 500, 600, 700, 800, 900, 1000, 1500, 2000, 5000 or more different microbeads in an array, each microbead corresponding to a different nucleic acid probe specific for a different target nucleic acid analyte.

In some embodiments, the nucleic acid probe is coupled to a surface of a reaction chamber, such as a tip. For example, the interior surface of the tip may be coated with nucleic acid probes specific for a single target nucleic acid analyte. Alternatively, the inner surface of the tip may be coated with two or more different nucleic acid probes specific for different target nucleic acid analytes. When two or more different nucleic acid probes are coupled to the same internal surface of the tip, each different nucleic acid probe may be coupled at a different known location, for example forming a different arrangement of loops or bands at different locations along the axis of the tip. In this case, a plurality of different nucleic acid analytes can be analyzed in the same sample by aspirating the sample to the tip and binding the nucleic acid analytes contained in the sample to nucleic acid probes at successive locations along the tip coating. The binding event can then be visualized as described herein, with the position of each band in the band pattern corresponding to a particular known nucleic acid analyte.

In some embodiments, the nucleic acid hybridization reaction is a sequencing reaction. The sequencing reaction may be performed directly from the sample nucleic acid, or may involve a pre-amplification step, such as reverse transcription and/or PCR. Sequence analysis using template-dependent synthesis can involve many different processes. For example, one of the earliest methods of DNA sequencing was the four-color chain termination Sanger sequencing method, in which a population of template molecules was used to create a population of complementary fragments. Primer extension is performed using a subset of dye-labeled terminator nucleotides, such as dideoxyribonucleotides, in the presence of four naturally occurring nucleotides, where each type of terminator (ddATP, ddGTP, ddTTP, ddCTP) contains a different detectable label. As a result, a set of nested fragments is created in which the fragments terminate at individual nucleotides in the template beyond the primer and are labeled in a manner that allows recognition of the terminating nucleotide. The nested population of fragments is then subjected to size-based separation, e.g., using capillary electrophoresis, and labels associated with each of the different sized fragments are identified to identify the terminating nucleotide. Thus, the tag sequences that move through the probes in the separation system provide a direct read of the sequence information of the synthesized fragments and, based on complementarity, obtain the sequence information of the underlying template (see, e.g., U.S. patent No. 5,171,534, incorporated herein by reference in its entirety for all purposes).

Other examples of template-dependent sequencing methods include synthetic sequencing methods in which individual nucleotides are repeatedly identified as they are added to a growing primer extension product. In one class of synthetic sequencing, a nucleic acid synthesis complex is contacted with one or more nucleotides under conditions that allow the addition of a single base with little or no extension beyond the base. The reaction is then interrogated or observed to determine whether a base is incorporated and to provide the identity of the base. In the second category of synthetic sequencing, the addition of nucleotides to the growing nascent strand is observed in real time during an uninterrupted reaction (e.g., no washing step).

an example of synthetic sequencing is pyrophosphate sequencing, which is a method of identifying the incorporation of nucleotides by determining the presence of a sequencing reaction byproduct, i.e., pyrophosphate, in the resulting synthesis mixture.specifically, a primer, polymerase template complex is contacted with a single type of nucleotide, if the nucleotide is incorporated, the polymerization reaction cleaves nucleoside triphosphates between the alpha and β phosphates of the triphosphate chain, releasing the pyrophosphate, then the presence of the released pyrophosphate is determined using a chemiluminescent enzyme reporting system that converts pyrophosphate with AMP to ATP, then measures ATP using luciferase to produce a measurable light signal, if light is detected, a base is incorporated, if light is not detected, a base is not incorporated, after an appropriate washing step, multiple bases are cyclically contacted with the complex to sequentially identify subsequent bases in the template nucleic acid. see, e.g., U.S. Pat. No. 6,210,891, which is incorporated herein by reference in its entirety for all purposes.

In a related method, a primer/template/polymerase complex is immobilized on a substrate and the complex is contacted with a labeled nucleotide. Immobilization of the complex may be by primer sequences, template sequences and/or polymerases and may be covalent or non-covalent. In general, preferred embodiments, particularly according to embodiments of the invention, provide for immobilization of the complex by attachment between a polymerase or primer and the substrate surface. Various types of linkages can be used for such attachment, including, for example, providing a biotinylated surface component using, for example, biotin-PEG-silane coupling chemistry, followed by biotinylation of the molecules to be immobilized, followed by linkage via, for example, a streptavidin bridge. Other synthetic coupling chemistries as well as non-specific protein adsorption can also be used for immobilization. In an alternative configuration, nucleotides with and without a removable terminator group are provided. After incorporation, the label is coupled to the complex and can therefore be detected. In the case of nucleotides with terminators, all four different nucleotides with independently identifiable labels are contacted with the complex. Incorporation of the labeled nucleotide prevents extension due to the presence of the terminator, and a label is added to the complex. The label and terminator are then removed from the incorporated nucleotide and the process repeated after an appropriate washing step. In the case of an unterminated nucleotide, a single type of labeled nucleotide is added to the complex to determine if it will incorporate, as with pyrophosphate sequencing. After removal of the labeling groups on the nucleotides and appropriate washing steps, the various nucleotides are circulated through the reaction mixture in the same process. See, for example, U.S. patent No. 6,833,246, which is incorporated herein by reference in its entirety for all purposes.

in yet another synthetic sequencing method, incorporation of different labeled nucleotides is observed in real time as template-dependent synthesis proceeds, specifically, as fluorescently labeled nucleotides are incorporated, separate immobilized primer/template/polymerase complexes are observed, allowing each added base to be identified in real time as it is added. in this method, a labeling group is attached to a portion of the nucleotides that are cleaved during incorporation.

A nucleic acid hybridization assay as described herein may be combined with one or more other assays, e.g., performed on different samples within at least one embodiment of the system described herein, or performed on the same sample. Different assays may be performed on one or more samples simultaneously or sequentially.

Electrophoresis

In some embodiments, the system comprises subjecting the analyte to an electrophoresis process. The present invention can be used to isolate, detect and measure one or more analytes in one or more samples of biological, ecological or chemical significance. Of particular interest are macromolecules such as proteins, polypeptides, sugars, and polysaccharides, genetic material such as nucleic acids and polynucleotides, carbohydrates, cellular material such as bacteria, viruses, organelles, cellular debris, metabolites, drugs, such as any of the other analytes described herein, and combinations thereof. Proteins of interest include proteins present in plasma, albumin, globulin, fibrinogen, clotting factors, hormones, interferons, enzymes, growth factors, and other proteins described herein. Other chemicals that can be isolated and detected using the present invention include, but are not limited to, pharmaceuticals, such as antibiotics, and agrochemicals, such as pesticides and herbicides.

Electrophoresis may include the use of gels and/or capillaries. Electrophoretic separation can be performed with or without the use of a molecular matrix (also referred to herein as a sieving matrix or medium, and a separation matrix or medium) to produce separation. When a matrix is not used as part of the capillary electrophoresis process, this technique is commonly referred to as Capillary Zone Electrophoresis (CZE). When the matrix is used in conjunction with a capillary electrophoresis process, this technique is commonly referred to as Capillary Gel Electrophoresis (CGE). Non-limiting examples of matrices used in electrophoresis processes include linear polymer solutions, such as poly (ethylene oxide) solutions, cross-linked polyacrylamide, and agarose. Suitable matrices may be in liquid, gel or particulate form.

In electrophoresis, the separation buffer is generally chosen such that it helps to dissolve or suspend the substances present in the sample. The liquid is typically an electrolyte containing both anionic and cationic species. Preferably, the electrolyte contains about 0.005 to about 10 moles/liter of ionic species, more preferably about 0.01 to about 0.5 moles/liter of ionic species. Examples of electrolytes for typical electrophoretic systems include mixtures of water with organic solvents and salts. Representative materials that can be mixed with water to produce a suitable electrolyte include: inorganic salts such as phosphates, bicarbonates, and borates; organic acids such as acetic acid, propionic acid, citric acid, chloroacetic acid and their corresponding salts, etc.; alkylamines, such as methylamine; alcohols such as ethanol, methanol and propanol; polyols, such as alkanediols; nitrogen-containing solvents such as acetonitrile, pyridine, and the like; ketones such as acetone and methyl ethyl ketone; and alkylamides such as dimethylformamide, N-methyl and N-ethylformamide and the like. The above ionic and electrolyte species are provided for illustrative purposes only. A researcher skilled in the art can formulate electrolytes from the above-described materials and optional materials such as amino acids, salts, bases, etc. to produce suitable supporting electrolytes for use in capillary electrophoresis systems. The voltage used for electrophoretic separation is not critical to the present invention and may vary widely. Typical voltages for capillary electrophoresis are about 500V to 30,000V, preferably about 1,000 to 20,000V.

In some embodiments, the electrophoresis process is a capillary electrophoresis process. In a typical capillary electrophoresis process, a buffer-filled capillary is suspended between two buffer-filled reservoirs. An electric field is applied across the ends of the capillary. The potential of the generated electric field is in the kilovolt range. The sample containing one or more components or substances is typically introduced at the high potential end and under the influence of an electric field. Alternatively, the sample is injected using pressure or vacuum. The same sample may be introduced into multiple capillaries, or different samples may be introduced into each capillary. Typically, the capillary array is held in a guide and the suction end of the capillary is immersed in a vial containing the sample. After the sample is drawn in by the capillary, the tip of the capillary is removed from the sample vial and immersed in a buffer solution, which may be in a common container or in a separate vial. The sample migrates toward the low potential end. During migration, components of the sample are electrophoretically separated. After separation, the components are detected by a detector. Detection may be achieved while the sample is still in the capillary or after the sample has left the capillary.

The channel length of capillary electrophoresis is chosen such that it is effective to achieve proper separation of the substances. Generally, the longer the channel, the longer it takes for the sample to migrate through the capillary. Thus, the substances can be separated from each other over a greater distance. However, longer channels widen the band and result in too long separation times. Typically, for capillary electrophoresis, the capillary is about 10cm to about 5 meters long, and preferably about 20cm to about 200cm long. In capillary gel electrophoresis, which typically uses a polymeric separation matrix, a more preferred channel length is about 10cm to about 100cm long.

The inner diameter (i.e., pore size) of the capillary is not critical, although small pore capillaries are more useful in highly multiplexed applications. The invention extends to a wide range of capillary sizes. Generally, the inner diameter of the capillary may range from about 5 microns to about 300 microns, preferably from about 20 microns to about 100 microns. The capillary length may typically range from about 100 to 3000mm, preferably from about 300 to 1000 mm.

Suitable capillaries are constructed from strong and durable materials that maintain their physical integrity when repeatedly used under the normal conditions of capillary electrophoresis. It is generally constructed of a non-conductive material so that a high voltage can be applied across the capillary without generating excessive heat. Inorganic materials such as quartz, glass, fused silica, and organic materials such as polytetrafluoroethylene, fluorinated ethylene/propylene polymers, polyvinyl fluoride, aramid, nylon (i.e., polyamide), polyvinyl chloride, polyvinyl fluoride, polystyrene, polyethylene, and the like, may be advantageously used to fabricate the capillary tube.

When excitation and/or detection is effected through the capillary wall, as described in more detail below, it is particularly advantageous for the capillary to be constructed from a transparent material. Transparent capillaries that exhibit substantially no fluorescence, i.e., fluorescence below background levels, when exposed to light used to illuminate the target species, are particularly useful where excitation is achieved through the capillary wall. One such capillary is available from Polymicro Technologies (Phoenix, Ariz.). Alternatively, a transparent non-fluorescing portion may be formed on the wall of an opaque or fluorescing capillary tube to enable excitation and/or detection through the capillary tube wall. For example, fused silica capillaries are often provided with a polyimide coating on the outer capillary surface to enhance their resistance to cracking. The coating is known to emit broad fluorescence when exposed to light having a wavelength below 600 nm. If a transmural excitation scheme is used without first removing the coating, the fluorescent background can mask the weak analyte signal. Thus, a portion of the fluorescing polymer coating may be removed by any convenient method, such as by boiling in sulfuric acid, by oxidation using a heated probe (e.g., an energized wire), or by scraping with a knife. In capillaries having an inner diameter of about 0.1mm or less, the width of the useful transparent portion is about 0.01mm to about 1.0 mm.

Blood coagulation assay

In some embodiments, the systems described herein include performing a coagulation assay on the analyte. Coagulation assays include, but are not limited to, assays that detect one or more coagulation factors and measure clotting time. The reading of the coagulation assay is typically clot formation, rate of clot formation, or time of clot formation. Blood coagulation factors include factor I (fibrinogen), factor II (prothrombin), factor III (tissue coagulation hormone), factor IV (calcium), factor V (procoagulant fibrinogen), factor VI (no longer considered hemostatic active), factor VII (turnover accelerating factor), factor VIII (antihemophilic factor), factor IX (plasma coagulation hormone component; Christmas factor), factor X (stuart factor), factor XI (plasma coagulation hormone precursor), factor XII (hageman factor) and factor XIII (fibrin stabilizing factor). Diagnosis of bleeding conditions such as hemophilia, in which one or more of the twelve coagulation factors may be deficient, can be accomplished by a wide range of coagulation tests. In addition, several probe tests have been developed to monitor the progress of thrombolytic therapy. Other tests have been developed to signal pre-thrombolytic or hypercoagulable states, or to monitor the effect of protamine administration to a patient during cardiopulmonary bypass surgery. Coagulation tests may also be used to monitor oral and intravenous anticoagulant therapy. Examples of three diagnostic clotting assays useful in the present invention are activated partial clotting hormone time (APTT), Prothrombin Time (PT), and Activated Clotting Time (ACT).

APTT detection assesses the common intrinsic pathway of coagulation. For this reason, APTT is often used to monitor intravenous heparin anticoagulant therapy. In particular, it measures the time to form a fibrin clot after addition of an activator (e.g., calcium) and phospholipids to a citrate-treated blood sample. Heparin administration has the effect of inhibiting clot formation.

PT probing assesses the extrinsic common pathway of coagulation (e.g. conversion of prothrombin to thrombin in the presence of calcium ions and tissue thromboplastin) and can be used to monitor oral anticoagulant therapy. The oral anticoagulant coumarin inhibits prothrombin formation. Thus, the detection is based on the addition of calcium and tissue thromboplastin to the blood sample.

ACT detection assesses the common intrinsic pathway of coagulation. It is often used to monitor anticoagulation by heparin therapy. ACT detection is based on the addition of an activator of the endogenous pathway to fresh whole blood to which no exogenous anticoagulant is added.

The coagulation assay may use turbidity measurements. In one example of a coagulation assay, a whole blood sample is collected into a negative pressure container (vacutainer) containing citrate and then centrifuged. The assay was performed with plasma to which sufficient excess calcium was added to neutralize the effect of citrate. For PT detection, tissue thromboplastin was provided as a dry reagent and reconstituted prior to use. The reagent is sensitive to heat and is therefore kept at4 ℃ with the apparatus. Aliquots of the sample and reagent were transferred to cuvettes heated at 37 ℃ and measured based on changes in optical density.

As an alternative to the nephelometric method, Beker et al (see Haemostatis (1982)12:73) have introduced a chromogenic PT reagent (Thromboquant PT). The assay is based on the hydrolysis of p-nitroaniline from the modified peptide Tos-Gly-Pro-Arg-pNA by thrombin and is monitored by a spectrophotometer. Coagulation can also be measured by a change or disruption of the liquid flow, for example in terms of a decrease in flow rate, an increase in flow time between two points and the formation of an obstruction to the liquid flow, for example in a capillary tube. The standard of normal coagulation outcome that can be compared to the probe outcome will vary with the method used and is known in the art or can be determined using a control sample (e.g., from a normal individual).

Cell counting

In some embodiments, the assay system is configured to perform a cytometry assay. Cytometry assays are commonly used to optically, electrically, or acoustically measure characteristics of individual cells. For purposes of this disclosure, "cells" may include non-cellular samples that are generally similar in size to cells of an individual, including but not limited to vesicles (e.g., liposomes), small populations of cells, virosomes, bacteria, protozoa, crystals, entities formed by polymerization of lipids and/or proteins, and substances bound to small particles such as beads or microspheres. Such features include, but are not limited to, size; a shape; particle size; light scattering pattern (or optical characteristic curve); whether the cell membrane is intact; concentration, morphology and spatiotemporal distribution of intracellular contents including, but not limited to, protein content, protein modifications, nucleic acid content, nucleic acid modifications, organelle content, nuclear structure, nuclear content, intracellular structure, internal vesicle content (including pH), ionic concentration and presence of other small molecules such as steroids or drugs; and cell surface (both cell membrane and cell wall) markers including proteins, lipids, carbohydrates, and modifications thereof. Cell counts can be used to determine the presence, amount, and/or modification of particular proteins, nucleic acids, lipids, carbohydrates, or other molecules by using appropriate dyes, stains, or other labeling molecules, whether in pure form, coupled to other molecules, or immobilized or bound to nanoparticles or microparticles. Properties that can be measured by cell counting also include measurement of cell function or activity, including but not limited to phagocytosis, antigen presentation, cytokine secretion, changes in expression of internal and surface molecules, binding to other molecules or cells or substrates, active transport of small molecules, mitosis, or meiosis; protein translation, gene transcription, DNA replication, DNA repair, protein secretion, apoptosis, chemotaxis, migration, adhesion, antioxidant activity, RNAi, protein or nucleic acid degradation, drug response, infectivity, and activity of specific pathways or enzymes. The cell count can also be used to determine information about the cell population, including but not limited to cell count, total population percentage, and variation in any of the above characteristics in the sample population. The assays described herein can be used to measure one or more of the above characteristics for each cell, which can facilitate the determination of correlations or other relationships between different characteristics. The assays described herein can also be used to independently measure multiple cell populations, for example, by labeling a mixed cell population with antibodies specific for different cell lines. The microscopy module may allow for histological, pathological, and/or morphological analysis to be performed with the device, but also facilitate the assessment of targets based on both physical and chemical characteristics. The tissue may be homogenized, washed, placed on a cuvette or slide, dried, stained (e.g., with an antibody), incubated, and then imaged. When combined with the data transfer techniques described elsewhere herein, these innovations have driven the transfer of images from CMOS/CDD or the like to a licensed pathologist for examination, which is not possible using conventional devices that perform flow cytometry only. The cytometer can measure surface antigens and cell morphology; surface antigens enable more sensitive and specific detection compared to traditional hematology laboratory devices. Interpretation of the cellular assay can be automated by gating one or more measurements; the gating threshold may be set by a specialist and/or learned from training data based on statistical methods; the gating rules may be specific for individual individuals and/or populations of individuals.

In some embodiments, the incorporation of the cell counter module into the point-of-service device provides measurements of cell attributes that are typically measured by common laboratory devices and laboratories for interpretation and review by regularly trained medical personnel, thereby improving the speed and/or quality of clinical decision making. The point-of-service device may thus be configured for cytometric analysis.

Cytometric analysis can be performed by, for example, flow cytometry or microscopy. Flow cytometry generally uses a flowing liquid medium which in turn carries individual cells to an optical, electrical or acoustic detector. Microscopy generally uses optical or acoustic means to probe fixed cells, usually by recording at least one magnified image. It should be understood that flow cytometry and microscopy are not entirely non-exclusive. As one example, flow cytometry assays may use microscopy to record images of cells delivered by a detector. Many targets, reagents, assays and detection methods of flow cytometry and microscopy may be the same. Thus, unless otherwise specified, the following description should be applied to these and other forms of art-known cytometric analysis.

The microscope objective can be finely positioned by an actuator, for example by a cam attached to a motor, to focus the image. The objective lens may be focused on one or more planes of the sample. Focusing can be automated by calculating the image sharpness of the digital image via an image analysis program and other methods.

Flow cytometry

Flow cytometry can be used to measure, for example, cell size (front scatter, conductivity), cell granularity (side scatter at various angles), DNA content, dye staining, and to quantify fluorescence from labeled markers. Flow cytometry may be used to perform cell counting, for example, by labeling the sample with a fluorescent label and flowing through a sensing device. The unlabeled sample may also be subjected to cell counting.

Preferably, up to 1000000 cells of any given type can be measured. In other specific examples, various numbers of cells of any given type may be measured, including but not limited to greater than or equal to about 10 cells, 30 cells, 50 cells, 100 cells, 150 cells, 200 cells, 300 cells, 500 cells, 700 cells, 1000 cells, 1500 cells, 2000 cells, 3000 cells, 5000 cells, 6000 cells, 7000 cells, 8000 cells, 9000 cells, 10000 cells, 100000 cells, 1000000 cells.

In some embodiments, flow cytometry may be performed in a microfluidic channel. Flow cytometry analysis can be performed in a single channel or in parallel in multiple channels. In some embodiments, flow cytometry may measure multiple cellular features sequentially or simultaneously. Flow cytometry can be combined with cell sorting, where the detection of cells satisfying a particular set of characteristics is diverted from a flowing stream and collected for storage, additional analysis and/or processing. It should be noted that such sorting can separate multiple cell populations based on different sets of characteristics, e.g., 3 or4 way sorting.

Microscopy

Microscopy methods that may be used with the present invention include, but are not limited to, bright field, oblique field illumination, dark field, disperse staining, phase contrast, Differential Interference Contrast (DIC), polarized light, epi-fluorescence, interference reflectance, fluorescence, confocal (including CLASS), Confocal Laser Scanning Microscopy (CLSM), structured illumination, stimulated emission impairment, electrons, scanning probes, infrared, laser, wide angle, light field microscopy, lensless on-chip holographic microscopy, digital and conventional holographic microscopy, extended field depth microscopy, light scattering imaging microscopy, reverse-convolution microscopy, defocused microscopy, quantitative phase microscopy, diffracted phase microscopy, confocal raman microscopy, scanning acoustic microscopy, and X-ray microscopy. As non-limiting examples, the magnification levels used for microscopy may include magnifications of up to 2x, 5x, 10x, 20x, 40x, 60x, 100x, 1000x, or higher. The level of magnification that is feasible will vary with the type of microscopy used. For example, images produced by some forms of electron microscopy may involve up to hundreds of thousands of times of magnification. Multiple microscopic images can be recorded of the same sample to generate time resolved data, including video. An individual or a plurality of cells can be imaged simultaneously by parallel imaging or by recording an image containing a plurality of cells. The microscope objective may be immersed in a medium to change its optical properties, for example by immersion in oil. The microscope objective can be moved relative to the sample by means of a rotating cam to change the focus. The cell count data may be processed automatically or manually, and may further include analysis of cell or tissue morphology, for example, by a pathologist for diagnostic purposes.

Cell counting can be performed using imaging and cytometry. In the case of brightly field-illuminable subjects, a preferred embodiment is to illuminate the subject from the front with white light and sense the cells with an imaging sensor. Subsequent digital processing will count the cells. In rare or small cells, a preferred embodiment is to attach a specific or non-specific fluorescent label and then illuminate the host field with a laser. Confocal scanning imaging is preferred. Preferably, up to 1000 cells of any given type can be counted. In other specific examples, various numbers of cells of any given type may be counted, including but not limited to greater than or equal to about 1 cell, 5 cells, 10 cells, 30 cells, 50 cells, 100 cells, 150 cells, 200 cells, 300 cells, 500 cells, 700 cells, 1000 cells, 1500 cells, 2000 cells, 3000 cells, 5000 cells. Cells can be counted using available counting algorithms. Cells can be identified by their characteristic fluorescence, size and shape.

In some microscopy embodiments, bright field illumination may be achieved by creating Koehler illumination using a white light source and a graded condenser. A bright field image of the cell of similar nature to forward scatter detection in flow cytometry can show cell size, phase dense material within the cell, and staining features in the cell if the cell has been previously stained. In one exemplary embodiment, the Wright-Giemsa staining method can be used to stain human whole blood smears. Bright field imaging shows a staining pattern characteristic of human white blood cells. Uniquely shaped red blood cells can also be identified in these images.

In some microscopy embodiments, dark field imaging may be achieved by using a ring light based illumination scheme or other available external or through dark field illumination schemes. Dark field imaging can be used, for example, to determine light scattering properties of cells, equivalent to side scattering in flow cytometry, for example when imaging human white blood cells. In dark field images, the features inside and outside the cell that scatter more light appear brighter, while the features that scatter less light appear darker. Cells, such as granular cells, have internal particles in a range of sizes (100-500nm), which scatter a lot of light and generally appear brighter in dark field images. Furthermore, the outer boundary of any cell may scatter light and may appear as a bright ring. The diameter of the loop can directly give the size of the cell. In addition, microscopy methods can also be used to measure cell volume. For example, the volume of red blood cells can be measured. To increase accuracy, cell volume can be calculated by converting red blood cells into spheres using anionic or zwitterionic surfactants and measuring the size of each sphere using dark field imaging.

In some microscopy embodiments, small cells or formed elements that may be below the diffraction-limited resolution limit of the microscope may be labeled with fluorescent labels; the sample may be excited with light of an appropriate wavelength and an image may be captured. Diffraction patterns of fluorescence emitted by labeled cells can be quantified using computer analysis and correlated with cell size. Computer programs for these specific examples are described elsewhere herein. To improve the accuracy of the method, cells can be transformed into spheres by using anionic and zwitterionic surfactants.

Cell imaging can be used to extract one or more of the following (but not limited to the following) for each cell:

a. size of cell

b. Quantitative measurement of cell size or light scattering (commonly known as side scattering, based on flow cytometry terminology)

c. Quantitative measurement of fluorescence in spectral channels imaged after compensation for cross-talk between spectral channels, or intracellular distribution patterns of fluorescence or other staining

d. Cell shape, as quantified by standard and custom shape attributes (e.g., aspect ratio, Feret diameter, kurtosis, moment of inertia, roundness, compactness, etc.).

e. Color, color distribution, and cell shape, in the case where the cells have been stained with a dye (no antibody or other type of receptor attached).

f. Intracellular pattern of staining or scattering, defined as the color or fluorescence of a quantitative indicator of a biological feature, such as morphology, e.g., the density of intracellular particles in dark field images, or the number and size of nucleolar lobes in Giemsa-Wright stained images of polymorphonuclear neutrophiles, among others.

g. Co-localization of cellular features shown by images acquired in different channels.

h. Individual cells, cell structures, cell populations, intracellular proteins, ions, carbohydrates and spatial location of lipids or secretions (e.g., to determine the source of secreted proteins).

A wide range of cell-based assays can be designed to use the information collected by cell counting. For example, it may be provided to perform a 5-part leukocyte differential measurement. The reportable value in this case may be, for example, the cell number of the following types of white blood cells per microliter of blood: monocytes, lymphocytes, neutrophils, basophils and eosinophils. Reportable values may also be used to classify leukocyte differentiation, or to identify T and B cell populations.

Fluorescence microscopy

Fluorescence microscopy generally involves labeling cells or other samples with fluorescent labels, described in more detail below. Microscopic imaging of fluorescently labeled samples can gather information about the presence, amount, and location of labeled targets at a given time or over a period of time. Fluorescence can also be used to enhance the sensitivity of detecting cells, cell structures, or cell functions. In fluorescence microscopy, a beam of light is used to excite a fluorescent molecule, which then emits light at a different wavelength for detection. Light sources that excite fluorophores are well known in the art and include, but are not limited to, xenon lamps, lasers, LEDs, and photodiodes. Detectors include, but are not limited to, PMTs, CCDs, and cameras.

Electron microscopy

Another non-limiting example of microscopy uses an electron beam instead of visible light, such as Transmission Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). In TEM, a beam of electrons is transmitted through a thin sample, and the interaction between the electrons and the specimen is mapped and magnified. TEM is thus capable of imaging up to a resolution of a single atom. TEM contrast may use bright field imaging mode, in which electrons are absorbed by the sample; a diffraction-contrast mode, in which electrons are scattered by the sample; electron Energy Loss Spectroscopy (EELS), which detects electrons that have interacted with a particular component of the sample based on their voltage; phase contrast or high resolution transmission electron microscopy; diffraction, which produces a unique diffraction pattern that can be computationally analyzed to determine the sample structure; three-dimensional imaging, in which a sample is rotated and imaged multiple times to reconstruct the overall three-dimensional structure.

Samples for TEM can be prepared by forming dilute solutions of molecules or cutting larger samples into layers up to several hundred nanometers thick. For negative-staining EM, the biological sample is typically spread on a grid, dried, and fixed with a negative staining reagent containing a heavy metal such as osmium, lead, uranium, or gold; one such staining reagent is uranyl acetate. For cryo-EM, the sample may be embedded in glassy ice and further cooled to the temperature of liquid nitrogen or liquid helium.

In a SEM, a focused electron beam forms a grating on a surface to produce secondary electrons, backscattered electrons, X-rays, light, current, and/or transmitted electrons. SEM can be used to visualize samples below 1nm in size at large depths of field to yield information about the 3D surface structure of the sample. SEM using backscattered electrons may be used with labels such as colloidal gold (e.g. attached to an immunological label) to better detect a specific target.

For SEM, the sample is typically free of water. Biological samples such as cells may be fixed to maintain their internal structure prior to drying, for example by evaporation, heating or drying with a critical point, in which water is in turn replaced by an organic solvent followed by liquid carbon dioxide. The conductive sample typically requires little or no additional sample preparation, and only needs to be mounted on a specimen holder compatible with a scanning electron microscope. The non-conductive sample may be coated with a thin layer of conductive material, such as gold, gold/palladium, platinum, osmium, iridium, tungsten, chromium, or graphite, which may enhance the signal, increase resolution, and reduce static charge buildup during irradiation. Other methods of increasing the conductivity of SEM samples include staining with OTO staining methods. For SEM imaging, the non-conductive sample does not need to increase conductivity. As some non-limiting examples, ambient SEM and Field Emission Gun (FEG) SEM may be used to image non-conductive samples.

Reagent

Cells can be prepared for cytometric determination by any method known in the art. The cells are in turn either fixed, stained and/or labeled with a detectable marker. Cells can be fixed by a variety of methods known in the art, including but not limited to heating, freezing, perfusion, immersion, and chemical fixation. Chemical fixation can be achieved by a wide variety of agents, including but not limited to crosslinking agents (e.g., formaldehyde, glutaraldehyde, other aldehydes and derivatives thereof), precipitation agents (e.g., ethanol and other alcohols), oxidizing agents (e.g., osmium tetroxide or potassium permanganate), potassium dichromate, chromic acid, mercury-containing fixatives, acetic acid, acetone, picrates, and HOPE fixatives. The cells may also be permeabilized, for example by using a surfactant, which may be useful for subsequent internal labeling or staining.

The cells may be stained with any optically detectable dye, stain or colorant, such as nucleic acid dyes (including intercalator dyes), lipophilic dyes, eggsWhite matter dyes, carbohydrate dyes, heavy metal dyes. Such dyes and stains or staining procedures include, but are not limited to, acid-fast bacillus staining, alcain blue/PAS staining, alizarin, alkaline phosphatase staining, aminostyryl dyes, ammonium molybdate, azure a, azure B, Bielschowsky staining, Bismark brown, cadmium iodide, carbocyanine, carbohydrazide, carboindocyanine, carmine, coomassie blue, congo red, crystal violet, DAPI, ethidium bromide, Diff-Quik staining, eosin, ferric chloride, fluorescent dyes, magenta, giemsa staining, Golgi-Cox staining, Gomori trichrome staining, Gordon Sweet stain, gram staining, grott urotropine staining, hematoxylin, hexamine, Hoechst staining, hyaluronidase alcain blue, indium trichloride, indocarbocyanine, indocyanine, iodine, Jenner staining, lanthanum nitrate, lead acetate, lead citrate, lead nitrate (II), lenoman staining, lenal staining, Luna blue staining, lucal staining, carbocyanine staining, gomir trichrome staining, cud staining, blue staining, blue staining, blue, malachite green, Masson Fontana staining, Masson trichrome staining, urotropin, methyl green, methylene blue, microglial staining, Miller elastic staining, neutral red, Nile blue, Nile red, Nissl staining, orange G, osmium tetroxide, Papanicolaou staining, PAS amylase staining, periodic acid, Perls Prussian blue, phosphomolybdic acid, phosphotungstic acid, potassium ferricyanide, potassium ferrocyanide, Pouchet staining, Propidium Iodide (PI), Prussian blue, Renal Alcian blue/PAS staining, Renal Masson trichrome staining, Renal PAS urotropine staining, rhodamine, Romanovsky staining, Caraway red, safranin O, silver nitrate, silver blue, sodium chloroaurate, Southgate's Mucinane staining, Sudan staining, Sybrr green, Sybro gold, SYTO staining, PRO Tsuvamide staining, Thiourinamide, uranyl acetate staining, uranyl staining, Kovosson staining, kovosson staining, uranyl staining, Nichon staining, Nichol staining, Nissin staining, Nissin blue, WG staining, Wright-Giemsa staining, Wright staining, X-Gal and Ziehl Neelsen staining. The cells can be treated with a leuco dye precursor, e.g., modified by an enzyme (e.g., by peroxidase or luciferase) or with an ion (e.g., Fe ion, Ca)²⁺Or H⁺) Combined and converted to detectable products upon treatment.

The cells canFurther labeled with a fluorescent label. Useful fluorescent labels include natural and artificial fluorescent molecules, including fluorescent proteins, fluorophores, quantum dots, and the like. Some examples of fluorescent markers that may be used include, but are not limited to: 1,5 IAEDANS; 1, 8-ANS; 5-carboxy-2, 7-dichlorofluorescein; 5-carboxyfluorescein (5-FAM); fluorescein Amide (FAM); 5-carboxynaphthoyl fluorescein; tetrachloro-6-carboxyfluorescein (TET); hexachloro-6-carboxyfluorescein (HEX); 2, 7-dimethoxy-4, 5-dichloro-6-carboxyfluorescein (JOE);NED^TM(ii) a Tetramethylrhodamine (TMR); 5-carboxytetramethylrhodamine (5-TAMRA); 5-HAT (hydroxytryptamine); 5-Hydroxytryptamine (HAT); 5-ROX (carboxy-X-rhodamine); 6-carboxyrhodamine 6G; 6-JOE; lightRed 610; lightRed 640; lightRed 670; lightRed 705; 7-amino-4-methylcoumarin; 7-amino actinomycin D (7-AAD); 7-hydroxy-4-methylcoumarin; 9-amino-6-chloro-2-methoxyacridine; ABQ; acid fuchsin; ACMA (9-amino-6-chloro-2-methoxyacridine); acridine orange; acridine red; acridine yellow; acriflavine; acriflavine Feulgen sitag; an autofluorescent protein; texas red and related molecules; thiadicarbocyanine (dicc 3); thiazine red R; thiazole orange; a thioflavin derivative; thiolyte; thiozole orange; tinopol CBS (Calcofluor White); TMR; TO-PRO-1; TO-PRO-3; TO-PRO-5; TOTO-1; TOTO-3; tricholor (PE-Cy 5); TRITC (tetramethylrhodamine-isothiocyanate); pure blue; TruRed; ultralite; fluorescein sodium B; UvitexSFC; WW 781; x-rhodamine; XRITC; xylene orange; Y66F; Y66H; Y66W; YO-PRO-1; YO-PRO-3; YOYO-1; interchelated dyes such as YOYO-3, Sybr green, thiazole orange; alexaMembers of the dye series (from molecular probes/Invitrogen) such as Alexa Fluor350, Alexa Fluor405, 430, 488, 500, 514, 532, 546, 555, 568, 594, 610, 633, 635, 647, 660, 680, 700 and 750; members of the Cy Dye fluorophore series (GEHealthcare) such as Cy3, Cy3B, Cy3.5, Cy5, Cy5.5, Cy 7;members of dye fluorophores (DenovoBiolabels) such as Oyster-500, -550, -556, 645, 650, 656; members of the DY-Labels series (Dyomics) such as DY-415, -495, -505, -547, -548, -549, -550, -554, -555, -556, -560, -590, -610, -615, -630, -631, -632, -633, -634, -635, -636, -647, -648, -649, -650, -651, -652, -675, -676, -677, -680, -681, -682, -700, -701, -730, -731, -732, -734, -750, -751, -752, -776, -780, -781, -782, -831, -480XL, XL, -481XL, -485XL, -510XL, -520XL, -521 XL; members of the ATTO series of fluorescent markers (ATTO-TEC GmbH) such as ATTO390, 425, 465, 488, 495, 520, 532, 550, 565, 590, 594, 610, 611X, 620, 633, 635, 637, 647N, 655, 680, 700, 725, 740; CALSeries orMembers of the series of dyes (Biosearch Technologies), e.g. CALGold 540, CAL560 of orange,570、CALRed 590, CALRed 610, CALRed 635,570 and670。

fluorescent labels may be conjugated to targeting moieties to allow specific binding or localization to, for example, a particular cell population, many of which are known in the art. Non-limiting examples include antibodies, antibody fragments, antibody derivatives, aptamers, oligopeptides such as Nuclear Localization Sequences (NLS), small molecules that act as specific ligands for receptors (including many hormones and drugs), nucleic acid sequences (e.g. for FISH), nucleic acid binding proteins (including repressors and transcription factors), cytokines, cell membrane specific ligands, enzymes, molecules that specifically bind to enzymes (e.g. inhibitors), lipids, fatty acids, and members of specific binding interactions such as biotin/iminobiotin and avidin/streptavidin.

The specifically labeled target may be natural or artificial and may comprise proteins, nucleic acids, lipids, carbohydrates, small molecules, and any combination thereof. This includes intracellular and cell surface markers. Intracellular markers include any molecule, complex or other structure within a cell. Some non-limiting examples include genes, centromere, telomeres, nuclear pore complexes, ribosomes, proteasomes, internal lipid membranes, metabolites such as ATP, NADPH and derivatives thereof, enzymes or enzyme complexes, chaperones, post-translational modifications such as phosphorylation or ubiquitination, microtubules, actin filaments, and many others. Cell surface markers include, but are not limited to, proteins such as CD4, CD8, CD45, CD2, CRTH2, CD19, CD3, CD14, CD36, CD56, CD5, CD7, CD9, CD10, CD11b, CD11c, CD13, CD15, CD16, CD20, CD21, CD22, CD79 22, CD103, CD117, CD154, GPA, HLA, KOR, FMC 22. In some embodiments, the target may be a specific region within the cell, for example targeting the interior of a specific organelle or membrane-bound vesicle. In some embodiments, the target may be the result of genetic or other manipulations, such as cloning Lac binding sites into the gene sequence for targeted binding of labeled Lac proteins.

Cells can be labeled by a variety of means, including but not limited to surface labeling, permeabilization of the cell membrane and/or cell wall, active transport or other cellular processes, diffusion across the membrane, carrier particles such as lipid vesicles or other hydrophobic molecules, and production by the cell (e.g., for recombinant fluorescent proteins).

In some embodiments, a sample comprising a mixed cell population can be processed prior to optical detection to enrich for detection of a target cell population. Some exemplary methods of enrichment include, but are not limited to, centrifugation, sorting (with or without labeling), selective killing of non-target cells, e.g., by lysis, and selective labeling to improve detection of target cells. For imaging, cells may be suspended in a liquid medium (preferred for flow cytometry), attached to a surface, or confined in a small volume, such as in a microfluidic well or channel.

One or more reagents, such as cell activators, stimulators, or inhibitors, may be added to the entire sample or portions of the sample to determine how the cells/sample react. Such agents may be non-specific (e.g., cytokines) or specific (e.g., antigens) or a combination thereof. The tissue samples may be incubated in the presence of one or more reagents under different environmental conditions for different time periods and analyzed in real time. The culture conditions may be varied over time based on the measured reaction, and additional reagents added over time as needed. Likewise, sensitivity to certain drugs, such as antibiotic resistance, can be examined using these techniques. The sample may be analyzed before, during, and after the administration of the agent. The exposure to one or more reagents may be sequential and/or repeated over time. The reagent concentration may be titrated based on the measured reaction.

Tissue samples (e.g., from biopsies) can be homogenized in a variety of ways, including by using a grinder, a disintegrator, driven by a pipette/nozzle, or with or without centrifugation of beads (e.g., nanotip beads), pushing the sample through mesh and/or microcolumns, or sonication. Fluorescence Activated Cell Sorting (FACS) may be performed with inclusion of flow and/or other cell separation methods, such as magnetic separation.

Spectral analysis

Spectroscopic analysis includes any and all assays that produce luminescence or change light (e.g., staining chemistry). This may include one or more of the following: spectrophotometry, fluorometry, photometry, nephelometry, refractometry, polarimetry and agglutination measurements.

Spectrophotometry refers to measuring the reflection or transmission of electromagnetic waves (including visible, UV, and infrared) by a subject. For example, spectrophotometry may be used to determine the concentration of nucleic acids in a sample, for example, by measuring absorbance at a wavelength of about 260; determining the protein concentration by measuring absorbance at a wavelength of about 280; and/or determining the salt concentration by measuring absorbance at a wavelength of about 230.

Other examples of spectrophotometry may include Infrared (IR) spectroscopy. Examples of infrared spectroscopy include near infrared spectroscopy, far infrared spectroscopy, laser-raman spectroscopy, raman confocal laser spectroscopy, fourier transform infrared spectroscopy, and any other infrared spectroscopy technique. Frequencies below about 650cm-1 are typically used for far infrared spectroscopy, frequencies above about 4000cm-1 are typically used for near infrared spectroscopy, and frequencies between about 650 and about 4000cm-1 are typically used for other types of IR spectroscopy. IR spectroscopy has many biomedical applications including cancer diagnosis, arthritis diagnosis, measuring chemical composition of biological fluids, measuring sepsis status, etc. IR spectroscopy can be used for solid samples such as tissue biopsies, cell cultures, or cervical smears; or for liquid samples such as blood, urine, synovial fluid, mucus, and the like. IR spectroscopy can be used to distinguish between normal and cancerous cells, as described in U.S. patent No. 5,186,162, which is incorporated herein by reference. IR spectroscopy can also be used on blood samples to detect markers for a variety of solid organ cancers. IR spectroscopy can also be used to determine cellular immunity in patients, for example to diagnose immunodeficiency, autoimmune disease, infectious disease, allergy, hypersensitivity and tissue transplant compatibility.

IR spectroscopy can be used to determine the glucose level in blood, which is useful for diabetic patients, for example, to monitor insulin response. IR spectroscopy can further be used to measure other substances in the blood sample, such as alcohol levels, fatty acid content, cholesterol levels, hemoglobin concentration. IR spectroscopy can also distinguish synovial fluid from healthy persons and arthritic patients.

in some embodiments, the fluorometric assay uses a substrate molecule that alters fluorescence based on enzymatic activity, e.g., from NAD + to NADH or vice versa, or generates β -galactosidase from a precursor molecule.

Colorimetry refers to measuring the transmitted color absorption of a subject, preferably by backlighting the subject with white light and detecting the results with an imaging sensor. Examples include some assays that use an oxidase or peroxidase in combination with a dye that becomes colored in the presence of hydrogen peroxide. One method for determining peroxidase activity in a whole cell suspension of human leukocytes is disclosed in Menegazzi et al, J.Leukocyte Biol52:619-624(1992), which is incorporated herein by reference in its entirety. Such assays may be used to detect analytes including, but not limited to, alcohol, cholesterol, lactate, uric acid, glycerol, triglycerides, glutamate, glucose, choline, NADH. Some enzymes that may be used include horseradish peroxidase, lactoperoxidase, microperoxidase, alcohol oxidase, cholesterol oxidase, NADH oxidase. Other non-limiting examples of colorimetric assays include dye-based assays to determine protein concentration, such as Bradford, Lowry, biuret, and nano-orange methods. The pH of the sample can also be determined by colorimetric assays with indicator dyes including, but not limited to, phenolphthalein, thymolphthalein, alizarin yellow R, indigo carmine, m-cresol purple, cresol red, thymol blue, xylenol blue, 2', 2 ″,4, 4' -pentamethoxytriphenylmethanol, rhodopsin 4B, m-amine yellow, 4-phenylazo diphenylamine, malachite green, quinaldine red, orange IV, thymol blue, xylenol blue, and combinations thereof.

Photometry does not use an illumination method because the subject emits its own photons. The emitted light may be weak and may be detected using a very sensitive sensor, such as a photomultiplier tube (PMT). Photometric assays include assays that produce chemiluminescence, such as those using luciferase or some using peroxidase.

For the turbidity method, a preferred embodiment of detection is to backlight the subject with white light and detect the result with an imaging sensor. For the turbidity method, the decrease in transmitted light intensity is measured. Turbidity methods can be used, for example, to determine the concentration of cells in solution. In some embodiments, the nephelometry measures by nephelometry.

Turbidity assays measure the light transmitted or scattered through a body in suspension, which is typically a substrate that binds to immunoglobulins such as IgM, IgG and IgA.

Polarimetry generally measures the electromagnetic wave polarization of a subject. Polarimetric analysis includes circular polarization dichroism, which can provide structural information, and light scattering assays, which can provide information about the size and/or shape of a subject. One non-limiting example of light scattering determination uses Dynamic Light Scattering (DLS). The subject used for these assays does not require a label.

Radioactivity determination

The radioactivity determination uses at least one radioactive isoform as a detectable label. Radiolabels may be used as labels for imaging or for counting enzymatic activity. Such enzyme assays can be measured at the end of the reaction (end-point assay) or multiple measurements during the course of the reaction (time course assay). As a non-limiting example, use on gamma phosphoric acid³²The P-labeled ATP can be used to determine the activity of the ATPase present in the sample. In another embodiment, labeled precursor compounds or other molecules can be introduced into cells or other samples to measure synthesis of product molecules ("pulses"). The introduction of the labeled precursor in this way may be followed by the addition of an unlabeled form of the precursor ("chase"). Some examples of pulse-chase assays include, but are not limited to, the use of insulin synthesis³Use of H-leucine as precursor and for protein synthesis³⁵S-methionine as a precursor. It should be noted that these types of assays do not necessarily require the use of radioactive labels, as is known to those skilled in the art.

Mass spectrometry

In some embodiments, at least a portion of the sample can be analyzed by mass spectrometry. The sample may be provided to the mass spectrometer as a solid, liquid or gas, and any of a variety of ionization techniques may be used, including matrix-assisted laser desorption/ionization (MALDI), electrospray (including electrospray, micro-spray and nano-spray), Inductively Coupled Plasma (ICP), glow discharge, field desorption, fast atom bombardment, thermal spray, desorption/ionization on silicon, atmospheric pressure chemical ionization, DART, secondary ion mass spectrometry, spark ionization, thermal ionization and ion attachment ionization. Ionization may form positive or negative ions. Methods for performing these techniques are well known in the art.

For solid and liquid mass spectrometry, the sample can be presented on a sample presentation device composed of any suitable material, which can be solid or liquid. The sample presentation surface may have attached thereto an enzyme or enzyme complex that chemically modifies or binds to the sample. Examples of chemical modifications include, but are not limited to, enzymatic cleavage, purification, and addition of chemical moieties.

In MALDI, the sample is typically premixed with a highly adsorbed matrix and then ionized by laser bombardment. MALDI samples are typically high molecular mass, thermally labile, nonvolatile organic compounds, preferably up to 30,000 Da. The sample may be presented in any suitable volatile solvent. For positive ionization, a trace amount of trifluoroacetic acid can be used. The MALDI matrix may be any material that dissolves biomolecules, absorbs light energy at frequencies readily accessible by a laser, and does not react with biomolecules. Suitable matrices include nicotinic acid, pyrazinoic acid, vanillic acid, succinic acid, caffeic acid, glycerol, urea or tris buffer (ph 7.3). Preferred bases include a-cyano-4-hydroxycinnamic acid, ferulic acid, 2, 5-dihydroxybenzoic acid, sinapic acid (or erucic acid), 3, 5-dimethoxy, 4-hydroxy-trans-cinnamic acid, other cinnamic acid derivatives, gentisic acid, and combinations thereof.

In electrospray ionization (ESI), the sample is typically dissolved in a volatile polar solvent such as acetonitrile and atomized at a capillary tip under a strong voltage (e.g., 3-4kV, or lower for smaller samples, such as for micro-and nano-sprays). The mass range of ESI samples is typically below 100Da to over 1 Mda. Atomization may be enhanced by flowing a mist of gas, such as nitrogen, through the capillary tip. The size of the resulting charged droplets is further reduced by solvent evaporation, assisted by a generally heated drying gas, such as nitrogen. Additional reagents may be added to the solvent to aid in ionization. As a non-limiting example, for positive ionization, trace amounts of formic acid may help the sample protonate, while for negative ionization, trace amounts of ammonia or volatile amines may help the sample deprotonate.

Analytes of mass spectrometry include, but are not limited to, proteins, carbohydrates, lipids, small molecules, and modifications and/or combinations thereof. Typically, proteins and peptides are analyzed with positive ionization, while sugars and oligonucleotides are analyzed with negative ionization. Analytes can be analyzed in whole or in fragments. Mass spectrometry can be used to determine the composition of a mixture, the overall size of a subject, the chemical structure, and sequencing, e.g., the sequencing of oligopeptides or oligonucleotides. In some embodiments, mass spectrometry can be used to determine binding interactions, such as, but not limited to, binding interactions between proteins and ligands (including small molecules, peptides, metal ions, nucleic acids, and other small molecules).

In some embodiments, tandem mass spectrometry can be used, wherein two or more analyzers are used in sequence, separated by a collision cell to separate (fragment) the test ions. Tandem MS is thus able to first determine the total mass of the body, then determine additional structural information based on how the bodies are separated. Examples of series spectroscopy include, but are not limited to, quadrupole-quadrupole, magnetic sector-magnetic sector, quadrupole-time of flight. Tandem spectroscopy is particularly suited for determining structure, including the structure of small organic molecules, as well as peptide or oligonucleotide sequencing. A dual light source for measuring absorbance and/or fluorescence includes a broadband light source for absorbance measurement and a laser diode for fluorescence measurement. CCD-based compact spectrophotometers typically use FPGA/CLPD to control the acquisition; however, the spectrometers provided herein use a general purpose microprocessor, which can provide greater flexibility in general purpose computing, as well as the ability to remotely update firmware. In addition, the spectrometer may be equipped with a general purpose camera that can interrogate the sample prior to reading to ensure sample/container integrity. Feedback such as this helps reduce catastrophic failures and allows for real-time correction.

X-ray photoelectron spectroscopy

X-ray photoelectron spectroscopy (XPS) or chemical analysis Electron Spectroscopy (ESCA) is a photoelectron spectroscopy method for detecting photoelectrons emitted from the surface of a sample to determine the components thereof. Photoelectron spectroscopy can be further classified into XPS and UV Photoelectron Spectroscopy (UPS) according to the light source.

ESCA involves irradiating the surface of a sample with ultraviolet or x-rays and detecting the characteristic photoelectrons emitted by the sample elements. XPS specifically refers to ESCA using x-rays. The photoelectrons are filtered by an electrostatic or magnetic analyzer that allows only electrons of a specified narrow energy band to pass through to the detector. The binding energy of the emitted electrons is unique to each element, allowing each element on the surface to be identified. The intensity of the detected beam is generally representative of the concentration of a given chemical component on or near the surface of the specimen. U.S. patent No. 3,766,381, which is incorporated herein by reference, describes such a system. ESCA and XPS can detect any element with an atomic number of 3 or more and can detect sample compositions up to 10nm from the surface. ESCA and XPS are therefore particularly suitable for determining the empirical formula of pure materials, detecting contaminants as low as ppm, and detecting the chemical or electronic state of elements on the sample surface. In XPS, the emitted electrons typically have a short inelastic free path in the solid sample. Thus, further information about the amount of the element (e.g., the depth to which the element extends from the surface) can be determined by analyzing the real-time perspective of the emitted electrons as they emerge from the surface. ESCA/XPS can be used to analyze samples including, but not limited to, inorganic compounds, semiconductors, polymers, metal alloys, elements, catalysts, glass, ceramics, pigments, paper, inks, wood, plant parts, cosmetics, teeth, bone, medical implants, biomaterials, viscous oils, glues, ion modifying materials.

Another method of sample analysis uses auger electrons, known as Auger Electron Spectroscopy (AES), which operates similarly to ESCA except that it uses a beam of electrons instead of UV or X-rays.

Chromatography

Chromatographic methods use different properties of solutes in a mixture to allow separation. Many different chromatographic methods are known in the art, including, but not limited to, paper chromatography, Thin Layer Chromatography (TLC), column chromatography, gas chromatography, liquid chromatography, affinity chromatography, displacement chromatography, ion exchange chromatography (cations and anions), hydrophobic interaction chromatography, particle size exclusion chromatography such as gel filtration, perfusion chromatography, push column chromatography, reverse phase chromatography, two-dimensional chromatography, high performance liquid chromatography, packed capillary chromatography, open tube liquid chromatography, pyrolytic gas chromatography, chiral chromatography, and the like.

Chromatography generally relies on a solid stationary phase and a mobile phase (solvent) carrying the sample. The stationary phase may comprise a solid polymer such as plastic, glass, other polymers, paper, cellulose, agarose, starch, sugar, magnesium silicate, calcium sulfate, silicic acid, silica gel, florisil, magnesium oxide, aluminum oxide (alumina), activated carbon, diatomaceous earth, perlite, clay, or other similar materials known in the art. The stationary phase may be treated or otherwise modified to have properties that slow the mobility of at least one solute in the sample mixture. For ion exchange chromatography, the stationary phase may comprise charged residues, such as anions that attract positively charged solutes. For size exclusion chromatography, the stationary phase may comprise pores, tunnels or other structures that may slow the migration of smaller solutes compared to larger solutes. For affinity chromatography, the stationary phase may comprise a binding moiety that specifically recognizes some of the solutes. Generally, different solutes have different equilibrium distributions. Thus, different solutes will move across the stationary phase at different rates depending on their relative affinities for the stationary phase on the one hand and the solvent on the other. As the components of the mixture (i.e. the analyte) separate, they begin to form a moving band or zone that can be detected on the stationary phase, as is typical on, for example, TLC, or they are eluted sequentially, as is typical but not necessary for column chromatography methods.

The separation results depend on many factors including, but not limited to, the stationary phase selection, the polarity of the solvent, the size of the stationary phase relative to the amount of material to be separated (e.g., the length and diameter of the column), and the elution rate. In some cases, a long column or a plurality of columns arranged in series may be required to effectively separate the sample. This is especially true when the sample has a relatively low distribution equilibrium between the stationary phase and the solvent. In other cases, the sample may be tightly bound to the sorbent material, and a different solvent may be required to elute the sample from the sorbent. As a non-limiting example, proteins or peptides with molecular weights greater than 1000 bind tightly to C-18 alkyl stationary phases in aqueous media. This binding is so strong that it is difficult to remove the proteins from the stationary phase efficiently with water. Generally, an organic elution agent such as acetonitrile, an alcohol (e.g., methanol, ethanol, or isopropanol), other relatively polar organic solvent (e.g., DMF), or mixtures thereof may be used as an elution agent to remove proteins from the stationary phase. Other examples include binding chromatography columns, where the sample binds to the stationary phase with such a high affinity that the sample needs to be eluted with a competing binding agent.

Chromatographic methods can be used to separate almost any substance from a mixture. Some non-limiting examples include isolating specific hormones, cytokines, proteins, sugars, or small molecules such as drugs from biological samples such as blood. The isolated sample may be more easily detected after elution or may undergo further separation, purification or processing. For example, nucleic acids can be isolated from a sample and used as templates for nucleic acid amplification. Other samples may also be isolated, such as toxins from environmental samples or targets of interest from lysed cells.

Ion exchange chromatography

Ion exchange chromatography relies on charge-charge interactions between sample components and the charge on a stationary phase (e.g., a resin packed in a column) and/or a mobile phase. In cation exchange chromatography, positively charged solutes bind to negatively charged stationary phase molecules, while in anion exchange, negatively charged solutes bind to positively charged stationary phase. In a typical embodiment, a solute is bound to a column in a solvent of low ionic strength, and then the bound molecules are eluted using a second elution solvent of higher ionic strength with a gradient of increasing ionic strength. In some examples, the gradient changes the pH or salt concentration of the eluent solvent. Ion exchange is well suited for purifying nucleic acids from mixed samples, which are generally negatively charged.

Common resins for anion exchange chromatography include, but are not limited to, Q-resin and Diethylaminoethane (DEAE) resin. Cation exchange resins include, but are not limited to, S resins and CM resins. Some commercially available resins include Nuvia, UNOsphere, AG, Bio-Rex, Chelex, Macro-Prep MonoBeads, MiniBeads, Resource Q, Source media, Capto IEX, Capto MMC, HiScreen IEX, HiPrep IEX, Sepharose Fast Flow, HiLoad IEX, Mono Q, Mono S, and MacroCap SP. Buffers used for anion exchange include, but are not limited to, N-methyl-guazine, L-histidine, bis-Tris propane, triethanolamine, Tris, N-methyl-diethanolamine, 1, 3-diaminopropane, ethanolamine, guazine, 1, 3-diaminopropane, guadine, and phosphate buffer. Buffers for cation exchange include maleic acid, malonic acid, citric acid, lactic acid, formic acid, succinic acid (butaneandioic acid), acetic acid, malonic acid, phosphate buffer, HEPES buffer, and BICINE.

Size exclusion chromatography

Size Exclusion Chromatography (SEC) separates solutes based on their volume and is typically used for macromolecules or macromolecular complexes. In SEC, the stationary phase consists of porous particles, so that molecules smaller than the pore size can enter the particles. Thus, smaller solutes have a longer flow path and longer transit time through the SEC column and are separated from larger solutes that cannot fit into the pore. Size exclusion chromatography may use aqueous or organic solvents, which may be referred to as gel filtration or gel permeation chromatography, respectively. Size exclusion chromatography can also be used to determine general volume information about a solute when compared to standard macromolecules whose volume is known. Size exclusion chromatography is also affected by the shape of the solute, making accurate volume determination generally impossible. In one example, size exclusion chromatography may be combined with dynamic light scattering to obtain absolute volume information about proteins and macromolecules. The resin used for SEC can be selected based on the volume of the solute of interest to enhance separation on the chromatography column. Commercially available resins for size exclusion chromatography include Superdex, Sephacryl, Sepharose and Sephadex resins. Examples of buffers used for SEC include, but are not limited to, Tris-NaCl, phosphate buffered saline, and Tris-NaCl-urea.

Affinity chromatography

Affinity chromatography exploits the differences in the affinity of individual solutes for surfaces by, for example, chelation, immunochemical binding, receptor-target interactions and combinations of these actions. Any sample for which a suitable binding partner is known (preferably dissociation constant (K)_d) Is 10^-6or less) are isolatable by affinity chromatography in some embodiments, the targets may be designed to contain artificial binding moieties such as polyhistidine, polyarginine, polyinosinic acid, GST, MBP or other peptide tags (which may be removed after chromatography), ligands for affinity chromatography AND their target molecules including but not limited to biotin AND avidin AND related molecules, monoclonal or polyclonal antibodies AND antigens thereof, procainamide (procainamide) AND cholinesterase, N-methylacridinium AND acetylcholinesterase, p-aminobenzamidine AND trypsin, p-aminophenol- β -D-thiogalactopyranoside AND β -galactosidase, chitin AND lysozyme, methotrexate AND dihydrofolate reductase, AND AND alcohol dehydrogenase, sulfonamide AND carbonic anhydrase, DNA AND DNA polymerase, complementary nucleic acid sequences, oxidized cystine AND glutathione reductase, aminobenzamidine AND urokinase, trypsin inhibitors of trypsin AND soybean trypsin, N6-aminocaproyl-3 ',5' -cAMP AND CAMP, pep AND MAK, AND NPK, NPA AND MPA, NPA, rPAnd fumarate hydratase; atropine or cobra venom and cholinergic receptors; 6-aminopenicillanic acid and D-alanine carboxypeptidase; phytohemagglutinin and epidermal growth factor receptors; alprenolol and adrenergic receptors; growth hormone and prolactin receptors; insulin and insulin receptors; estradiol or diethylstilbestrol and estrogen receptors; dexamethasone and glucocorticoid receptor; hydroxycholecalciferol and vitamin D receptors. Suitable ligands include, but are not limited to, antibodies, nucleic acids, antitoxins, peptides, chelators, enzyme inhibitors, receptor agonists, and receptor antagonists. The term "antibody" as used herein refers to immunoglobulins such as IgA, IgG, IgM, IgD and IgE, whether monoclonal or polyclonal in origin. The binding and elution methods used for affinity chromatography binding pairs depend on the binding pair used and are generally well known in the art. As an example, a solute with a polyhistidine tag can be purified using resins including, but not limited to, commercially available resins such as Superflow Ni-NTA (Qiagen) or Talon Cellthru Cobalt (Clontech). Polyhistidine-labelled solutes can be eluted from such resins, for example, with buffers comprising imidazole or glycine. The buffer used for ion exchange chromatography may be selected such that the binding pair used is soluble in the buffer. The buffer is typically a single phase aqueous solution and may be polar or hydrophobic.

The resin to which the targeting ligand is bound may be selected based on the targeting ligand and the buffer to be used.

Hydrophobic interaction chromatography

Hydrophobic Interaction Chromatography (HIC) relies on hydrophobic interactions between a solute and a stationary phase. Generally, HIC is performed with a buffer of high ionic strength to increase the strength of hydrophobic interactions, and elution is achieved by decreasing the ionic strength of the buffer composition, e.g., pH, ionic strength, addition of chaotropic agents or organic reagents, e.g., ethylene glycol. Changing the pH of the mobile phase can also affect the charge, and thus the hydrophobicity of the substrate, to produce a more efficient separation. Non-limiting examples of resins for HIC include agarose, sepharose, cellulose or silica particles, which may be modified with benzyl, straight or branched chain alkyl groups containing from 2 to 50 carbon atoms with any degree of saturation, including octyl, decyl, dodecyl, tetradecyl, hexadecyl, octadecyl and eicosyl. Resins comprising hydrophobic polymers may have particular utility because they do not require the resin to be coated with hydrophobic functional groups. Such solid hydrophobic polymers comprise a matte surface of entangled hydrophobic polymer chains having a molecular weight of from about 10,000 daltons to about 10,000,000 daltons. The polymer may alternatively be porous. Suitable polymeric materials include, for example, polyethylene, polypropylene, polyethersulfone, polystyrene, polydivinylbenzene, polytetrafluoroethylene, polymethylmethacrylate, polydimethylsiloxane, and blends thereof. The polymeric support may be in any form including, for example, particles, beads, cards, sheets, fibers, hollow fibers, and semipermeable membranes.

Electrochemical measurements

Electrochemical analysis of liquid samples typically uses electrodes immersed in the liquid sample to make an electrochemical determination of the type of analyte, a measurement of the concentration of the analyte, or both. The electrodes are spaced apart from one another, and an electrolyte in the sample provides ionic communication between the electrodes. In most cases, the sample is stationary during the measurement; in some cases, the sample flows through the electrochemical detector while the sample is in liquid motion, such as in the case of flow injection analysis. The size of the electrodes may define the volume of sample required for the measurement. The limitations on sample volume and the need for rapid measurements may require the use of microelectrodes when the sample volume is not sufficient to cover the surface area of a conventionally sized electrode. Samples that can be measured by electrochemical analysis include, but are not limited to, biological fluids such as treated or untreated blood or plasma, biological sample solutions, and liquid environmental samples.

the reagent generally comprises an enzyme and a mediator, which is a chemical species having two or more oxidation states of different electrical activity potentials that allows a reversible mechanism of electron/charge transfer to the electrode.

In assays where electroactive species in a liquid sample are measured without any reagents at all, the conductive layer that forms the working electrode need not have any reagents deposited thereon. As is well known, electrochemical measurements can be made by using a working electrode coupled to a reference electrode. The measurement may involve a potential change (potentiometry) or current generation (amperometry). The electrodes themselves do not exhibit specificity for the analyte. Electrode specificity may be imparted by having an enzyme that reacts with only one of the multiple analytes in the analyte mixture (in the case of a biosensor), or by employing a filtration technique that will selectively allow only one of the multiple analytes in the mixture to pass through the filtration device. In the electrochemical measurement of certain analytes, such as dopamine in the brain, the determination of interferents in the "dummy" electrode of a biosensor is one example where the electrochemical measurement is performed without the use of any reagents on the working electrode surface. See, for example, U.S. patent No. 5,628,890, which is incorporated herein by reference.

In amperometric measurements, a constant voltage is applied at the working electrode relative to the reference electrode, and the current between the working electrode and the counter electrode is measured. The reaction of an electrochemical cell has two components-the catalytic (glucose reaction component) and the induced current (solution resistance component). If the resistance of the solution is minimized, the electrochemical cell's reaction will have a significantly higher glucose reaction component at any given time as compared to the solution resistance component. Thus, a good correlation with glucose concentration can be obtained from electrochemical cell reactions even in measurement times as short as one second. If the solution has a high resistance, the voltage experienced at the working electrode will lag significantly behind the applied voltage. This lag is significantly higher for a two-electrode system compared to a three-electrode system. In the case of the two-electrode system, the iR value between the working electrode and the reference electrode is significantly higher than in the three-electrode system. In a three electrode system, no current flows between the working electrode and the reference electrode, and thus the voltage drop is low. Thus, once the charging current (faraday current) decays to a minimum (within two to three milliseconds), the observed currents are all catalytic currents. In a two-electrode system, the charging current does not decay until the voltage at the working electrode reaches a steady state (reaches the applied voltage). Thus, in a two-electrode system, there is a slow decay of the response curve.

The channels of the electrochemical cell may be filled with the liquid sample by any of a number of methods. For example, filling may be by capillary attraction, chemically assisted wicking, or vacuum. Alternatively, the liquid sample may flow through the channel. The manner in which the electrochemical cell is filled depends on the application, such as a single use of the sensor or continuous measurement in flow injection analysis.

In one example, an electrochemical measurement may be used to measure the glucose level in a blood sample, which may be helpful in determining the amount of insulin to be administered. Glucose is usually measured by amperometry in the presence of an enzyme that specifically uses glucose as a substrate.

One enzyme currently used is Glucose Oxidase (GOD) because it is very specific to glucose, does not react with any other oligosaccharides, and is insensitive to temperature variations. However, glucose oxidase has the disadvantage of being very sensitive to the presence of oxygen. Thus, variations in the oxygen level of the blood sample can prevent accurate measurement of glucose levels. To reduce or eliminate the effect of oxygen concentration, a mediator may be used to accelerate electron transfer. Some non-limiting examples of such mediators include ferrocene, its derivatives, and osmium complexes, such as disclosed in U.S. patent No. 5,393,903, which is incorporated herein by reference.

An alternative enzyme for glucose determination may be Glucose Dehydrogenase (GDH), which has the advantage of being insensitive to the presence of oxygen. However, glucose dehydrogenases have the disadvantage of lower glucose specificity and interference by other sugars, oligosaccharides and oligosaccharides (such as maltose), which leads to an overestimation of the glucose level.

Multivariate analysis

The apparatus and systems provided herein can be used for multivariate analysis. This may support the characterization of the clinical outcome of the subject. The devices and systems provided herein can be used to assist the end user in the diagnosis, prognosis, and treatment of clinical outcomes.

The devices and systems provided herein can be used for multivariate analysis, in some cases with the aid of a probabilistic or reference space. In some cases, the systems and devices provided herein are configured FOR collecting data FOR use with the METHODS provided in U.S. patent application No. 12/412,334 ("METHODS AND SYSTEMS FOR associating with communications," to Michelson et al, which is incorporated herein by reference in its entirety. In one example, system 700 (including one or more of modules 701-706) is configured to process samples to help determine a trajectory, speed, and/or acceleration of treatment or progress of a condition (e.g., a health or disease condition) of a subject. The trajectory may indicate a likelihood of progressing to a clinical outcome. In another example, the system 700 collects data for use in trend analysis.

All containers (e.g., cuvettes, tips), methods, SYSTEMS and devices described in U.S. provisional patent application No. 61/435,250 ("SYSTEMS and methods FOR same USE maximum) and U.S. patent publication No. 2009/0088336 (" MODULAR POINT-OF-CARE DEVICES, SYSTEMS, AND USEs FOR same USE maximum "), filed on 21/1/2011, are all incorporated herein by reference in their entirety.

Authorization detection

Referring now to fig. 75, one or more specific examples of various authorization probes will now be described. It should be understood that the devices and/or systems described herein may be configured for use with one or more of the following sounding paradigms. At least some of the embodiments herein provide systems and methods for collecting and transmitting data about and often representative of a sample such that further analysis of the sample does not require physical transport of the sample. The various features described herein may be applied to any particular application set forth below or to any other type of diagnostic or assay system. At least some of the specific examples herein may be applied as a stand-alone system or method, or as part of an integrated system, such as in a system between a laboratory, a healthcare professional, and a sample collector. It should be understood that different features of the specific examples herein may be understood independently, collectively, or in combination with each other.

Fig. 75A shows a specific example of a system that includes a laboratory 8110, a designated sample collector 8120, and a healthcare professional 8100. The device 8130 may be provided at a designated sample acquisition instrument. As a non-limiting example, the device 8130 may be selected from any of the devices described herein.

In one specific example described herein, the sample acquisition instrument may be a first location and the laboratory may be provided at a second location. The first location and the second location may be different locations. The first location and the second location may be positioned such that they are not proximate to each other. The first location and the second location may be located such that they are remote from each other. The healthcare professional may be provided at the third location, although he/she may be attached to, employed by, or under contract with the laboratory. The third location may be a different location than the first location and the second location. The third location may be positioned such that it is not proximate to the first location or the second location. The laboratory, healthcare professional, and sample collector may all be in different locations from one another. In one example, the laboratory, healthcare professional, and/or sample collector may be at a separate facility. Alternatively, one or more of them may be co-located.

A laboratory may be an entity or facility or system or device capable of performing clinical exploration or analysis of acquired data. Laboratories may provide controlled conditions under which scientific research, experiments, and measurements may be performed. The laboratory may be a medical laboratory or a clinical laboratory in which detection regarding clinical samples may be performed or analysis may occur regarding data collected from clinical samples in order to obtain information regarding patient health that is suitable for diagnosis, prognosis, treatment and/or prevention of a disease. The clinical specimen may be a sample collected from a subject. Preferably, as further detailed elsewhere herein, the clinical specimen may be collected from the subject at a sample collection instrument located at a facility separate from the laboratory. Clinical specimens may be collected from a subject using a device placed on or in a designated sample collector or subject.

In some embodiments, the laboratory may be a certification laboratory. The certification laboratory may be an authorized analysis facility. In some specific examples, the authorized analysis facility may comprise a contracted analysis facility. For example, a certification laboratory or other laboratory may send images to a specialist at another laboratory (which may be a certification laboratory) for analysis.

Any description herein of a laboratory may apply to an authorized analytical facility, and vice versa. In some cases, the laboratory may be certified by a government device or a professional association. The laboratory may accept certification or supervision by a supervisory device. In one example, the laboratory may be certified by an entity, such as the centers for medicare and medicaid services (CMS), the American College of Pathologists (College of American Patholoists), ISO standards 15189 or 17025, or their equivalent. For example, the authorized analytical facility may be a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory in the united states or its equivalent entity in a foreign jurisdiction. Still alternatively, it should be understood that particular examples of the devices, systems, and/or methods described herein may be configured to comply with CLIA, ISO standard 15189 or 17025, any of the authentication standards listed herein, and/or other similar standards or authentications.

Authorized analytical facilities are typically supervised or supervised. For example, a laboratory may have oversight by a committee-certified entity (which may include one or more committee-certified personnel). In some embodiments, monitoring may include verifying one or more clinical probes. Supervision may also include evaluating performance of, making corrections to, calibrating, running controls, repeating, adjusting, or analyzing one or more clinical probes. Supervision may include evaluation of one or more sets of data to provide quality control for clinical detection. An authorized analysis facility may have one or more qualified personnel to provide supervision. For example, one or more pathologists or other healthcare professionals may review the data and/or analysis processed by the facility. At an authorized analysis facility, a trained pathologist or other certified health care professional may provide supervision. In some cases, the certified healthcare professional providing the supervision may be one or more of the following: a pathologically certified doctor, a doctor with laboratory training or experience in the professional service field for which the healthcare professional is responsible, or an individual with experience or laboratory training in the profession.

Supervision may further include authenticating healthcare professionals as follows: which may establish procedures and rules in the laboratory, deal with emerging issues, and/or train/evaluate laboratory personnel. Supervision may also include, but is not limited to: selecting a probe method, validating probe procedures and establishing probe performance characteristics of a laboratory, enrolling a capability validation plan for participation in HHS approval, establishing a quality control plan appropriate for the performed probes, establishing parameters that analyze acceptable levels of performance, ensuring that these levels are maintained throughout the probe process, addressing technical issues and ensuring that remedial action is taken if the probe system deviates from established performance specifications, ensuring that patient probe results are not reported until all corrective action has been taken, determining training requirements and ensuring that each individual performing a probe receives regular on-duty training and education, evaluating competency of all probe personnel and ensuring that employees retain their competency in performing probe procedures (e.g., there are programs for employee evaluation: direct observation of probe performance, recording/reporting of monitoring results, reviewing probe results in the middle of an audit, logging/reporting of probe results, verifying probe results in the middle of an audit, etc.), Recording, etc., performance of watchful maintenance, performance of assessment probes, assessment problem solving capabilities), and/or evaluating and recording the performance of individuals responsible for moderate complexity probes (e.g., once every half year during the first year; at least once a year thereafter unless the detection method or instrumentation is changed). Supervision may include examining and/or verifying the functionality of a laboratory procedure or device, and/or the validity of collected and/or generated data. Supervision may ensure the quality of the rest of the matter and/or place the data in such a condition: at which time the healthcare professional can rely on it to provide diagnosis, treatment, including but not limited to prophylactic treatment. Supervision may include experientially reviewing the probe. Supervision may include one or more, two or more, or any number of the items described elsewhere herein.

In some cases, supervision may be provided by a supervisory software program rather than a certified healthcare professional. In some cases, one, two or more types of oversight provided may be implemented by an oversight software program. A combination of supervisory software programs and healthcare professionals may be employed to provide supervision. In some cases, one, two, or more types of supervision may be implemented on a software program by a healthcare professional. For example, a healthcare professional can determine the procedures and rules associated with a software procedure. In some cases, the software program may be self-learning. The software program may access an ever-increasing pool of data and/or an ever-evolving rule or program.

In some embodiments, the supervisory software program may be provided on the device. The supervisory software program may be provided on the sample collector, on the device or off the device. The software program may be provided in a laboratory, such as an authorized analytical facility. The software program may be provided at an authorized analysis facility and extended to cover devices operating at locations remote from the authorized analysis facility. In some cases, the device may receive an update to the supervisory software program. The updates may or may not be provided by the laboratory. The supervisory software may be stored in memory and may include a computer readable medium containing code, instructions or logic that may be capable of performing the steps. Some specific examples herein provide for supervision of the integrity of the analysis at the point of the analyzer and the operation of the regulatory compliance device at the sample collector such that results generated by the analysis can be utilized by a healthcare professional to diagnose or treat the subject, wherein supervision is performed using a processor alone or in conjunction with an individual affiliated with an authorized analysis facility. Some entities provide analysis integrity oversight at the analysis site and oversight-compatible equipment operation at the sample collection site, which can be used by medical professionals to diagnose or treat patients using these immediately generated measurements, either alone by the processor or by users affiliated with authorized analysis sites, which may be, but are not limited to, laboratories that comply with CLIA or ISO standards.

In some cases, the supervisory software may include one or more algorithms that can examine the sample for qualitative and/or quantitative evaluations of the executable. The supervisory software program may look for outliers, may determine whether qualitative and/or quantitative assessments were performed properly, may perform one or more comparisons with records or data points, may perform statistical analysis of the assessments, or any other supervisory action as described elsewhere herein. The supervisory software may be capable of performing one or more calibrations and/or diagnostics. The supervisory software may remotely initiate and command a device separate from the analyzer site to perform one or more calibrations and/or diagnostics. Alternatively, the supervisory software may run on a device remote from the analyzer site and at the same time run at the analyzer site.

Authorized health care professionals at the analysis facility can receive and/or view the data. A healthcare professional of an authorized analysis facility may be attached to or associated with the authorized analysis facility. In some cases, a healthcare professional may be employed by or under contract with an authorized analysis facility. The healthcare professional can be located at an authorized analysis facility, can be located remotely from an authorized analysis facility, or within another analysis facility (e.g., hospital, prominent center, professional lead route/team). In some cases, the healthcare professional need not be always on-site at the time of performance of the probe or when the authorized analytical facility receives the data, but may be contacted on an as-needed basis to provide the consultation. A healthcare professional can be contacted to provide on-site, telephonic, and/or electronic consultation.

The healthcare professional providing the supervision may be a different individual or the same individual than the healthcare professional that may receive the report from the authorized analysis facility to diagnose, treat, monitor, or prevent the disease for the subject. For example, the pathologist of the authorized analysis facility may be a different individual than the prescribing physician of the subject. The authorized healthcare professional of the analysis facility can be an examining healthcare professional or a supervising healthcare professional. The healthcare professional that can receive the report can be a healthcare professional who subscribes to the detection experienced by the subject. Different healthcare professionals may provide the analysis and different healthcare professionals may provide the supervision. Alternatively, the same healthcare professional may provide both analysis and supervision.

The designated sample acquiring instrument may be a point of service (POS) site. Any disclosure herein of a sample acquisition instrument may also apply to a point-of-service location, and vice versa. The point of service location where the sample may be collected from or provided by the subject may be a location remote from the laboratory. The sample collector may have a facility separate from the laboratory. The sample may or may not be freshly collected from the subject at the sample collector. Alternatively, the sample may be collected elsewhere from the subject and brought to the sample collector. The sample collection instrument at the point-of-service site may be a blood collection center or any other body fluid collection center. The sample acquiring instrument may be a biological sample acquiring center. In some embodiments, the sample collector may be a retailer. Examples of retailers are provided in further detail elsewhere herein. Other examples of sample collectors may include hospitals, clinics, offices of healthcare professionals, schools, day care centers, health centers, assisted living quarters, government agencies, ambulatory medical care units, mobile units, emergency vehicles (e.g., airplanes, boats, ambulances), or residences. For example, the sample collector may be the subject's home. The sample collector may be at a sample acquisition site and/or a health assessment and/or treatment site (which may include any sample collector described elsewhere herein, including but not limited to emergency rooms, doctor's offices, emergency services, screening booths (which may be at a remote location), healthcare professionals who walk into one's home to provide home care). The sample acquiring instrument may be any location where a sample from a subject is received by the device. Any location can be designated as a sample collector. The designation may be made by any party including, but not limited to, a laboratory, an entity associated with a laboratory, a government device, or a regulatory device. Any description herein regarding a sample collector or service point may relate to or be applicable to a retailer, hospital, clinic, or any other example provided herein, and vice versa.

The sample acquiring device may be provided. The apparatus may be configured to receive a sample. The device may be referred to as a sample acquisition device. The device may also be referred to as a sample processing device. The device may also be referred to as a reader device. Any description of a reader device may be applicable to any device that may be capable of receiving and/or processing a sample. The device may receive a sample taken from a subject at a sample acquisition instrument or a sample carried to a service location by a subject or a representative of a subject. The device may collect the sample directly from the subject, or may collect the sample from the subject using an intermediate device or technique. Examples of acquisition techniques and apparatus are described in more detail elsewhere herein.

In some cases, the device may be placed in or on a subject. For example, the device may be swallowed by a subject (see, e.g., U.S. patent publication No. 2006/0182738, U.S. patent publication No. 2006/0062852, U.S. patent publication No. 2005/0147559, U.S. patent publication No. 2010/0081894, all of which are hereby incorporated by reference in their entirety). The device may be a pill, or have another specification that can pass through the digestive tract of the subject. Still alternatively, the device may be implanted in the subject. For example, the device may be subcutaneously implanted in a subject. In another example, the device may be worn by the subject. The device may be attached to the subject by tape, adhesive, integrated into a garment, or any other technique. The device may comprise one or more needles or micro-needles that can penetrate the skin of the subject. The device may be a patch wearable by the patient. The device may include an automated blood collection cassette. The cassette may be disposable. One or more disposable components may be used to collect a sample from a subject. The disposable component can provide the sample to a non-disposable device. Alternatively, the disposable component may be a sample processing device.

The device may receive a sample from a subject at a time. Alternatively, the device may receive samples from the subject periodically. This may be done at regularly scheduled intervals or in response to one or more detected conditions. The device may alternatively, in turn, administer therapy to the subject. The device may administer one or more therapeutic agents to the subject. The therapeutic agent may be administered at scheduled intervals or in response to one or more detected conditions. The therapeutic agent may be administered in response to one or more conditions detected from the sample.

In some cases, the device may be provided to the subject at a designated sample acquisition instrument. Alternatively, the subject may obtain or contact the device at any other location.

Examples of samples may include various liquid or solid samples. In some cases, the sample may be a sample of bodily fluid from the subject. The sample may be an aqueous sample or a gaseous sample. In some cases, a solid or semi-solid sample may be provided. The sample may comprise tissue and/or cells collected from a subject. The sample may be a biological sample. Examples of biological samples may include, but are not limited to, blood, serum, plasma, nasal swab or nasopharyngeal wash, saliva, urine, gastric fluid, spinal fluid, tears, stool, mucus, sweat, cerumen, oil, glandular secretions, cerebrospinal fluid, tissue, semen, vaginal secretions, interstitial fluid derived from tumor tissue, ocular fluid, spinal fluid, pharyngeal swab, breath, hair, nails, skin, biopsy punch, placental fluid, amniotic fluid, umbilical cord blood, emphatic fluid, body cavity fluid, sputum, pus, microbiota, meconium, breast milk, and/or other excretions. The sample may comprise nasopharyngeal wash. Examples of a subject tissue sample may include, but are not limited to, connective tissue, muscle tissue, neural tissue, epithelial tissue, cartilage, cancerous samples, or bone. The sample may be provided from a human or animal. The sample may be provided from a mammal, vertebrate, such as a murine, simian, human, farm animal, sport animal or pet. Samples may be taken from a living or dead subject. The sample may be freshly collected from the subject or may undergo some form of pre-treatment, storage or transport.

One or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, ten or more, twelve or more, fifteen or more, or twenty or more different types of samples may be collected from the subject. A single type of sample or multiple types of samples may be taken from a subject at the same time or at different times. A single type of sample or multiple types of samples may be received or capable of being received by the device at the same time or at different times. Multiple types of samples may be processed by the apparatus in parallel and/or sequentially. For example, the device may be capable of receiving both body fluid and tissue, or a fecal sample and body fluid. In another example, the device may be capable of receiving multiple types of bodily fluids, such as blood and urine. For example, a device may be capable of receiving one or more types, two or more types, three or more types, four or more types, five or more types, six or more types, seven or more types, eight or more types, ten or more types, or twenty or more types of bodily fluids.

Different collection devices of the apparatus or the same collection device may be used to collect multiple types of samples.

The subject may provide a sample, and/or the sample may be collected from the subject. The subject may be a human or an animal. The subject may be a mammal, a vertebrate, such as a murine, simian, human, farm animal, sport animal or pet. The subject may be alive or dead. The subject may be a patient, a clinical subject, or a preclinical subject. The subject may undergo diagnosis, treatment, monitoring, and/or disease prevention. The subject may or may not be under the care of a healthcare professional. The subject may be a human of any age, infant, toddler, adult, or elderly.

Any volume of sample may be provided from the subject. Examples of volumes may include, but are not limited to, about 10mL or less, 5mL or less, 3mL or less, 1 microliter (μ L, also used herein as "uL") or less, 500 μ L or less, 300 μ L or less, 250 μ L or less, 200 μ L or less, 170 μ L or less, 150 μ L or less, 125 μ L or less, 100 μ L or less, 75 μ L or less, 50 μ L or less, 25 μ L or less, 20 μ L or less, 15 μ L or less, 10 μ L or less, 5 μ L or less, 3 μ L or less, 1 μ L or less, 500nL or less, 250nL or less, 100nL or less, 50nL or less, 20nL or less, 10nL or less, 5nL or less, 1nL or less, 500pL or less, 100nL or less, or 50pL or less, or 100nL or less, or 1 or less, or less. The amount of sample may be about one drop of sample. The amount of sample may be the amount collected by a pricked finger or a finger prick. The amount of sample may be that collected by a micro-needle or an intravenous hemospast. Any volume may be provided to the device, including the volumes described herein.

A healthcare professional can include a person or entity associated with a healthcare system. The healthcare professional can be a healthcare provider. The healthcare professional may be a doctor. A healthcare professional may be an individual or device that provides prophylactic, therapeutic, promotional, or rehabilitative healthcare services to a subject, home, and/or cell in a systematic manner. Examples of healthcare professionals can include doctors (including general and specialist doctors), dentists, audiologists, speech pathologists, physician assistants, nurses, midwives, pharmacists/pharmacists, dieticians, therapists, psychologists, massagers, clinical physicians, physical therapists, phlebotomists, occupational therapists, optometrists, emergency medical technicians, paramedics, medical laboratory technicians, medical prosthetics technicians, radiology technicians, socioers, and numerous other human resources trained to provide some type of healthcare service. The healthcare professional may or may not prescribe a qualification. Healthcare professionals may be working at or affiliated with hospitals, healthcare sites, and other service providers, or may also work in academic training, research, and management departments. Some healthcare professionals may provide care and treatment services to patients in private homes. The community health care workers may work outside of the formal healthcare facilities. The healthcare service manager, medical records and health information technician, and other support personnel may also be healthcare professionals or affiliated with the healthcare provider.

In some embodiments, the healthcare professional may already be familiar with the subject or have communicated with the subject. The subject may be a patient of a healthcare professional. In some cases, a healthcare professional may have prescribed a subject that is undergoing clinical detection. A healthcare professional may have instructed or advised the subject to undergo clinical testing at a sample collector or by a laboratory. In one example, the healthcare professional can be a basic healthcare physician of the subject. The healthcare professional can be any type of physician (including general and specialist physicians) of the subject.

The healthcare professional can receive the report from an authorized analysis facility. The healthcare professional receiving the report may be the healthcare professional making the reservation or the healthcare professional at the analysis facility and/or the sample collection meter.

Laboratory 8110 may communicate with sample collector 8120 and healthcare professional 8100. The laboratory may communicate with any number of sample collectors and healthcare professionals. For example, a laboratory may communicate with 1 or more, 2 or more, 3 or more, 5 or more, 10 or more, 15 or more, 20 or more, 30 or more, 50 or more, 100 or more, 200 or more, 500 or more, 1000 or more, 5000 or more, 10000 or more, 100000 or more, or 1000000 or more sample collectors and/or healthcare professionals. In some systems, 1,2,3, 4, or more laboratories may be provided that may communicate with any number of sample collectors and/or healthcare professionals. The laboratories may or may not communicate with each other. The sample collector, laboratory, and/or healthcare professional may be geographically dispersed anywhere. In some embodiments, the sample collectors and/or healthcare professionals in communication with the laboratory may be in the same geographic area (e.g., town, city, state, region, country). Alternatively, sample collectors and/or healthcare professionals in communication with the laboratory may be dispersed anywhere around the world.

The laboratory may communicate with the healthcare professional and the sample collector in any manner known in the art. In some embodiments, the laboratory may communicate directly with a device located in or on the sample acquisition instrument or the subject. Such communication may be via electronic signals, radio frequency signals, optical signals, cell phone signals, or any other type of signal that may be transmitted via a wired or wireless connection. Any transmission of data or the description of electronic data or transmissions described elsewhere herein may occur via electronic signals, radio frequency signals, optical signals, cellular signals, or any other type of signal that may be transmitted via a wired or wireless connection. For example, data may be electronically transmitted from the sample collector to the laboratory, and vice versa. Data may be transmitted to the laboratory from a device that may be on a sample collector or in or on the subject, and vice versa. Similarly, data may be electronically transmitted from the laboratory to the healthcare professional, and vice versa.

By way of example, and not limitation, communication may be through a network such as: a Local Area Network (LAN), a Wide Area Network (WAN) such as the internet, a personal area network, a telecommunications network such as a telephone network, a mobile network, a wireless network, a data providing network, or any other type of network. The communication may utilize wireless technology, such as bluetooth or RTM technology. Alternatively, various communication methods may be utilized, such as dial-up wired connections using modems, direct links such as TI, ISDN, or cable lines. In some embodiments, the wireless connection may use an exemplary wireless network such as a cellular network, a satellite or pager network, GPRS, or a local data transfer system such as an Ethernet network or a beacon ring over a LAN. In some embodiments, the device may communicate wirelessly using an infrared communication component. To provide for communication, device 8130, personal computer, server, laptop, tablet, mobile phone, satellite phone, smart phone (e.g., iPhone, Android, Blackberry, Palm, Symbian, Windows), personal digital assistant, bluetooth device, pager, landline telephone, or other network device may be used. Such a device may be a communication enabled device. It should also be appreciated that the device 8130 may implement the network connectivity techniques described herein using any network connectivity hardware and/or software. This includes the network connectivity techniques described in text and icons in association with fig. 83-88.

The laboratory may communicate with a device in the sample collector or in or on the subject. The device from the sample acquiring instrument may communicate with any communication enabled device in the laboratory. The devices may provide data to a cloud computing infrastructure that is accessible by any communication enabled device of the laboratory. The device may transmit data to a laboratory.

The data provided by the device may include data about a sample from a subject. The data may be information necessary and/or sufficient for qualitative and/or quantitative evaluation of the sample. The data may include information for supervision. The data may include information for analysis. The data may be an electronic representation of the sample. The electronic representation of the sample may include an electronic representation of the entire sample and/or any portion thereof. The data may be electronic data. In some cases, the data may be electronic bits representing the sample or reaction or reagent. The data may be digital and/or analog. The data may represent one or more measurable parameters related to, based on, or otherwise pertaining to the sample.

The data may represent the sample and/or any portion thereof. In some embodiments, the data represents a preparation of the collected biological sample. Data may be collected before, during, and/or after sample preparation. Data may be collected over time. The data may include information of one or more conditions in which preparation of the collected biological sample occurred. Examples of such conditions may include one or more of the characteristics listed in the following group: biological sample size, biological sample concentration, biological sample mass, temperature, or humidity. Such conditions may include environmental conditions. The environmental condition may refer to the condition of the sample and/or surrounding the sample. The environmental conditions may be provided before, during, and/or after the sample is received by the device, prepared by the device, and/or data is transmitted by the device.

The data may include the amount, concentration, ratio, purity, or other information of samples, reagents, diluents, detergents, dyes, or any other materials that may be involved in sample preparation, reaction, and/or control/calibration on the device. Physical and/or chemical properties and/or chemical reactions of the sample and/or other materials may be measured at one or more points in time and may be aggregated into data. In some embodiments, the data may determine whether a sample, reagent, diluent, detergent, dye, or any other material is suitable for use in the apparatus for preparation of the sample and/or to allow subsequent qualitative and/or quantitative evaluation. For example, the data may indicate any error condition, which may indicate that the sample and/or any other material has become bad or is otherwise unsuitable. In some cases, data is collected during any procedure performed by the device.

In some embodiments, the data may represent a chemical reaction that may be run by the apparatus. The chemical reaction may include a chemical reaction with or without the sample. The chemical reaction may include one or more reagents that can react with the sample. The chemical reaction may include a control or calibration reaction. The data representative of the reaction may include one or more measurements of the chemical reaction. The data may also include the rate or speed of the chemical reaction, and/or the acceleration of the chemical reaction. The data may include the degree of completion of the chemical reaction (e.g., whether the chemical reaction has begun, whether the chemical reaction is proceeding, whether the chemical reaction is complete, how far the chemical reaction has progressed-e.g., 10%, 50%, etc.). The data may contain information about control reactions and chemical reactions involving the biological sample. These reactions may occur simultaneously and/or sequentially. The data may relate to one or more chemical reactions that may or may not occur simultaneously. The data may relate to one or more sample preparation steps that may or may not occur simultaneously. Data may also include physical processing, such as centrifugation, shredding, or any other action described herein, which may be represented by data bits. The data may be used for supervision performed functionally on-board, remotely by a healthcare professional, and/or by an external device configured to give such supervision.

In some examples, the data may be one or more images and/or audio data representative of the sample. The image may be a digital image or an analog image. The audio data may be digital and/or analog. The data may include video representing a sample. The image may comprise a video image. The data may include electronic data representing digital images and/or audio data of the sample. In one example, the data may include video imaging, which may take changes over time. For example, video may be provided to provide an assessment or determination of dynamic actions such as lysis, agglutination, mixing, movement, etc. of cells or other molecules in a sample or matrix.

Data may be collected one or more times. The data may be acquired at discrete points in time, or may be acquired continuously over time. Data collected over time may be aggregated and/or analyzed. In some cases, the data may be aggregated and available for longitudinal analysis over time in order to facilitate diagnosis, treatment, and/or disease prevention.

Data may be collected from the device over time. Aggregated data from a single device specifying a sample may be useful to facilitate qualitative and/or quantitative evaluation of the sample. For example, it may be useful to determine how a sample reacts and/or changes over time to provide diagnosis, treatment, and/or disease prevention.

In some embodiments, the data may be displayed in an experimental report, a medical record, or any other type of display. Through longitudinal analysis of high integrity data, which may be obtained more frequently or frequently over time through the described infrastructure, the display may show patient health, provider's level of care, disease regression, progression, and/or onset.

Data may be collected from multiple devices. Aggregated data from multiple devices may be useful to facilitate qualitative and/or quantitative evaluation of a sample. The aggregated data may include data received at multiple devices regarding samples collected from a single subject. Alternatively, the aggregated data may comprise data received at a plurality of devices about samples collected from other subjects. The aggregated data may be collected and/or stored in a database. The database may be accessed to provide data to perform longitudinal analysis that takes into account data collected in the past. Trends and changes over time can be monitored. Multiple devices may be standardized and/or may provide data of sufficient quality, accuracy, and/or precision to aggregate the data and thereby perform longitudinal analysis. Very little or no change between devices may be provided. The device may also create a standardized environment in which sample preparation may occur. The standardized environment may also be provided during a chemical reaction. The device may also provide standardized pre-analytical steps. Multiple devices may be distributed globally. This may provide a global assessment infrastructure that may better allow detection of disease progression and/or regression. By normalizing the device, the data can be analyzed longitudinally to see the velocity of the marker over time in one or more subjects. The data may be analyzed and/or displayed to consumers, providers, and/or payers (e.g., health plans, employers, government payers, etc.) in the form of laboratory reports or electronic medical records or decision support systems. Such display may include displaying data over time, which may include trend analysis or other analysis of the change in value, rate of change, or rate of change.

The data may be of a quality suitable for longitudinal analysis over time. Suitable quality of data may be useful for experimental reports and/or electronic medical records that may incorporate data acquired over time. This may include data collected over a long period of time (e.g., multiple visits, or based on multiple samples) or a shorter period of time (within a single visit, or based on a single received sample). The data may be of sufficient quality, accuracy and/or precision for longitudinal analysis. For example, a sample may be taken multiple times from a subject. Samples may be taken from a subject at different times. The samples may be collected at predetermined intervals or according to a predetermined schedule. Alternatively, a sample may be collected from a subject when one or more conditions or events trigger the collection. Multiple acquisitions of a sample may allow analysis of the sample over a period of time, allowing longitudinal analysis. In some embodiments, to allow longitudinal analysis, the data may have a high degree of precision and/or accuracy. In one example, the data may have a time-varying coefficient of 20% or less, 15% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, 0.5% or less, or 0.1% or less. In some cases, the plurality of devices may provide data having a time-varying coefficient of 20% or less, 15% or less, 10% or less, 9% or less, 8% or less, 7% or less, 6% or less, 5% or less, 4% or less, 3% or less, 2% or less, 1% or less, 0.5% or less, or 0.1% or less.

Data over time may be analyzed longitudinally. This may include the change in data over time, the rate of change of data over time, or any derivative thereof. For example, the speed and/or acceleration of data changes may be collected and/or analyzed. The increase and/or decrease in data values and/or the various rates of change may be beneficial in determining diagnosis, treatment, and/or disease prevention.

The device is capable of processing a sample collected from a subject to yield data for subsequent analysis. The device may be configured to facilitate collection of a sample from a subject. The device may be configured to receive a sample from a subject. The device may be configured for preparing a sample for clinical detection to detect and/or quantify an analyte of interest. The device may contain one or more reagents useful for clinical detection. Preparation or clinical detection may include a chemical reaction with an agent. The apparatus may include one or more detectors that may be capable of detecting signals generated by processing the sample. The device may transmit data about the sample. The data about the sample may include raw data from the detected signal relating to the unreacted sample, the sample that has undergone a reaction, and/or the device configuration. In some cases, the device may pre-process some of the raw data to bring it into a desired format and transmit the pre-processed data. In some cases, the device may perform one or more analysis steps and transmit the analyzed data. Alternatively, the device does not perform any pre-processing and/or analysis. The pretreatment and/or analysis may occur in a laboratory. In some cases, the pretreatment and/or analysis may occur at both the facility and the laboratory. The laboratory may also include hospitals available to its pathologists, so that data can be transferred to the excellence center for analysis of different types of specific conditions.

In one scenario, the device may perform the sample preparation steps without performing any analysis or accepting any oversight. The data from the sample preparation step may be sent to a laboratory, which may perform the analysis, and which may be an analysis facility including a supervised authority. In another scenario, the device may perform one or more sample preparation steps, and may perform the analysis on-board. Data from the analysis may be sent to an authorized analysis facility, which may provide oversight. Alternatively, the supervision may take place onboard the device.

In some embodiments, the monitoring may include a review of the data in raw form, pre-processed form, or after analysis. Supervision may occur for qualitative and/or quantitative evaluation of the sample. Examples of qualitative assessments of a sample may include, but are not limited to, a trial of an image, video, or audio file. Examples of quantitative assessments of a sample may include numerical values indicative of a signal, a series of signals, or a level of presence or concentration of an analyte. Supervision may include one or more, or two or more, of the examples provided elsewhere herein. Supervision may be provided by a healthcare professional of an authorized analysis facility. In some other cases, supervision may be provided by a software program or an automated auditing system. The software program and/or automated review system may or may not be reviewed or attended to by qualified personnel, such as healthcare professionals (e.g., laboratory supervisors).

The device may copy the manual analysis program. In some cases, the apparatus may automatically perform multiple steps, such as pipetting, preparing the filtrate, heating, and/or measuring color intensity. The device may be used in conjunction with a material to measure one or more analytes. The device may measure the presence or concentration of one or more analytes. The apparatus may comprise a component comprising a reagent, which component may act as a reaction unit. Examples of device components and steps that may be taken by a device may be described in more detail elsewhere herein.

The laboratory may communicate with a healthcare professional. The laboratory may generate reports based on the analyzed data. In some cases, the laboratory may analyze raw data or pre-processed data provided from the device. Alternatively, the laboratory may receive the analyzed data from the device. The laboratory may or may not perform further analysis and/or supervision from the analyzed data received from the device.

The laboratory and/or device may generate a report that may present the analyzed data in a meaningful or desirable manner. The report may have the format: which may enable viewers of the report to rely on the report to make medical decisions. The laboratory and/or the device may transmit the report to a healthcare professional (or laboratory supervisor). In some embodiments, a pathologist, other healthcare professional, or other qualified person may review the report prior to transmitting the report to the healthcare professional. Reviewing a healthcare professional can review the report or a qualitative and/or quantitative evaluation useful for generating the report prior to transmission to the subscribing healthcare professional. The examination or supervision can occur at the laboratory on the analyzed data and/or reports. Alternatively, the inspection or supervision may take place onboard the device. The healthcare professional receiving the report may or may not rely on the report to make a diagnosis, treatment, and/or disease prevention of the subject.

The laboratory and/or device may also provide a report to the subject. The report provided to the subject may be the same or different than the report provided to the healthcare professional. The report provided to the healthcare professional may have more detail, or vice versa. The format may be different or may be the same between reports provided to the subject and the healthcare professional. Alternatively, the laboratory and/or device does not provide a report to the subject. The subject may receive information based on reports from a healthcare professional. The device or laboratory may automatically provide a report of the experiment directly to the consumer either when performing the probing and/or making the analysis, or upon sending to a physician for review and/or after review by a physician.

Any transmission of data and/or reports may include use of the cloud computing infrastructure. The sender may provide data to or have data on the cloud computing infrastructure. One and/or more recipients (e.g., healthcare professionals or patients) may access the cloud computing infrastructure. The cloud computing infrastructure may be provided on the sender side and/or the receiver side. Alternatively, conventional fixed data storage techniques may be employed.

Fig. 75B shows a retailer 8170 having a processing device 8172 in communication with a laboratory 8160. A laboratory or reader device may communicate with the healthcare professional 8150. As previously noted, any discussion herein of retailers or other examples of sample collectors may be applicable to any type of sample collector, and vice versa. The retailer may be provided at a first location and the healthcare professional may be provided at a second location. The first location and the second location may be different locations. In some embodiments, the first location and the second location are not proximate to each other. The laboratory may be provided at a third location. The third location may be a different location than the first location and/or the second location. For example, the first, second and third locations need not be proximate to each other. The first, second and/or third sites may be located in different facilities. Alternatively, the first, second and/or third sites may all be the same site (service site).

A retailer may be an entity that sells products or services. In some specific examples, the product or service may relate to health or medical care. For example, a retailer may sell a pharmaceutical or healthcare product and/or insurance. In some specific examples, the retailer may be a pharmacy (e.g., a retail pharmacy, a clinical pharmacy, a hospital pharmacy), a pharmacy, a chain, a supermarket, or a grocery store. Examples of retailers may include, but are not limited to, Walgreens, CVS Pharmacy, Duane read, Walmart, Target, Riteaid, Kroger, Costco, Kaiser Permanente, or Sears.

The retailer may be provided at the retailer site. In some embodiments, the retailer may be in a different geographic location than the healthcare professional and/or laboratory location. Alternatively, the healthcare professional may be provided at the retailer site.

The retailer 8170 can have a sample processing device 8172 at the retailer's site. In some specific examples, a retailer may have 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, or 10 or more sample processing devices at the retailer site. The sample processing device may be a point of service device. The sample processing device may be capable of communicating with the communication-enabling device. For example, sample processing devices at a retailer site may communicate with each other. Alternatively, the sample processing device may communicate with other reader devices at different locations, such as other sample collectors or within or on the subject. The sample processing device may communicate with other types of communication-enabled devices, such as computers and/or biometric devices in a laboratory. Such communication may be wired or wireless.

The sample processing device 8172 may be configured to receive a sample. The sample processing device may be configured to collect a sample directly from a subject. The sample processing device may be configured to perform one or more sample preparation steps on a subject. The sample processing device can be configured to run an assay. In some embodiments, the sample processing device can be configured to run one or more assays. The sample processing device may be capable of performing multiple assays on a single sample. The device is configured to perform at least 2,3, 4,5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 100, 200, 500, 1000 or more assays, as needed. Multiple assays can be run simultaneously in parallel. One or more control assays and/or calibrators (e.g., including configurations with calibrator controls for assays/probes) may also be incorporated into the device and performed in parallel, if desired. In some cases, assays may be run sequentially or in any combination of sequential and parallel based on the sample. The reader device may implement one, two, or more chemical reaction or other process detection (e.g., shredding). The sample processing device may be configured to detect one or more signals related to the sample. The sample may be a bodily fluid sample, a biological sample, or any other example as provided elsewhere herein.

In some specific examples, sample processing apparatus 8172 may include a cassette 8174. The cartridge may be removable from the sample processing device. In some specific examples, the sample may be provided to a cartridge of the sample processing apparatus. Alternatively, the sample may be provided to another portion of the sample processing device. The cartridge and/or apparatus may contain a sample collection unit that may be configured to receive a sample. The sample processing device is described in further detail elsewhere herein. The cassette and the device may be integrated into a single device, or may be separable devices. The device may include a pill or patch that may be linked to a mobile device or other network device for processing.

Subject 8176 may be provided at retailer 8170. A subject may provide a bodily fluid sample to sample processing device 8172 and/or to cartridge 8174 of the device. The bodily fluid may be drawn from the subject and provided to the device in a variety of ways including, but not limited to, finger prick, blood collection, injection, and/or pipetting. Body fluids may be collected using intravenous or non-intravenous methods. Body fluids may be provided using a body fluid collector. The body fluid collector may comprise a scalpel, a miniature needle, a porous membrane (e.g., for a pill), a capillary tube, a pipette, a syringe, a phlebotomist, or any other collector described elsewhere herein. In one specific example, a scalpel punctures the skin and retrieves the sample, for example, using gravity, capillary action, suction, or vacuum force. The scalpel may be part of the sample processing device, part of a cartridge of the device, part of the system, or a separate component. When desired, the scalpel may be activated by a variety of instruments, electrical, electromechanical or any other known activation device or any combination of such methods. In one example, a finger of the subject (or other portion of the subject's body) may be punctured to produce a bodily fluid. The body fluid may be collected using a capillary tube, pipette, or any other device known in the art. The capillary or pipette may be separate from the device and/or cartridge or may be part of the device and/or cartridge. The transfer apparatus may not require additional processing steps and may be precoated with anticoagulant or other pretreatment in a single step. In another specific example, where an active means is not required, the subject may simply provide the body fluid to the device and/or cartridge, such as may occur with a saliva sample, or with a pierced body part in direct contact with a surface. The collected liquid may be placed in the device. The body fluid collector may be attached to the device, removably attachable to the device, or may be provided separately from the device.

Cassette 8174 can be inserted into, or otherwise interface with, sample processing device 8172. The cartridge is removable from the sample processing device. In one example, the sample may be provided to a sample acquisition unit of the cartridge. The sample may be provided directly to the cartridge. The sample may or may not be provided to the sample collection unit via the body fluid collector. The body fluid collector may be attached to the cartridge, removably attachable to the cartridge, or may be provided separately from the cartridge. The body fluid collector may or may not be integral with the sample collection unit. The cartridge may then be inserted into the sample processing device. Alternatively, the sample may be provided directly to the sample processing device, with or without the sample processing device utilizing a cartridge. The cartridge may contain one or more reagents that may be used in the operation of the sample processing apparatus. Alternatively, one or more reagents may already be provided on-board the sample processing device.

The cartridge may or may not be disposable. The cassette may be specifically configured for one or more types of clinical detection. For example, a first cassette may have a first configuration to support a first set of probes, while a second cassette may have a second configuration to support a second set of probes. Alternatively, a generic cartridge may be provided which is configurable for the same selected set of detections. In some cases, a generic cassette may be dynamically programmed for certain detections by remote or onboard protocols.

When the cartridge is inserted into the sample processing device, one or more components of the cartridge may be in liquid communication with other components of the sample processing device. For example, if the sample is collected in a cassette, the sample may be transferred to other parts of the sample processing apparatus. Similarly, if one or more reagents are provided on the cartridge, the reagents may be transferred to other parts of the sample processing device, or other components of the sample processing device may be brought to the reagents. One or more components of the cartridge may be transferred to other parts of the sample processing apparatus in an automated manner, and vice versa. In some embodiments, the reagent or assembly of cassettes may be left on-board the cassette. In some embodiments, jets that require pipelining or maintenance (e.g., manual or automated maintenance) are not included.

The sample processing device may be configured for placement in or on a subject. The sample processing device may receive a sample from a subject through a housing of the device. For example, if the sample processing device is swallowable or implanted in a subject, it may include a housing or biocompatible coating. The biocompatible coating may be permeable to the desired sample. The sample may penetrate through a coating or housing of the sample processing device to be received by the sample processing device. If the sample processing device is on a subject, the sample may be received through a housing and/or coating of the device. Alternatively, the sample may be received using one or more needles or micro-needles (which may or may not be provided on the cartridge portion of the device) which may be provided on the device.

The sample processing device may be configured to facilitate sample acquisition, prepare a sample for clinical testing, and/or may contain one or more reagents useful for clinical testing. In some embodiments, the sample processing device may be configured to run one or more probes from the sample. Chemical reactions or other processing steps may be performed with or without the sample. In some embodiments, an assay, such as an immunoassay or a nucleic acid assay, may be run. Examples of steps and/or probes that may be prepared or run by a device may include, but are not limited to: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscometric assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and/or other types of assays, centrifugation, separation, filtration, dilution, enrichment, purification, precipitation, comminution, incubation, pipetting, transport, cell lysis, or other sample preparation steps, or combinations thereof. Sample processing may include chemical reactions and/or physical treatments. Sample processing may include assessment of histology, morphology, kinematics, kinetics, and/or sample status, which may include such assessment for cells. The device may perform 1 or more, 2 or more, 3 or more, or4 or more of these steps/probes.

The sample processing device may be configured to perform one, two or more assays on a small body fluid sample. As described elsewhere herein, one or more chemical reactions may occur on a sample having a volume. For example, one or more chemical reactions may occur in a pill having a volume less than a femto liter (femtoliter). In one example, the sample acquisition unit is configured to receive a volume of bodily fluid sample equivalent to a single drop or less of blood or interstitial fluid. The sample acquisition unit may be capable of acquiring a volume of a bodily fluid sample without puncturing the skin of the subject. In one example, light may be illuminated in order to optically measure the sample. In additional examples, non-invasive analysis may be performed using ultrasound, MRI, or scanning.

The device may be able to perform all on-board steps in a small amount of time. For example, it may take about 3 hours or less, 2 hours or less, 1 hour or less, 50 minutes or less, 45 minutes or less, 40 minutes or less, 30 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 5 minutes or less, 4 minutes or less, 3 minutes or less, 2 minutes or less, 1 minute or less, 50 seconds or less, 40 seconds or less, 30 seconds or less, 20 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 500ms or less, 200ms or less, or 100ms or less from the time of collection of a sample from a subject to the transmission of data and/or to the analysis. The amount of time from receiving a sample within the device to transmitting data and/or performing an analysis by the device may take about 3 hours or less, 2 hours or less, 1 hour or less, 50 minutes or less, 45 minutes or less, 40 minutes or less, 30 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 5 minutes or less, 4 minutes or less, 3 minutes or less, 2 minutes or less, 1 minute or less, 50 seconds or less, 40 seconds or less, 30 seconds or less, 20 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 500ms or less, 200ms or less, or 100ms or less.

A laboratory, device, or other entity or software may perform the analysis on the data in real time. The analysis may include qualitative and/or quantitative evaluation of the sample. A laboratory, device, or other entity may analyze data over 48 hours or less, 36 hours or less, 24 hours or less, 12 hours or less, 8 hours or less, 6 hours or less, 4 hours or less, 3 hours or less, 2 hours or less, 1 hour or less, 45 minutes or less, 30 minutes or less, 20 minutes or less, 15 minutes or less, 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 30 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, or 1 second or less. The analysis may include a comparison of the data to one or more thresholds. The analysis may or may not include a trial by a pathologist or other qualified personnel. The time to take into account the analysis may or may not include the time to generate a report based on the data. The time taken to take the analysis may or may not include the time taken to transmit the report to the healthcare professional.

The device 8172 may be provided by the laboratory 8160 to a sample collector 8170. The device may be sold to, rented/rented by, or used as a location where a laboratory may conduct sample collection and/or other steps.

Similarly, one or more cassettes 8174 may be provided by laboratory 8160 to sample acquisition instrument 8170. Alternatively, the cassette may be provided by another source. The cassette may be sold to, rented/rented by the sample collector, or may be utilized as part of a location where a laboratory may collect a sample and/or perform other steps. The cassettes may be from the same or different sources as the apparatus.

Laboratory 8160 may have a processor 8162 and a communication unit 8164. The laboratory may be provided within a facility. The processor and the communication unit may be provided within a facility. A laboratory may have one or more processors and one or more communication units.

Processor 8162 may be configured to generate reports for healthcare professional 8150. The processor may be on the server side with software to perform the processing. The processor may generate reports based on data received from the sample processing device 8172, or may provide oversight or analysis. The processor may perform a qualitative and/or quantitative evaluation of the sample. In some specific examples, the processor may compare data received from the sample processing device to a threshold. The threshold may be for one or more analytes. The comparison may include a comparison of whether the data value is greater than, equal to, or less than a threshold. The comparison may include whether the data value is qualitatively and/or quantitatively the same as the threshold. The comparison may include one or more forms of statistical or physiological analysis of the data with respect to one or more stored values. Examples may include best fit analysis, and/or analysis such as curve fitting, extrapolation, interpolation, regression analysis, least squares, mean calculation, multivariate, simulation analysis, or variational calculation. The processor may analyze data received from the sample processing device. The processor may be configured to perform one or more steps of a statistical analysis of the data.

In some embodiments, a threshold may refer to a single value. The threshold may be a numeric value or an alphanumeric value. The threshold may be a string or any other form of data. A threshold may refer to a series of values and/or a set of values. The threshold may refer to a single value or multiple values. The plurality of values may fall within one or more continuum. Alternatively, the plurality of values may be discrete. Examples of threshold ranges may include 1-100 units or 5-10 units, and examples of threshold sets may include values falling within a list selected from 1 unit, 3 units, 5 units, 8 units, 13 units, 20 units, or 50 units. Units may refer to any size or measurable quantity. Such values are provided as examples only. In some cases, the processor may compare one or more images, video or audio files, or other data. The processor may make this comparison for one or more reference images, video or audio files, or other data. The algorithm may be capable of evaluating one or more characteristics of a file or other data. In some cases, the processor may automatically classify the files for viewing by a healthcare professional.

The processor may be able to access one or more data stores 8166a, 8166b, which may contain stored information. The stored information may include thresholds for one or more analytes. A threshold value may be useful for determining the presence or concentration of the one or more analytes. The threshold may be useful for detecting situations in which an alarm may be useful. The data storage unit may include any other information regarding sample preparation or clinical testing that may be run on the sample. The data storage unit may include records or other information that may be useful for the healthcare professional to generate a report. The data storage unit may also be capable of storing a computer readable medium that may include code, logic, or instructions for causing a processor to perform one or more steps.

In some embodiments, data storage unit 8166a may be provided at laboratory 8160. The processor may be able to access the local data storage unit. In another embodiment, the data storage unit 8166b may be provided remotely from the laboratory. For example, the data storage unit may be provided at the sample acquisition meter 8170, or with the healthcare professional 8150. The data storage unit may be provided on the device. Alternatively, the data storage unit may be provided at any other location. The processor may utilize any combination of data storage unit locations. For example, the processor may access a data storage unit that may be provided in and outside of a laboratory.

In some embodiments, the data storage unit may be an Electronic Medical Record (EMR) or an EMR database. The data storage unit may include information associated with the subject. The information associated with the subject may include a medical record of the subject, a health history of the subject, identification information associated with the subject, payment information associated with the subject, or any other information associated with the subject. The data storage unit may be a payer database. The data store may include information associated with payers such as health insurance companies or government payers. Such information may include treatment records, insurance records, or financial information associated with the subject.

One or more communication units 8164 may be provided at laboratory 8160. The laboratory may be at the same location or a different location as the sample acquisition or processing center or the provider or hospital office/location, or may be substantially the same as the sample acquisition or processing center or the provider or hospital office/location. Any description of a laboratory herein may be applicable to any other location provided herein, and vice versa. The communication unit may be configured to receive data from the device 8172. The communication unit may receive data regarding a sample of the subject from a device at the sample collector 8170. The communication unit may receive information about the subject from the device and/or the sample acquisition instrument. The communication unit may receive identification information about the subject. The communication unit may receive information from the device and/or any other machine (e.g., biometric device, mobile device) or entity associated with the sample acquisition instrument.

Communication unit 8164 may be configured to transmit data to device 8172 and/or any other machine or entity associated with sample acquisition meter 8170. In some embodiments, the communication unit may provide the one or more procedures to the device. In addition to receiving data, the communication may provide procedures. The protocol may enable sample collection, prepare samples for clinical testing, or allow for chemical reactions using one or more reagents on the device. The protocol may enable the running of clinical probes on the device. The protocol may enable detection of the presence and/or concentration of an analyte on the device. Any description of the detection and/or analysis of the presence and/or concentration of an analyte may include and/or be applicable to the assessment of a disease condition. The protocol may enable pre-processing of raw data and/or analysis of data on the device.

The communication unit may allow a two-way communication unit between the sample collector and the laboratory. The communication unit may allow two-way communication between the sample acquiring device or a sample processing device in or on the subject and the processor in the laboratory. In some specific instances, one or more procedures may be transmitted to the device based on data transmitted by the device. The data transmitted by the device may include subject identification information, information based on generated and/or detected signals relating to the sample or reaction, device identification information, cassette identification information, or any other information transmitted from the device. Data may be collected from the device according to the protocol provided to the device. The protocol may manage the type of data collected and the actions performed by the device. In some embodiments, based on the data collected from the device, a subsequent set, two or more sets of protocols may be sent to the device. Data from the device may provide feedback that may govern further actions to be taken by the device as commanded by the procedure.

In alternative embodiments described herein, the laboratory need not send the protocol to the device. The protocol may be stored locally on the device. Alternatively, the system may provide the protocol to the device. The procedures may be provided from an entity external to the device. The protocol may be on a cassette.

The laboratory may have an output unit that may display or transmit a report to a healthcare professional. The output unit may be a video display. Alternatively, the output unit may be a communication unit. In one example, the output unit may be a touch screen. Touch screens can have inherent imaging capabilities through built-in sensors, which can include LEDs or other light sources.

A device may have one or more identifiers. The device may be able to transmit the device identifier to the laboratory. One or more components of the device may have an identifier. For example, the cassette may have one or more identifiers. The cassette identifier may be readable by the device. For example, when a cassette is provided to the device, the device may automatically read the cassette identifier. The device may transmit the cassette identifier or other component identifier to the laboratory. The device, cartridge, or other component identifier may accordingly provide information regarding the configuration and/or capabilities of the device, cartridge, or other component. For example, the identifier may indicate which reagents or device components are available. The protocol may be transmitted from the laboratory to the device based on identification information received or approved from the device to the laboratory. The procedure may be run on the device based on the identification information.

The identifier may be a physical object formed on the device, cassette or other component. For example, the identifier may be read by an optical scanner. In some embodiments, the camera may capture an image of the identifier, and the image may be analyzed to identify the device, cassette, or other component. In one example, the identifier may be a barcode. The barcode may be a 1D or 2D barcode. In some embodiments, the identifier may transmit one or more signals that may identify the device, cassette, or component. For example, the identifier may provide an infrared, ultrasonic, optical, audio, electrical or other signal that may indicate the identity of the device, cassette or component. The identifier may utilize a Radio Frequency Identification (RFID) tag. The identifier may be stored on a memory of the device, cartridge or other component. In one example, the identifier may be a computer readable medium.

The communication unit 8164 may be configured to transmit data to the healthcare professional 150. In some embodiments, the communication unit may transmit a report or analysis generated based on data related to the sample. The communication unit may communicate with a network device used by a healthcare professional. For example, the communication unit may be capable of communicating with a computer, tablet computer, or mobile device of a healthcare professional.

Alternatively, another entity or source may generate and/or transmit reports to a healthcare professional. For example, a laboratory may analyze data provided by a device in or on a sample acquisition instrument or subject, or provided by a laboratory, hospital, sample acquisition center, or any other location described herein. The laboratory, device, or another entity may generate a report or analysis based on the analyzed data. The report may include longitudinal data over time, which may include the concentration or presence of one or more analytes, or the change in disease state over time. The reports and/or analyses may utilize clinical outcome assessments, such as those described in U.S. patent publication No. 2009/0318775, which is hereby incorporated by reference in its entirety. The lab, device, other entity, or additional entity may transmit the report to a healthcare professional. Multiple rounds of analysis or data processing may occur through one or more entities. The entities may be provided at different facilities. Alternatively, some of the entities may be provided at the same facility.

In some embodiments, the processor, the communication unit, and the data storage unit may be provided on the same machine. Alternatively, two or more of the processor, the communication unit and the data storage unit may be provided on the same machine. The machine may be a computer or any other network device as described elsewhere herein. Two or more of the processor, the communication unit, and the data store may be located on a computer located in a laboratory. Alternatively, the processor, communication unit and data store may all be located on different machines. In some cases, multiple processors, communication units, and data storage units may be provided, which may be distributed across one or more machines.

FIG. 76 shows a sample processing device 8200 in communication with one or more other devices 8204a, 8204b via a network 8202.

The sample processing apparatus may be further described elsewhere herein. The sample processing device may be configured to receive one or more cassettes. The sample processing device may be configured to receive a sample from a subject. The sample processing device may be configured to facilitate collection of a sample, prepare a sample for clinical testing, and/or implement a chemical reaction or other chemical or physical process using one or more reagents. The sample processing device may be configured to detect one or more signals related to the sample. The sample processing device may be configured to run the probe. The detecting may include running one or more chemical reactions. The sample processing device may be configured to identify one or more properties of the sample. In some specific examples, the device may not be configured to perform qualitative and/or quantitative evaluations of the sample on-board the device. Alternatively, the device may perform such qualitative and/or quantitative evaluations. For example, the sample processing device may be configured to detect the presence or concentration of an analyte or analytes in a sample (e.g., in or through a bodily fluid, exudate, tissue, or other sample) or a disease condition. Alternatively, the sample processing device may be configured to detect a signal that can be analyzed to detect the presence or concentration of one or more analytes (which may be indicative of a disease condition) or a disease condition in the sample. The signal may be analyzed onboard the device or at another location. Running the clinical probe may or may not include any analysis or comparison of the acquired data.

The sample processing device 8200 can be configured to communicate over the network 8202. The sample processing device can include a communication module that can interface with a network. The sample processing device may be connected to the network via a wired connection or wirelessly. The network may be a Local Area Network (LAN) or a Wide Area Network (WAN), such as the Internet. In some embodiments, the network may be a personal area network. The network may include a cloud. The sample processing device may be connected to the network without an intermediate device. Any other description of the network provided herein may be applicable.

In some specific examples, the sample processing device 8200 can communicate with another device 8204a, 8204b over the network 8202. The other device may be a communication enabled device. For example, the other device may be a client computer or a mobile device comprising a video display, wherein at least one display page comprises data. The other devices may be any type of networked device, including but not limited to: a personal computer, server computer, or laptop computer; personal Digital Assistants (PDAs), such as Palm-based devices or Windows CE devices; a telephone, such as a mobile phone, a smart phone (e.g., iPhone, Android, Blackberry, etc.), or a location-aware portable phone (such as GPS); a roaming device, such as a network-connected roaming device; wireless devices, such as wireless email devices or other devices capable of wireless communication with a computer network; or any other type of network device that is likely to communicate and process electronic transactions over a network. Any discussion of any device mentioned may also be applicable to other devices, including devices described elsewhere herein. The sample processing devices can communicate with one or more, two or more, three or more, or any number of other devices. Such communications may or may not be simultaneous. Such communication may include providing data to a cloud computing infrastructure or any other type of data storage infrastructure accessible by other devices.

Other devices 8204a, 8204b that can communicate with the sample processing device 8200 can have a video display. The video display may include components on which information may be displayed in a user-perceptible manner, such as, for example, a computer monitor, cathode ray tube, liquid crystal display, light emitting diode display, touch pad or touch screen display, and/or other means for emitting a visually-perceptible output as is known in the art. The video display may be electronically connected to the client computer according to hardware and software known in the art.

In one implementation of the embodiments described herein, a display page may include a computer file residing in memory, which may be transmitted from a server over a network to a client computer or other device that may store it in memory. A client computer may receive a tangible computer-readable medium that may contain instructions, logic, data, or code that may be stored in a persistent or temporary memory of the client computer, or that may affect or initiate actions by the client computer in some manner. Similarly, one or more devices may communicate with one or more client computers across a network and may transfer computer files residing in memory. One or more devices may transfer computer files or links that may provide access to other computer files.

At the client computer 8204a, mobile device 8204b, or any other network device as described elsewhere herein, the display pages can be interpreted by software resident in the memory of the client computer, mobile device, or network device, causing the computer files to be displayed on the video display in a manner that is perceptible to the user. The display pages described herein may be created using software languages known in the art, such as, for example: hyper document markup language ("HTML"), dynamic hyper document markup language ("DHTML"), extensible hyper document markup language ("XHTML"), extensible markup language ("XML"), or another software language that can be used to create computer documents that can be displayed in a manner that is perceptible to a user on a video or other display. Any computer readable medium with logic, code, data, instructions may be used to implement any software or steps or methods. When the network comprises the Internet, the display page may comprise a web page of the type known in the art.

A display page according to the present invention may include embedded functionality including software programs stored on a memory device, such as, for example, a VBScript subroutine, a JScript subroutine, a JavaScript subroutine, a Java applet, an ActiveX component, an asp.

The display page may contain well-known features of graphical user interface technology such as, for example, frames, windows, scroll bars, buttons, icons, and hyperlinks, as well-known features such as a "pointing" interface or a touch screen interface. Pointing to and clicking on a graphical user interface button, icon, menu option, or hyperlink is also referred to as "selecting" the button, option, or hyperlink. Display pages according to the present invention may also incorporate multimedia features, multi-touch, pixel sensing, IR LED based surfaces, vision based interactions with or without a camera.

The user interface may be displayed on a video display and/or display page. The user interface may display a report generated based on the analyzed data about the sample. The report may include information about the presence or concentration of one or more analytes. The user interface may display raw data or analyzed data about the sample. The data may include information about the presence or concentration of one or more analytes. The user interface may display an alert. One example of an alarm may be if an error is detected on the device, or if the analyte concentration exceeds a predetermined threshold.

In some specific examples, one or more network devices 8204a, 8204b may be provided at a laboratory facility. A network device at the laboratory may receive or access data provided by the sample processing device 8200. In some other embodiments, one or more network devices may be provided at a healthcare professional site. In some embodiments, both the laboratory device and the healthcare professional device may be capable of receiving or accessing data provided by the sample processing device. In additional examples, the one or more network devices may belong to a subject. One or more of the laboratory, healthcare professional, or subject may have a network device capable of receiving or accessing data provided by the sample processing device. One or more laboratory healthcare professionals and/or subjects, or network devices of laboratories, healthcare professionals, and/or subjects, may be authenticated prior to gaining access to the data. For example, to access the data, a laboratory person, a healthcare professional, and/or the subject may have a login ID and/or password. In some embodiments, the data may be sent to an electronic mailbox of a laboratory technician, a healthcare professional, and/or the subject.

In some embodiments, the sample processing device may provide data to a cloud computing infrastructure. A network device (e.g., a network device of a laboratory, healthcare professional, or other entity) may access the cloud computing infrastructure. In some embodiments, on-demand provisioning of computing resources (data, software) may occur via a computer network rather than from a local computer. The network device may contain very little software or data (perhaps with only a minimal operating system and web browser) and thus act as a basic display terminal connected to the internet. Because the cloud may be a basic delivery device, cloud-based applications and services may support any type of software application or service. Information provided by the sample processing device and/or accessed by the network device may be distributed across various computing resources. Alternatively, they may be stored in one or more fixed data storage units or databases.

Fig. 77A illustrates a high-level example of a sample processing device 8300. The sample processing device may be provided anywhere including the sample acquiring instrument. The sample processing device may be in or on the subject, or may be carried by the subject. The sample processing device can be easily moved or transportable. The sample processing device is movable with the subject. The sample processing device may be a desktop device or a handheld device. The sample processing device may be located remotely from the laboratory. Any number of sample processing devices may be geographically distributed in any manner. For example, one or more sample collectors may have one or more devices.

The sample processing apparatus 8300 can be configured to receive a removable cassette 8350. The removable cartridge and/or the device may have any other characteristics or components as described elsewhere herein. The removable cartridge may be configured to receive and/or deliver a sample to the apparatus. The removable cartridge may have one or more reagents provided thereon. For example, fig. 77B provides a view of one or more reagents provided on a removable cartridge. Alternatively, one or more reagents 8370 may be provided on-board the device, such as shown in fig. 77A. The device may comprise one or more reagent units which may comprise and/or confine one or more reagents. The reagents may be provided initially on the device and the reagents may be provided to reagent units from or on the cartridge or both on-board the device and within the cartridge.

In other embodiments, the sample processing apparatus need not have a removable cassette. One or more of the functions as described for the cassette may be provided by the device itself.

As described elsewhere herein, the sample processing apparatus and/or cartridge may contain all of the reagents, liquid-phase reagents, and solid-phase reagents necessary to perform one or more chemical reactions and/or other processing steps, including physical processing. For example, for a luminescent ELISA assay, the reagents within the device may include a sample diluent, detector conjugates (e.g., three enzyme-labeled antibodies), a surface labeled with an antibody binder, a wash solution, and an enzyme substrate. Additional reagents may be provided as needed. In some embodiments, reagents may be incorporated into the device to provide for sample pretreatment. Examples of pretreatment reagents include, but are not limited to, leukocyte lysis reagents, reagents that release analyte from binding factors in the sample, enzymes, and detergents. The pretreatment reagents may also be added to a diluent contained within the apparatus.

Reagents according to the present invention include, but are not limited to, wash buffers, enzyme substrates, dilution buffers, conjugates, enzyme-labeled conjugates, DNA amplification agents, sample diluents, wash solutions, sample pretreatment reagents, including additives such as detergents, polymers, chelating agents, albumin binding reagents, enzyme inhibitors, enzymes, anticoagulants, hemagglutination agents, antibodies, or other materials necessary to run an assay on a device. The enzyme-labeled conjugate may be a polyclonal or monoclonal antibody labeled with an enzyme that produces a detectable signal when reacted with an appropriate substrate. Non-limiting examples of such enzymes are alkaline phosphatase and horseradish peroxidase. In some embodiments, the reagent comprises an immunoassay reagent. Reagents defining the specificity of the assay may be provided which may in turn or may include, for example, monoclonal antibodies, polyclonal antibodies, proteins, nucleic acid probes or other polymers such as affinity matrices, carbohydrates or lipids. In general, reagents, particularly those that are relatively unstable when mixed with a liquid, are separately confined in a defined area (e.g., a reagent unit) within the device and/or the cassette.

In some embodiments, the reagent unit may comprise a small volume of reagent. For example, the reagent unit may generally contain from about 5 microliters or less to about 1 milliliter of liquid. In some embodiments, the cell may contain about 20-200 microliters of liquid. In other embodiments, the reagent unit contains 100 microliters of liquid. In one specific example, the reagent unit contains about 40 microliters of liquid. The reagent unit may comprise any volume described elsewhere herein, which may comprise a sample volume. The volume of liquid in the reagent unit may vary depending on the type of assay being run or the body fluid sample being provided. In one embodiment, the volume of reagent need not be predetermined, but must exceed a known minimum. In some embodiments, the reagents are initially stored dry and dissolved when an assay running on the device is initiated.

The sample processing apparatus may include a display 8310. The display may be a video display or other type of user interface. The display may function as a user interface. The display may allow a user to operate the sample processing device. The display may be configured to receive input from the user relating to the identity of the subject, other information about the subject, information about the sample, information about one or more clinical probes, information about sample preparation steps, information about a laboratory, and/or information about a healthcare provider.

The display may output information to the device operator. In operation of the device, the display may prompt the operator to perform one or more steps. The display may display information about the collected sample, the subject, and/or data related to one or more performed preparatory steps or performed chemical reactions. The display may output information regarding one or more automated processes that may be implemented by the device. The display may provide one or more alerts for detected errors or when one or more parameters are met (e.g., certain detected signals exceed a predetermined threshold). The display may display the results on the device.

The sample processing device 8300 may include one or more components that may be useful for collecting samples, preparing samples for clinical detection, and/or running chemical reactions or other detection or analysis. The sample processing device may also contain one or more components that may be useful for detecting one or more signals about the sample or device components. For example, the sample processing device may include, but is not limited to, a sample acquisition unit, centrifuge, magnetic separator, filter, pipette or other liquid handling system, container, receptacle, assay unit, reagent unit, heater, thermal block, cytometer, spectrophotometer, imaging system, microscopy, light source, photodetector, photometer, temperature sensor, motion sensor, or sensor for an electrical property. Liquid can be transferred from one component to another via a liquid handling system such as a pipette, channel, or pump.

In some embodiments, the liquid handling system may be a pipette. The pipette may be a multiheaded pipette. In some cases, each pipette head may be of the same type or may be of a different type. For example, the pipette head may be a vented pipette and/or a positive displacement pipette. In some cases, the liquid handling system may be capable of picking up and/or removing one or more pipette tips. Pipette tips can be added individually or removed from the pipette head. The pipette head can transfer the pipette tip from the first position to the second position. Pipette tips may be capable of being connected to and forming a liquid-tight seal with a pipette head, or screwed into or otherwise attached. The sample or other liquid may be aspirated and/or dispensed by the pipette tip.

The pipette tip may have an inner surface and an outer surface. The pipette tip may have a first port and an opposing second port. In some embodiments, both the first port and the second port may be open. In some embodiments, the first port may have a diameter that is larger than a diameter of the second port. The pipette tip may or may not be coated with reagents and/or capture binders such as antibodies. In some cases, the interior surface of the pipette tip may be coated with reagents and/or capture binders. The chemical reaction may take place within the pipette tip. The chemical reaction may occur within the pipette tip when the tip is attached to the pipette tip, or when the tip is detached from the pipette tip. Alternatively, the chemical reaction may occur within one or more vessels. The pipette may deliver a sample or other liquid to the container or aspirate a sample or other liquid from the container. The pipette tip may be capable of being at least partially inserted into the container.

A pipette may be utilized to transfer a sample or other liquid within the device. The pipette may assist in the preparation of the sample. The pipette may assist in the operation of the chemical reaction.

The sample processing device may be capable of performing at least one sample preparation step, and/or running 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, or 50 or more chemical reactions. The device may be capable of performing 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more, 10 or more, 20 or more, 30 or more, or 50 or more different types of assays. These may occur simultaneously and/or sequentially. Sample preparation and/or chemical reactions that may occur may be managed by protocols that may be individualized for the needs of the subject and/or sent back and forth from a server and/or stored or input locally. The needs of the subject may be based on a prescription or instructions that the subject has received from a healthcare professional. The apparatus may be configured to accommodate a wide range of sample preparations and/or chemical reactions.

The sample processing device 8300 can include one or more detectors 8360, which can be capable of detecting one or more signals related to the sample. The detector may be capable of detecting all emissions from the electromagnetic spectrum. Alternatively, the detector may be capable of detecting emissions from a selected range of the electromagnetic spectrum. For example, the light detector may detect a light signal relating to a chemical reaction that has occurred on the device. The electrical property sensor or other sensor may detect a voltage, current, impedance, resistance, or any other electrical property of the sample. The temperature sensor may determine a temperature of a thermal block on which the sample may be disposed. The sensor may determine the speed of the centrifuge. The sensor may determine the position, velocity, and/or acceleration of the pipette, and/or the successful performance of the procedure.

One or more detectable signals may be detected by the detector 8360. The detectable signal may be a luminescent signal including, but not limited to, photoluminescence, electroluminescence, chemiluminescence, fluorescence, phosphorescence, or any emission from the electromagnetic spectrum. In some embodiments, one or more labels may be employed during the chemical reaction. The label may allow the generation of a detectable signal. Methods for detecting labels are well known to those skilled in the art. Thus, for example, when the label is a radioactive label, the detection means may comprise a scintillation counter or photographic film as in autoradiography. When the label is a fluorescent label, it can be detected by: the resulting fluorescence is detected by exciting the fluorescent dye with light of an appropriate wavelength, and detecting the resulting fluorescence, for example, by microscopy, visual inspection, via photographic film, by using an electronic detector such as a digital camera, Charge Coupled Device (CCD), or photomultiplier and photocell, or other detection device. In some cases, the camera may utilize a CCD, CMOS, may be a lensless camera (e.g., a frankencera camera), an open source camera, or may utilize any other visual detection technique known in the art or later developed. In some specific examples, the imaging device may employ 2D imaging, 3D imaging, and/or 4D imaging (including changes over time). Similarly, enzyme labels are detected by providing the enzyme with an appropriate substrate and detecting the reaction products produced. Finally, simple colorimetric labels are often simply detected by observing the color associated with the label. For example, conjugated gold is often pink in color, while various conjugated beads are in the color of microbeads.

In some embodiments, an imaging unit may be provided. Examples of imaging units may include any detector and/or light detection device as described elsewhere herein. For example, the imaging unit may be a camera that may utilize a CCD, CMOS, may be a lensless camera (e.g., a frankencera camera), an open source camera, or may utilize any other visual detection technique known in the art or later developed. The imaging unit may capture still images and/or may capture moving images. For example, the imaging unit may take a series of digital images. The imaging unit may capture a video image. The imaging device may be a camera or sensor that detects and/or records electromagnetic radiation and associated spatial and/or temporal dimensions.

In one example, the imaging unit may take one or more digital images of the sample. For example, the imaging unit may take an image of a tissue sample. The photographs of the tissue sample may be transmitted to a pathologist or other healthcare professional. Analysis and/or supervision of an image of a tissue sample may occur. The analysis and/or supervision may occur onboard or remotely by a healthcare professional or software program. In other examples, the imaging unit may take an image of the sample, and/or any form of sample preparation such as a chemical reaction or physical processing step that occurs with the sample. For example, a video of the chemical reaction may be taken. Any description of data herein may also apply to data representing an image, and vice versa.

The sample processing device 8300 can have a processor 8330 that can provide instructions to one or more components of the device. The processor may act as a controller that may instruct one or more components of the device. For example, the processor may provide instructions to the pipette to aspirate or dispense a liquid. The processor may provide instructions to control the temperature of the heater (which may also or alternatively be a heating and/or cooling device). The processor may provide instructions to the light detector to detect one or more signals. The processor may also receive instructions and/or collected data. For example, the processor may act according to one or more procedures. The protocol may be provided onboard the device or may be provided from a source external to the device. The processor may also receive data regarding the signals detected by the device. The processor may or may not analyze the signals detected by the device. The processor may or may not compare one or more detected signals to a threshold.

A communication module 8340 may be provided on the device 8300. The communication unit may be part of a laboratory or an arrangement including a device. The communication module may allow the device to communicate with an external machine. For example, the communication module may receive one or more procedures or sets of instructions from an external source. In some embodiments, the external source may be a laboratory. The communication module may also allow the device to transmit data to an external machine. Data may be transmitted via the transmission unit. For example, the device may transmit data to a laboratory or healthcare professional. The device may transmit data to a cloud computing infrastructure, which may be accessible by a laboratory, healthcare professional, or other entity. The communication module may allow wireless and/or wired communication.

The sample processing apparatus 8300 can also include a power module 8320. The power module may connect the device to an external power source or may be provided as an internal local power source. For example, the power module may connect the equipment to a power grid or utility. The device may include a plug connectable to an electrical outlet. The device may be connected to any other external power source, which may include a power generation device such as a generator, or any renewable energy source (e.g., solar, wind, hydro, geothermal), or energy storage source (e.g., battery, supercapacitor). The power module may be a local power source. For example, the power module may be an energy storage device, such as a battery or a super capacitor. Any battery chemistry known in the art or hereafter developed may be used. Alternatively, the local power source may include a local energy producing device, such as a device that utilizes renewable energy. The power module may provide power to run the rest of the sample processing device.

One or more components of the apparatus may be contained within a housing. The housing may partially or completely enclose the components of the device. A display may be provided on the housing so that the display may be visible.

The device may be a desktop device. The device may be portable or wearable. Multiple devices may be housed in a single room. The device can have a height of less than, greater than, or equal to about 4m³、3m³、2.5m³、2m³、1.5m³、1m³、0.75m³、0.5m³、0.3m³、0.2m³、0.1m³、0.08m³、0.05m³、0.03m³、0.01m³、0.005m³、0.001m³、500cm³、100cm³、50cm³、10cm³、5cm³、1cm³、0.5cm³、0.1cm³、0.05cm³Or 0.01cm³Total volume of (c). The device may have a footprint that covers a lateral area of the device. In some embodiments, the device footprint may be less than, greater than, or equal to about 4m²、3m²、2.5m²、2m²、1.5m²、1m²、0.75m²、0.5m²、0.3m²、0.2m²、0.1m²、0.08m²、0.05m²、0.03m²、100cm²、80cm²、70cm²、60cm²、50cm²、40cm²、30cm²、20cm²、15cm²、10cm²、7cm²、5cm²、1cm²、0.5cm²、0.1cm²、0.05cm²Or 0.01cm². The device can have a transverse dimension (e.g., width, length, or diameter) or height of less than, greater than, or equal to about 4m, 3m, 2.5m, 2m, 1.5m, 1.2m, 1m, 80cm, 70cm, 60cm, 50cm, 40cm, 30cm, 25cm, 20cm, 15cm, 12cm, 10cm, 8cm, 5cm, 3cm, 1cm, 0.5cm, 0.1cm, 0.05cm, or 0.01 cm. The lateral dimensions and/or heights may be different from each other. Alternatively, they may be the same. In some cases, the device may be a tall, thin device, or may be a short, wide device. The ratio of height to transverse dimension may be greater than or equal to 100:1, 50:1, 30:1, 20:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:20, 1:30, 1:50, or 1: 100.

The device may have any weight. The device may be capable of being manually lifted by a person. The device may be capable of being on or in a person. The device may be molded or mounted to a floor, wall, ceiling and/or wall. The size and/or shape of the device may be swallowable by a person. Examples of the weight of the apparatus may include, but are not limited to, less than, greater than, or equal to about 20kg, 15kg, 10kg, 8kg, 6kg, 5kg, 4kg, 3kg, 2kg, 1kg, 0.7kg, 0.5kg, 0.3kg, 0.1kg, 0.05kg, 0.01kg, 5g, 1g, 0.5g, 0.1g, 0.05g, or 0.01 g.

In some embodiments, the above-described methods are implemented, alone or in combination, by means of one or more systems and apparatuses provided in patent co-pending application No. PCT/US11/53188 (attorney docket No. 30696-740.601), the contents of which are incorporated herein in their entirety.

Fig. 78 shows an example of a sample collection, processing, and analysis method. One or more of the following steps may occur in such a method. The order of the steps may be changed, or one or more steps may be optional or may be replaced with another step.

The method can include collecting a sample 8400 from a subject, preparing the sample for running a chemical reaction 8410, allowing a chemical reaction with one or more reagents 8420, detecting signals 8430 regarding the sample, chemical reaction, and/or equipment components, pre-processing the detected signals without performing an analysis, analyzing data 8450, generating a report 8460 based on the data, transmitting the report 8470, providing the report to a healthcare professional 8480, and/or displaying the report on equipment and/or a screen or other display device.

One or more of these steps may be provided by any device or entity. The divisions illustrated in the figures are provided by way of example only and are in no way limiting. For example, the sample can be collected 8400 outside the apparatus 8490. Alternatively, the sample may be collected directly at the device, or may be collected by the device. This may occur at the sample collector. The sample preparation 8410, the chemical reaction 8420, or the signal detection step 8430 may be performed by the apparatus 8490.

In some embodiments, the sample may be prepared for subsequent qualitative and/or quantitative evaluation. Such sample preparation steps for evaluation may include one or more of sample preparation 8410, chemical reaction 8420, and/or signal detection 8430 steps. In some embodiments, the sample may be processed by: by receiving the sample 8400, and/or preparing the sample for subsequent qualitative and/or quantitative evaluation, data necessary for the subsequent qualitative and/or quantitative evaluation is produced. Sample processing may also include transmitting data from the device. In some cases, the data may be transmitted to a healthcare professional of an authorized analysis facility.

1, 2, or all of these steps may occur, and 1, 2, or all of the occurring steps may occur at a device located at the sample acquisition instrument. Alternatively, they may occur at another entity, such as a laboratory. The point-of-service location near or on the subject's body (e.g., a residence) may be a laboratory or a sample collector.

The data collected by the device may be in a raw state. This includes the signal detected at the device. The data is either subjected to pre-processing 8440. The data pre-processing does not perform actual data analysis or comparison to any threshold. Data preprocessing may involve altering the format of the data. In some cases, data pre-processing may occur at the device 8490 located at the sample acquisition instrument. The pre-processed data may then be transmitted to a laboratory. Alternatively, data pre-processing 8440 may occur at laboratory 8492. The raw data may be sent from the device to a laboratory where the pre-processing may occur. Alternatively, no pretreatment occurs in this process.

Data analysis 8450 may occur according to the specific examples described herein. The data analysis may include subsequent qualitative and/or quantitative evaluation of the sample. Quantitative and/or qualitative analysis may involve the determination of clinical relevance of a biological sample or lack thereof. The data analysis may include one or more comparisons of the data to a threshold. The comparison may be used to determine the presence or concentration of one or more analytes, or may be useful for the assays and/or pathological analyses described elsewhere herein. Data analysis may occur at laboratory 8492. In some embodiments, the laboratory may be a certification laboratory. The data that may be analyzed may be raw data or pre-processed data. The apparatus may process the sample without analyzing the sample. Data analysis does not occur on devices in such a scenario. In some embodiments, processing the sample on the device does not result in a determination of the presence or concentration level of 1 or more analytes, 2 or more analytes, 3 or more analytes, 4 or more analytes, 5 or more analytes, 6 or more analytes, 7 or more analytes, 8 or more analytes, 9 or more analytes, 10 or more analytes, 12 or more analytes, 15 or more analytes, or 20 or more analytes. In some cases, processing the sample on the device does not result in a signal that is a cardiac marker,Determination of the presence or concentration of 1 or more of the classes of blood gas, electrolytes, lactate, hemoglobin, or coagulation factors, or any number of analytes, including those described elsewhere herein. In some embodiments, processing the sample on the device does not result in a determination of the presence or concentration of 1 or more, 2 or more, 3 or more, or any number of analytes (including those described elsewhere herein) that are: sodium, potassium, chloride, TCO₂Anionic interstitial, ionic calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO₂、PO₂、HCO₃Base excess, sO₂Kaolin ACT, diatomaceous earth ACT, PT/INR, cTnl, CK-MB and BNP. In some cases, processing the sample does not include a display of the presence or concentration of 1 or more, or any number of, analytes belonging to the following categories (including those described elsewhere herein): cardiac markers, blood gas, electrolytes, lactate, hemoglobin, or blood coagulation factors. Similarly, in some cases, processing the sample does not include a display of the presence or concentration of 1 or more, or any number of, analytes (including those described elsewhere herein) belonging to: sodium, potassium, chloride, TCO₂Anionic interstitial, ionic calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO₂、PO₂、HCO₃Base excess, sO₂Kaolin ACT, diatomaceous earth ACT, PT/INR, cTnl, CK-MB and BNP.

The data analysis may include qualitative and/or quantitative evaluation of the sample. The qualitative and/or quantitative evaluation of the sample can result in a determination of the presence or concentration of 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 10 or more, 15 or more, or 20 or more analytes. In some examples, the analyte may belong to a category that is involved in one or more of the following types of studies and/or analyses: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and/or other types of assays or combinations thereof. The analyte detected may involve one or more types of reactions selected from: chemistry-conventional chemistry, hematology (including cell-based assays, coagulation and male morbidities), microbiology-bacteriology (including "molecular biology"), chemistry-endocrinology, microbiology-virology, diagnostic immunology-general immunology, chemistry-urinalysis, immunohematology-ABO blood group and Rh type, diagnostic immunology-syphilis serology, chemistry-toxicology, immunohematology-antibody detection (blood transfusion), immunohematology-antibody detection (non-blood transfusion), histocompatibility, microbiology-mycobacterial science, microbiology-mycology, microbiology-parasitology, immunohematology-antibody recognition, immunohematology-compatibility detection, pathology-histopathology, pathology-oral pathology, blood flow, blood, Pathology-cytology, radiobiological assay, and/or clinical cytogenetics. The one or more measurements may include: proteins, nucleic acids (DNA, RNA, hybrids thereof, microRNA, RNAi, EGS, antisense strands), metabolites, gases, ions, particles (which may include crystals), small molecules and metabolites thereof, elements, toxins, enzymes, lipids, carbohydrates, prions, tangible elements (e.g., cellular entities (e.g., whole cells, cellular debris, cell surface markers)). In some embodiments, the one or more analytes belong to the class of cardiac markers, blood gas, electrolytes, lactate, hemoglobin, or coagulation factors. In some embodiments, the one or more analytes can include sodium, potassium, chloride, TCO₂Anionic interstitial, ionic calcium, glucose, urea nitrogen, creatinine, lactate, hematocrit, hemoglobin, pH, PCO₂、PO₂、HCO₃Base excess, sO₂Kaolin ACT, diatomaceous earth ACT, PT/INR, cTnl, CK-MB and/or BNP.

The analyzable data may be provided from the device 8490 or may be modified in the laboratory 8492 or other entity prior to analysis. In another specific example described herein, the data analysis 8450 may occur on-board the device, and not in the laboratory. Alternatively, the data analysis may occur on the device or in a laboratory at the same time, or the device may be a laboratory. The analysis may occur at a point-of-service location, such as a home, office, doctor's office/hospital, retailer's point-of-presence, or other point-of-service location. Any description herein of a laboratory site or other site may be applicable to any other point-of-service site described elsewhere herein.

A report 8460 may be generated based on the data. The report may be based on the analyzed data 8450, or may be based on the data in its raw or preprocessed form. The report may be generated based on a qualitative and/or quantitative evaluation of the sample. The report may be generated in a laboratory 8492, such as an authorized analytical facility. Alternatively, the report may be generated at the device, or by any other entity. A report 8470 may be transmitted. The report may be transmitted by the same entity that generated the report. Alternatively, different entities may transmit the report. The report may be transmitted by a laboratory 8492, device 8490, cassette, or any other entity, such as an authorized analytical facility.

The report may be received by a healthcare professional 8480. The healthcare professional can be provided at a location separate from the equipment 8490 and/or the laboratory 8492. The healthcare professional may be able to rely on the report for the purpose of diagnosing, treating and/or providing disease prevention to the subject.

Thus, as previously described, any one or more of these steps may be optional. Any one or more of these steps may be performed by the device 8490 in or on a sample collector or subject, or may be performed in the laboratory 8492 or in any other entity. In some embodiments, the location where the data analysis 8450 steps may be performed may be certified, or may be subject to inspection or supervision.

The apparatus may be configured to process a sample. Sample processing may include receiving the sample 8400 and/or preparing the sample for subsequent qualitative and/or quantitative evaluation as necessary to produce the subsequent qualitative and/or quantitative evaluation. Preparing a sample for subsequent qualitative and/or quantitative evaluation may include one or more sample preparation steps 8410, chemical reaction or physical processing steps 8420, and/or detection steps 8430. Processing the sample may include adding one or more reagents or fixatives. Sample processing may alternatively include electronic transmission of data. The data can be transmitted to an authorized healthcare professional of the analysis facility and/or displayed on a screen. Data may be transmitted and/or displayed simultaneously.

Sample 8400 can be collected from the subject by any means described elsewhere herein. For example, a finger prick may take a sample from a subject. In other examples, fecal matter, urine, or tissue may be collected in an operating room and/or an emergency room, or any other sample collection device described elsewhere herein may be utilized. The collected sample may be provided to the device 8490. Sample acquisition may occur at the sample acquirer or elsewhere. The sample may be provided to a device at the sample acquisition instrument.

Still alternatively, the sample 8410 may be prepared for a chemical reaction and/or a physical processing step. The sample preparation step may include one or more of the following: centrifugation, separation, filtration, dilution, concentration, purification, precipitation, incubation, pipetting, transport, chromatography, cell lysis, cell counting, crushing, grinding, activation, sonication, micro-column treatment, treatment with magnetic beads or nanoparticles, or other sample preparation steps. The sample may be transferred within the apparatus. Sample preparation may include one or more steps for separating blood into serum and/or particulate fractions or separating any other sample into various components. Sample preparation may include one or more steps for diluting and/or concentrating blood or other biological samples. Sample preparation may include adding anticoagulant or other components to the sample. Sample preparation may also include purification of the sample. Sample preparation may involve changing the density of the sample and/or creating a density profile of the sample. In some cases, the higher density portion of the sample may be separated from the lower density portion of the sample. Sample preparation may include separating the solid components of the sample from the aqueous components of the sample. In some examples, sample preparation may involve centrifugation, incubation, and/or cell lysis. Sample preparation may include causing a sample to flow, such as laminar flow. Sample preparation may include transporting a sample from one part of the apparatus to another. Sample preparation may include incubating the sample. Sample preparation may include processes for rendering a biological sample available prior to performing a chemical reaction and/or running an assay. The sample preparation step may render the biological sample ready for running one or more clinical tests, which may include adding a series of reagents, running a protocol, and/or running an assay.

Still alternatively, the sample may undergo a chemical reaction with a reagent 8420. The chemical reaction may occur after the sample preparation step. Alternatively, the chemical reaction need not follow the sample preparation step. The sample preparation step may occur before, after, and/or simultaneously with the chemical reaction. In some embodiments, preparing the sample for qualitative and/or quantitative evaluation may include allowing a chemical reaction to proceed. One or more types of assays, as described elsewhere herein, may occur. For example, the sample preparation step (or, for example, a chemical reaction that may occur in preparing a sample for qualitative and/or quantitative evaluation) may include one or more of the following types of chemical reactions selected from: immunoassays, nucleic acid assays, receptor assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscosity assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and/or other types of assays or combinations thereof. In some embodiments, a heater and/or a thermal block may be employed. The chemical reaction may include providing the sample at a desired temperature. The chemical reaction may also include maintaining and/or changing the temperature of the sample before, during, and/or after the chemical reaction. Any description herein of a chemical reaction may include any type of reaction that may occur in a device. For example, a chemical reaction may include a physical interaction, a chemical interaction, and/or other physical interaction or transformation. In some embodiments, a display (such as a screen) or sensor in the device may be imaged externally. For example, the apparatus may be capable of MRI, ultrasound or other scanning.

Sample preparation and/or chemical reaction may occur in response to one or more instructions. The instructions may be stored locally on the device or may be provided from an external source. In some embodiments, the external source is a laboratory. In some embodiments, the sample preparation and/or chemical reaction procedure may be self-learning. For example, they may be able to learn different ways to prepare the sample and/or prepare it for analysis. In some embodiments, the sample preparation process may be able to self-adjust to take advantage of various sample preparation techniques, given a set of parameters. Sample preparation adjustment or maintenance may or may not be dependent on detected signals associated with the sample and/or associated with operator supplied parameters and/or instructions. The sample preparation procedure may be self-learning. One or more controllers that may provide instructions for performing sample preparation and/or chemical reactions may be capable of self-learning.

The adjustment may be made in response to a new instruction that may be generated locally on the device or may be provided from an external source. For example, the new instructions may be updated and/or pushed down from an external source. There may be a dynamic process: in which sample preparation and/or chemical reaction and/or physical processing steps are performed according to changeable instructions. Any description herein of sample preparation and/or chemical reaction may also include any physical processing steps.

One or more signals 8430 may be detected from the device. The signal may be detected after the sample preparation step has been completed and/or after a chemical reaction and/or physical processing step has occurred. The signal may be based on readings of samples that may or may not have undergone an assay. The signal may be based on a measurement associated with the device.

In some cases, one or more additional sample preparation steps may occur. For example, additional sample preparation for qualitative and/or quantitative evaluation may occur. Such preparation may be based on at least one of: prior preparation of the biological sample and/or data analysis by a healthcare professional. Reflection detection may occur based on previous results. The reflection detection can occur in an automatic and dynamic manner before, during or after detection/analysis. Previous evaluations may yield further probes that may be automated.

Still alternatively, the data may undergo pre-processing 8440. The raw data of the detected signal may or may not undergo pre-processing. The preprocessing may affect the format of the raw data. For example, preprocessing may normalize the format of the data. Preprocessing may transform the data into a desired form. The preprocessing may occur without performing any data analysis. In some embodiments, the preprocessing may change the form of the data without changing the content of the data. In some cases, the preprocessing does not compare the data to any thresholds or perform any evaluation decisions.

The data can be analyzed 8450 as described elsewhere herein. The data analysis may include subsequent qualitative and/or quantitative evaluation of the sample. Still alternatively, the report may be generated based on raw data, pre-processed data, or analyzed data. The report and/or data may be transmitted to a healthcare professional. The software system may perform chemical and/or pathological analyses, or these analyses may be distributed among a combination of laboratories, clinics, and recommended/contracted professionals (e.g., laboratories offered to experts in some diseases and John's Hopkins laboratories or have them engaged in work as part of/in certification laboratories).

In some embodiments, the report may be reviewed before being transmitted to a healthcare professional. In some cases, the data may be reviewed before or after the report is generated. The trial may be performed by one or more pathologists or other qualified personnel. A pathologist may be associated with laboratory 8492. The pathologist may or may not be physically present at the laboratory facility. A pathologist may be employed by the laboratory. For authorized analytical facilities, supervision may be provided via supervision means. In some specific examples, the laboratory may be a CLIA certified laboratory. A committee certified entity (which may include committee certified personnel) may review the data/reports and provide a measure and verification of quality control. In some embodiments, the entity authenticated by the committee may include one or more pathologists.

In some specific examples, the device may be an authenticated device. The device may be under supervision of a supervision means. A committee certified entity can review the data/reports of the device and provide metrics and verification of quality control, calibrator performance, probing. The healthcare professional can review and/or provide oversight of the data/reports from the device. Alternatively, a software program may be provided that can examine the data generated by the device. The software program may be created by or under the examination of a healthcare professional. The software program may be maintained by authorized personnel, such as healthcare professionals.

FIG. 82 illustrates an example of a system that provides sample processing, analysis, and supervision.

Figure 82(i) shows an example of apparatus 8800 that may be capable of performing the sample processing 8802 step. The device may be able to communicate with a laboratory 8810. The laboratory may be able to perform subsequent analysis 8812 steps and may provide oversight 8814. The supervision and/or analysis may be provided by a healthcare professional and/or a software program. The device may communicate with the laboratory through a network 8850, including any of the networks described elsewhere herein. A cloud computing infrastructure may be provided. The apparatus may be provided in or on a subject, or in a sample collector. The laboratory may be an authorized analytical facility, such as a CLIA-certified facility, which may be a device or cassette.

Fig. 82(ii) shows an example of a device 8820 that may be capable of performing the sample processing step 8822 and the analysis step 8824. The device may be able to communicate with a laboratory 8830. The laboratory may be able to provide oversight 8832. Supervision may be provided by a healthcare professional and/or a software program. The device may communicate with the laboratory through a network 8860, including any of the networks described elsewhere herein. A cloud computing infrastructure may be provided. The cloud computing infrastructure may be part of a system/infrastructure/device. The device may be provided in or on the subject, or on a sample collector. The laboratory may be an authorized analytical facility, such as a CLIA-certified facility.

Fig. 82(iii) shows an example of a device 8840 that may be capable of performing the sample processing step 8842, the analysis step 8844, and providing oversight 8846. In some embodiments, the supervision may be provided by a supervisory software program on the device. The device may communicate with a network 8870, including any of the networks described elsewhere herein. A cloud computing infrastructure may be provided. The device may be provided in or on the subject, or on a sample collector. In some embodiments, the device may be authenticated by the supervising means. In some embodiments, the device may be CLIA-authenticated.

In some embodiments, methods for evaluating biological samples may be provided. The method may include receiving and/or preparing a sample onboard the device. The method may include performing the analysis on the device on-board. Alternatively, the method may include performing the analysis outside of the device and/or remote from the device. For example, the analysis may occur in a laboratory or be performed by an accessory device of the laboratory. In some embodiments, the analysis may occur on-site and off-site simultaneously.

The analysis may be performed by a healthcare professional in the laboratory or any other accessory device of the laboratory. The analysis may be performed by a software program. The processor may execute one or more steps of a software program to implement such analysis. In some embodiments, 1, 2, or more types of analysis may be provided by an analysis software program. In some embodiments, the analysis may be performed by a healthcare professional and a software program simultaneously. In some examples, the analysis may be performed by a software program carried by the device, by a healthcare professional outside of the device, and/or by a software program outside of the device.

The method may further comprise providing supervision of the analysis. The method may include performing the supervision on the device onboard. Alternatively, the method may include performing the supervision outside of and/or remote from the device. For example, the supervision may take place in a laboratory or by an accessory device of the laboratory. In some embodiments, the supervision may occur on-device and off-device simultaneously.

In some specific examples, the analysis may be performed by a healthcare professional and the supervision may be performed by the healthcare professional, the analysis may be performed by the healthcare professional and the supervision may be performed by a software program, the analysis may be performed by a software program and the supervision may be performed by the healthcare professional, or the analysis may be performed by a software program and the supervision may be performed by a software program. The same healthcare professional or a different healthcare professional may be used for analysis and/or supervision. The same software program or a different software program may be used for analysis and/or supervision. Any description of a laboratory, healthcare professional, software, and/or infrastructure that may perform supervision may also apply to the analysis, or vice versa.

Supervision may be performed by a healthcare professional in the laboratory or any other accessory device of the laboratory. The supervision may be performed by a software program. The processor may execute one or more steps of a software program to implement such supervision. In some embodiments, the supervision may be performed by a healthcare professional and a software program simultaneously. In some examples, the supervision may be performed by a software program onboard the device, by a healthcare professional outside of the device, and/or by a software program outside of the device. Any combination of analysis and supervision may be provided.

Fig. 79 illustrates a Laboratory Benefit Management (LBM) entity 8510 in communication with a payer 8500 and a sample acquirer 8520. The LBM may communicate with payers at payor sites and sample collectors at service site sites. The LBM may be provided at a facility at the LBM site. The LBM may be at a different location than the payer and the sample collector. In some embodiments, the sample collector may be any retailer, insurance company, entity, or sample collector as described elsewhere herein. For example, payers, LBMs and service points may be provided in different facilities.

LBM8510 may be an entity. For example, an LBM may be a company, a business, an organization, a partner business, a business enterprise, or one or more individuals who may form an entity. The LBM may be configured to communicate with one or more other entities regarding financial transactions and services. The LBM may provide instructions regarding financial matters and services and manage financial processes.

Payer 8500 may be an entity that may make payment or partial payment for one or more health or medical related services of the subject. The payer may contract or agree with the subject or sponsor of the subject to provide some form of medical insurance. The payer may be a public payer or a private payer. In some cases, the payer may be a government payer or a health insurance company. Examples of government payers may include, but are not limited to, medical insurance, medical subsidies, federal government employee healthcare welfare programs, the refund military health administration, national child health insurance program, military health system/TRICARE, indian health service, or other fee-funded health insurance programs. Examples of various types of private payers may include, but are not limited to, Health Maintenance Organization (HMO), preferred medical service organization (PPO), independent clinic association (IPA), point of service (POS) programs, or managed medical or loss compensation insurance. Examples of Health insurance companies may include, but are not limited to, Aetna, Blue Cross Blue Shield Association, CIGNA, Kaiser Permanente, Humana, Health Net, United Health Group, or Wellpoint.

The sample acquirer 8520 may be a point-of-service location. A sample collector may be provided at the point-of-service location. Any discussion of a service point may also apply to a sample collector at the site of the service point. The point of service location may be a location remote from the LBM where samples may be collected from or provided by the subject. In some embodiments, the sample collector may be a retailer. Examples of point-of-service locations and retailers are provided in further detail elsewhere herein. In some embodiments, the sample acquisition instrument can comprise a device as further detailed elsewhere herein.

The LBM may receive information from the sample collector and/or may receive information from the payer. The LBM may provide information to the sample collector and/or may provide information to the payer. The LBM may communicate with the payor and the sample collector in any manner known in the art or later developed, including but not limited to using sample processing devices, network devices, mobile devices, telephone, mail, courier, delivery, or any other communication techniques described elsewhere herein. The communication may occur over a network, including any of the forms of networks described elsewhere herein. One-way or two-way communication may be provided between the LBM and the payer, and between the LBM and the sample collector. The LBM, payor and sample collector may have one or more communication units. The communication unit may be configured to provide communication between the LBM, the payer, and the sample collector. The communication unit may be configured to provide wireless communication or wired communication.

The LBM may also perform financial transactions with payers and with sample collectors. In some cases, the financial transaction may be a two-way financial transaction, or may be a one-way financial transaction. In one example, the payer may pay for the LBM. The LBM may pay for the sample collector. The payment provided by the LBM to the sample collector may be derived from a payment received by the LBM from a payer.

The LBM, payor and sample collector may have a processor and memory that can record communications and/or payments. The LBM, payor and sample collector may interact with one or more third parties that may record communications and/or payments. The one or more third parties may be financial devices. The processor may access one or more memories that may contain information regarding payments received or paid out. For example, the LBM may have a processor that accesses one or more memory or data storage units containing information about payments received from payers and payments provided to the sample collection instruments.

Payment may be provided based on use of the equipment provided with the sample acquisition instrument. The LBM may require payment from the payor based on the use of the device. The LBM may provide payment to the sample collector based on the use of the device. Alternatively, the LBM may require payment from the sample collector based on the use of the device.

The LBM may include one or more data stores containing subject information, or may have the ability to access information about the subject, including: an insurance status of the subject, a common payment status of one or more clinical probes previously made and yet to be made, a medical record about the subject, payment information about the subject, identity information of the subject, or other information associated with the subject or a financial transaction associated with the subject.

In some alternative embodiments, the payer may receive an electronic bill from the sample collector and/or the LBM. In some cases, the healthcare professional may receive electronic payment from the sample collector and/or the LBM.

FIG. 80 illustrates a laboratory welfare system provided in accordance with specific examples described herein. Service point 8620 may communicate with laboratory 8630. The service point may be a sample acquisition instrument and any description herein of a service point may also apply to a sample acquisition instrument, and vice versa. The service point may also communicate with LBM8610, while LBM8610 may also communicate with payer 8600. The LBM and laboratory may communicate with a healthcare professional 8640. Subject 8650 can provide a sample to a point of service.

Service point 8620 can be a sample collection center that can have a device configurable to facilitate collection of a biological sample from subject 8650. As previously described, the sample may be collected from the subject at the point of service, or may be provided to a device at the point of service.

The sample collection center may be able to communicate with a laboratory 8630. The laboratory may be a certification laboratory. The sample collection center may communicate with the laboratory via sample processing equipment located at the sample collection center. The sample collection center may additionally communicate with the laboratory. Data collected by the device may be transmitted from service point 8620 to the laboratory. Such data may relate to a sample collected from a subject. Any type of data previously described herein, including raw data, pre-processed data, or analyzed data, may be provided to the laboratory.

The laboratory may provide equipment to the point-of-service location. In one example, a laboratory may sell or lease/rent equipment to a sample collection center. The laboratory may require payment from the sample collection center in connection with the sale and/or lease of the device to the sample collection center. The sample collection center may provide payment to the laboratory based on ownership or use of the device. The apparatus may be operated by an apparatus operator. An operator may be attached to the service point location. The operator may be an employee or otherwise affiliated with the sample collection center. The operator may or may not have received training regarding the use of the equipment. The sample collection center may be another entity separate from the laboratory. The sample collection center may be attached to the service point site or may be operated by a separate entity. The sample collection center can be any point of service location described elsewhere herein, including but not limited to retailers (e.g., Blue Cross, Blue Shield, Health Net, Aetna, Cigna), hospitals, medical facilities, and any other point of service. In one example, the device may be operated by a technician or other individual associated with a retailer or other service point. The laboratory may function as a wholesaler of equipment. Alternatively, one or more intermediate entities may be provided that may purchase the device from a laboratory and, in turn, offer/sell the device to a point-of-service location.

In an alternative example, a laboratory may pay a point of service location for providing equipment at a sample collection center that may be located at the point of service location. The laboratory may pay the point of service location for allowing use of the device at the point of service location and for allowing set up of the sample collection center at the point of service. For example, a laboratory may be allowed to lease space at a retailer where the laboratory may set up a sample collection center with one or more devices. The apparatus may be operated by personnel with or without training for use of the apparatus. The equipment operator may be attached to a laboratory. The equipment operator may or may not be an employee of the laboratory. The point of service site may be used by the equipment and equipment operators as a sample collector remote from the laboratory.

The laboratory may provide cassettes to the point-of-service location. The cartridge may be configured for insertion into or otherwise interfacing with a device. The cartridge may or may not be disposable. The laboratory may or may not provide disposables to the service site for use with the device. Any description herein of the cartridge may also apply to the disposable article, and vice versa. In one example, a laboratory may sell cassettes to a sample collection center. The sample collection center may be attached to the service point site and/or a separate entity. The sample collection center may be operated by the point-of-service location and/or a separate entity. The laboratory may require payment from the sample collection center in connection with the sale of the cassette to the sample collection center. The sample collection center may provide payment to the laboratory regarding the cassette. An operator of the device may be attached to the service point location. The laboratory may act as a wholesaler of cassettes. Alternatively, one or more intermediate entities may be provided that may purchase cassettes from a laboratory and, in turn, offer/sell cassettes to a point-of-service location.

In an alternative example, the laboratory does not have to require payment from the sample collection center in relation to providing the cassette at the sample collection center. The apparatus may be operated by personnel with or without training for use of the apparatus. The equipment operator may be attached to a laboratory. The equipment operator may or may not be an employee of the laboratory. The point-of-service site may be used by equipment and equipment operators as a sample collector remote from the laboratory. For devices that are operable by individuals affiliated with a laboratory, cassettes may be used as part of the sample collection service at the point-of-service location.

Laboratory 8630 may be able to communicate with healthcare professional 8640. The healthcare professional may be located at a separate site from the laboratory and the point of service. A healthcare professional may or may not have an existing relationship with subject 8650. A healthcare professional may have prescribed the subject, travel to a point-of-service location and perform one or more surveys. The healthcare professional may or may not have a relationship with a point of service or with a laboratory. In some embodiments, the laboratory may send a report to a healthcare professional. The medical report may be based on data collected from a device at the point of service. The medical report may be based on an analysis of data collected from the device. In some embodiments, the data analysis may include comparing the collected data to one or more thresholds to determine the presence or concentration of at least one analyte. In some embodiments, a laboratory may have a processor that: the processor may be configured to access a data storage unit that may have information associated with the one or more thresholds. The analysis may occur at a laboratory 8630, and the report may be generated at the laboratory. Alternatively, the analysis may occur in the device and the report may be generated by the device or in a laboratory.

In some embodiments, a report can be provided to the subject 8650. The report transmitted to the subject may or may not be the same as the report provided to the healthcare professional 8640. The reports may be sent simultaneously, or the healthcare professional may receive the reports first, or vice versa.

LBM8610 may be provided that may communicate with payers 8600 and service points 8620. The LBM may or may not be in communication with the healthcare professional 8640 and/or the laboratory 8630.

Laboratory 8630 and LBM8610 may be separate entities. The laboratory and LBM may be independent enterprises, companies, organizations, devices, partnerships, one or more individuals, or any other type of entity described elsewhere herein. The laboratory and LBM may be registered as independent legal entities. The LBM may be a laboratory welfare manager and the laboratory may be a wholesaler. The laboratory and LBM may reside in separate facilities. Alternatively, they may share facilities.

LBM8610 may charge payer 8600 based on the use of the device at service point 8620. For example, the LBM may collect a fee from the payer for each use of the device. The magnitude of the fee may depend on one or more factors, such as the type of use of the device (e.g., the number of analytes whose presence and concentration are detected, the number of chemical reactions, the amount of sample preparation, the type of reactions that occur, the number of device components used), the analysis performed on data collected from the device (e.g., more complex analyses may result in a different fee than simpler analyses), the relationship of the payer to the subject, and the relationship of the payer to the point of service, if any. The LBM and payor may enter into an agreement that may determine a payment plan between the payor and the LBM.

LBM8610 may provide payment to service point 8620 based on the use of devices at the service point. For example, the LBM may provide payment to the service point once per device use. In another example, the LBM may provide payment to the service point based on the amount of time the device is located at the service point. The magnitude of the cost may depend on one or more factors, such as the type of use of the device (e.g., the number of analytes whose presence and concentration are being detected, the number of chemical reactions, the amount of sample preparation, the type of reactions that occur, the number of device components used), the analysis performed with respect to data collected from the device (e.g., more complex analyses may incur a different cost than simpler analyses). The LBM and the service point may agree upon an agreement that may determine a payment plan between the service point and the LBM and LBM. In alternative embodiments, the LBM may provide payment to the laboratory 8630, and any description herein of providing payment to a service point may also apply to the laboratory. The LBM may provide payment to the laboratory rather than to the service point; or provide payment to the laboratory in addition to providing payment to the service point.

In some embodiments, LBM8610 may separate the payment collected from payer 8600 into technical and professional fees. In one example, the LBM may provide payment to a healthcare professional 8640 based on a professional fee. The LBM may provide payment to the sample collection center 8620 based on the technical fee. In some embodiments, the sample collection center may be operated by a service point, such as a retailer, hospital, or any other service point. In some embodiments, the sample collection center may be operated by a laboratory. Payment may be provided to an entity at the service point site or to a laboratory that may be operating a sample collection center at the service point site.

The LBM may make a decision on how to divide the payment from the payor. Technical and/or professional expenses may be based on agreements that the LBM may have with healthcare professionals, service points, and/or laboratories. The professional fee may also or alternatively be based on an agreement that the healthcare professional may have with the payer and/or the laboratory.

The LBM may further divide the payment from the payer into transaction fees. The transaction fee may be an amount that goes to the LBM. The LBM may be able to hold a portion of the payment paid by the payer.

FIG. 81 illustrates an example of a laboratory welfare manager/wholesaler model according to specific examples described herein. A retailer 8700 (or other service point), such as a pharmacy, may have one or more sample processing devices located at the retailer's point of care. A retailer technician may operate the sample processing device and may place a cartridge into the device 8710. The cartridge may or may not contain a sample taken from the subject at the retailer point of care.

The laboratory welfare manager 8720 may be an LBM as described elsewhere herein. The laboratory welfare manager may be an entity.

A laboratory welfare administrator 8720 and wholesaler 8730 may be provided within the model. The laboratory welfare administrator and the wholesaler may be separate entities. The laboratory welfare managers and wholesalers may be independent legal entities, business entities, businesses, partnerships, organizations, and/or groups of one or more individuals. The laboratory welfare managers and wholesalers may reside in different facilities or in the same facility.

The laboratory benefits manager 8720 may communicate with one or more payers 8740. The laboratory welfare manager may invoice the payor for the service. The payer may pay the laboratory benefit manager. For example, a laboratory benefits manager may require a fee of $ a (e.g., provide a value example — $28) from a payer who pays $ a to the laboratory benefits manager. The lab welfare manager may reserve LBM fees. For example, $ b (e.g., $1 providing a numerical example) cost may be reserved by the laboratory benefit manager.

Laboratory benefits manager 8720 may reimburse retailer 8700 for the balance of the amount. For example, a laboratory benefits manager may pay the retailer the remaining $ c (e.g., $ 27). For example, $ c may equal $ a minus $ b.

The retailer may also have fees associated with the laboratory welfare manager and/or wholesaler. For example, a retailer may have a brokerage fee that the retailer may pay to a laboratory welfare administrator. In one example, the broker cost is $ d (e.g., provide a numerical example — $ 8). The retailer may also issue purchase orders or pay for products. For example, the retailer may pay for the purchase or use of devices and/or cassettes at the retailer's point of care. The retailer may pay the laboratory benefits manager. Alternatively, the retailer may pay the wholesaler for the purchase or use of the device and/or cartridge. In one example, the payment for the product may be $ e (e.g., provide a value example — $ 9).

From the perspective of a laboratory welfare administrator, there may be financial benefits to following the model. For example, a laboratory welfare administrator may charge a LBM fee based on device usage. For example, the LBM fee may be $ b per transaction. The laboratory welfare manager may also charge an agent fee from the retailer. For example, a laboratory benefits manager may charge $ d for administration. In some cases, the laboratory welfare administrator may also collect product fees from the retailer. For example, a laboratory welfare administrator may charge a product fee of $ e.

From the retailer's perspective, there may be financial benefits to following the model. For example, a retailer may collect $ c of service revenue. Service revenue may be provided by a laboratory welfare manager. The laboratory benefits manager may provide service revenue based on payments collected from payers. The lab benefit manager may deduct the LBM fee from the amount charged from the payer, and may pass the remaining amount to the retailer as a service revenue. In additional embodiments, the laboratory benefits manager may also deduct a professional fee that may be provided to a healthcare professional or other entity, and transfer the remainder of the balance to the retailer as service revenue. Thus, as shown in fig. 81, the total revenue may be provided from the service revenue of $ c. The cost borne by the retailer includes a management fee (e.g., the $ d fee shown) and/or a product fee (e.g., the $ e fee shown). The cost may be about $ f (e.g., provide a numerical example- $ 17). $ f may equal $ d plus $ e. The cost incurred by the retailer may be less than the service revenue. For example, a retailer's gross profit of $ g (e.g., providing a numerical example — $10) is illustrated. In some cases, $ g $ c minus $ f.

The following table illustrates examples of models.

Any dollar amount is provided by way of example only and should not be construed as limiting. Any value may be inserted for each dollar value.

In some embodiments, the subject may be associated with a payer. For example, a payer, such as a health insurance company, a government payer, or any other payer as described herein, may provide insurance coverage to a subject. The payer may pay some or all of the subject's medical bill. In some embodiments, the identity of the subject may be verified when the subject reaches the point of service. The subject's identity may be verified using the device and/or by personnel at the point of service. For example, a person at the point of service may view the subject's identification card and/or insurance card. The device may or may not capture an image of the subject and/or acquire one or more biometric parameters from the subject. Verification may occur onboard the device. Alternatively, the subject's identity may be collected at a service point and may be further verified at another entity or location. For example, a laboratory, healthcare professional, or payer may verify the subject's identity. The device, laboratory, healthcare professional, and/or payer may be able to access subject information, such as electronic health records. Verification may occur quickly and/or in real-time. For example, validation may occur in 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. The verification may be automated without any human intervention.

The system may verify the identity of the subject against the system's records, insurance coverage, in order to prevent fraud or for any other purpose. The verification may be performed by the device. Verification may occur at any time. In one example, the identity of the subject may be verified prior to preparing a sample of the subject for probing. The identity of the subject may be verified prior to providing the sample to the device and/or cartridge. Verification of the subject's identity may be provided before, after, or simultaneously with verification of the subject's insurance coverage. Verification of the subject's identity may be provided before, after, or simultaneously with verification that the subject has received a prescription to be subjected to said qualitative and/or quantitative assessment. Verification may be through communication with a healthcare provider, laboratory, payer, laboratory welfare manager, or any other entity. Authentication may occur by accessing one or more data storage units. The data storage unit may include an electronic medical records database and/or a payer database. Verification may occur quickly and/or in real-time. For example, validation may occur in 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. The verification may be automated without any human intervention.

The verification may include information provided by the subject. For example, the verification may include scanning the subject's identification card and/or insurance card. Verification may include taking a picture of the subject and/or the subject's face. For example, the verification may include taking a two-dimensional or three-dimensional snapshot of the subject. A camera may be used that may provide a two-dimensional digital image of the subject and/or may be capable of creating a three-dimensional or four-dimensional image of the subject. The four-dimensional image of the subject may include changes over time. Verification may include taking a picture of the subject's face for identification. Verification may include taking a picture of another portion of the subject's face for identification, including but not limited to the patient's whole body, arms, hands, legs, torso, feet, or any other part of the body. The verification may employ a video camera and/or microphone that may capture additional visual and/or audio information. Verification may include comparing the subject's movements (e.g., gait) or sounds.

Verification may include entering personal information related to the subject, such as the subject's name, insurance policy number, answers to key questions, and/or any other information. Verification may include taking one or more biometric readings of the subject. For example, the verification may include a fingerprint, handprint, footprint, retinal scan, temperature reading, weight, height, audio information, electronic reading, or any other information. Biometric information may be collected by the device. For example, the device may have a touch screen on which the subject may place the palm of the subject for reading by the device. The touch screen may be capable of scanning one or more body parts of the subject and/or receiving temperature, electrical, and/or pressure readings from the subject. Alternatively, the device may receive biometric information from other devices. For example, the device may receive the weight of the subject from a weighing apparatus separate from the device. The information may be sent directly from the other device (e.g., via a wired or wireless connection) or may be entered manually.

Verification may also include information based on a sample collected from the subject. For example, the validation may include a genetic marker of the subject. When the sample is provided to the device, the device can use at least a portion of the sample to determine a genetic signature of the subject. For example, the device may perform one or more nucleic acid amplification steps and may determine key genetic markers for the subject. This may form a genetic marker for the subject. The genetic marker of the subject may be obtained before, after, or simultaneously with processing the sample on the device. The subject's genetic signature may be stored on one or more data storage units. For example, the subject's genetic signature may be stored in the subject's electronic medical record. The collected genetic marker of the subject may be compared to the genetic marker of the subject (if it is present) that has been stored in the record. Any other unique identifying characteristic of the subject may be used to verify the identity of the subject.

Methods for amplification of nucleic acids (including DNA and/or RNA) are known in the art. The amplification method may involve a temperature change, such as a thermal denaturation step; or may be an isothermal process that does not require thermal denaturation. The Polymerase Chain Reaction (PCR) uses multiple cycles of denaturation, adhesion of primer pairs to the opposite strand, and primer extension to exponentially increase the copy number of the target sequence. Denaturation of the adhered nucleic acid strands can be achieved by applying heat, increasing the local metal ion concentration (e.g., US6277605), ultrasonic radiation (e.g., WO/2000/049176), applying a voltage (e.g., US5527670, US6033850, US5939291, and US6333157), and applying an electromagnetic field in conjunction with a primer (e.g., US5545540) that is bound to a magnetically responsive material, which patents and patent applications are hereby incorporated by reference in their entirety. In a variation known as RT-PCR, complementary DNA (cDNA) is generated from RNA using Reverse Transcriptase (RT), and the cDNA is then amplified by PCR to produce multiple copies of the DNA (e.g., US5322770 and US5310652, which are hereby incorporated by reference in their entirety).

An example of an isothermal amplification method is strand displacement amplification, commonly referred to as SDA, which uses the following cycles: primer pair sequences adhere to opposite strands of a target sequence, primer extension in the presence of dntps to produce a double semiphosphorothioated primer extension product, endonuclease-mediated nicking of a semimodified restriction endonuclease recognition site, and polymerase-mediated primer extension from the 3' end of the nick to displace an existing strand and generate fragments for the next round of primer adhesion, nicking production, and strand displacement, resulting in geometric amplification of the product (e.g., US5270184 and US5455166, which are hereby incorporated by reference in their entirety). Thermophilic SDA (tSDA) uses thermophilic endonucleases and polymerases at higher temperatures in essentially the same process (European patent No. 0684315, which is hereby incorporated by reference in its entirety).

Other Amplification methods include Rolling Circle Amplification (RCA) (e.g., Lizardi, "Rolling circle replication Reporter Systems", U.S. Pat. No. 5,854,033), Helicase-Dependent Amplification (HDA) (e.g., Kong et al, "Helica Dependent Amplification Nucleic Acids", U.S. patent application publication No. US2004-0058378A 1), and loop-mediated isothermal Amplification (LAMP) (e.g., Notomi et al, "Process for synthesizing Nucleic Acid Acids", U.S. Pat. No. 6,410,278), which is hereby incorporated by reference in its entirety, isothermal Amplification using transcription initiated from promoter sequences by RNA polymerases, such as may be incorporated into oligonucleotide primers) in some cases, transcription-based Amplification methods in the field include Nucleic Acid sequence-based Amplification, also referred to as US (e.g., US 5138), Amplification methods based on RNA sequences, such as the Amplification methods commonly used in the field, such as Amplification by NASENTO DNA polymerase, such as the Amplification methods incorporated by NASENTO DNA polymerase, NASENTO DNA replication technology, such as the polymerase, NASENT-copy technology DNA Amplification methods (US) including the linear RNA-DNA Amplification methods commonly used in combination with the nucleotide sequences of RNA found in US DNA sequences, such as the DNA polymerase, DNA Amplification methods (E) and the amplified DNA Amplification methods commonly used in the genomic DNA Amplification methods of RNA found in the genomic DNA sequences of the genomic DNA of.

Nucleic acid amplification for subject identification can include sequential, parallel, or simultaneous amplification of multiple nucleic acid sequences, e.g., about, less than about, or greater than about 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 50, 100, or more target sequences. In some embodiments, the entire genome or entire transcriptome of the subject is non-specifically amplified, the products of which are probes for one or more recognition sequence features. Identifying sequence features includes any feature of a nucleic acid sequence that can serve as a basis for distinguishing between individuals. In some embodiments, individuals are uniquely identified with a selected statistical significance using an identification sequence of about, less than about, or more than about 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 50, 100, or more. In some embodiments, the statistical significance is about or less than about 10^-2、10^-3、10^-4、10^-5、10^-6、10^-7、10^-8、10^-9、10^-10、10^-11、10^-12、10^-13、10^-14、10^-15Or smaller. Examples of recognition sequences include restriction fragment length polymorphisms (RFLP; Botstein, et al, am. J. hum. Genet.32:314-331, 1980; WO90/13668), single nucleotide polymorphisms (SNPs; Kwok, et al, Genomics31:123-126,1996), random amplified polymorphic DNA (RAPD; Williams et al, nucleic acids Res.,18:6531-6535,1990), simple sequence repeats (SSRs; Zhao and Kochert, plantatMol. biol.21:607-614, 1993; Zietkiewicz, et al, Genomics20:176-183,1989), amplified fragment length polymorphisms (LP; Vos, et al, nucleic acids Res. 4421: 4407, 1995), short tandem repeats (STS), variable number of tandem repeats (AST), variable number of tandem repeats (Webster. TRT., MRT. TM. Ser. J. 1989), amplified fragment length polymorphisms (SRT; GentM. Ser. 16: 11, rT. Ser. J. sub. Ser. sub.18, SEQ ID. NO: 11, PCR), amplified fragment length polymorphisms (SRT. Ser. 16, SEQ ID. NO: 11, SEQ ID NO: ORF. NO: 18, SEQ ID NO. 11, SEQ ID NO. 16, SEQ ID NO. 11, SEQ, retrotransposon-based insertion polymorphisms (RBIP), short interspersed elements (SINE), and sequence-specific amplification polymorphisms (SSAP). Further examples of identification sequences are known in the art, for example in US20030170705, which is incorporated herein by reference. A gene signature may consist of multiple recognition sequences of a single type (e.g., SNPs), or may include a combination of two or more different types of recognition sequences in any number or combination.

Genetic markers can be used in any process requiring identification of one or more subjects, such as paternal or maternal paternity testing, immigration and inheritance disputes, animal breeding tests, twins egg type detection, close-relative breeding tests for humans and animals; evaluation of transplant compatibility, such as bone marrow transplantation; identification of human and animal remains; controlling the quality of the cultured cells; forensic testing such as forensic analysis of semen samples, blood stains and other biological materials; characterization of the genetic makeup of the tumor by detecting loss of heterozygosity; and determining the allele frequency of the specific recognition sequence. Samples used to generate genetic markers include evidence from a crime scene, blood, bloodstain, semen, seminal plaques, bone, teeth, hair, saliva, urine, feces, nails, muscle or other soft tissue, cigarettes, stamps, envelopes, dandruff, fingerprints, items containing any of these materials, and combinations thereof. In some embodiments, two or more gene signatures are generated and compared. In some embodiments, the one or more genetic markers are compared to one or more known genetic markers, such as genetic markers contained in a database.

The system may also verify whether the subject has received instructions from a healthcare professional to undergo clinical exploration. The system may thus verify whether the subject has received a subscription from a healthcare professional to make a qualitative and/or quantitative evaluation of the biological sample. For example, the system may verify whether the subject has received a prescription from a healthcare professional to accept the probe. The system can verify whether the subject has received instructions from a healthcare professional to provide a sample to the device. The system may also verify whether the subject is authorized to travel to a particular service point subject to detection. Authentication may occur with the aid of a device. Verification may occur at any time. In one example, the authorization of the subject to accept the test may be verified prior to preparing a sample of the subject for testing. The authorization of the subject to accept the detection may be verified prior to providing the sample to the device and/or cartridge. Verification of the authorization of the subject may be provided after verifying the identity of the subject. Verification of the authorization of the subject may be provided before or after verifying that the subject has insurance coverage for clinical probes. The system may verify whether the subject is covered by a qualitative and/or quantitative evaluation of the sample by health insurance, wherein the verifying step is performed before, after or simultaneously with processing the biological sample by means of the device or transmitting data from the device. Verification may be through communication with a healthcare provider, laboratory, payer, laboratory welfare manager, or any other entity. Verification may occur quickly and/or in real-time. For example, validation may occur in 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. The verification may be automated without any human intervention.

The system may also verify whether the subject has insurance coverage for the clinical probe. The system may verify whether the subject has insurance coverage for providing the sample to the device. The system may also verify that the subject has insurance coverage for traveling to the service point and undergoing detection. Verification may occur at any time. In one example, the insurance coverage of a subject may be verified before preparing a sample of the subject for detection. The insurance coverage of the subject may be verified prior to providing the sample to the device and/or cartridge. Verification of the insurance coverage of the subject may be provided after verifying the identity of the subject. Verification of the insurance coverage of the subject may be provided before or after verifying that the subject has received a prescription to be subjected to a clinical survey. Verification may be through communication with a healthcare provider, laboratory, payer, laboratory welfare manager, or any other entity. Authentication may occur with the aid of a device. Verification may occur quickly and/or in real-time. For example, validation may occur in 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. The verification may be automated without any human intervention.

The system may also verify whether the clinical probe is appropriate for the subject. The system may verify that the subscription for qualitative and/or quantitative evaluation is within a set of rule limits. Such rule limits may form guidelines. Such rule limits may be those of a payer, prescribing physician or other healthcare professional making the reservation, a laboratory, government or regulatory device, or any other entity. Such verification may depend on one or more known characteristics of the subject, including but not limited to, gender, age, or past medical history. A clinical decision support system may be provided. The system may be capable of accessing one or more medical records or information associated with the subject. The system may be able to access records related to the identity of the subject, the insurance coverage of the subject, past and current medical treatments of the subject, biological characteristics of the subject, and/or prescriptions provided to the subject. The system may be able to access electronic health records and/or recall patient records and history. The system may also be able to call out payer records, such as insurance and financial information about the subject. Authentication may occur with the aid of a device.

In some embodiments, the system may be able to access one or more records databases and/or payer databases prior to providing qualitative and/or quantitative assessments. In some cases, the system may be able to determine which records database and/or payer database to access before providing the qualitative and/or quantitative rating, and/or before accessing the database. The system may make such a determination based on the identity of the subject, the payer information for the subject, information collected about the sample, proposed qualitative and/or quantitative assessments, and/or any other information.

In one example, an inappropriate detection may be a pregnancy test for a male subject or a detection of PSA (prostate specific antigen) levels for a female subject. Such detection may be outside the rules limits of the payer or prescribing physician. Such a booking error may be detected by reviewing the detection of the booking and information associated with the subject. Such associated information may include a medical record of the subject or identifying information about the subject. In one example, the appropriateness of the probing is verified before preparing a sample of the subject for probing. The adequacy of detection of the subject may be verified before, after, or simultaneously with providing the sample to the device and/or cartridge. Verification of the adequacy of detection of the subject may be provided after or before verifying the identity and/or insurance coverage of the subject. The verification may be through communication with a medical care provider, laboratory, payer, laboratory welfare manager, or any other entity. The clinical decision support system may run quickly and/or in real-time. For example, validation may occur within 10 minutes or less, 5 minutes or less, 3 minutes or less, 1 minute or less, 45 seconds or less, 30 seconds or less, 20 seconds or less, 15 seconds or less, 10 seconds or less, 5 seconds or less, 3 seconds or less, 1 second or less, 0.5 seconds or less, or 0.1 seconds or less. The clinical decision support system may be automated without any manual intervention.

In some embodiments, the qualified person may assist in acquiring the identity of the subject and/or providing a sample from the subject to the device. Qualified personnel may be authorized technicians that have been trained in using the equipment. The qualified person may be a designated operator of the apparatus. The qualified person may or may not be a medical care professional. In some embodiments, the identity of qualified personnel may be verified. The identity of the qualified person may be verified before, after, or concurrently with receiving the biological sample, electronically transmitting data from the device, and/or analyzing the transmitted data. The identity of the qualified person may be verified before, after, or simultaneously with verifying the identity of the subject. The identity of the qualified person may be verified using one or more of the techniques described elsewhere herein.

Network connectivity method

It should be understood that one or more specific examples of the liquid analyzer, one or more of the other diagnostic devices described herein, or other hardware may use one or more techniques to increase the likelihood of maintaining network connectivity. It should be understood that in at least some specific examples, the network-enabled device can be a liquid analyzer with and/or connected to a network connectivity device that supports connectivity techniques as described herein. In some specific examples, this may involve a network connectivity module in a liquid analyzer or other diagnostic device. Alternatively still, the network connectivity hardware and/or software may be part of the liquid analyzer system and in communication with the liquid analyzer, but may or may not be physically coupled to the liquid analyzer. Other configurations are not excluded as long as the liquid analyzer is in communication with the network connectivity module to provide improved reliability and/or performance in network connectivity. This provides a number of advantages, including but not limited to: the likelihood that the liquid analyzer, one or more of the other diagnostic devices described herein, or other hardware is capable of receiving and/or transmitting diagnostic procedures, calibration procedures, sample data, etc. from and/or to a server or other device remote from the device at the point of service is increased.

At least some of the methods provided herein enable network-enabled electronic devices to connect and reconnect to a network, and in some cases optimize and/or improve their network connectivity. In some cases, the methods provided herein enable network-enabled electronic devices to connect to a network that is optimal in view of one or more connectivity criteria (or rules) provided herein. In other cases, if an optimal connection is not established, the methods provided herein enable network-enabled electronic devices to continuously optimize network connectivity in view of changing conditions.

The term "network" as used herein refers to a Local Area Network (LAN), a Metropolitan Area Network (MAN), or a Wide Area Network (WAN). In some cases, the network comprises an internetwork. The network includes wired and/or wireless components.

The term "router" as used herein refers to a device that forwards or relays data packets across one or more networks.

The term "network provider" as used herein refers to one or more computer systems or devices used to provide or facilitate network connectivity to electronic devices. In some cases, the network provider is a router or a plurality of routers.

The term "electronic device" as used herein refers to a computer device configured for connection to a network. In some cases, the electronic device is a portable electronic device. Examples of electronic devices include smart phones (e.g.,a functional telephone,A telephone,) Notebook computers, tablet personal computers (e.g.,) And desktop computers (e.g., work meters, servers), cameras, gaming machines (e.g.,xbox), television, music player (e.g., MP3 player, radio, CD player), and video player (e.g., DVD player). The electronic device may be included in other components. For example, the electronic device may be part of a residential or commercial building, a vehicle, or an aircraft.

The term "network-enabled device" as used herein refers to an electronic device configured to connect to, reconnect to, and communicate with one or more electronic devices via a network. In some examples, network-enabled devices (also referred to herein as "network devices") include smart phones and Personal Computers (PCs). By way of example, the network-enabled device is a desktop Personal Computer (PC), a notebook PC, a mainframe computer, a set-top box, a personal digital assistant, a mobile phone, a media player, a web pad, a tablet PC, or a smart phone. In some cases, a network-enabled device includes a network interface for facilitating network connectivity. The network interface includes, for example, an ethernet network interface for connecting to a network through a wired connection, or a wireless interface for connecting to a wireless provider, which in turn provides connectivity to the network. The network enabled device may include a plurality of wireless interfaces. The wireless provider may include one or more of a Wi-Fi (or WiFi) router and one or more channel access methods. In some cases, the channel access method is selected from Frequency Division Multiple Access (FDMA), Wavelength Division Multiple Access (WDMA), Orthogonal Frequency Division Multiple Access (OFDMA), orthogonal frequency division multiple access (OFDM) -based, single carrier FDMA (SC-FDMA) (or linear precoding OFDMA (LP-OFDMA)), Time Division Multiple Access (TDMA), Code Division Multiple Access (CDMA) (or Spread Spectrum Multiple Access (SSMA)), direct sequence CDMA (DS-CDMA), frequency hopping CDMA (FH-CDMA), Orthogonal Frequency Hopping Multiple Access (OFHMA), multi-carrier code division multiple access (MC-CDMA), Space Division Multiple Access (SDMA), packet mode channel access methods (e.g., contention-based random multiple access methods), duplexing methods (e.g., Time Division Duplex (TDD), Frequency Division Duplex (FDD)), global system for mobile communications (GSM), GSM with packet, and the like, Bluetooth packet mode communication, ieee802.11b Wireless Local Area Network (WLAN), high performance radio local area network (HIPERLAN/2) wireless network, and g.hn. The wireless provider may be configured for second generation wireless telephony (2G), third generation mobile telecommunications (3G), fourth generation mobile wireless standards (4G) or lte-advanced (lte) communication standards. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

The network enabled device may comprise a plurality of interfaces. In some cases, the network-enabled device includes an ethernet interface and a wireless interface for connecting with a WiFi router, a CDMA provider, and/or a GSM provider.

The term "static" as used herein in the context of network parameters refers to network parameters that do not change for a limited period of time, such as a set or predetermined period of time. A static Internet Protocol (IP) address is an address that does not change for a predetermined (or set) period of time. In some cases, the static IP address is a private IP address. A static Uniform Resource Locator (URL) is a network (or networder) address that does not change for a predetermined period of time. In some cases, the static URL is a dedicated URL, such as a URL that is dedicated to an entity (e.g., business, individual). The static URL may be associated with one or more servers of the entity.

The term "connectivity" as used herein refers to network-enabled electronic devices being in network communication with a network provider, such as a router (e.g., wired router, wireless router). A network-enabled device has connectivity with a network provider if the network-enabled device is capable of communicating with the network provider, such as making network reachability probes to the network provider or sending data (e.g., data packets) to or receiving data from the network provider.

In one embodiment described herein, a method for establishing network connectivity for a network-enabled device includes connecting a network-enabled electronic device (also referred to herein as a "network-enabled device") to a network provider. Next, the network enabled device conducts a network reachability probe ("ping") with a first server having a static Internet Protocol (IP) address with the aid of a network provider. The network enabled device also performs network reachability probes by means of a network provider to a second server having a static Uniform Resource Locator (URL). Network reachability probes may be performed on the first server and the second server simultaneously or sequentially (i.e., either the first server is after the second server, or the second server is after the first server). Next, the network enabled device determines whether to maintain connectivity with the network provider based on whether the network enabled device receives a response from the first server and/or whether the network enabled device receives a response from the second server. In each case, the response may be an acknowledgement by the network enabled device of network reachability probes to the first server and the second server.

In some cases, upon network reachability detection for a second server having a static (or dedicated) URL (e.g., "google. The network reachability probe ("ping") packet is then sent to the second server (located at the resolved IP address). A response is generated by the second server and sent to the network provider and then to the network enabled device. The absence of a response from the second server may indicate that the second server has failed (or is unavailable or unreachable), or that a DNS server in communication with the network provider has failed. In such a case, the network-enabled device may conduct a network reachability probe to a third server having a dedicated URL (e.g., "yahoo. A DNS server in communication with the network provider resolves the URL to an IP address of the third server. The network reachability probe (ping) packet is then sent to a third server (located at the resolved IP address). If the network enabled device does not receive a response from the third server, the network enabled device may conclude that: a DNS server communicating with a network provider fails. In such a case, the network-enabled device connects to another network provider and repeats the above steps.

In some cases, the network provider is selected from the group consisting of a wireless router, a bluetooth router, a wired router, a cellular network router, a Radio Frequency (RF) device, and an opto-electronic device. The first server has a static IP address (e.g., "123.123.123.123"), and the second server has a static URL (e.g., "google. In some cases, such as a network update, the static URL is updated.

In some cases, the first server is identified by a user-determined IP address, i.e., an IP address determined or provided by a user operating the network-enabled device. In such a case, the user can, for example, enter the IP address of the first server into a network configuration tool of the network-enabled device. Similarly, in some cases, the second server is specified by a user-determined URL. For example, in the network configuration tool, the user provides a string that defines the URL of the second server.

In one particular example, network reachability probes are performed simultaneously to a first server and a second server. In another particular example, network reachability probes are performed on a first server before a second server. In yet another specific example, network reachability probes are performed on the second server before the first server. Network reachability probing of the first and second servers involves sending (or directing) network reachability probe packets from the network-enabled device to each of the first and second servers. In another embodiment, network reachability probes are performed only on the first server or only on the second server. In such a case, the response after network reachability probes to the first server or the second server is evaluated to determine whether connectivity is maintained with the network provider.

In some embodiments, network reachability probes are made to additional servers. In one particular example, a third server having a static IP address or a private (or static) URL is probed for network reachability. In another specific example, network reachability probes are made to at least 2, or 3, or 4, or 5, or 6, or 7, or 8, or 9, or 10, or 20, or 30, or 40, or 50, or 60, or 70, or 80, or 90, or 100 other servers, where each server has a static IP address and/or a dedicated URL.

In some cases, when network reachability detection is made to a first server, the network enabled device sends network reachability detection packets to the first server. Similarly, in some cases, when performing network reachability probes to a second server, the network-enabled device sends network reachability probe packets to the second server. The network reachability probe packet may include one or more predetermined characters or strings (e.g., "Hello world"). In some cases, the network reachability probe packet contains a file with machine-encoded data, such as a media file (e.g., an encoded media file).

In some cases, the network-enabled device connects to another network provider (e.g., a router) if no response is received from one or both of the first server and the second server. The network-enabled device then performs network reachability probes for the first server and the second server, as described above.

In some cases, if a response is received from one or both of the first server and the second server, the network-enabled device connects to the second network provider based on at least one predetermined network connectivity criterion ("network connectivity criterion") selected from the group consisting of: bandwidth of another network provider, cost of maintaining connectivity with another network provider, cost of transferring information by means of another network provider, download rate of another network provider, and upload rate of another network provider. For example, if the second network provider supports higher network bandwidth than the first network provider, the network enabled device connects to the second network provider. In such a case, all connections with the first network provider may be terminated. In some cases, the network-enabled device continues to determine whether other network providers can provide improved network connectivity relative to the second network provider based on one or more network connectivity criteria (or rules) provided herein.

In some embodiments, the network-enabled device maintains connectivity with a network provider if the first server responds to the network-enabled device and/or the second server responds to the network-enabled device in response to network reachability probes being made to the first server and the second server. In one particular example, connectivity is maintained if both the first server and the second server respond to the network-enabled device in response to network reachability probes to the first server and the second server by the network-enabled device. In another particular example, connectivity is maintained if either of the first server and the second server responds to the network enabled device. In one example, the response from the first server is sufficient to cause the network-enabled device to maintain connectivity with the first network provider. However, in some cases, if the first server is not responsive to the network-enabled device and/or the second server is not responsive to the network-enabled device, the network-enabled device connects to another network provider.

Even if the first server and the second server respond to the network-enabled device, the network-enabled device may connect to another network provider if one or more network connectivity criteria are not met. In one example, a network enabled device connects to another network provider if network bandwidth is below a predetermined limit. In some cases, a network enabled device connects to another network provider if the network bandwidth is below a certain threshold, such as, but not limited to, about 100kbit/s, or 500kbit/s, or 1Mbit/s, or 2Mbit/s, or 5Mbit/s, or 10 Mbit/s. In one embodiment, a network enabled device connects to another network provider if network bandwidth is below a predetermined limit (such as a user-defined limit).

In one example, if the first server and/or the second server are not responding to the network-enabled device, or if one or more network connectivity criteria (e.g., network bandwidth above a predetermined limit) are not met, the network-enabled device connects to a second network provider and network reachability probes are made to the first server and the second server, either sequentially or simultaneously, by way of the second network provider.

In some cases, connecting to the second network provider includes terminating connectivity with the other network provider. Next, the network enabled device determines whether to maintain connectivity with the second network provider based on whether the network device received a response from the first server and/or whether the network device received a response from the second server.

In some cases, if the network enabled device does not receive a response from the second server, the network enabled device determines that it is not in network communication with a Domain Name System (DNS) server. This may be due to, for example, a failed DNS server. In some cases, the first server is a Domain Name System (DNS) server.

In some cases, the second server includes one or more servers for hosting URLs. In one example, the second server is a dedicated server for hosting URLs.

Fig. 83 illustrates a method 9100 for connecting a network-enabled device (also referred to herein as a "network device") to a network, according to one specific example described herein. In a first step 9105, a network device is connected to a network provider, such as a wired or wireless network router. Next, in a second step 9110, the network device performs network reachability probing for the first server with a static IP address. In a third step 9115, the network device performs network reachability probing for the second server with a static URL. Next, in a fourth step 9120, the network device determines whether responses (e.g., network reachability probe packets) are received from the first server and the second server. If no response is received from the first server and the second server, then in a fifth step 9125 the network device connects to another network provider and the method 9100 is repeated. If responses are received from the first server and the second server, then in an optional sixth step 9130, the network device determines whether one or more network connectivity factors provided herein, such as bandwidth, upload rate, and/or download rate, are met. If one or more network connectivity factors are not met, the network device connects to another network provider and method 9100 is repeated. However, if one or more network connectivity factors are satisfied, then in a seventh step 9135, the network device maintains a connection (e.g., wired connection, wireless connection) with the network provider. The user operating the network device will then use the network as desired, such as browsing the world wide web or sending and receiving e-mail, for example.

The network device may connect to another network provider using the same network interface (e.g., a WiFi interface) or using another network interface. In one example, in step 9105, the network device connects to a WiFi router using a first wireless interface (e.g., a WiFi interface) of the network device. After step 9130, the network device connects to a GSM or CDMA provider using a second wireless interface configured to enable the network device to communicate with the GSM or CDMA provider, and method 9100 is repeated using the second wireless interface.

Alternatively to step 9120, the network device determines whether a response is received by the second server having a static URL. In such a case, if a response is received, the network device maintains a connection with the network provider. In such a case, the response from the first server may be used for various network diagnostic purposes, such as upload rate and download rate.

Alternatively to or in conjunction with network reachability probing of the first server and the second server by the network enabled device, establishing connectivity with the network provider includes directing data packets from the network enabled device to the first server and the second server. In some cases, data packets may be used instead of or in conjunction with network reachability probe packets.

In some embodiments, a method for establishing network connectivity for a network device includes connecting to a network provider and directing a first data packet to a first server having a static Internet Protocol (IP) address. The first data packet is directed by means of a network provider. That is, the network provider causes the network device to communicate with the first server. Next, the network device directs the second data packet to a second server having a static Uniform Resource Locator (URL). The second data packet is directed by means of the network provider. That is, the network provider causes the network device to communicate with the second server. The first and second data packets are directed to the first and second servers, respectively, sequentially or simultaneously. In some cases, the network device directs the second data packet to the second server before directing the first data packet to the first server. Next, the network device determines whether to maintain connectivity with the network provider based on a comparison of one or more data packets received by the network device from the first server and the second server. In some cases, the comparing includes performing a checksum to determine a similarity between the data packet received by the network device and the first data packet and the second data packet.

Next, the network enabled device determines whether any data packets are received from the first server and/or the second server. In some cases, if the network device does not receive a data packet from the first server or the second server, the network device terminates the connection with the network provider and connects to another network provider if available. The data packet may not be received from the first server and/or the second server for various reasons, such as, for example: a link between the network provider and the first and/or second server is broken, the network fails, the integrity of the network is poor, or the first and/or second server is malfunctioning.

In some cases, the first server is a Domain Name System (DNS) server. In one example, the first data packet and/or the second data packet is a loopback request packet.

In some cases, the second server includes one or more servers for hosting URLs. In one example, the second server is a dedicated server for hosting URLs.

In some cases, a network-enabled device (also referred to herein as a "network device") directs a first data packet to a first server by first performing a network reachability probe to the first server. Upon successful network reachability detection to the first server, the network device directs the first data packet to the first server. Similarly, the network device directs the second packet to the second server by first performing a network reachability probe to the second server. After successfully performing network reachability probe to the second server, the network device directs the second packet to the second server. The network device then determines various network connectivity factors based on the time taken to receive the data packets from the first and second servers, the time taken to upload the first and second data packets to the first and second servers, or whether the received data packets match the data packets transmitted to the first and second servers.

The network device maintains connectivity with the network provider if a first received data packet of the one or more data packets received by the network device is the same as a first data packet directed to the first server. However, in some cases, the network device maintains connectivity if the first received packet is at least about 1%, or 5%, or 10%, or 15%, or 20%, or 25%, or 30%, or 35%, or 40%, or 45%, or 50%, or 55%, or 60%, or 65%, or 70%, or 75%, or 80%, or 85%, or 90%, or 95%, or 99% similar to the first packet. Such similarity may be evaluated by comparing the data packets to each other, for example, by comparing strings to each other if the data packets are strings.

Similarly, if a second received data packet of the one or more data packets received by the network device is the same as a second data packet directed to a second server, the network device maintains connectivity with the network provider. However, in some cases, the network device maintains connectivity if the second received packet is at least about 1%, or 5%, or 10%, or 15%, or 20%, or 25%, or 30%, or 35%, or 40%, or 45%, or 50%, or 55%, or 60%, or 65%, or 70%, or 75%, or 80%, or 85%, or 90%, or 95%, or 99% similar to the second packet.

If the checksum of the first received data packet matches the predetermined data packet, a connection to the network provider may be maintained. In one example, if the first received packet matches a predetermined string (e.g., "Hello world"), connectivity is maintained. In other cases, connectivity to the network provider is maintained if the checksum of the second received data packet matches the predetermined data packet. Alternatively, if the first data packet matches the first received data packet and/or the second data packet matches the second received data packet, connectivity to the network provider is maintained. In some cases, connectivity is maintained if the first and second data packets all match the first and second received data packets, respectively.

In some cases, a network-enabled device (also referred to herein as a "network device") connects to another network provider if a first received packet is different from a first packet and/or a second received packet is different from a second packet. In one example, the network device searches, looks up, and connects to another network provider, such as another wireless router.

One or both of the first data packet and the second data packet may be used to determine upload and download rates for a network provided by a network provider. In one example, the network enabled device uses the rate at which first packets are uploaded to and downloaded from a first server and/or the rate at which second packets are uploaded to and downloaded from a second server to determine the upload rate and download rate, which may be the average upload rate and download rate of the network. For example, the upload rate is averaged using one or more upload rates to the first server and the second server, and the download rate is averaged using one or more download rates from the first server and the second server. This, in turn, may enable the network-enabled device to determine whether to maintain connectivity with a network provider or connect to another network provider.

If the network provider does not provide network access or if the network access provided by the network provider does not satisfy one or more network connectivity criteria or factors (e.g., upload rate, download rate, or network cost), the network device connects to another network provider and repeats the method outlined above. In one example, if a network device connects to another network provider, the network device directs a first data packet to a first server and a second data packet to a second server. The first data packet and the second data packet are directed (or sent) to the first server and the second server, respectively, by means of another network provider. In such a case, the network device also determines whether to maintain connectivity with another network provider based on a comparison of one or more data packets received by the network device from the first server and the second server, as described above.

In some cases, a network device terminates its connection with another network provider after connecting to the other network provider. In other cases, however, the network device maintains its connection (or connectivity) with one or more other network providers. This may enable the network device to find and establish the network connectivity if and when improved network connectivity becomes available.

Fig. 84 shows a method 9200 for connecting a network-enabled device (also referred to herein as a "network device") to a network, according to one specific example described herein. Again, although other devices are not excluded, the network device described herein may be a liquid analyzer or other diagnostic device possessing network connectivity hardware and/or software that supports the connectivity techniques described herein.

In a first step 9205 of one particular example described herein, a network device connects to a network provider such as, but not limited to, a wired or wireless network router. Next, in a second step 9210, the network device directs the first data packet to a first server having a static IP address. In a third step 9215, the network device directs the second packet to a second server having a static URL. Next, in a fourth step 9220, the network device determines whether any data packets are received from the first server and/or the second server. The network device may continuously monitor any received packets or at predetermined intervals, such as every 1 second, 10 seconds, 30 seconds, 1 minute, 5 minutes, or 10 minutes. In some cases, if no data packet is received, the network device connects to another network provider in a fifth step 225 and the method 200 is repeated. In other cases, if a data packet is received from at least one of the first server and the second server, the network device determines whether the data packet received by the network device is the same as the first data packet or the second data packet in a sixth step 230. In one example, if a first received data packet is received by the network device from a first server and a second received data packet is received by the network device from a second server, the network device determines whether the first received data packet is identical to the first data packet and whether the second received data packet is identical to the second data packet. If the data packets are not the same, the network device connects to another network provider and the method 9200 is repeated.

In one particular example, if the at least one received data packet is the same as the first data packet or the second data packet, connectivity to the network provider is maintained. In another specific example, if a first received data packet from a first server is the same as a first data packet and a second received data packet from a second server is the same as a second data packet, connectivity to the network provider is maintained.

In some cases, in seventh step 9235, the network device determines whether one or more network connectivity factors provided herein, such as bandwidth, upload rate, and/or download rate, are met when the network device is entering or exiting the network through the network provider. In some cases, if the one or more network connectivity factors are not satisfied, the network device connects to another network provider and method 9200 is repeated. However, if the one or more network connectivity factors are satisfied, then in an eighth step 9240, the network device maintains a connection (e.g., wired connection, wireless connection) with the network provider. The user operating the network device may then use the network as desired. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

In some embodiments, connecting to the network provider first must locate the network provider in the search location. In one embodiment, the seek position is a predetermined position determined by a user of the network-enabled device. The predetermined location may be a place of business or residence, or a public place (e.g., park, street). In another embodiment, the seek position is within a predetermined radius from the user position. In some cases, the search location has a radius of at least about 1 meter ("m"), or 2m, or 3m, or 4m, or 5m, or 6m, or 7m, or 8m, or 9m, or 10m, or 20m, or 30m, or 40m, or 50m, or 60m, or 70m, or 80m, or 90m, or 100m, or 200m, or 300m, or 400m, or 500m, or 600m, or 700m, or 800m, or 900m, or 1000m, or 2000m, or 3000m, or 4000m, or 5000 m. In some cases, the seek position is determined by the user or updated by the network device when the user changes his or her position.

In some cases, once the network-enabled device has connected to the network provider, the network-enabled device determines whether to maintain connectivity to the network provider based on one or more network connectivity criteria selected from the group consisting of: network bandwidth ("bandwidth"), cost of maintaining connectivity with a network provider, cost of transferring information by means of a network provider, download rate, and upload rate. In some cases, if other network providers can provide improved network conditions, the network enabled device makes similar determinations about another network provider and connects to the other network provider.

In one example, a network device connects to a first network provider (e.g., a wireless router) and performs network reachability probes for a first server (having a static IP address) and a second server (having a dedicated URL). When responses are received from the first server and the second server, the network device determines whether network access via the first network provider is optimal (or preferred) by calculating an upload rate and a download rate of the network provided by the first network provider. If the upload and download rates are above a predetermined limit, the network device maintains its connection with the first network provider and the user may enter and exit the network through the first network provider. In some cases, the network device may also connect to a second network provider and perform network reachability probes for the first server and the second server. The connection with the second network provider may be made while the network device is still connected to the first network device. Alternatively, the network device may terminate its connection with the first network provider and connect to the second network provider. When responses are received from the first server and the second server, the network device determines whether network connectivity via the second network provider is optimal by calculating an upload rate and a download rate of the network provided by the first network provider. If the upload and download rates are improved relative to the upload and download rates provided by the first network provider, the network device terminates its connection with the first network provider and maintains (or establishes) its connection with the second network provider. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

In some cases, when the network-enabled device has the option of connecting to the network using multiple network providers (e.g., two, five, or ten network providers), such as the first network provider or the second network provider, the network-enabled device uses the second network provider if the network-enabled device determines that the network conditions using the second network provider are optimal, improved, or preferred over the network conditions using the first network provider. Such a scenario may be relevant if the network-enabled device has made network reachability probes to the first and second servers by means of the first and second network providers, and received responses by the network-enabled device in both cases. The network enabled device uses the second network device (relative to the first network device) based on determining at least one network connectivity criterion selected from the group consisting of: bandwidth of the second network provider, cost of maintaining connectivity with the second network provider, cost of transferring information by the second network provider, download rate of the second network provider, upload rate of the second network provider, and connectivity mode (i.e., wired connectivity or wireless connectivity). As an example, if the network-enabled device determines that the cost of connecting and using the network via the second network provider is lower than the cost of connecting and using the network via the first network provider, the network-enabled device enters and exits the network via the second network provider. As another example, if the network-enabled device determines that the network bandwidth via the second network provider is greater than the network bandwidth via the first network provider, the network-enabled device accesses the network via the second network provider. As yet another example, if network access via the second network provider is through a wired connection and network access via the first network provider is through a wireless connection, and the wired connection is preferred over the wireless connection, the network-enabled device accesses the network via the second network provider.

In some embodiments, a method for establishing network connectivity for a network device comprises: connecting to a network provider, and performing network reachability probing for a first server having a static Internet Protocol (IP) address and/or a second server having a static (or dedicated) Uniform Resource Locator (URL) by means of the network provider. Next, terminating the connection with the network provider based on any one of network termination conditions selected from the group consisting of: (a) the network device does not receive a response from the first server and/or the second server after the network reachability probe, (b) the network bandwidth of the other network provider is higher than the network bandwidth of the network provider, (c) the network cost of the other network provider is lower than the network cost of the network provider, (d) the network access provided by the other network provider is more robust than the network provided by the network provider, (e) the connectivity between the network device and the other network provider is via a wired connection and the connectivity between the network device and the network provider is via a wireless connection, and (f) the other network provider is closer to the network device than the network provider. In some cases, the connection with the network provider is terminated based on any two, or any three, or any four, or any five network termination conditions selected from the group. In other cases, the connection with the network provider is terminated based on all network termination conditions.

Connectivity between the network device and the first network provider is via wired or wireless network access point connections. That is, in some cases, connectivity between a network device (also referred to herein as a "network-enabled device") and a first network provider is through a wired connection (e.g., coaxial cable, opto-electronic), while in other cases, connectivity with the first network provider is through a wireless connection (e.g., WiFi, bluetooth). A network provider connects to a network via a wired or wireless connection to one or more machines that may access the network, such as one or more servers that provide network access to a global information network.

In some embodiments, a method for establishing network connectivity for a network device includes connecting the network device to a first network provider. Next, the network device performs network reachability probes for the first server and the second server by way of the first network provider. In some cases, one or both of the first server and the second server have a static IP address. In other cases, one or both of the first server and the second server have a static URL. In other cases, the first server has a static IP address and the second server has a static URL.

Next, if the second network provider satisfies one or more criteria not satisfied by the first network provider, the network device terminates its connection with the first network provider and subsequently (or concurrently) establishes a connection with the second provider. In one embodiment, the one or more criteria are selected from the group consisting of: (a) whether the network device receives a response from the first server and/or the second server after performing the network reachability probe, (b) whether a network bandwidth of the second network provider is higher than a network bandwidth of the first network provider, (c) whether a network cost of the second network provider is lower than a network cost of the first network provider, (d) whether a network ingress and egress provided by the second network provider is more robust than a network provided by the first network provider, (e) whether a connection between the network device and the second network provider is via a wired connection and a connection between the network device and the first network provider is via a wireless connection, and (f) whether the second network provider is closer to the network device than the first network provider. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

In some cases, in response to the network device performing network reachability probes to the first server and the second server, the connection between the network device and the first network provider is terminated if the network device does not receive a response from the first server or the second server. Alternatively, the connection is terminated if the network device does not receive a response from the first server and the second server.

In some cases, a method for establishing network connectivity for a network-enabled device includes the network-enabled device connecting to a first network provider (e.g., a wireless router) and locating a second network provider. The second network provider has a higher level of prioritization than the first network provider based on one or more predetermined network connectivity criteria. For example, the second network provider has a higher network bandwidth than the first network provider. Next, the network enabled device connects to a second network provider. The one or more predetermined network connectivity criteria are selected from the group consisting of network bandwidth, network cost, and proximity of the network device to the network provider.

In some cases, the network-enabled device selects a network provider from a list of network providers generated by the network-enabled device. The list may include network providers within a predetermined location or within a predetermined search radius, such as at least about 1 meter ("m"), or 2m, or 3m, or 4m, or 5m, or 6m, or 7m, or 8m, or 9m, or 10m, or 20m, or 30m, or 40m, or 50m, or 60m, or 70m, or 80m, or 90m, or 100m, or 200m, or 300m, or 400m, or 500m, or 600m, or 700m, or 800m, or 900m, or 1000m, or 2000m, or 3000m, or 4000m, or 5000 m. The network providers may be ranked by a priority order determined based on network connectivity factors. Alternatively, the network providers can be ranked based on whether the network-enabled device received a response after network reachability probing the first server and/or the second server. The network provider at the top of the list may have received responses from both the first server and the second server, while the network provider at the bottom of the list may not have received responses from either the first server or the second server. The ordering may be a weighted ordering. In some cases, the ordering may be weighted by network connectivity factors. In one example, the network bandwidth weighting is based on-i.e., unweighted rank order x network bandwidth/total network bandwidth accumulated across all network providers in the list.

The rank order may be saved in a storage location of the network enabled device, such as in a data file or memory location, and manually updated by a user or updated at predetermined intervals, such as every 1 second or more, or 2 seconds or more, or 3 seconds or more, or 4 seconds or more, or 5 seconds or more, or 10 seconds or more, or 30 seconds or more, or 1 minute or more, or 5 minutes or more, or 10 minutes or more, or 30 minutes or more, or 1 hour or more, or 12 hours or more, or 1 day or more.

In one example, a first network provider has a higher level of prioritization than a second network provider if the first network provider supports higher network bandwidth than the second network provider. The network device connects to the first network provider from the list, but continuously or intermittently determines whether the network connection is optimal or whether another network provider provides more preferred network access. If network access through the second network provider is preferred over the first network provider, e.g., if the second network provider provides cheaper internet access or higher network bandwidth, the network device terminates the connection with the first network provider and connects to the second network provider.

In one particular example, the network device connects to the network provider only if the network device successfully performs network reachability probes to the first and second servers (i.e., the network provider receives responses after performing network reachability probes to the first and second servers). In one embodiment, the first server has a static Internet Protocol (IP) address and the second server has a static (or dedicated) Uniform Resource Locator (URL).

In some cases, the second network provider is located by searching for other network providers within a predetermined or user-selected search radius of at least about 1 meter ("m"), or 2m, or 3m, or 4m, or 5m, or 6m, or 7m, or 8m, or 9m, or 10m, or 20m, or 30m, or 40m, or 50m, or 60m, or 70m, or 80m, or 90m, or 100m, or 200m, or 300m, or 400m, or 500m, or 600m, or 700m, or 800m, or 900m, or 1000m, or 2000m, or 3000m, or 4000m, or 5000 m. The network device then generates a list of network providers within the search radius.

Fig. 85 shows a method 9300 for generating a ranked list of network providers, according to a specific example described herein. In a first step 9305, a network enabled device searches for network providers (e.g., WiFi access points, 2G networks, 3G networks, 4G LTE networks, 5G networks, and/or other networks). In one embodiment, the search is performed within a predetermined search radius, such as a radius of at least about 1 meter ("m"), or 2m, or 3m, or 4m, or 5m, or 6m, or 7m, or 8m, or 9m, or 10m, or 20m, or 30m, or 40m, or 50m, or 60m, or 70m, or 80m, or 90m, or 100m, or 200m, or 300m, or 400m, or 500m, or 600m, or 700m, or 800m, or 900m, or 1000m, or 2000m, or 3000m, or 4000m, or 5000 m. In another embodiment, the search radius is a user selected search radius. In yet another embodiment, the search is conducted within a predetermined or user-selected location, such as a building (e.g., shopping mall, school). In another embodiment, the search radius is selected by the device using pre-programmable instructions.

Next, in a second step 9310, the network enabled device generates a list of network providers based on the search made in the first step 9305. In a third step 9315, the network enabled device ranks the network providers based on one or more primary network connectivity factors. In one embodiment, the one or more primary network connectivity factors are selected from the group consisting of: bandwidth, cost of maintaining connectivity with the network provider, cost of transmitting information by the network provider, download rate, upload rate, and whether network reachability probe packets are received from a first server and/or received from a second server (see above). In one example, a network provider that provides network connectivity at a lower cost than another network provider has a higher level. In another specific example, the one or more network connectivity factors include proximity to a network provider. In such a case, a network provider that is close to the network-enabled device (e.g., measured in terms of signal strength) has a higher ranking than another network provider that is further away from the network-enabled device. The network enabled device generates a sorted list based on one or more primary network connectivity factors.

In an alternative embodiment, in a third step 9315, a ranking table of network providers is generated by assigning random positions to one or more network providers on the list generated in the second step 310. This is done by means of a random number generator or a pseudo-random number generator. In such a case, a network provider that originally has a lower level of rank than another network provider may instead appear at the top of the network provider sorted list. As another alternative, the list of network providers in second step 9310 is populated in the order in which the network providers are identified by the network enabled devices, and the third step 9315 is eliminated. In one example, the list of network providers is populated in the order in which the network providers respond to the network enabled devices, such as, for example, in the order in which the network enabled devices probe network reachability of the network providers. In such a case, the first response is the first on the list, the second response is the second on the list, and so on. In another specific example, the list of network providers is populated in the order in which the network enabled device receives some identifiable material from the network provider. The identifiable material includes text or other data that allows the network-enabled device to identify each network provider.

Next, in a fourth step 9320, the network enabled device probes network providers on the sorted list based on one or more secondary network connectivity factors. The one or more secondary network connectivity factors are selected from the group consisting of: bandwidth, cost of maintaining connectivity with the network provider, cost of transmitting information by the network provider, download rate, upload rate, and whether network reachability probe packets are received from a first server and/or received from a second server (see above). In one example, if the sorted list is randomly populated, the secondary network connectivity factors help refine the list to identify preferred or more preferred network providers. For example, a network provider is preferred if it provides a predetermined limit or greater than the upload rate, download rate, and/or network bandwidth ("bandwidth") of other network providers on the sorted list.

Next, in a fifth step 9325, the network enabled device reorders the list of network providers based on the results of the probing in fourth step 9320. In some cases, probing the network provider based on one or more secondary network connectivity factors does not cause any reordering of the lists generated in second step 9310 and third step 9315.

In a sixth step 9330, the network-enabled device connects to the network provider at the top of the reordered list generated in fifth step 9325. In some cases, method 9300 is repeated to continually or periodically update the network provider list so that the most preferred network provider is at the top of the list. In one example, if the order of the network providers changes, the network enabled device connects to the new network provider at the top of the list. In other cases, the method 9300 is repeated manually, such as by a request from a user operating the network-enabled device. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

In one embodiment, the network-enabled device stores the list of network providers in a list or data file in a memory, cache, or other storage location (e.g., hard disk) of the network-enabled device. In other embodiments, the network-enabled device stores a list of network providers on a server. In some cases, the list is continuously updated, and the server contains the latest list of network providers. Providing the location of the network-enabled device along with a list of network providers enables generation of a map of preferred network providers as a function of location if the network-enabled device has Global Positioning Service (GPS) features or is capable of triangulating its location.

Network connectivity guidelines

Another specific example described herein provides network connectivity criteria (or rules). Such rules may be used to determine which network provider to employ for network ingress and egress. For example, the rules may specify the network provider to be selected based on upload and download rates. In such a case, the network-enabled device connects to a network provider and performs network reachability probes for a first server having a static IP address and a second server having a static URL. This is repeated for any other network provider. A list of network providers is generated having network reachability probes that enable the network enabled device to successfully probe network providers of the first server and the second server. In one specific example described herein, the network enabled device selects the network provider from the list that provides the highest upload and download rate.

In some embodiments, the network connectivity rule is selected from a bandwidth of another network provider, a cost of maintaining connectivity with another network provider, a cost of transferring information by way of another network provider, a download rate of another network provider, and an upload rate of another network provider.

In some embodiments, the network connectivity rules include (a) whether the network device receives responses from the first server and the second server after performing the network reachability probes to the first server and the second server, (b) whether the network bandwidth of the second network provider is higher than the network bandwidth of the first network provider, (c) whether the network cost of the second network provider is lower than the network cost of the first network provider, (d) whether the network ingress and egress provided by the second network provider is more robust than the network provided by the first network provider, (e) whether the connectivity between the network device and the second network provider is via a wired connection and the connection between the network device and the first network provider is via a wireless connection, and (f) whether the second network provider is closer to the network device than the first network provider.

The network connectivity rules may be stored on a network location accessible by the network-enabled device or in a storage location (e.g., memory, hard disk, cache) of the network-enabled device. The network connectivity rules may be updated manually or at predetermined times, such as at predetermined intervals (e.g., at system or software updates). Network connectivity rules are in some cases user defined. In such a case, the user modifies the network connectivity rules of the user's network-enabled device. In one example, a user defines a rule that specifies that network connectivity is to be established using a network provider that supports fastest network ingress and egress and lowest network cost.

In some embodiments, the network connectivity rules (or criteria) are dynamic. In one particular example, the network connectivity rules may vary with the location of the network-enabled device. In one example, the network connectivity rules in a first geographic location (e.g., new york, usa) are different from the network connectivity rules in a second geographic location (e.g., paris, france).

In some cases, the network-enabled device determines the location of the network-enabled device and the loaded or downloaded network connectivity rules to be used at that location by means of a global positioning system, such as a Global Positioning Service (GPS). In some cases, the network-enabled device loads a preset (or default) rule, and once network ingress and egress has been established using the default rule, the rule is then updated with the location-specific rule. The default rules may be stored on the network-enabled device.

Location-specific (location-based) rules may enable users to optimize network connectivity across geographic locations. Network access at one location may be optimized using a different set of rules than optimizing network access at another location. By way of example, network access in paris may be optimized by means of a GSM provider rather than a CDMA provider-although network-enabled devices may be able to access the network through either a GSM or CDMA provider. This may be the case, for example, if the user has an agreement plan with a GSM provider and not with a CDMA provider.

In some cases, the rules may be time-based rules. Time-based rules provide rules that change according to time, such as according to time of day, day of week, week of month, month of year, and so forth. In some cases, a network-enabled device uses one or more morning rules for detecting network connectivity in the morning, one or more afternoon rules for detecting network connectivity in the afternoon, and one or more evening rules for detecting network connectivity in the evening. The morning, afternoon, and evening rules may change based on network entry and exit costs, upload rates, and/or download rates for these time periods.

In some cases, the rules may be bandwidth-based rules, where the rules may change based on a predetermined level of bandwidth available to the network enabled device. For example, if a network-enabled device has exhausted its provisioned bandwidth through a network provider, the network connectivity rules may require that the network-enabled device use another network provider. Some rules may require certain network connectivity guidelines based on the bandwidth available to the network-enabled device (i.e., available data or consumed data). In one example, if the network device has not exhausted its allocated bandwidth (e.g., 10 gigabits per month) through the first network provider, the network device will use the first network provider; however, if the network device has exhausted its allocated bandwidth, the network device will use a second network provider. This may be useful in situations where the network device would incur an excess usage fee if it were using the first network provider.

In some embodiments, the network-enabled device connects to the network through a peer device, such as another network-enabled device. Thus, a peer may appear as a network provider. In such a case, when certain conditions are met, the network enabled device has rules that may require the network enabled device to connect to a peer when certain conditions are met, such as when connectivity through the peer is preferred over connectivity via the network provider. This may be the case, for example, if a network-enabled device has exhausted its distribution bandwidth (or other usage limitation) for a particular network provider, and network connectivity through that network provider would be prohibitively costly.

Figure 88 shows a first network energising apparatus 9605 and a second network energising apparatus 9610. The second network enabled device 9610 has connected to a network provider 9615, which network provider 9615 in turn is connected to a network 9620, such as an intranet or internet. The connection can be through a wired or wireless network interface of the first network enabled device 9605 and the second network enabled device 9610. In the example shown, the connection is through a wireless interface of a first network enabled device 9605 and a second network enabled device 9610; the connection between the first network enabled device 9605 and the second network enabled device 9610 is wireless (dashed double arrow). In some cases, the second network enabled device 9610 has successfully probed for network reachability for a first server with a static IP address and a second server with a static URL. Further, the second network enabled device 9610 may have satisfied certain network connectivity rules, such as geographic location based rules (e.g., the second network enabled device 9610 has selected the network provider 9615 based on the geographic location of the second network enabled device 9610).

In some embodiments, the network-enabled device connects to a network provider (e.g., a router or peer device) that is a trusted network provider-i.e., the network-enabled device trusts the network provider. This trust is established by means of a trust protocol. For example, the user may generate a list of trusted network providers, or the user's network-enabled device may maintain a record of network providers that the user has previously selected to use.

In other cases, the trust protocol may be provided by a system having one or more servers that provide trust protocols for network-enabled devices. Such trust protocols may be location-based. The trust protocol may be included in the connectivity rules of the network-enabled devices that may be updated manually or periodically.

In some embodiments, a first network-enabled device can communicate with a network (an intranet or the Internet) by connecting to a second network-enabled device communicatively coupled to the network. In such a case, the second network enabled device may have connected to the network provider and successfully made a network reachability probe for the first server having the static IP address and the second server having the static URL. The first network enabled device may in turn provide network connectivity to a third, fourth or more network enabled devices. In some cases, a first network-enabled device can receive updates (e.g., rule updates, software updates) from a network via network connectivity of a second network-enabled device.

Network credit

In another specific example described herein, network credits are provided for enabling a network-enabled device to connect to a network through a peer device (e.g., another network-enabled device) already connected to the network. In some embodiments, the network credit provides an incentive to the network-enabled device to provide network connectivity to another network-enabled device; in such a case, other network enabled devices may be more inclined to network connectivity through a peer device than a non-peer device type network provider (e.g., a router).

In one non-limiting embodiment, a first network-enabled device connects to a second network-enabled device that has successfully connected to the network through a router (e.g., a WiFi connection or a connection through a CDMA access point). In some cases, network connectivity of a first network enabled device through a second network enabled device may be preferred if connectivity through the second network enabled device is less expensive than connectivity through a non-peer device type network provider, or if the second network enabled device provides preferred signals or bandwidth as compared to a non-peer device type network provider. This may be the case if a first network enabled device has exhausted its allocated bandwidth through a particular network provider, such as a router to which a second network enabled device is connected. In exchange for providing a network connection to the first network enabled device, the second network enabled device receives network credits from the first network enabled device.

It should be understood that any device may be equipped with any of the network connection techniques described herein, such as, but not limited to, those shown in fig. 1-23. For example, in one example, the electronic communication device is part of, or is associated with, a fluid analyzer, a diagnostic device, or other detection device as described.

In some embodiments, the network credit provides an incentive for the network-enabled device to connect to the network through point-to-point connectivity (see, e.g., fig. 88). In one particular example, network credit is a commitment to future payment, such as at a predetermined rate or a rate agreed upon by a user of a network-enabled device upon a point-to-point connection. In another embodiment, network credit is a commitment to future network usage. In such a case, if a first network enabled device uses network credit from the first network enabled device to pay for network access for a second network enabled device, the first network enabled device can provide network access to the second network enabled device at some point in time in the future.

Network credits may be negotiated between network enabled devices to avoid access restrictions, such as bandwidth and usage time. For example, if a first network enabled device uses network credits to pay a second network enabled device for network ingress and egress, the network credits may provide a certain bandwidth (e.g., 2 megabits/second, 30 minutes) of the first network enabled device to the second network enabled device at some point in the future. Alternatively, the network credit may be a commitment to pay a predetermined or negotiated amount. In some embodiments, the predetermined or negotiated amount is less than a cost of network connectivity through the non peer-to-peer device type network provider.

Network connectivity system

In another specific example described herein, a system for establishing network connectivity for a network device includes a network connectivity system configured for locating a network provider. The network connectivity system is configured to establish a connection with a network provider, perform network reachability probing by the network provider for a first server having a static Internet Protocol (IP) address, perform network reachability probing by the network provider for a second server having a static Uniform Resource Locator (URL), and determine whether to maintain connectivity with the network provider based on whether the network device receives a response from the first server and/or whether the network device receives a response from the second server.

In some cases, the network connectivity system is part of, or associated with, an electronic device (such as a portable electronic device). The network connectivity system may be a subsystem of a larger system. In one example, the network connectivity controller is a network card and associated software in the portable electronic device. In another example, the network connectivity controller is a stand-alone system configured to provide network connectivity with the electronic device.

The network connectivity system includes one or more appliances selected from the group consisting of a Central Processing Unit (CPU), memory (e.g., flash memory), a transmitter, and a communication vehicle (e.g., a serial communication vehicle). The transmitter may be a radio frequency ("RF") transmitter or a photo-transmitter. The one or more instruments or components may be interconnected, such as by way of a circuit or system board (e.g., motherboard) in a network connectivity system.

Fig. 86 shows a system 9400 having an electronic device 9405, a first network provider 9410, a second network provider 9415, a first server 9420, and a second server 9425 according to one specific example described herein. The first server 9420 communicates with a first network provider 9410 and a second network provider 9415 over a first network 9430, such as an intranet or the internet 9435. The second server 9425 communicates with a first network provider 9410 and a second network provider 9415 over a second network, such as the internet 9435. The first server 9420 may be connected to the internet 9435.

The electronic device 9405 includes a network connectivity system for connecting the electronic device 9405 to a first network provider 9410 and network reachability detection to the first 9420 and second 9425 servers or directing first data packets to the first 9420 server and second data packets to the second 9425 server as described above. The network controller includes computer-executable instructions for facilitating the methods described herein (see below).

It should be understood that any device may be equipped with any of the network connection techniques described herein, such as, but not limited to, those shown in fig. 1-23. For example, in one example, the electronic device 9405 can itself be, be part of, or interface with a fluid analyzer, diagnostic device, or other detection device as described.

In some cases, the electronic device 9405 is a portable electronic device, such as a notebook computer, tablet PC, or smart phone. In other cases, the electronic device 9405 is a stationary electronic device, such as a desktop computer or a server. The electronic device 9405 can be connected to a first network provider 9410 and a second network provider via a wired or wireless communication mode. As shown, the electronic device 9405 communicates with a first network provider 9410 and a second network provider via wireless communication.

The first network provider 9410 and the second network provider 9415 are wireless routers. In other cases, the first network provider 9410 and/or the second network provider 9415 are wired routers or other devices configured to facilitate communication of the electronic device 9405 with the network 9435. Additionally, system 9400 can include other network providers that communicate with network 9435.

In one example, the electronic device 9405 connects to a first network provider 9410 and performs network reachability probes for the first server 9420 and the second server 9425. If the electronic device 9405 receives a response from the first server 9420 and the second server 9425, the electronic device 9405 maintains its connection with the first network provider and the user can access the internet 9435. Otherwise, the electronic device 9405 connects to a second network provider 9410 and performs network reachability probes for the first 9420 and second 9425 servers and waits for a response.

In the event that a response is received from both the first server 9420 and the second server 9425 (such as via the first network provider 9410), the electronic device 9405 can determine whether to maintain connectivity with the first network provider 9410 in view of the various connectivity factors provided herein. For example, if the network speed of the first network provider 9410 is below a predetermined limit (e.g., 100kbit/s), the electronic device 9405 terminates connectivity with the first network provider 9410 and connects to the second network provider 9415.

The electronic device 9405, or components of the electronic device 9405 (e.g., a network controller), can include Random Access Memory (RAM) for supporting rapid transfer of information to and from a Central Processing Unit (CPU) and to and from storage modules, such as one or more storage units including magnetic storage media (i.e., hard disks), flash storage media, and optical storage media. In addition, the system may include one or more storage units, one or more CPUs, one or more RAMs, one or more read-only memories (ROMs), one or more communication PORTs (COM PORTs), one or more input/output (I/O) modules, such as I/O interfaces, network interfaces for enabling the system to interact with internal networks, including other systems and subsystems, and the Internet, including the world Wide Web. The storage unit may include one or more databases, such as relational databases. In some cases, the system further includes one or more of a data repository and a relational database for storing information (e.g., network providers, network connectivity history). FIG. 87 illustrates a functional block diagram icon of a general-purpose computer hardware platform configured for use with the methods and systems provided herein.

The electronic device 9405 can include, for example, a data communication interface for packet communication and/or network reachability detection to other systems, such as a server. In some cases, the electronic device 9405 includes a Central Processing Unit (CPU) in the form of one or more processors for executing program instructions. The electronic device 9405 can include an intercom communication vehicle, program storage, and data storage for various data files to be processed and/or communicated by the system, although the system can also receive programming and data via network communication. The hardware components, operating system and programming language of such devices are conventional in nature and are assumed to be well known to those skilled in the art. Of course, the device functions may be implemented in a distributed manner on many similar platforms to spread the processing load (see below). Electronic devices and systems provided herein may include subsystems and modules for dispersing and/or distributing tasks.

In some specific examples, the electronic device 9405 includes a network controller having a processor for performing the methods provided above. The processor is configured to execute machine readable code (source code or compiled object code) to facilitate the methods in the embodiments described herein.

In some specific examples, the device 9405 includes a user interface for displaying a list of one or more network providers to a user. The user interface is in some cases a Graphical User Interface (GUI). In one particular example, the GUI shows a sorted list of network providers, with the more preferred network provider at the top of the list. In another particular example, the GUI enables the user to select a network provider from a list of network providers. In some cases, the network provider list is generated by means of one or more network connectivity criteria as described above.

Thus, each specific example of the method listed above may be embodied in programming. Examples of processes for technologies may be referred to as "products" or "articles of manufacture," typically in the form of executable code and/or associated data carried or embodied in some type of machine-readable medium. A "storage" type medium may include any or all of the tangible memory of a computer, processor, etc., or associated modules thereof, such as various semiconductor memories, tape drives, disk drives, etc., that may provide non-transitory storage for software programming at any time. From time to time, the entire software or portions of the software may communicate over the internet or various other telecommunications networks. Such communication may, for example, support loading of software from one computer or processor into another computer or processor, for example, into the computer platform of an application server from a management server or host. Media that can carry software elements include optical, electrical, and electromagnetic waves, such as the physical interface between devices over a region, the networking through wired and optical landlines, and the use of media over various air links. The physical components that carry such waves, such as wired or wireless links, optical links, etc., can also be considered as media carrying software. Unless limited to being non-transitory, a tangible "storage" medium, such as a computer or machine "readable medium," as used herein, refers to any medium that participates in providing instructions to a processor for execution.

A machine-readable medium may take many forms, including but not limited to, tangible storage media, carrier wave media, or physical transmission media. Non-volatile storage media include, for example, optical or magnetic disks, any storage device such as in any one or more computers or the like, such as may be used to implement the databases and the like shown in the figures. Volatile storage media includes dynamic memory, such as the main memory of such computer platforms. Tangible transmission media include coaxial cables; copper wire and fiber optics, including the cables that make up the communications bus within the computer system. Carrier-wave transmission media can take the form of electrical or electromagnetic signals, or acoustic or light waves, such as those generated during Radio Frequency (RF) and Infrared (IR) data communications.

Thus, common forms of computer-readable media include, for example: a floppy disk, a flexible disk, hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD, or DVD-ROM, any other optical medium, punch cards, paper tape, any other physical storage medium with patterns of holes, a RAM, a ROM, a PROM, and EPROM, a FLASH-EPROM, any other memory chip or cartridge, a carrier wave transporting data or instructions, a cable or link transporting such a carrier wave, or any other medium from which a computer can read program code and/or data. Many forms of such computer-readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution.

Method steps may be implemented by a program product including machine-executable instructions, such as program code in the form of program modules, executed by systems or machines in networked environments, for example. Generally, program modules may include routines, programs, objects, components, data structures, etc. that perform particular tasks or implement particular abstract data types. Machine-executable instructions, associated data structures, and program modules represent examples of program code for executing steps of the methods disclosed herein. The particular sequence of such executable instructions or associated data structures represents examples of corresponding acts for implementing the functions described in such steps.

In some cases, the systems and methods provided herein are implemented in a networked environment using logical connections to one or more remote computers having processors. The logical connections may include a Local Area Network (LAN) and/or a Wide Area Network (WAN), for example. Such networking environments may be found in office-wide or enterprise-wide computer networks, intranets, and the Internet, and may use a variety of different communication protocols. Those skilled in the art will appreciate that such network computing environments may encompass many types of computer system configurations, including personal computers, hand-held devices, multiprocessor systems, microprocessor-based or programmable consumer electronics, network Personal Computers (PCs), servers, minicomputers, mainframe computers, and the like.

It should be noted that while the flow charts provided herein (e.g., fig. 83 and 84) show a particular order of method steps (also referred to herein as "steps"), it should be understood that the order of these steps may differ from that depicted. Further, two or more steps may be performed concurrently or with partial concurrence. Such variations may depend on the software and hardware systems chosen, as well as on the designer's choices. It is understood that all such variations are within the scope of the present invention. Likewise, software and web implementations of the present invention could be accomplished with standard programming techniques with rule based logic and other logic to accomplish the various database searching steps, correlation steps, comparison steps and decision steps.

Examples of the invention

Example 1

The device is located in an area having three WiFi routers within wireless range of the device's network antenna. The network device is connected to a first WiFi router. The device performs network reachability probes for a first server having a static IP address and a second server having a dedicated URL (e.g., "google. Upon network reachability detection of the second server, a DNS server in network communication with the first WiFi router resolves the IP address of the second server. The network reachability probe packet is then sent to the second server at the parsed IP address. The device computer maintains connectivity with the first WiFi router if the device receives responses from the first server and the second server. The devices are in turn connected to the internet to receive and/or transmit desired information. If the device does not receive a response from one or both of the first server and the second server, the device connects to the second WiFi router. By way of non-limiting example, any device on which the techniques described herein may be implemented is not limited to the examples shown in FIGS. 1-23.

Example 2

The user is on an airplane with multiple network access points (WiFi hotspots). The user's smart phone automatically scans and generates an in-out point list. Next, the user's smart phone connects to a first network access point and performs network reachability detection for a first server having a static IP address and a second server having a dedicated URL. Network reachability probes to the second server must use a ping command (e.g., "ping www.Google.com") targeting the URL. The DNS server will resolve the IP address of the URL to then probe the second server for network reachability using the resolved IP address. If the user's smart phone receives responses from both the first server and the second server, the user's smart phone maintains its connection to the first network entry and exit point and the user enters and exits the network. If the user's smart phone does not receive a response from one or both of the first server and the second server, the user's smart phone connects to the second network access point and repeats the above steps. While this example is described in the context of a wireless-enabled phone, it should be understood that the same concepts may be applied to a liquid analyzer or other diagnostic device with network connectivity hardware and/or software to implement the techniques described herein.

Example 3

A tablet PC (e.g., iPad) has a first wireless interface configured for communication with one or more WiFi routers and a second wireless interface configured for communication with a GSM provider. The tablet PC connects to the WiFi router using a first wireless interface and performs network reachability probes for a first server having a static IP address and a second server having a static URL. Next, the tablet PC connects to the GSM provider using the second wireless interface and performs network reachability probes for the first server and the second server. The tablet PC then evaluates the network connectivity via the WiFi router and the GSM provider with the aid of the processor of the tablet PC to determine whether the connection via the WiFi router and/or the GSM provider meets certain predetermined network connectivity criteria (or rules). The tablet PC determines network connectivity via the WiFi router to be preferred because network connectivity via the WiFi router provides higher upload and download rates and is less expensive than connectivity via the GSP provider. The tablet PC then uses the WiFi router for internet access. While this example is described in the context of a tablet PC, it should be understood that the same concepts may be applied to a liquid analyzer or other diagnostic device with network connectivity hardware and/or software to implement the techniques described herein.

While the above is a complete description of the preferred embodiments of the invention, it is also possible to use various alternatives, modifications, and equivalents. The scope of the invention should, therefore, be determined not with reference to the above description, but instead should be determined with reference to the appended claims along with their full scope of equivalents. Any feature (whether preferred or not) may be combined with any other feature (whether preferred or not). The appended claims should not be construed to include device-plus-function limitations unless such limitations are expressly set forth in the given claims with the phrase "device for …". It should be understood that the meaning of "a", "an", and "the" as used herein in the description and throughout the claims that follow includes plural references unless the context clearly dictates otherwise. In addition, the meaning of "in …" as used in the description herein and throughout the claims that follow includes "in …" and "on …" unless the context clearly dictates otherwise. Finally, the meanings of "and" or "as used in the description herein and throughout the claims that follow include both connectivity and compartmentalization and are used interchangeably unless the context clearly dictates otherwise. Thus, in the context of using the terms "and" or, "the use of such conjunctions does not preclude the meaning of" and/or, "unless the context clearly dictates otherwise.

Further, concentrations, amounts, and other numerical data may be presented herein in a range format. It is to be understood that such a range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a size range of about 1nm to about 200nm should be interpreted to include not only the explicitly recited limits of about 1nm and about 200nm, but also include individual sizes such as 2nm, 3nm, 4nm, and sub-ranges such as 10nm to 50nm, 20nm to 100nm, and the like.

This document contains material which is subject to copyright protection. For example, all pictures shown here are copyrighted material. The copyright owner (applicant herein) is not objected to the facsimile reproduction by anyone of the patent document and disclosure, as it appears in the patent and trademark office patent file or records, but otherwise reserves all copyright rights whatsoever. The following notice should apply: copy 2012Theranos, Inc.

Claims (19)

1. A system, comprising:

a housing; and wherein the housing comprises:

(a) a plurality of modules, a single module of the plurality of modules comprising a sample preparation meter, a measurement meter, and a detection meter,

wherein the sample preparation meter is configured to implement at least one sample preparation procedure, the assay meter is configured to perform one or more assays and to receive a plurality of assay units,

wherein each assay unit is (a) liquid isolated from each other, (b) configured to perform the one or more assays, and (c) independently movable;

wherein the single module is detachable from the housing and interchangeable with another module of the system;

wherein each assay performed within each assay unit is configured to produce a detectable signal;

and wherein the detector is configured to detect a signal from each assay;

and (b) a sample handling system comprising a pipette nozzle, wherein the pipette nozzle is configured to (i) engage with a pipette tip to transfer a sample or reagent within or from the single module to another module within the housing of the system and (ii) engage with assay units to transport each assay unit from the assay meter to a location where the signal is detectable by the detector.

2. The system of claim 1, further comprising:

a cytometer configured to perform cell counting on the sample.

3. The system of claim 1, wherein the one or more assays are selected from the group consisting of immunoassays, nucleic acid assays, receptor-based assays, cytometric assays, colorimetric assays, enzymatic assays, electrophoretic assays, electrochemical assays, spectroscopic assays, chromatographic assays, microscopic assays, topographic assays, calorimetric assays, turbidimetric assays, agglutination assays, radioisotope assays, viscometric assays, coagulation assays, clotting time assays, protein synthesis assays, histological assays, culture assays, osmolarity assays, and combinations thereof.

4. The system of claim 1, wherein the system is configured to process or assay a sample having a volume less than or equal to 250 μ l.

5. The system of any of claims 1-4, wherein the sample processing system comprises a pipette configured to ingest, dispense, and/or transfer a biological sample.

6. The system of any of claims 1-4, further comprising:

an imaging device configured to image one or more of the group consisting of an acquired biological sample, a processing of the biological sample, and a reaction performed on the system.

7. The system of any one of claims 1-4,

the system is configured to detect a plurality of analytes or disease conditions from the sample, the plurality of analytes differing from each other by more than an order of magnitude.

8. The system of any one of claims 1-4,

the system includes a sample acquisition unit configured to draw a fluid or tissue sample from a subject.

9. The system of any one of claims 1-4,

the system has a coefficient of variation of less than or equal to 15%.

10. The system of any of claims 1-4, further comprising:

a control unit having computer executable commands configured to perform a point of service at a specified location.

11. The system of any one of claims 1-4,

the sample preparation meter includes a sample acquisition unit configured to acquire a biological sample from a subject.

12. The system of claim 6,

the imaging device is a camera or sensor for detecting and/or recording electromagnetic radiation and associated spatial dimensions and/or temporal dimensions.

13. The system of claim 6,

the system stores and/or transmits electronic data representative of the resulting image to an external device via a communication unit included in the system.

14. The system of any of claims 1-4, further comprising:

a centrifugal machine.

15. The system of any of claims 1-4, configured for bidirectional communication with an external device via a communication unit comprised in the system, wherein the communication unit is configured for transmitting data to the external device and receiving instructions with the system.

16. The system of any of claims 1-4, further comprising:

a control unit having computer executable commands for performing a service point service at a designated location by means of at least one of the sample preparation meter, the meter and the probe; and

wherein the sample processing system comprises at least one pipette having a pipette nozzle configured to be connected to a tip removable from the pipette nozzle, wherein the pipette is configured to transport no more than 250uL of liquid within or between the prep, meter and/or detector.

17. The system of claim 16,

the pipette is configured to dispense and/or aspirate no more than 100uL of liquid through the tip.

18. The system of claim 16,

the tip is configured to retain a sample having a volume of no greater than 100 uL.

19. The system of claim 16,

a control unit having computer executable commands is configured to perform a point-of-service at a location selected from the group consisting of a retail outlet, a subject's home, a health assessment/treatment location, or an office.