CN101374757B - Methods for fluidic structures, devices, methods and instrument configurations - Google Patents

Abstract

A fluid handling structure comprising: an actuation zone (03, 08) to control fluid flow within the structure; and a plurality of actuation components (09, 11, 12, 13) within the actuation zone (03, 08); wherein the actuation area (63, 68) is constructed and arranged to trigger or control each of the plurality of actuation members (09, 11, 12, 13). The fluid handling structure includes: a fluid channel (204); and a deformable material (202); wherein the microfluidic channel is at least partially defined by a deformable material (202). A fluidic device comprising: at least one channel (403) defining a path for electromagnetic waves to travel. A method of performing an instrument function, the method comprising: an insert is coupled to the instrument, the insert including one or more of program code, data, or instructions that implement the functions to be performed.

Description

Methods for fluidic structures, devices, methods and instrument configurations

technical field

The present invention generally relates to structures, devices and methods for manipulating the flow of fluid, optionally within a structure having at least one dimension substantially less than 10 millimeters, but typically less than 1 millimeter. More particularly, the present invention relates to fluid handling structures that allow for the external handling of fluid within the device. A single actuator may act on more than one fluid handling structure. Fluid handling schemes may involve the use of movable parts, electrodes and semi-permeable membranes or combinations thereof. The deformable member may deform directly into the fluid handling structure, or indirectly as part of the fluid handling structure, to cause or prevent pressure or shape changes within the fluid handling member. Gas permeable membranes can be used to restrict fluid flow within structures for pumping, valve control, chemical storage and injection, filtration, or degassing.

The present invention also generally relates to structures, devices and methods employing deformable or movable components to manipulate the flow of fluid, optionally within a structure having at least one dimension generally less than 10 millimeters but typically less than 1 millimeter. More particularly, the present invention relates to fluid handling structures comprising deformable members that can be used as pumps or valves. The deformable member can function in a variety of ways, for example it can be deformed into or as part of a fluid handling structure to create flow restriction, or increase pressure, or induce flow of contained fluid.

The present invention additionally relates generally to apparatus and methods for fabricating flow cells for use in fluid flow and optionally having at least one dimension substantially less than 10 millimeters but typically less than 1 millimeter. Measured in a structured device. More particularly, the present invention relates to submillimeter scale devices and structures and methods of fabricating them that facilitate the measurement of the interaction of electromagnetic waves with fluids flowing therein.

The present invention also relates generally to systems and methods for software and data processing, and more particularly to systems for upgrading, configuring, or transferring information to a device through the use of one or more plug-ins that may be used primarily for other purposes and methods.

Background of the invention

Certain structures and/or methods are discussed below. However, the discussion below should not be construed as an admission that these structures and/or methods constitute prior art. Applicants hereby reserve the right to state that such structures and/or methods do not constitute prior art.

Literature and methods for fluid manipulation

There has been increasing interest in developing microscale systems for fluid analysis. These developments are already underway as they offer the advantage of miniaturization. In particular, improvements in performance over traditional laboratory equipment can be obtained in terms of automation, reproducibility, speed, cost and size. This rapidly growing field includes micro total analysis systems (μTAS), or "lab on a chip" devices. Most of this early work was performed on silicon or glass substrates using existing techniques developed in the 70's and 80's for the semiconductor industry.

Many different pumping and valve control schemes have been integrated into miniaturized devices. The simplest solution is capillary wicking, which uses surface tension to force fluid flow in a suitable capillary environment. However, in properly shaped capillaries, this technique has limited ability to uptake samples. Electrokinetic flow is another commonly used technique, but is limited in substrate and fluid medium choice due to surface charge-fluid interaction and Joule heating, and is potentially hazardous for many portable diagnostic applications due to the use of high drive voltages . Electrokinetic flow can also be used to induce flow in connecting channels that cannot withstand electrokinetic pumping, see US Patent No. 6012902; however, the same electrokinetic limitations still exist in the electroactive region and system drive voltage.

In terms of versatility, pressure driven pumps are the preferred method for fluid delivery. However, to date, pressure pumps integrated into microdevices have required relatively complex instrumentation systems to control the actuators that operate the microdevices. Examples of this type of approach can be seen in the pneumatically operated and piezoelectrically driven micropumps of US Patent No. 6,073,482 described in US Patent Publication Nos. The need for such an instrument limits the use of the device to the size and cost constraints of ancillary instruments. Another problem inherent in the operation of known devices is the inherent inefficiency and reliability of fluid handling operations. Channels with deformable membranes are prone to leaks due to the need to conform the movable part to the channel dimensions. Also, complex manifolds and large areas are required on microdevices for complex fluid manipulations.

Additionally, pressure pumps integrated with microdevices typically have complex three-dimensional geometries with multiple one-way valves that are complex to manufacture and thus have reliability issues. Examples of this type of geometry using polymeric materials can be seen in US Patent Nos. 5,718,567 and 6,073,482. US Patent No. 6619311 and US Patent Application Publication US2002/0148992A1 have disclosed similar three dimensional membrane-based valve topologies employing multilayer polymer films. However, the overall relative complexity of the structure and the requirement for pneumatic operation raises problems associated with couplings and transitions, and their application is limited to those where a pneumatic supply can be provided.

A simpler valve design is provided by US Patent No. 6408878, which proposes micro fluidic channels cast within an elastomer. The presence of a second channel or structure within the elastomer is required to allow deflected flow into the first channel due to actuation, usually by pneumatic force. This technique is not suitable for large-scale production because of the need to form the microstructure in the elastomer, i.e. the proposed multi-stage casting method is a slow batch process.

Traveling wave pumps have been fabricated in miniaturized silicon devices using electrically deformable membranes, see US Patent Nos. 5,705,018 and 5,096,388. However, due to the materials used and the special processing required, this production method is limited to batch semiconductor manufacturing processes and is relatively expensive. U.S. Patent No. 6,408,878 discloses a polymer multi-valve pump that produces a peristaltic-type motion by using three or more valves deformed alternately into a fluid channel to give a pseudo-traveling wave, but the manufacture is also limited to batch Processing procedure.

What is required for many portable and low-cost applications are methods to increase device efficiency and to simplify or reduce the size and cost of ancillary equipment. The devices and methods described in the prior art do not provide efficient, easy-to-use, small, lightweight, inherently reliable, or variable for high-volume mass production for small-scale pumping, valve control, and other fluid manipulations. The (scaleable) method.

Alternative Measuring Devices and Methods

Crucial to the usability of microfluidic devices is the ability to analyze the properties of the fluids they comprise. Many methods and techniques are used to measure these properties including electromagnetic radiation disturbances, such as optics, and corresponding detection strategies. These measurements based on absorption, transport and luminescence (phosphorescence and fluorescence) are problematic at the small scales used by these devices. Most of these problems are due to the very small signal response caused by harsh size constraints, reduced path lengths, and reduced fluid volumes.

Capillary and microfluidic optical-based detection techniques typically employ instruments that themselves have wave-disturbing elements to focus photons into small chambers or channels of fluidic devices. Problems with these techniques include: alignment difficulties due to small fluidic dimensions; size of components used; signal loss. Another way to improve these aforementioned limitations is to integrate optical components in the same part as the fluidic components.

An example of a microfluidic device with integrated optics is described in US Patent No. 6,100,541. Here the optical components are integrated into the bulk structure adjacent to the microchannels in the bulk structure. A polymer structure with integrated prisms adjacent to microfluidic channels is described therein.

In order to measure large fluid changes on such small scales (typically less than 10 mm), it is generally believed that increasing the path length can improve the detector response. In transmission and absorption based detection, the signal response is proportional to the path length through the fluid (Beer's Law). Also, as is the case with luminescence measurements, better signals can be produced with more light emitting reporters. For example, in capillary electrophoresis, it is known that the use of a "Z cell" configuration to increase the optical path length improves detection.

It is known to provide increased path length detector units in microfluidic devices using fiber optic coupling and silicon or glass etching techniques. These manufacturing processes are often expensive and not suitable for high-volume production of single-use devices. Examples of such devices are disclosed in US Patent Nos. 5599503 and 6490034, which provide methods for fabricating microfluidic devices with detector units for absorbing UV or visible radiation. Inlet or outlet radiation is redirected along the channel of the microfluidic device by reflection from angled inlet or outlet walls with (US Patent 5599503) or without (US Patent No. 6490034) multiple reflections. The system is fabricated using silicon etch techniques. However, silicon-based fabrication of disposable microfluidic devices is commercially challenging, especially with the inherently high unit price and significantly low unit volume of this particular substrate class.

An alternative method for passing optical radiation longitudinally along the channel axis is disclosed in US Patent No. 6,224,830. The device generates multiple transfers across the fluidic channel to increase absorption in small detector regions (less than 200 μm). However, the fundamental problem of this technique is that the loss of light energy due to multiple reflections and the boundary transition of materials limit the size and sensitivity of the fluid detection unit.

A common way to couple light to a fluidic device is to use an optical fiber that interfaces directly with the fluidic manifold. These headers are usually machined from a single monolithic piece of material, and thus greatly limit their geometry. Microfluidic devices are often fabricated from multiple layers of materials forming complex fluidic manifolds. This multilayer design can cause coupling and alignment difficulties when coupling the fiber to the fluidic pathway. US Patent No. 6,867,857 discloses methods for polymer-based microfluidic devices and involves the use of fiber optic ports to couple a multilayer fluidic device to an external flow cell. However, this approach employs a separate manufacturing process for each part and raises alignment and dead volume issues, and increases device size and unit cost.

A similar approach to the previously described silicon-based reflectors is provided in US Patent No. 6900889, which discloses polymeric microfluidic devices for detection of fluorescent point light sources. The disclosed method passes a laser light along a trajectory that spans the length of a microchannel to excite fluorescent markers in a fluid contained in a polymeric microfluidic device. Light emitted by the marker is then detected through the lid of the microchannel. This technique does not require a laser beam to be scanned along the channel to detect fluorescent markers. However, this method employs a light detection member or reflective surface separate from the microfluidic device. Furthermore, the device is not suitable for transmission and absorption based measurements as it does not provide a mechanism for recovering or measuring the optical properties of the light after it has passed through the sample fluid. Another limitation is that the system only provides point light sources (indicators) for detecting radiation perpendicular to the fluidic channel. This further limits the technology because of the slow signal response of point sources and the inability to increase signal (and thus sensitivity) by focusing light.

US Patent No. 6906797 describes a polymeric microfluidic device with reflective channels for directing light through multiple channels for fluorescent spot detection. Since measurements are made across the width of the channel, this technique is limited in its signal response in a manner similar to the previous examples, and further loss of light due to separation of light from the fluidic channel through a different medium . Also, there is no way to aggregate signals from point sources.

The prior art devices and methods described above do not provide a low-cost integrated method for proper absorption, transport and fluorescence detection in a microfluidic device. The present invention fulfills the need for a low cost polymer device, providing a device with enhanced optical properties within the flow cell, which is inherently reliable and variable for high throughput mass production.

Instrument configuration method

There are many different types of instruments. For example, some types of instruments are devices that control experiments or gather information from the environment, unit, or material being tested. Other instruments may perform data analysis or data processing, including display to the user or data storage. Examples of instruments include: digital multimeter; oscilloscope; DNA sequencer; pressure sensor; PDAs); digital music players, etc.

An insert is a removable or connectable device, which may be a sensor, cartridge, cassette, eg a microfluidic device that cooperates with an instrument eg by providing it with certain functionality. The insert can be, for example, a memory stick, a smart card, or a rigid or flexible printed circuit.

Inserts are often designed for specific purposes, or purposes such as whole blood metabolite monitoring, electrochemical analysis of mineral samples, or DNA amplification from bacteria, to name a few such specific purposes. If the instrument is dedicated to a specific application and sensor type, all necessary program operating procedures, or example protocols, can be included in the instrument without the need for on-chip recognition (on-chip recognition) to distinguish between pluggable devices, because they are all same.

However, when multiple types of inserts are used in the same instrument, the instrument must distinguish each insert so that the correct protocol.

Typically, the user selects which insert is used, or manually configures the instrument to use each insert. Alternatively, the insert itself indicates its own functionality to the instrument. Typically this is done using a serial number or product code, and the instrument then references its internal program code to establish the appropriate application protocol for the particular insert type (eg, Figures 51 and 52). Typically, this information has been encoded in a number of different formats, including: electrical encoding via electrode connections, resistance values, or integrated circuits; optical encoding via barcodes; magnetic encoding via magnetic strips; and mechanical encoding. For microfluidic inserts, US Patent No. 6,495,104 describes a standard method of encoding information to indicate chip functionality to instruments.

The disadvantage of this instruction is that the instrument software still needs to include all program information for the operation of the device. The instrument therefore needs to include all codes for possible applications before leaving the manufacturer, or needs to be provided with a software upgrade package for each new application after sale. Likewise, after sale, support in software upgrades is required to correct software defects, as is often the case with scientific instruments, requiring support in new calibration or operating data.

Usually, these upgrades are provided to users in the form of new software versions or upgrade patch packs on disk or CD-ROM. This is usually only for major updates or upgrades, as frequent releases of upgrade media and requiring users to install new upgrades are considered problematic. With the development of World Wide Web installations, remote upgrades can be performed as long as the instrument is connected to a suitable network.

An additional disadvantage of providing a single upgrade for a new instrument application is the development cost of providing the new application and associated installation package. Such an upgrade method also introduces the possibility of bugs or system outages due to the increased code complexity of the software itself, as well as potential incompatibilities caused by multiple upgrades and incomplete sequence history. Additionally, allowing an instrument to be upgraded in this manner also leaves the instrument open to unauthorized "hacking", which creates additional reliability and warranty issues for the manufacturer or vendor.

In addition, whether upgrade service delivery is done with physical disk or via remote means including email and the Internet, there are additional transport considerations related to the cost of delivery and technical issues.

A disadvantage of the prior art approach of retaining the entire program code on the instrument is that including all instrument operating protocols in one program has inherent security risks. Putting the instrument's program operation entirely within the instrument means that reverse engineering may be easier, allowing unauthorized use of the instrument, and/or manipulation with third-party inserts, or even duplication of the entire instrument.

Traditional methods of software protection include the use of serial numbers, remote licensing services and/or files, and dongle protection. However, these methods do not prohibit skilled operators from accessing onboard applications to operate the instrument or use external inserts. An example of bypassing a program's authorization code is to "hack" the program and bypass the authorization code interrogation, thereby allowing full program operation without authorization.

The present invention describes new methods and systems to overcome the aforementioned limitations by ensuring that some or all of the upgrade data, program code, test data, or related information is maintained within the insert.

Contents of the invention

Literature and methods for fluid manipulation

According to a first aspect of the present invention there is provided a fluid handling structure comprising: an actuation zone for controlling fluid flow within the structure; and at least one actuation component within the actuation zone; wherein the actuation zone is arranged to activate Or control at least one actuating member. In certain embodiments, the actuation zone includes a controller to control fluid flow within the device.

In another embodiment, a microfluidic device is provided comprising a controller for controlling fluid flow within the device, wherein the controller is capable of simultaneously triggering more than one pumping or valving associated with fluid flow within the device. part.

According to one embodiment, the controller can be operated manually or pneumatically. However, any suitable operating device may be used. For example, the controller may operate electromagnetically, mechanically, hydraulically, by sound, or by piezoelectricity, among others.

According to a second aspect of the present invention, there is provided a fluid handling structure comprising: an actuation region utilizing control of fluid flow within the structure; at least one of a flow chamber or channel; a semi-permeable structure forming at least one boundary of the flow cavity or channel Membrane, the semi-permeable membrane arranged to allow passage of control fluid into the flow chamber or channel, thereby facilitating, restricting or stopping fluid flow within the flow chamber or channel. The control fluid may comprise any suitable fluid and may also be, for example, a liquid, a gas or a combination thereof. One embodiment includes a second semipermeable membrane forming a second boundary of the flow chamber, channel, or fluidic network. There is no need for the second boundary to be in direct communication with the flow chamber or channel. For example, it can additionally flow along the network.

In another embodiment, a microfluidic device is provided that includes a semipermeable membrane that restricts the passage of fluids and/or particles therethrough. According to aspects of the invention, the passage of fluids, such as gases or liquids, is delayed or prevented. Membranes according to aspects of the present invention may be employed to provide functions such as separation, defoaming, filtration, pumping, valve control, mixing, filling, dosing, and the like. For example, according to one embodiment, fluid cannot pass through the membrane until a certain internal pressure is reached at which point the fluid will pass through the membrane. This particular embodiment can be used for sample storage and injection, pumping, valve control.

According to another embodiment, the membrane allows the passage of gas but not liquid (it is blocked) for functions such as degassing, pumping, valve control, reagent storage and infusion. According to another embodiment, the membrane filters particles from the fluid. These particles may, for example, include cells, microorganisms, macromolecules, antigens, and the like.

According to another embodiment, a recirculation fluidic network is provided. The recirculation fluidic network may for example comprise at least one of an inlet; a pump or a valve or a debubbler. The recirculation fluidic network may also include a detection chamber. In some embodiments, the inlet may additionally function as a bubble eliminator.

According to another embodiment, the instrument-card interface is configured such that the card provides some pneumatic plumbing. According to another embodiment, the pump and valve controller are driven by the same accumulator.

Fluid pumping, valve control, degassing, filtration, sampling, reagent storage, and controlled dosing can be used to execute complex chemical protocols. A common problem in microfluidics is the precise delivery of fluids in extremely small quantities. The present invention encompasses a variety of fluid handling structures that include movable members, semipermeable membranes, electrodes, or combinations thereof. By providing a controller capable of triggering more than one component at the same time, device operation, and thus the instrumentation requirements for the fluid handling components, can be simplified. Actuation can be performed manually by the user directly, or with the aid of an instrument. Methods for overcoming the problems of filling, sampling, injection, reagent storage, mixing and foaming are also disclosed as part of the present invention.

According to another aspect of the present invention there is provided a fluid handling structure comprising: a fluid channel; and a deformable material; wherein the fluid channel is at least partially bounded by the deformable material and the deformable material is arranged to create a confinement or compression point within the channel . In some embodiments, confinement may optionally enable the establishment of a traveling fluid wave within the channel. The structure may further include a rigid base, wherein the fluid channel is at least partially formed within the rigid base.

In another embodiment, an apparatus is provided comprising: a channel at least partially defined by a deformable material, wherein deformation of the deformable material is capable of establishing a traveling fluid wave within the channel. According to one embodiment of this aspect of the invention, the device is a microfluidic device.

According to further embodiments of this aspect of the invention, the fluid wave is created by instantaneously applying a force to the fluid at a single location along the channel. According to another embodiment of this aspect of the invention, the device is a microfluidic device, which is not made of silicon. Preferably, it is a stacked microfluidic device, and preferably, it does not utilize electromagnetic mechanisms to create fluidic waves.

According to a further aspect of the present invention, there is provided a method of pumping a fluid in a microfluidic channel comprising: utilizing a deformable material to generate a traveling fluid wave within the channel.

According to another aspect of the present invention, there is provided a microfluidic device, comprising: a microfluidic channel at least partially defined by a deformable material, wherein the cross-section of the deformable material is substantially larger than the cross-section of the channel, and the deformable material is Deformed sufficiently that it can at least partially enter the channel and thereby affect fluid flow within the channel. The deformable material according to this aspect of the invention may be of any suitable type. An experienced worker will be able to easily identify suitable materials. For example, a particular elastomeric compound has suitable properties.

Deformable materials include, but are not limited to, polymers, polymer composites, metals, and glass. In cases where the deformable material is too stiff to deform sufficiently, the deformable material is constructed to allow deformation, and/or combined with or replaced by other materials with suitable elastic properties, such as rubber, Santoprene ^™ , polymers ( Dimethicone), poly(dimethylsiloxane), nitrile, polyurethane, silicone, polyisoprene, polybutadiene, polychloroprene, polyisobutylene, or poly(phenylene Ethylene-butadiene-styrene), etc.

The use of a deformable material capable of establishing a traveling fluid wave within the channel provides a simple geometry enabling the required precision of fluid transfer and at the same time facilitating low cost mass production. Furthermore, the invention enables a more economical distribution between expensive actuation components and low cost fluid handling components. According to a preferred embodiment, the actuation member is external to the fluid treatment device comprising deformable material. A fluid handling device according to the present invention may be made of a polymeric material and fluid flow is created by deforming all or part of the fluid handling component, for example to restrict, pressurize, or induce fluid flow.

As used herein, the term "fluid" refers to a gaseous or liquid phase material.

As used herein, the term "actuation zone" refers to the area on a fluid handling device on which an actuator acts.

Optical measuring device and method

The present invention also provides methods and devices for systematically combining flow cells with longitudinal optical pathways (eg, microfluidic systems). In particular, devices and methods are provided for passing light longitudinally along the channel and for deliberately focusing the exiting light and thereby enhancing the signal response by other devices described herein and thereby enhancing the selected measurement system sensitivity.

Therefore, in one aspect of the present invention, there is provided a fluidic device comprising: at least one channel constituting a path for the travel of electromagnetic waves. In some embodiments, the path is generally longitudinal for at least a portion of the length of the channel. In some embodiments, the path is generally perpendicular or transverse to at least a portion of the length of the channel. In other embodiments, the path is generally perpendicular or transverse to at least a portion of the length of the channel. The electromagnetic waves may include at least one of visible light, ultraviolet light, microwaves, radio waves, x-rays, and gamma rays.

In a further aspect of the invention, apparatus is provided comprising: a channel adapted to measure a property of a fluid within the channel based on electromagnetic waves, wherein the measurement is enabled by causing the electromagnetic wave to travel substantially longitudinally along at least part of the channel.

According to one embodiment, the electromagnetic waves are visible light. However, any form of electromagnetic waves suitable for the purpose may be used. Thus, for example ultraviolet or infrared light, microwaves, radio waves, x-rays and likewise gamma rays can be used.

Devices according to the invention may be used for any suitable purpose involving optical sensing. According to one embodiment, the device is used in microfluidic applications.

According to further embodiments, the device is a microfluidic device and comprises layers bonded (eg, bonded) to form a microfluidic device ('stacked' device). According to another embodiment, the device comprises at least one optical window to allow electromagnetic waves (eg light) to enter and/or exit the channel. According to further embodiments, the device is not made of silicon or silicon-based materials.

In one embodiment, light enters the flow cell through an optically transparent window at one end of the channel, where reflective or refractive means direct the light path to a path along the longitudinal direction of the channel or flow cell. Light levels are maintained (or light loss is minimized) throughout the channel by providing reflective surfaces, or appropriate refractive index changes to maximize total internal reflection along the length of the channel or flow cell of. At the detection point, reflective and/or refractive structures guide and, if necessary, concentrate the light exiting the channel for detection purposes.

In another embodiment, a flow cell is provided which is capable of illuminating or detecting longitudinally and/or transversely.

The methods and devices of this aspect of the invention are applicable to microfluidic devices produced by conventional batch-based and roll-to-roll manufacturing processes, including but not limited to laser machining, die-cutting, embossing, injection molding, and lamination method.

As used herein, the term "microfluidic" or "fluidic" refers to the handling, manipulation or process of fluids in a structure having at least one dimension which may be less than a millimeter.

As used herein, the term "ray" refers to more than one photon of electromagnetic radiation traveling in substantially the same direction.

As used herein, the term electromagnetic radiation refers to energy in the form of photons or waves, and includes either visible, ultraviolet or infrared light and waves of radiation such as microwaves, radio waves, x-rays, gamma rays, and the like.

Instrument configuration method

The present invention also provides methods for software or firmware upgrades, and methods for controlling instruments by using additional components within one or more removable inserts.

According to one aspect of the invention, there is provided a method of performing a function using an instrument, the method comprising coupling an insert with the instrument, the insert including one or more of program code, data or instructions enabling the performance of the function. Instruments may include, for example: digital multimeters, oscilloscopes, spectrometers, chemical analyzers, bioanalyzers, DNA sequence analyzers, pressure sensors, temperature sensors, pH sensors, electrochemical analysis devices, mobile phones, computers, personal digital assistants or digital multimedia player.

In another embodiment, there is provided a method of assuming a function using (i) an instrument and (ii) an insert having proprietary functional data, comprising: (a) engaging the insert to the instrument, (b) Data is transmitted to the instrument, and (c) the instrument performs the function.

According to another aspect of the invention there is provided an insert configured for use with an apparatus to perform a function, the insert comprising one or more of program code, data or instructions enabling the performance of the function. Inserts may include, for example: sensors, cartridges, cassettes, microfluidic devices, flash cards, memory sticks, smart cards, or printed circuits or other memory storage components.

In another embodiment, an insert is provided for an instrument to perform a function, wherein the insert includes function-specific data required by the instrument to perform the function.

According to another aspect of the present invention, there is provided a method of upgrading software or firmware of an instrument, the method comprising: coupling an insert to the instrument; and transmitting some or all program codes, data or instructions to the instrument thereby completing the upgrade. Instruments may include, for example: digital multimeters, oscilloscopes, spectrometers, chemical analyzers, bioanalyzers, DNA sequence analyzers, pressure sensors, temperature sensors, pH sensors, electrochemical analysis devices, mobile phones, computers, personal digital assistants, or Digital multimedia player.

In another embodiment, there is provided a method of upgrading the software or firmware of an instrument, wherein the instrument is used by an insert, comprising: (a) coupling the insert to the instrument, and (b) by transferring data from the insert to the instrument to upgrade the instrument.

According to a further aspect of the invention, an insert is provided for use with an instrument to perform a function, wherein the insert includes data for upgrading software and firmware of the instrument.

According to another aspect of the present invention, there is provided a method of establishing an interaction between an instrument and an add-in having interaction-specific data, comprising: (a) coupling the add-in to the instrument, (b) transferring data from the add-in to the instrument, and (c) The instrument completes the function.

Typically, the primary use of the insert is the consumable function required for the normal operation of the instrument. By providing additional functions on the plug-in, user operations are simplified, new product development cycles are minimized, and product data security and product intellectual property are further protected. In general, some or all of the data used for upgrades, or for instrument operating protocols, may be included in part or in whole on one or more removable inserts in accordance with the present invention.

The present invention provides an instrument and insert architecture in which one or more physically functional inserts normally used in the instrument become part of the software/firmware upgrade path for the instrument. More specifically, the insert or inserts include some or all of the upgrade information. This method simplifies user operations because the process of upgrading software is automatic; there is no need to install new software from other media. Additionally, logistic overhead is reduced by eliminating the need to produce and distribute separate upgrade media.

The present invention provides program code, data or instructions to be distributed between the instrument and one or more removable inserts (in varying ratios, for example from 1:0 to 1:1 to 0:1). More specifically, general-purpose subroutines may be provided on the instrument and application-specific executables, and/or operational data may be provided on one or more removable inserts, which may primarily function as disposable consumables to accommodate and perform chemical tests and analyzes on biological samples while the instrument is physically controlled.

The distributed architecture minimizes the software development associated with the development of new applications for the instrument and its coupled inserts. Universally programmed instruments are then able to accept new applications without requiring the user to upgrade the software, and also avoid any "uninvented" requirements for application or instrument designers to anticipate new ones.

The present invention provides improved user operability and operational automation by providing data from the insert to the instrument to automate some or all of the application operations and provide user defined settings. Thereby, user interaction is simplified, which enhances system reliability and simplifies instrument operation.

Furthermore, the invention provides additional software security since the program execution instructions do not have to be present in the instrument. In a particular embodiment, the insert carries instructions to configure the instrument for a particular application of the insert. According to this embodiment, the invention creates a more difficult reverse engineering approach, since successful copying requires a complete understanding of the program's execution. If, in the unlikely event that the instrument and insert interaction ends up being reverse engineered, the resulting executable program only reveals the data used to make the specific application for which the specialized insert was applied, and does not Expose additional data.

The present invention also allows for incremental and permanent changes to the usage data contained on the insert, making it impossible for a reverse engineered instrument to operate with the new insert.

Upgrade information or distributed program data can be encoded onto one or more inserts and can be in many different formats including, but not limited to: electrical encoding through electrode connections; resistance values; magnetic strips; integrated circuits; optical coding; and mechanical coding.

An additional advantage of having upgrade and configuration data within the insert is an additional security feature that requires a match between the instrument, interface and mating insertable device.

As used herein, for convenience, the term "consumable insert" also refers to an insert that has one or more uses.

As used herein, the words "device" and "apparatus" are interchangeable in meaning and use.

Description of drawings

Literature and methods for fluid manipulation

Figure 1 is a schematic diagram of an actuation zone for fluid treatment. The outer circle represents the actuation area, the line through the center represents the fluid containing structure, such as a channel or tube, and the shaded circle represents the actuation component.

Figure 2 is a schematic diagram of some possible actuation components. Figure 2(a) is an infusion pump where fluid is held within the actuator and injected into the device through the inlet upon actuation. Figure 2(b) shows an in-line pump, which is a pump with an inlet and an outlet. Figure 2(c) is a switch valve or variable flow valve. Figure 2(d) is a one-way valve.

Figure 3 is a schematic illustration of a single actuator actuating more than one actuation member. As an example, three actuating members are grouped and operated by the same actuator. Figure 3(a), (b) and (c) show the in-line pump set, injection pump set and valve set connected to each channel, respectively. Figure 3(d) shows an example of an alternative geometry where a single unvalved channel intersects two valved channels, the valves of the valved channels can be configured to inject fluid into the main channel. Figure 3(e) shows two pumps connected in parallel operated by the same actuator, the pumps may operate in unison or at different parts of the actuation cycle.

Figure 4 is a schematic illustration of a single actuator actuating more than one type of actuation member. Figure 4(a) shows three separate channels with separate actuation means, in this case the central channel is actuated to pump while the two outer channels are closed by valves. Figure 4(b) shows a single channel with a pump divided into two valved channels. Figure 4(c) shows an infusion pump with four valved outlets. Figure 4(d) illustrates an inline pump intersecting valved and unvalved channels.

Figure 5 illustrates actuation components within the same channel operated by the same actuator. Figure 5(a) shows an inline pump with downstream valves. Shut-off valves may be provided at various points during the actuation cycle, or valves may be provided to limit the flow rate, effectively allowing controlled volumetric dosing. Figure 5(b) shows a similar controlled dosing system, but using an infusion pump. Figure 5(c) shows a peristaltic type pump configured with three valves that are activated separately and operated by the same actuator.

Figure 6 shows a dual actuator system to inject a fixed volume of one stream into the other. Each stream is individually actuated to pump fluid and valve the additional stream to prevent excess flow into the additional fluid system, beyond the injection volume.

FIG. 7 illustrates two actuator systems similar to those illustrated in FIG. 6 . A fixed volume of fluid indicated by a dotted line is injected into another stream indicated by a dotted line. Valving is only used for one stream, since it is preferable to be able to use geometry, pressure and surface effects to direct the fluid. In this case, the back pressure in the solid line is higher due to the reduced cross-sectional area of its channels.

Figure 8(a) illustrates an example of an actuation zone with multiple actuation components. The two central channels are connected together by two circular one-way valves, allowing pumping to be performed upon actuation, as shown in Fig. 8(b). The rectangular part is an on-off valve that allows deformation of the membrane to block the channel to stop flow during actuation, as shown in Fig. 8(c). Figure 8(d) shows the operation of both types of valves operating as pumps, where the filling action causes the membrane to deform upwards, allowing fluid to flow into the pumping chamber, while on the emptying cycle, the membrane is compressed against the base of the chamber, Closing the inlet hole and deforming the membrane into the lower channel allows fluid to pass through with outlet restriction. Figure 8(e) shows a three-way valve configuration where a deformable layer is used to close a specific port when pressure is applied from the opposite port.

Figure 9 is a schematic representation of a pumping system with downstream membranes for debubbling or check valves. Figure 9(a) illustrates an inline pump with a downstream defoamer, and Figure 9(b) illustrates an example of an injection pump with a downstream check valve.

Figure 10 is a cross-sectional view of a channel with vents for degassing while retaining fluid.

Figure 11 is a top view of a base with a fluid inlet with channels connected to an oval groove with an outlet connected to a vent for degassing.

Figure 12 shows the vent above the continuous channel. Figure 12(a) is a top view showing a larger surface area vent compared to channel size.

Figure 12(b) is a cross-sectional view along the passage of the same vent.

Figures 13(a)-13(b) illustrate the operation of the degasser where a modulating type valve is used on the outlet.

Figures 14(a)-14(b) show a combined vent and valve structure controlled by a single actuator to accomplish channel/slot loading.

Figures 15(a)-15(b) show a semipermeable membrane that acts as an inlet filter and a barrier to sample introduction until pressure is applied to force fluid through the membrane.

Figure 16 shows a controlled dosing or reservoir scheme where fluid is introduced and retained in a chamber until pressure is applied to open a valve and release the fluid.

Figures 17(a)-17(b) show the vent passage with application of forward or reverse fluid pressure, operating as a valve or pump.

Figure 18 shows how the vent and valve combine to form a pumping system. Figure 18(a) illustrates the filling of the pumping chamber with fluid by a negative pressure gradient across the exhaust port, which removes gas and draws fluid. Figure 18(b) illustrates fluid ejected from the pumping chamber by a positive pressure gradient applied across the exhaust port.

Figures 19(a)-19(b) show multiple permeable membranes within a microchannel network operating as pumps or valves under applied fluid pressure.

Figure 20 illustrates a button-type actuator incorporating electrode pads which are activated during the actuation operation. Figure 20(a) shows a plan view of the electrodes within the actuation zone, which also includes a vent hole in the central portion to allow pressure to be transmitted to another layer within the device to trigger another actuation component. Figures 20(b) and 20(c) are side view cross-sections of the electrode structure before and during actuation, respectively.

Figures 21(a)-21(b) show a cross-section of a button-type actuator incorporating the electrode and button-type interface shown in Figure 20, with the vent hole connected via a semi-permeable membrane using valved inlet and outlet to the pumping chamber.

Figure 22 shows a schematic of the recirculation fluidics network.

Figures 23(a)-23(b) show two illustrations of different approaches, allowing pressure gradients to be released to prevent bubble formation. In particular, these figures illustrate expanded fluidic channels.

Figure 24 shows a top view of a multi-layer recirculation fluidics network. The recirculation network connects directly from the inlet to the pump, then to the one-way valve, the injection port, the deformable actuation zone including the vent and one-way valve, the split mixer, the detection chamber, the pressure-relief structure, and then to the back to the input stage.

Figure 25 shows a top view composite image of a multi-layer device comprising two controlled dosing fluidic networks with pumps, valves, defoamers, detection tanks, and pressure relief structures.

Figures 26(a) and (b) show plan and side views, respectively, of a card with pneumatically pumped and valved regions connected to external instrumentation.

Figures 27(a)-27(c) show a transverse cross-section of a microchannel with at least one flexible wall, in this example the top layer being a flexible wall. Figure 27(a) shows displacement of the deformable material by the bearing into the channel, which effectively blocks the channel and creates a closed valve condition. Figure 27(b) shows that three or more in-line pumps can alternate their on and off states to produce a pumping action. In short, when the valve is closed, the fluid it is pushing is moved, and when the valve is opened again, the fluid is moved to fill the vacated volume. If a valve close to an open or closed valve is closed, fluid will be restricted from moving in and out in that direction, whereas if the valve is open, fluid will flow in or out in an unrestricted direction. Figure 27(c) shows a pumping regime in which a traveling wave along the channel is generated by moving a partially or fully closed valve axially along the channel to squeeze the fluid in front of it. Traveling waves according to the invention may be generated by any suitable method. For example, a sliding or rolling bearing actuator passing through a deformable material that defines one side of a channel can similarly roll a circular actuator along the channel (thus pushing a wave of fluid in each instance in front of the moving actuator). ).

Figure 28 illustrates an example of a valve configuration. Figures 28(a)-(c) show a channel with a single flexible wall that is thinner than the depth of the channel. The channel structure can be etched into the substrate, as shown in Figure 28(a), the substrate consists of multiple layers, as shown in the 2-layer structure in Figure 28(b), and can include other layers on top of the flexible layer , as shown in FIG. 28(c), wherein the covering layer includes a recess on the channel covering the flexible layer. The deformable material can also be thinner than the depth of the channel, as illustrated in Figures 28(d) to 28(l), and can cover more than one channel. Pressure applied to the deformable material adjacent to the channel can cause the deformable material to deform into the channel, effectively blocking the channel and causing valving. The deformable material can also be constrained in other directions by being positioned within other structures. Figures 28(e) to 28(g) illustrate the deformable material positioned within the recess. Figure 28(h) shows in a similar fashion a deformable material in the form of a tubular cross-section within a structure on a microchannel. Figures 28(i) to 28(l) illustrate examples where the layer over the deformable material is a single protective cover layer. Whereas Figures 28(m) to 28(p) illustrate a cover layer that can be used as a deformable material and can be formed or shaped to self-produce deformation in a specific manner, similar to employing a button-type contact interface.

Figure 29 illustrates some examples of the above described valves under the effect of a force applied adjacent to a channel recess. Figure 29(a) illustrates a membrane deformed into a microchannel by a range of forces applied to a recess. Figure 29(b) illustrates a thick flexible layer deformed under the application of a force in a range greater than that of the microchannel, the deformable material deforms into the microstructure. Figures 29(c) to 29(e) illustrate changes in a deformable material defined by structures that limit the expansion of the deformable material under an applied force.

Figure 30 illustrates a channel formed in an elastomeric material. Figures 30(a), (b) and (c) show a construction in which the channel walls are formed on three sides by elastomeric layers, the channels being closed by the adjoining layers. Figure 30(d) shows channels formed entirely within the elastomeric substrate.

Figure 31 illustrates a channel with restrictions placed along the length of the channel to reduce backflow.

Figure 32 shows a schematic illustration of linear and radial pumping channels. The tubes in Figure 32(a) are straight or linear channels, and the arrows indicate the direction to move the valve or traveling wave pump. Other geometries may be employed, and an alternative configuration is shown in Figure 32(b) in which the valve or traveling wave tube is moved in a radial direction. The ends of the tubes are joined to additional channels or structures to enable fluid flow.

Figure 33 illustrates a top view of a multilayer device using a radial pump configuration connected to fluidic channels extending to 3-valve positions and inlet/outlet ports.

Figure 34 shows an example of a drive mechanism for deforming a material by mechanical means, and thus generating fluid flow by traveling waves. The actuation structure may be rigid, or deformable to allow the actuation surface to adapt to the microstructured valve element. They can be applied perpendicular to the valve surface, or moved parallel to the surface. Examples shown are: spheres (Fig. 34(a)); rods (Fig. 34(b)); rotating enclosures that confine several non-rotating spheres (Fig. 34(c)); As a structure, the rotating table is arranged to contact only one surface by pendulum action (Fig. 34(d)); the rotating cam (Fig. 34(e)); and the rotating scraper (34(f) )).

FIG. 35 illustrates an exploded view of a radial bearing pump with two actuating heads for deforming the elastomeric layer of the device of FIG. 33 .

Optical measuring device and method

Figures 36(a)-36(d) show plan views of microfluidic channel configurations in which transmissive windows are separated to allow electromagnetic waves to travel longitudinally along the fluidic channel. Figure 36(a) illustrates a plan view of three channels showing the location of transmissive windows at suitable distances along the fluidic channel to allow electromagnetic energy to enter or exit the fluidic channel. In this particular embodiment, the electromagnetic energy is in the form of light. Figure 36(b) shows a single fluidic channel with a similarly transmissive window suitably arranged, where the direction of fluid flow changes upon approaching the window. Figure 36(d) shows a single fluidic channel with similar transmissive windows suitably arranged, where fluid flow entering or leaving the channel arrives or leaves via multiple paths.

Figure 37(a) shows a cross-sectional view of a three-layer device with an optical window just between the channel and the substrate surface. Figure 37(b) shows a cross-sectional view of a multilayer device with integrated optical paths between the fluidic channels and the device surface. Figure 37(c) shows a cross-sectional view of a multilayer device incorporating a prismatic structure labeled (04) to guide light longitudinally along a channel.

Figure 38 shows a step-by-step fabrication process of a 3-layer device incorporating a reflective coating.

Figure 39 shows a 2-layer device fabrication process incorporating a reflective coating.

Figures 40(a)-(c) illustrate various 2-layer and 3-layer device configurations using reflective layers.

Figures 41(a)-(c) provide examples of prisms incorporated into fluidic devices.

Figure 42 provides an example of an integrated multiple prism system.

43(a)-43(b) illustrate the integration of optical fibers within the device. Figure 43(c) shows the fiber optic bundle positioned close to the microfluidic device.

Figures 44(a) and 44(b) show simplified diagrams of corner cube reflectors.

Figure 45(a), (b) and (c) show corner cube reflectors used in or with microfluidic devices.

Figure 46(a) and (b) are simplified diagrams of prism structures to assist in aligning and directing light.

Figures 47(a) to (j) show examples of flow cells with prisms and reflective structures for improved signal response and imaging.

Figure 48 shows an example of a flow cell with longitudinal and transverse detection.

Figure 49(a)-(c) show the detector and source regions closely positioned on the device.

Figures 50(a)-(b) show waveguides that can be made, for example, by injecting and then curing an optically transparent material, or placing an already formed lightguide within a vacuum structure.

Instrument configuration method

Figure 51 is a schematic illustration of a prior art upgrade path. The upgrade package is provided to the user, usually in the form of an executable file of an installation wizard, which guides the user through the installation process and adds new program code into the instrument program.

Figure 52 is a schematic illustration of prior art operation of an instrument with a removable insert. The instrument includes the entire program with all required subroutines for any required operation. Inserts include serial numbers or product codes that allow the instrument to unlock its own program sections or provide "goto" type instructions to allow execution of specific sections or subroutines of code stored in the instrument.

Figure 53 is a schematic illustration of the present invention where an insert includes some or all of the upgrade information.

Figure 54 is a schematic illustration of a distributed architecture in accordance with the present invention.

Figure 55 is a schematic illustration of one embodiment of the pathway of the present invention, where the instrument includes general purpose programs and specific program subroutines, but does not include the operation code required by the specific application program required to operate the plug-in. Plug-ins include instructions to call instrument subroutines to operate the instrument for the target application.

Figure 56 is a schematic illustration of a path according to another embodiment of the present invention.

Detailed ways

Fluid manipulation literature and methods

Various embodiments of the invention include: a controller to control the flow of fluid in the device; and various fluid handling structures including one or more movable members, semi-permeable membranes, electrodes, sensors, or combinations thereof.

A controller according to the invention may take any suitable form, and preferably includes an actuator to activate components associated with fluid flow within the device.

The fluid handling or actuation components may be made from any suitable material. For example, they can be made from a single shaped substrate or from multiple substrates. The fluid handling structure may be formed in any suitable way, for example it may be formed in a monolithic substrate or from several layers of the substrate.

The actuator may be external to the device or part of the fluid treatment device, or formed by part of the fluid treatment device and an external separate element.

Actuation may be performed by any suitable means, for example it may be performed directly by the user manually, or directly with the assistance of an instrument, or automatically.

According to one embodiment, the actuator is pneumatic pressure provided through an interface with an external instrument.

According to further preferred embodiments described, the deformable material deforms within the device and applies pneumatic or hydraulic pressure using an external mechanical actuator to apply pressure to the device, or manually actuated by the operator's fingers. Thus, according to these preferred embodiments, the deformable substrate may be an integral part of the fluid handling structure, while the actuation mechanism is separate. The mechanical actuators may take any suitable form, for example they may include: bearings; pins; pistons; wobble plates; cams; Other desirable embodiments may include the use of energy applied in different ways, for example, by instruments or devices including optical, electrostatic, electrical, resistive, piezoelectric, electromagnetic, pneumatic, hydraulic, linear and magnetic actuators.

The actuation zone may cover the entire surface or only part of the surface. Figure 1 is a schematic representation of an actuation zone (03) comprising an actuation member (01) with cross channels (02).

The actuation zone may be on the outer surface of the fluid treatment component or inside the fluid treatment device.

According to one embodiment, the actuation zone or part thereof may be a movable part which, for example, changes shape under the effect of applied pressure. The movable material may be an elastomer or any other suitable movable material that changes shape under applied pressure.

In another embodiment, the actuation region comprises a bistable or monostable material, such as a polymer or composite material, which is capable of changing shape from a predetermined geometry to another predetermined geometry, and upon actuation ( For example, the actuation force) is removed or revoked, and can still be changed back or caused to return to the original state and position. Examples of such arrangements include push button type actuators which may be operated eg manually, thermally, electrically or mechanically and which have been suitably formed to allow movement under an actuation force.

The movable part may deform directly into the fluid handling structure, or indirectly act on parts of the fluid handling part to cause or prevent pressure or shape changes within the fluid handling part.

The actuation zone may be larger than the actuation component.

Actuation component operations include, but are not limited to, flow control, pumping, valve control, diffusion, droplet delivery, mixing, separation, switching, dosing, injection, sensing, catalysis, water absorption, water removal, and Other fluid handling operations that are triggered or prevented from being triggered. For purposes of illustration, Figure 2 shows a schematic illustration of several of these components. Fig. 2(a) shows the infusion pump (04), Fig. 2(b) the pump (05), Fig. 2(c) an on-off or variable valve, and Fig. 2(d) a one-way valve.

The same actuator can operate more than one actuation member. Examples are shown in Figures 3-7. This arrangement simplifies device operation and thus simplifies instrumentation requirements for fluid handling components by reducing actuation controls and space requirements. Operational efficiency can also be enhanced by combining multiple actuation components operated by the same mechanism for different functions such as pumping, valve control, mixing, injection, controlled dosing, switching and other fluid handling operations.

A schematic illustration of more than one actuation member of the same type operated by one actuation zone is shown in FIG. 3 . Figure 3(a) shows three in-line pumps (09) connected to three separate channels (10) actuated by the same mechanism (08). Figure 3(b) shows three infusion pumps (11) connected to three separate channels (10) operated by the same actuation zone (08). Figure 3(c) shows three on-off or variable valves (12) connected to three separate channels (10) operated by the same actuation zone (08). By combining these actuation components from separate channels from the same actuation zone; throughput, size, cost and simplicity can be improved by requiring only a single actuation mechanism to operate all components from the same actuation zone; and demanding The application of the timing of the actuation components can be done simply and precisely. Figure 3(d) shows an example of channel (10) interleaving, where four channels have switches or variable valves (12) operated by the same actuation zone (08), enabling controlled dosing by a single operation. Into or out of all valve channels. Figure 3(e) shows an example of two in-line pumps (09, 13) operated by the same actuation zone (08) on opposite strokes (applied pressures) of the same actuation mechanism, whereby when starting from each When the passages (10) from the two pumps are connected in parallel, the pumping efficiency is improved by performing the pumping action on both the forward and reverse cycles of the actuating mechanism.

A schematic illustration of more than one actuation member of more than one type operating in one actuation zone is shown in FIG. 4 . Figure 4(a) shows an inline pump (17) and two on-off or variable valves (16) on separate channels (15) operated by the same actuation zone (14). Figure 4(b) shows on-off or variable valves (16) on separate channels (15) operated by the same actuation zone (14). If the variable valve is set to different flow rates, the pumped fluid can be repeatedly dispensed to either valve outlet. Figure 4(c) shows an infusion pump (18) connected to four channels (15) with on-off or variable valves (16) operated by the same actuation zone (14), allowing the infused fluid to be dispensed to each channel. Figure 4(d) shows a schematic representation of an in-line pump (17) within four intersecting channels (15) comprising on-off or variable valves (16), all actuated by the same Zone (14) operation. This configuration provides flow control of the pumped fluid into or out of the valved passage.

The pumping schematic shown in Figure 5 shows three types of pumps which cause fluid to be dispensed from a common channel or container. Figure 5(a) shows an in-line pump (21) that connects two on-off or variable valves (22) on a separate channel (20) operated by the same actuation zone (19) and varies depending on the valve configuration. Divides the pumped medium into two channels. Figure 5(b) shows an infusion pump (23) that connects two on-off or variable valves (22) on a separate channel (20) operated by the same actuation zone (19) and varies depending on the valve configuration. Divide the injected medium into two channels. Figure 5(c) shows two sets of three switches or variable valves (22) on separate channels (20) operated by the same actuation zone (19). By configuring each valve for sequential actuation, peristaltic-type action can be achieved with a single actuation in either channel.

According to the invention, even if actuated by the same actuator, the actuating parts can operate differently depending on their composition and geometry. Examples of this include: pumps that operate at different flow rates due to their geometry; and valves, some of which are turned closed and others open during actuation; or variable valves, which are turned Settings to restrict flow to different levels; or components, which are triggered by the same actuator at different times. An example of an arrangement providing for controlled dosing is shown in FIG. 5 . Such valves can be set in a variety of ways to provide controlled dosing. For example, they may be set to close at various points during the actuation cycle, or to limit the flow rate, effectively allowing a controlled volumetric dosing process to occur.

According to another aspect of the invention, the actuation members can be operated differently with the same actuator depending on their configuration. Figure 3e shows an example of such a configuration, where two pumps are connected in parallel, operated by the same actuator. The actuation components may operate in unison or in different parts of the actuation cycle, for example, one pump advancing fluid on the downstroke of the actuation cycle and another pump advancing fluid on the upstroke.

In another embodiment, multiple valves can be operated by the same actuator, thereby creating a peristaltic action to induce fluid flow by alternating the on and off states of the multiple valves. A peristaltic type pump consisting of three differently triggered valves operated by the same actuator is shown in Figure 5c.

Multiple actuation zones can be combined for fluid treatment operations. Examples of such arrangements are shown in Figures 6 and 7, where one stream crosses the other to allow a predetermined volume transfer between the two streams. In the example of Figure 6, the streams (23, 24) are alternately activated by the pump and valve actuation zones (26, 27) so that the injected stream flows, and the non-pumped stream due to the actuation of the pumped stream And is controlled by the valve. This prevents backflow of one fluid into the passage of the other, except at the point where they intersect, thereby providing controlled dosing and controlled plugging of the fluids so that the fluids can be injected into the other fluid stream . In the schematic illustration of Figure 7, stream (30) is pumped by (28) and if the back pressure in channel (32) is high, the fluid passes through channel (32) at (31) and through (29) valve outflow. Thus, when (29) is activated, fluid along channel (32) is pumped without backflow into (30) due to the activation of the valve of (29). Thus, if fluid is introduced from (28) before (29) triggers, the fluid blocked at the intersection of the two streams (31) is injected and delivered along with the fluid pumped from (29).

Figure 8(a) shows an embodiment of such an actuation zone (33), where the two central passages are connected together by two circular one-way valves (34), allowing pumping to be performed upon actuation, as shown in 8(b), where the arrows indicate the direction of fluid flow during alternating actuation cycles, and (34a) and (34b) denote up and down actuation cycles, respectively. Whereas the rectangular actuating member (35) of Fig. 8(a) is an on-off valve that allows the membrane (36) to deform to block the channel thereby stopping flow during actuation, as shown in Fig. 8(c), where the valve section is shown Out for on (35a) and off (35b) modes. Another embodiment shown in Figure 8(d) shows the operation of two types of valves operating as a pump. The filling action (37) causes the membrane (36) to deform upwards, allowing fluid to enter the pumping chamber, and during the emptying cycle (38), the membrane (36) is pressed against the base of the chamber closing the inlet orifice and deforms the membrane into the The lower channel allows the passage of fluid under the restriction in front of the outlet channel. Another example of a three-way valve is provided in Figure 8(e), where a deformable layer (40) is used to close a specific port when pressure is applied from the opposite port (39), the applied pressure deforms the membrane to cover the unapplied pressure port. A membrane can be positioned to one side of a cavity or channel to close a particular port by default, and only open when pressure is applied from the initially closed port.

Another aspect of the invention may include one or more semi-permeable membranes that can be used as vents or check valves to allow passage of eg air under low pressure while preventing fluid flow. Examples include, but are not limited to: microporous or fibrous membranes having a bubble point pressure greater than >0 psi. A preferred embodiment uses a hydrophobic membrane with a pore size of less than 0.9 μm, preferably less than 0.5 μm, and most preferably less than 0.2 μm. Wherein when the pore size is less than 0.2 μm, the membrane is preferably used for biological organism trapping. A semipermeable membrane can be used, for example, as a vent for debubbling of a fluid handling device due to filling, dead volume, and operations such as pumping, an example of which is shown in Figure 9(a), where an inline pump ( 43) Incorporating a bubble remover (41) at the downstream end. The semipermeable membrane can also be configured with a check valve, an example of which is shown in Figure 9(b), where the infusion pump (44) has a downstream end exhaust port (42) for operation as a check valve. This configuration allows for reliable storage and handling of fluid in the structure, with fluid only injected into the system when actuated. Figure 10 shows a cross-section of a channel with a bubble eliminator. A fluid (47) with air bubbles (45) passes through a semi-permeable membrane (46), where the air bubbles (45) are preferably removed through the membrane due to a pressure difference (48) across the membrane, where the pressure difference is lower than the air bubbles continue along the channel The pressure difference required to travel.

In another embodiment, a vent (50) is arranged to degas the structure (49) to ensure complete filling of the channels or cavities (52, 53). The packing materials may be of any suitable type, for example they may be fluid or solid. The example in Figure 11 depicts a vent for degassing arranged at the downstream end of the detection chamber (53) to remove the air initially present in the structure when fluid is introduced from the inlet (51).

In another embodiment, the use of surface tension and geometry can be used to assist in directing liquid across the vent while removing gas. Figure 12 (a) and 12 (b) have described the plan and cross-sectional view of example device (55) respectively, and device (55) has the vent (56) of relatively large surface area on microchannel (54), so that For gas exhaust. Microchannels extend through the bottom surface of the vent cavity (57), and surface tension in the channels and in the vent cavity helps guide fluid along the channel while gas is released into the cavity and then exits across the vent (56). In another embodiment, Figure 13 shows an example of a vent structure that uses a regulator valve (60) feature to prevent air from passing through the vent. The liquid only passes through the regulating valve (60) when a certain pressure is reached in the exhaust chamber (61). Since the regulated pressure is above the bubble point of the permeable membrane, the gas (59) will preferably exit through the permeable membrane (58) (Fig. 13(a)). When the vent chamber (61) is filled with liquid and pressure is applied, the deformable membrane (62) will deform to allow the liquid to flow to the outlet (Figure 13(b)).

In another embodiment, a vent can be combined with a deformable structure and a one-way valve, or a restriction for loading liquid or pumping. For example, Fig. 14 (a) and (b) have described respectively the top view and the side view of the debubbler type vent (63), as shown in Fig. 13, the vent (63) is in the deformable structure (66) Combined with check valve (67) under action. Here the one-way valve (67) is configured to release pressure by allowing air to pass (65) when the deformable structure (66) is compressed, and to seal when the deformable material returns to its original state. Thus, a negative pressure is created in the device, which draws fluid from the channel to fill the cavity (64) with a known volume. Other pumping mechanisms can then be used to squeeze this known volume of fluid through the debubbler within the device, as shown in the recirculation network in FIG. 22 .

In another embodiment, the exhaust port can be configured for sample filtration and fluid control. Figure 15(a) depicts the semi-permeable membrane (68a) over the inlet slot. Components within the sample that are small enough to pass through the membrane pass through the membrane (68a) and enter the device under the effect of an applied pressure differential above the bubble point of the membrane. Effectively filters samples and delays sample entry until pressure is applied. Figure 15(b) provides two semi-permeable membranes arranged on the inlet of the fluidic device. The first semi-permeable layer (68b) in contact with the sample is configured as an absorbent medium to initially absorb and contain the sample in a defined location, thereby allowing controlled formulation when pressure is applied to both sides of the filtering semi-permeable layer (68a). The measured volume of sample enters the device. In this example, the sample wicks through the absorbent material before being fed into the device by applying pressure. With a sufficient pressure gradient, only the sample in the exposed region directly above the membrane moves into the device.

In another embodiment, a semi-permeable membrane (72) can be used to accomplish controlled volume dispensing and storage. Figure 16 shows an example where a reagent or sample can be injected through a membrane into the depicted large chamber (70), which will fill a known volume. A small vent area (73) is provided to remove air and relieve pressure during filling so that the outlet valve is not released. When the device needs to be injected, pressure is applied to the semi-permeable membrane (72) (vent area sealed or pressure equalized), pressurizing the flow chamber, forcing liquid out of the inlet channel (71) through the pressure relief valve (69). A similar approach is to load the sample by injecting the storage chamber (70) eg through the elastic layer, whereby a separate venting region (73) is not required as any exposed semi-permeable membrane (72) can perform the venting function.

In another embodiment, fluid can be introduced through a semi-permeable membrane to perform a valving or pumping function. Figure 17(a) and (b) show the exhaust port (72) arranged at the intersection of two channels and at the end of the channel, respectively. Fluid within the device can be controlled by applying another fluid (73) (eg, liquid and gas) that can flow preferably through the semi-permeable membrane (72). In this example, the applied gas (73) can be used to drive the liquid (74) through the channel network or to stop the fluid flow. Bubble point pressure (surface tension) prevents the liquid from passing through the membrane. Geometries can also be used in combination with semi-permeable membranes to restrict fluid flow.

In another embodiment, the exhaust port (78) can be combined with a one-way valve (75) to form a pumping system. An example of such a system is shown in FIG. 18 . Figure 18(a) depicts the filling of the pumping chamber (77) with fluid by a negative pressure (76a) gradient across the exhaust port (78) removing air and drawing fluid. Figure 18(b) depicts fluid ejected from the pumping chamber by a positive pressure (76b) gradient applied across the exhaust port. Air movement can be provided by an external pneumatic interface or an integrated actuator, such as a push button type pump, as depicted in FIG. 20 .

In another embodiment, more than one semipermeable membrane is used for fluid control within the structured network. Figure 19 shows an example where two semipermeable membranes (81a, 81b) with different bubble points are used. The applied negative pressure (79a) can be used to draw fluid from the channel (80a) through the semi-permeable membrane (81b) and then reduce the pressure or use a first gas with a bubble point higher than the applied pressure gradient (79a). Two semi-permeable membranes (81a) make it possible to prevent liquids from passing through the layer (81a). Positive pressure (79b) can then be applied (Fig. 19(b)) to force fluid through the outlet (80b), which may include a restriction, valve or other flow control feature.

In another embodiment, electrodes are included in the actuation zone to provide electrical switching for sensor operation, circuit operation, or actuation event detection. An example is shown in Figure 20, which depicts a button-type actuation zone (84) incorporating electrode pads (82) that are activated during the actuation operation. In this example, holes in the substrate (83) are provided for relieving pressure during actuation of the structure (84), the pressure induced by the actuation can then be used within the device to effect the actuation under the substrate.

In another embodiment, a button-type or other deformable structure is combined with a semi-permeable membrane. This provides advantages for chemical storage, injection, pumping, valve control and other fluid manipulation operations by providing a controlled actuation volume. Figures 21(a) and (b) depict a two-stage pumping scheme where the fluid pumping chamber (91 ) is kept separate from the large actuation volume (90) within the deformable actuation structure (87). These two geometries can then be configured to provide optimized pumping conditions; the volume within the deformable structure (90) is used to control the pumping pressure, and the fluid pumping on the other side of the semi-permeable membrane (86) Volume (91) is used to define the pumping volume. In addition, the semi-permeable membrane (86) can be used to block corrosive or otherwise harmful fluids to the deformable actuation structure (87), for example to prevent liquids from eroding electrode sensors on the deformable structure. In the example shown in Figure 21, the downward actuation force (89) deforms the deformable structure (87), reduces the actuation volume (90), pressurizes the pumping chamber, thereby forcing fluid through the one-way valve (88) and out through channel (85b). By removing the actuation force (89) and returning the deformable actuation structure (87) to its original shape, the negative pressure draws fluid through the one-way valve (88) into the fluid pumping chamber (91).

In an alternative, the deformable actuation structure (87) can act as an infusion pump by containing a fluid in the actuation volume (90), which is kept out of the channel of the device until acting on the deformable structure Actuation of causes the internal pressure to rise beyond the membrane retention point.

In another embodiment, a recirculating fluid system is provided. By using degassing components, the outlet can be connected to the inlet and air introduced into the system is removed before the fluid flows to the functional area. In this way, fluids are able to mix more efficiently and pass through the functional zone multiple times. This has advantages in many applications including sample preparation, e.g. cross-flow filtration, solid chemistry, detection in microfluidic systems. Figure 22 shows a schematic representation of the recirculation fluidic network with inlet (92), pump (93), bubble eliminator (94), and detection chamber (95). Arrows (96) indicate the direction of fluid flow when pumping.

In other embodiments, an internal relief structure (97) is used to prevent the formation of air bubbles in undesired areas. For example, Figure 23 depicts two such structures that can be used in channel (98), near the outlet of the recirculation network, to avoid the suction force of the pump separating the fluid chain at the next lowest pressure point. In some instances, this is at or near the detection zone, which can be negatively affected by bubble formation. By introducing these extra wide regions (97), the fluid is preferably separated at this point rather than close to the detection region.

Figure 24 shows a top view of a multi-layer recirculation fluidics network. The connection sequence of the recirculation network is: from the inlet (108) including the semi-permeable membrane for filtration and sample loading; directly connected to the in-line pump (99) in the actuation zone (102); followed by the one-way valve ( 100); Injection port with a check valve (101) for preventing backflow; Comprising a pressure reducing valve and an exhaust port (103) for removing air bubbles and a check valve ( 104) of the deformable actuation zone (102), which ensures that the positive pressure in the actuation zone is released through the return air system (109) and the negative pressure draws fluid from the sample inlet (101) for controlled volume sample loading splitting, diverting, and then recombining liquid streams for improved diffusion-based mixing split mixer (105); detection chamber (106); pressure relief structure (107); and then connected back to input stage (108) , for fluid recirculation in fluidic systems.

In another embodiment, Figure 25 depicts a top view composite image of a multilayer device (110) comprising two controlled metering fluidic networks with pumps, valves, bubble eliminators, test tanks, and decompression structures. The output of each network feeds into one of the inputs of the other network, and without the relief structure, emptying the access slots would create a suction force in the outlet of the opposing fluidic network, thus possibly causing bubbles in the detection zone. The top two buttons allow fluid to be pumped from their respective inlet slots and provide a one-way valve to prevent backflow if only one pump is actuated at a time. The bottom two pumps are configured to provide a controlled volume of injection fluid from an internal tank into fluid pumped through the network from another tank, in a manner similar to stream injection analysis techniques. In detail, when actuated, inline pumps (111) and (112) pump fluid through a one-way valve (113a or 113b) that prevents backflow into either pump. Actuation control of the pumps (111, 112) determines the ratio of the two fluids pumped from their respective input tanks (114, 115). Gas is removed from the pumped fluid through the debubbler (116a). The defoamed fluid is then pumped through the detection chamber (117a), through the relief valve (118b), and then to the inlet tank (119) of the inline pump (120). The in-line pump (120) is then used to move the pump through the one-way valve (125b), through the common injection chamber (121), through the actuated stop valve (122b), through the debubbler (116b), pressure relief valve (118a ) and drain the carrier fluid from the tank (114). One-way valve (125a) prevents flow of carrier fluid into inline pump (123), and actuation stop valve (122b) is actuated by inline pump (120) to prevent fluid flow to tank (124) during a flow cycle. When the in-line pump (123) is operating, the fluid in the tank (124) is recirculated through the one-way valve (125a), the injection chamber (121), the open actuation stop valve (122b), and back to the tank (124) . During the actuation cycle, one-way valve (125b) prevents flow from entering pump (120), and actuation stop valve (122b) is triggered to prevent fluid flow to debubbler (116b).

In one embodiment, the on-board pumping and valving of the device is actuated by external pneumatic instrumentation with configurable pneumatic interconnection provided by card (126). The described configuration provides a robust and very flexible platform that can be configured to employ cards for many different applications, as the card configures not only the internal valve and pump setup, but also the external valve connections (131). Figure 26 shows a plan view (Figure 26a) and a side view (Figure 26b) of an example device where the common chamber (127) above the pumping zone (128) is pressurized from an external pressure source through an orifice (130) (positive and negative pressure) to provide a common pumping action to all pumps under the action of a common pressure chamber (127) (more than one pressure chamber may be used and operated independently). Fluid movement within the card is allowed or not allowed based on the valving configuration within the card, which is pneumatically controlled by an external instrument valve (129). The pressure applied to the internal valve structure is controlled by external valves (129) and can be positive, negative, or atmospheric due to their connection to the booster pumping chamber (127) and atmosphere, which can be configured by the card . Instrument valve (129) is connected to the card via port (132) through ferrule (133).

The present invention also includes fluid handling structures that include deformable members that can act as pumps or valves. The deformable member may deform into the fluid handling structure, or act on a portion of the fluid handling structure, to create a restriction to flow or an increase in pressure.

Part or all of the fluid handling structure may be deformed. This restriction can be used to control fluid movement in steady state single valves, multiple valves, or in moving valve operation, see Figures 27(a), 27(b) and 27(c), respectively. In Figure 27, a channel is defined by a substrate (203) and a deformable material (202). In Figure 27(a), a single bearing (201) moves perpendicular to the length of the channel (204), deforming the elastomeric material (202) and thus sealing a portion of the channel (204). In Figure 27(b), three bearings (201) deform the deformable material (202) into the channel structure (204) to create a peristaltic type pumping action by alternating their actuation to enter/exit the channel. In Figure 27(c), the bearing (201) moves along the length of the channel (204), and the deformable material enters the channel (204) to squeeze the fluid in the channel in the direction of bearing movement.

According to one embodiment, the outer part comprises an actuating portion which, in contact with the fluid handling part, partially deforms the channel, causing pinching of the channel, thus allowing valve operation by opening (figure 28) or closing (figure 29) the channel .

Figure 28 shows a different embodiment of the invention prior to actuation using a combination of deformable material (205) and non-deformable material (206) to create a fluid handling structure (208). The deformable material may be an elastomer (205), as shown in Figures 28(a) to 28(h), or other material (207), as shown in Figures 28(m) to 28p), which, for example, Change shape under stimuli such as pressure. Figures 28(i) to 28(l) show how deformable materials (205, 207) can be combined to form a fluid handling structure (208).

Figure 29 illustrates deflection of deformable material (210) upon actuation (209) into different fluid handling structures. Different external actuators can be used alone or in combination. They should preferably be suitably dimensioned to produce the most efficient deformation under actuation. An example is a circular bearing deflecting deformable material into a semicircular channel. An alternative approach shown in Figures 29(c) to 29(f) is to shape and or constrain the deformable material to ensure that the material (210) deflects into the fluid handling structure upon actuation (209).

A deformable material according to aspects of the invention may be of any suitable type. A preferred embodiment comprises a deformable material which is an elastomer. Preferably, the deformable material is elastic so as to return to its pre-deformed shape and position once the stimulus to deform is removed. Thus, for example, upon removal of the actuator, a deformable elastomeric material compressed into the channel by the actuator will most preferably automatically return to a position outside the channel.

In another embodiment, the deformable material is a bistable or monostable material, such as a polymer or a composite metal, which is capable of changing shape from a predetermined geometry to another predetermined geometry and then once removed or Withdrawal of the stimulus can restore or cause restoration to the original state and position. Examples of this could include manually, thermally, electrically or mechanically operated pushbutton type actuators, which have been suitably formed as raised or recessed structures.

The liquid handling component may be made from a single formed substrate or from multiple substrates. The fluid handling structure may be formed to a monolithic substrate or defined by several layers of the substrate.

The fluid handling structure (211 ) may be partially or entirely formed within the deformable material (212), as shown in FIG. 30 . Figures 30(a) and 30(b) show a deformable material (212) comprising a fluid handling structure (211) partially defined by a substrate (213). In Figure 30(a), the deformable material (212) is on the surface of the substrate (213), while in Figure 30(b), the deformable material (212) is in contact with the substrate (213) and into the substrate (213 )Inside. Figures 30(c) and 30(d) show a fluid handling structure (211) formed within a deformable material (212) and sealed by another deformable layer (212), while in Figure 30(d), The fluid handling structure (211) is integrally formed within the deformable material (212).

The deformable material may be a film thinner than the deflection distance, or a monolithic deformable material where the depth of the deformable material is greater than the desired deflection. Larger deformable materials offer the advantage of simplifying the actuation mechanism by allowing a larger area of applied pressure, which can induce deformation into smaller structures.

The deformable material may be on the outer surface of the fluid handling component or within the fluid handling device.

The deformable material can cover the entire surface or part of it. For example, it can include gasket or O-ring geometry.

The deformable material may be flush with the surface or extend above the surface of the channel.

The deformable material can be deformed into one or more fluid handling structures.

In another embodiment, multiple steady state valves made of deformable material can be used to induce fluid flow by alternating their on/off states to create a peristaltic type action (Fig. 27(b)).

Deformable or microfluidic structures may be combined with other fluid confinement elements, such as diffusion nozzles or valves, to form part of a pump or pumping mechanism. These valve control structures can be placed adjacent to the pumping chamber, as indicated by the arrows in Figure 28(o) and Figure 28(p), or along the length of the pumping chamber or channel. Valves disposed along the length of the channel may include directional flow inhibiting structures such as progressive channel restriction or one-way valves. Figure 31 shows a channel (217) formed in the base (215) with a contoured surface to provide a one-way valve action when the deformable material (214) is deflected. In this example, a rolling bearing (218) moving in the direction of the arrow squeezes the fluid (216) ahead of the bearing along the contoured surface (217). The fluid pressure built up in front of the bearing deflects the membrane (214), pushing the fluid (216) along the contour.

According to another embodiment, movement of the actuator causing deformation in the fluid handling structure may produce a pumping action by causing a wave-like action that forces fluid to flow along the channel. Figures 32(a) and 32(b) provide schematic illustrations of the pumping zones resulting from linear (220) or radial (221) actuation motions along the surface of the fluid treatment device that induce fluid flow (219) . Figure 33 depicts a top view of a multilayer device configured using a radial pump (224) connected to a microfluidic channel (225) leading to three valve positions (222) and in/out exit (223). Since the deformation of the elastomer proceeds along the length of the channel, in many cases no valve is required to prevent backflow because the deformation is maintained into the channel.

These particular embodiments use mechanical actuators to apply pressure to the deformable channel structure perpendicular to the direction of the channel, and neutralize or reduce the force parallel to the deformable substrate layer to reduce friction. The deformable substrate may be an integral part of the microfluidic chip, while the rotating part or actuator may be part of an attached or accompanying instrument or such controlled device. An example of a mechanical actuator is shown in FIG. 34 and may include, for example, a ball (227) and bearing assembly (228), a pin and piston (226), a wobble plate (229), a cam (230) and a scraper ( 231). Other desirable embodiments may include manual actuation, such as with an operator's finger, or through the use of energy applied by instruments or devices including electrostatic, electrical, resistive, optical, piezoelectric, electromagnetic, pneumatic, Hydraulic, linear and magnetic force actuators. The example shown in FIG. 35 depicts an exploded view of a radial bearing pump with two actuation heads used to deform the elastomeric layer for the device described in FIG. 32 . One bearing head assembly is used to perform the pumping action, while the other operates close to the valve. The bearing assembly includes a ball (234) housed within a housing (232) mounted on a gear assembly (235, 236) connected to a drive rod (238). The whole assembly is translated and driven to rotate 90° to rotate the bearing assembly and is held together by a fixed pin (233) connecting the housing (237) to the instrument.

Optical measuring device and method

The following description of certain preferred embodiments refers to light as the electromagnetic wave used in the device. However, those skilled in the art will understand that certain embodiments are equally applicable to other electromagnetic waves.

The purpose of an optical fluid detection cell is to direct light rays into and out of the channel to enhance detection sensitivity and thereby detector response when analyzing fluids, materials processed by fluid flowing through or contained within the cell. The structures, devices and methods disclosed herein are applicable to longitudinal and transverse measurements in fluid detection cells.

For analyzing the incident light after traversing the fluid contained in the detection cell, analytical methods include, but are not limited to, in-channel colorimetry, luminescence (phosphorescence and fluorescence), absorption and transmission.

The fluid in the detection unit can be stationary or moving.

The molecules being analyzed can be anywhere within the channel, for example, they can be within the fluid, bound to the detection cell wall, or attached to another substance within the detection cell.

Off-chip optics, such as lenses and filters, can also be used to concentrate and condition the rays of light incident on and transmitted from the device.

Devices according to the invention may incorporate any known electromagnetic radiation transmitting, reflecting, refracting, modifying, or segmenting components. Examples of such components include, but are not limited to, the following absorptive, reflective, refractive, or diffractive components as part of a single or multiple optical elements; ), lenses (concave, convex, spherical, aspherical, Fresnel lenses), prisms (for guiding and separating light, beam splitters, collimators), refractive surfaces (materials with different refractive indices, forming moth-eye microscopic structure to reduce reflections at the surface), surface coatings for changing the refractive index (e.g. optical coatings of thin metal layers), diffraction gratings, mirrors (planar, spherical, aspherical, Fresnel, corner cube reflectors mirrors) and filters (absorptive, dichroic, binary filters).

According to one embodiment, the device is a multilayer device and the monolithic device is partly or entirely polymeric. Fluidic or optical components can be made by removing or replacing material throughout the bulk device or cutting out entirely through layers. Devices according to the invention can be manufactured by batch, serial, or continuous production techniques. Such techniques include, but are not limited to, embossing, injection molding, stamping, roll cutting, ion or chemical etching, laser processing, and thermoforming.

In one embodiment, either or both the light source S and the detector D can be positioned perpendicular to the fluid carrying channel. Figures 36(a) to 36(d) show top views of microfluidic channels (401 and 402) with transmissive windows (301) on the top surface for illumination and or detection. In these embodiments, the detection zone is positioned longitudinally along the microfluidic channel (402) passing between the transmissive windows (301).

A cross-section of a device with a longitudinal detection zone is shown in Figure 37(a), (b) and (c), where photon redirecting elements are used to direct electromagnetic radiation through the device. S and D refer to the light source and light detector, respectively. Figure 37(a) shows angled reflectors (412) at either end of the channel (403) that redirect between generally vertical and horizontal directions through the waveguide (301) in the device (303) ) light path (302). Figure 37(b) shows an example where an angled reflective surface (412) is used to guide the light path within the device (303). The light path (302) can traverse the fluidic or non-fluidic waveguides (404, 406) and pass between layers within the device by redirecting light through transmissive windows or ports (405) between the layers. The device may also incorporate prismatic structures to guide light within the device. An exemplary device (303) incorporating prismatic or refractive structures is shown in Figure 37(c). In this example, the fluid-filled detection channel (304) has angled end walls to direct the light path (302) through the top layer of the device, along the detection channel (304), and out through the bottom layer.

In one embodiment, reflective features (mirror surfaces or higher refractive index materials) are added to the walls of the microfluidic channels to avoid losses through the channel walls. Figures 38 and 39 provide examples of fabrication steps for fabricating reflective components in microfluidic channels by reflective film deposition. Figure 38 shows the four steps to fabricate a 3-layer device by cutting away an entire layer to create voids or fluidic channels (307). The coating (306) is added before bonding the layers together or after an intermediate step, bonding certain layers before finally sealing the coated microfluidic channels (408). Whereas Fig. 39 shows the fabrication steps of a 2-layer device shaped by techniques such as embossing or injection molding followed by reflective layer deposition and then assembly. In this example, building and coating is performed on the substrate layer (305) prior to assembly to create the coated microfluidic channel (407). The reflective film (306) can be deposited after construction using sputtering or chemical vapor deposition techniques, or by methods such as hot stamping (as often used in the printing industry for decorative coating). Hot stamping offers the ability to deposit relatively thick metal films, and in some cases complex multilayer structures, in a simple stamping process that is easily integrated into e.g. web-based or roll-to-roll ( reel to reel) in the continuous production scheme of production. Hot stamping can be performed before or after embossing or lamination processes to further build up or coat the deposited film.

In other embodiments, light guides (or waveguides) are provided within the device for directing light rays to the detection unit, and in some cases along the length of the detection unit. The cross-sections shown in Figure 40(a) and (b) show examples of detection cells with coated channels for enhanced internal reflection. Figure 40(a) shows an example of three substrate layers (309) forming a microfluidic waveguide (409) with a reflective surface (308). Light approximately perpendicular to the top or bottom surface in the microfluidic channel and close to the angled surface structure is directed longitudinally along the length of the channel and reflected at the other end of the channel to exit through the surface opposite the entrance surface . Figure 40(b) shows an example of 4 base layers (310) combined to provide a waveguide through multiple layers. In this example, the waveguide structure (410) has a reflective surface (311) and may be formed by voids within the layer. These voids can be empty or filled with transmissive material. Coatings can also be applied to layer surfaces not in contact with the waveguides or fluidic structures (313) as shown in Figure 40(c), where a reflective (312) layer is provided on the bottom substrate surface to allow Incident radiation is reflected approximately perpendicular to the top surface after passing through the microfluidic channel or void (314).

Dichroic, absorbing and other filters may also be incorporated, for example by coating the surface of one or more layers of the device.

In other embodiments, different refractive components are incorporated, including but not limited to prisms and materials with different refractive indices. Figure 41(a) shows prism (411) and lens (319) structures that are imprinted into the layers prior to bonding to form a three-layer (315) microfluidic device. In this example, incident light (317) is directed through a rib structure into two opposing microfluidic channels (316) and then reflected at either end of the channel to be externally focused by a concave mirror structure (319) to the device. A reflective layer or coating (318) is used to increase photon yield. A similar structure is shown in Figure 41(b), where a three-layer (324) microfluidic device combines concave lenses (320) and convex lenses (325) for light collection (322), and a reflective surface (321) for to guide light through the void or fluidic channel (323). Figures 41(a) and (b) incorporate lenses on the top surface of the device to help focus light. Whereas Fig. 41(c) incorporates lens components that are in-line within the detection unit to focus light within the device, for example into the waveguide, or to or from external components. In this example, a 3-layer substrate (326) device is shown with concave lenses (331) to focus the incident radiation and convex lenses (327) to focus the radiation as it traverses the detection cell. Reflective surfaces (328) are used to minimize light (329) loss along the channel (330) walls.

According to another aspect of the invention, integrated lens components can be fabricated in single layer or multilayer systems. These lens systems may or may not be coplanar with the microfluidic channels. In many instances, this allows simple fabrication of the lens component using the same method used to form the channel.

Additional embodiments can accommodate optically displacing elements outside of the fluid delivery channel or detection unit. For example: Figures 41(a), 41(b) and 41(c) show lenses fabricated in the same part as the fluid detection unit, but not integrated with the detection unit. Other lenses, such as Fresnel or aspheric mirrors, work equally well.

A multi-lens system can also be fabricated in the device to improve light guiding, see Figure 42. This example shows a multi-lens element for collimating radiation (335), comprising convex lens (333) and concave lens (334) components aligned to channels or voids (332).

Certain embodiments use optical fibers, which may or may not employ additional lens components for enhanced signal coupling. Figures 43(a) and (b) show the fluidic device (336) with individual optical fibers (338) arranged longitudinally relative to the microfluidic channel (337). Fiber optic bundles may also be employed and in certain preferred embodiments extend externally to the fluidic portion. In one such example, Figure 43(c) shows a tapered fiber optic bundle (340, 341 ) positioned adjacent to a microfluidic device (339) for signal acquisition and/or illumination.

Additional ribs and reflective structures can be used to focus or direct light for improved signal response. A corner cube reflector, for example, as shown in Figure 44, provides parallel light return and can be used to enhance exposure and signal acquisition. Figure 44(a) provides a single corner cubic element (342) that reflects radiation (343) parallel to the incident path. Similarly, Figure 44(b) shows a cross-section of a corner cubic cell array (344) that reflects incident radiation (343). Reflectors can be positioned laterally or vertically within the microfluidic device, either in or close to the fluidic channels, for example, Figure 45(a) shows a longitudinally positioned reflector formed in a strip Microfluidic detection with reflective walls at the end of the flow cell. (347) provides an indication of the direction of fluid flow through the detection unit. Radiation (346) incident on the surface is collimated by the surface structure (349) before entering the fluidic channel with reflective walls and corner cube ends (345). The radiation (346) is then reflected back along the detection unit and exits the device (348). An alternative approach is shown in Figure 45(b), where the fluidic device (350) incorporates a reflector array (354) positioned laterally relative to the detection unit (352). The radiation (351) is first collimated by the parallel surface structure (353), then traverses the flow channel, and is then reflected on the approaching return path. Reflectors (358) can also be positioned outside the microfluidic device, as shown in Figure 45(c), to simplify fabrication of the device. In this example, a 3-layer microfluidic device (355) incorporates a detection cell (356) positioned close to the array of reflectors, allowing radiation (359) to pass completely through the device (355) before being reflected.

Collimators (349, 353, 357) are used to help direct the radiation so that the light is approximately parallel and perpendicular to the surface.

Similarly, additional reflector and prismatic surface combinations can increase photon density by directing radiation. Figure 46 depicts examples of ray tracing for rib and collimated surface structures, respectively. Both of these techniques can be used to provide a more collimated beam and, when combined with additional structures, can lead to improved signal response. Figure 46(a) depicts an array of prisms on the surface of a substrate that refracts or reflects radiation (360) depending on the angle of incidence in order to control the angle of radiation exit. Figure 46(b) shows a surface structure (362) with walls perpendicular to the substrate surface (361) to collimate incident radiation (364). Refraction or internal reflection on the structure walls (362) provides collimated radiant output (363).

Some examples of how ribs and collimating surface structures can be used in fluidic devices are shown in Figures 47(a) to (j). These structures are illustrated as 2-layer substrate devices, but are equally applicable to additional multi-layer devices. These structures can also be used in the example of single layer devices, such as microscope slides, where the surface of the slide or coverslip is patterned. An example of such a structure is the use of corner cube reflectors on the underside of a microscope slide to enhance the microarray and additionally the fluorescence on the opposite surface of the slide by simply reflecting a large number of beams perpendicular to the slide surface imaging. The detection cells or voids (371) can be part of the fluidic network and are depicted here in cross-section or longitudinal section. The structured surface (365) and or reflective surface (366) are configured to guide photons through the fluidic channel in a lateral direction, a longitudinal direction, or both.

Figure 47(a) shows the use of a collimating structure (365) positioned close to the fluidic channel (371). The structure reduces light loss due to scattering and random emission by collimating photons passing through these surface structures.

Figure 47(b) shows the use of a collimating structure (365) positioned close to a fluidic channel (371) with reflective walls (366). In this example, photons entering the channel at the end of the collimating structure (365) are reflected by the sloped walls into the channel (371). Reflective walls (366) improve photon containment within the channel (371). Photons exit the channel (371 ) at the end of the channel near the reflective sloped wall where they are recollimated (365) and exit the device. This method does not apply to the imaging segment of the channel (371), but improves photon yield when collecting data from the entire channel (371).

Figure 47(c) illustrates the use of prismatic structures (367) within channels (371). These structures (367) can also be used to help collimate photons passing through their structures by reflecting photons that have a larger angle of incidence relative to the normal to their surface. The angle of the prismatic surface structure thus determines the acceptance angle of the photons. This is particularly useful in improving the signal-to-noise response in applications such as luminescence by separating excitation and emitted photons. Collimated excitation photons incident perpendicular to the structured surface are reflected, while a fraction of random emitted photons pass through the prismatic structure.

In Figure 47(d), reflective surfaces (366) can be added to increase photon yield by reflecting photons back across the channel (371), these surfaces can also take the form of structured reflectors (368), e.g. Corner cubic, spherical, or aspheric reflectors. By making the reflectors part of the channel surface, as shown in Figure 470, light loss at material boundaries is reduced and, in some applications, it is possible to attach materials within structures to improve point source imaging, such as microarrays or Microsphere Imaging. However, placing surface structures inside channels is not suitable for some applications because it hinders fluid interactions and may also require farther optical centers.

Figures 47(g) and (h) include a prismatic layer (367) close to and on the surface of the channel (371 ), respectively. In Figure 47(g), the addition of prismatic structures (367) to the reflective layer (366) provides a collimator that increases photon yield by reflecting photons that have passed through the prismatic structures (367).

Lenses can also be incorporated into the structure to focus light entering/exiting the fluidic device. The examples in Figures 47(i) and 47(j) show devices incorporating an aspheric type lens (369) and a Fresnel type lens (370), respectively.

The example in Figure 48 is used for light path tracing (372) for longitudinal illumination and point source imaging (377). Incident light from the source is focused by an aspheric lens (376) onto a reflective wall (375), which deflects the light path by 90 degrees along the length of the channel to illuminate a point source of light. Excitation photons passing through the channel (373) are then reflected at the wall on the opposite end of the channel, focused externally by the lens (376). The emission of a point source within the channel can be calibrated by (375) reflection and (374) to improve signal response. Combining longitudinal and lateral photon-guiding elements has many advantages, some examples of which are shown in FIGS. 47 and 48 .

This configuration can provide a single detector unit, which is suitable for most types of photon detection methods. For example, many techniques require increased optical path length for high-resolution protocol-based analysis, or require imaging along the length of the channel.

Different detection methodologies can be combined for multiparameter measurements. For example for fluorescence microarray analysis, longitudinal absorption measurements can conclude the introduction of a reagent or detect the presence of gas bubbles, while the luminescent point light source under analysis is imaged laterally.

Improved signal-to-noise ratios are obtained in many cases, which is especially important for luminescence-based measurements where the excitation and emission wavelengths are close together. Interference from the excitation wavelength can be minimized by longitudinal excitation and transverse detection.

In some instances where the detector and source are on the same side of the device, the instrumentation is simplified with minimal packaging.

In one embodiment, the detector and source region are positioned adjacently on the device. Figure 49(a) shows an example of this in a device (378) where photons (383) enter a transparent region (379) where they can be conditioned before being reflected longitudinally and pass through another transparent (380) region shoot out. Such adjustments may include gratings, prisms, phosphors, illuminants, or filters that alter the spectral content or shape of the beam. Longitudinal reflections can be performed through an external waveguide (381 ), as shown in 49(b), or within the device through an internal waveguide (382), as shown in Figure 49(c). An advantage of having the light path (383) through the light modulating element on the device in this way is that the card can be designed to meet the needs of a dedicated application. This enables the instrument to operate a variety of inserts or devices without having to change the instrument optics.

Figures 50(a) and 50(b) show further examples for fabricating waveguides. Waveguides manipulate incident light at material boundaries by reflection or transmission. Typical fabrication methods in microfluidic devices in the past have involved using entire planar materials, directly inserting optical fibers into the sensor system, or photolithographically patterning the surface in a manner similar to semiconductor device fabrication. In the example of Figure 50(a), a suitable tool (386) is used to apply a refractive material (387) to a pre-formed channel (384) in a fluidic device (385). The refractive material is cured to form a cured shaped reactive waveguide (388) in the fluidic device. The preformed waveguide (389) in Figure 50(b) is inserted into the fluidic device (390). The included waveguide (393) is then sealed by a sealing layer (391) to produce a combined waveguide and fluidic device (392).

One approach for improving the waveguide properties of transparent materials is to increase the difference in refractive index at material boundaries. Changes in surface properties at these boundaries can cause changes in the refractive index for enhanced reflection or transmission. In certain thin film depositions, modified surfaces can be provided for waveguiding and reflective surfaces, for example, a silver coating (tens or hundreds of nanometers) is deposited to provide a negative refractive index.

To guide electromagnetic energy in complex geometries, channels can be formed with pre-built layers. The channels formed can then be filled if desired. These structures can be filled by injecting and then curing a transparent material, or placing the formed waveguide into a vacuum structure fill, as shown in FIG. 50 .

Instrument configuration method

The present invention also provides methods whereby all or some of the upgrade information, operational data, or software architecture for an instrument can be included in or on an insert whereby an instrument can include some or all A software module for the operation of templates or basic programs, but does not include all the data required to fully operate the instrument, some of which is provided by removable inserts. Inserts can be recognized when connected to an instrument and operate in accordance with data change programs encoded into one or more inserts.

The insert may or may not be primarily used for other purposes required for standard operation of the instrument, such as a SIM card for a mobile phone or a microfluidic chip for an analytical device. The Insert is recognized when inserted into a matching instrument, and the instrument's functional program is executed in cooperation with the functionality of the instrument and the data encoded into the Insert.

In one embodiment, the plug-in includes access and authorization information, allowing user services to access certain functions or features of the instrument, such as new application and protocol data, user settings, device features or functionality.

In another embodiment, the present invention provides improved user operability and operational automation brought about by plug-ins that provide data to the instrument to automate some or all of the application's operations and provide user-defined settings, thus simplifying user interaction, which enhances system reliability and simplifies instrument operation.

In another embodiment, the plug-in includes access or authorization information that allows the user service to access remote features. These remote features can include Internet sites for upgrades, experimental or application information, or local area networks for instrument and computer system access.

Embodiments of the invention may include data contained within the Insert relating to use of the Insert or the instrument. Data can be stored on the insert during production and can include user, experimental and application information. Examples of this type of data include factory settings, calibration information, user information, device usage, collected data, sensor data, settings, sampling or operating location information (e.g., GPS tracking of samples), time and date stamps, production data and quality control, tracking, and other information usable by the instrument, user, or instrument/device/insert manufacturer

In another embodiment, the data may be written to, or updated in the field by the user or the instrument before, during, or after use. Information written in the field may also include user data, sample or procedure location information entered by the user or by the instrument via a global positioning system, results, instrument settings, test conditions, application information, and other user or instrument data.

In another embodiment, the plugin includes user profile information. Allows the user to automatically configure the instrument based on the user's personal settings, or to teach the instrument about operations the user typically performs or requests. This can be performed directly by instructions on the insert, or generally by learning an algorithm of the software on the instrument, analyzing the previous actions of the current user, or another user.

One embodiment of the present invention describes an instrument and add-in architecture in which one or more add-ins are part of a software upgrade path for an instrument, and more particularly, add-ins include upgrade information. An example of the architecture is shown in FIG. 53 . The method of integrating new software information onto the insert allows the instrument to immediately accept new insert application, calibration or program data without requiring the user to upgrade the software via other media, thus simplifying user operations and reducing manufacturer overhead. An additional advantage of using a consumable insert to carry upgrade data is that it requires the mating instrument to have the correct interface to connect to the mating insertable device, adding a security feature.

Another embodiment of the present invention provides operating system software built with core machine management functions and built-in application-specific modules and controlled by the plug-in to configure the instrument to meet the market or when required customer's demand,

In one embodiment, an object-oriented approach is employed, where the instrument includes program subroutines and functions to perform all common and low-level operations such as acquiring data, selecting data channels, pumping, switching valves, setting temperatures, template GUIs, etc. . In one embodiment, the general-purpose subroutine in the instrument is operable to perform one or more of the following actions: acquiring data, selecting an acquisition channel, controlling pumping, controlling valve switching, setting temperature, configuring a graphical user interface, and one or more of program code, data or instructions that enable the instrument to operate as an insert for a particular application

One or more plug-ins include the application's calls and variables to instrument subroutines and functions. This approach is illustrated by the example shown in FIG. 54 . This approach allows the Insert to control the operation of the instrument and a GUI for the Insert's particular application. Examples of program flow can be seen in Figures 55 and 56, where a plug-in starts an application and transfers, or enables transfers between programs, operational data or variables to perform functions by the instrument.

In another embodiment, a non-object-oriented approach can be used, where the instrument includes program code to perform all common and low-level operations, such as acquiring data, selecting acquisition channels, pumping, switching valves, setting temperatures, template GUIs wait. One or more Inserts include code and or variables to enable operation of the instrument for the specific application of the Insert. This approach allows the Insert to control instrument operation and a GUI for the Insert's specific application.

This distributed architecture (eg, FIG. 54 ) minimizes the software development associated with the development of new applications for the instrument and its associated inserts. A universally programmed instrument can accept new applications without requiring the user to upgrade the software.

Furthermore, the present invention provides additional software security since executable program instructions do not reside within the instrument. Inserts only carry instructions to configure the instrument for the specific application of the particular insert. This approach offers a more difficult path to reverse engineering, since a full understanding of the program's execution is required. If the interaction of the instrument and the Insert is reverse engineered, the resulting executable program only reveals data for the proprietary application of the manufactured Insert.

A further object of the invention is that the information and data contained in the insert can be written or read, or both.

According to another embodiment, the inserter can transfer its entire operating code to volatile memory on the instrument, retaining only its identification and data storage and data reading functions, thus making it a "one-time use" device and once inserted If the software is removed from the instrument, all operating codes will be destroyed. This prevents unauthorized access to the opcode included in the insert, since it can only be read by the mating instrument, and because the opcode only exists in the volatile memory of the mating instrument when the insert is inserted, And once the instrument is turned off or the insert is removed or the operating procedure is completed, whichever occurs first, the opcode is automatically and permanently erased.

The inserts described here can be single or multiple. Inserts can be removable storage devices such as flash drives, sensors or microfluidic cartridges. Data on the insert can be stored in a number of different formats including, but not limited to, barcodes, on-board memory, microprocessor or other integrated circuits, electrical interconnects or resistive, radio frequency, optical, mechanical or electromagnetic forms.

The foregoing are specific embodiments of the present invention, especially microfluidic embodiments. It should be understood that the embodiments described here are for illustrative purposes only, and those skilled in the art can make numerous substitutions and modifications without departing from the spirit and scope of the present invention. It is intended to embrace all such modifications and substitutions within the scope herein as they come within the scope of the claims of the present invention or their equivalents.

Throughout this specification (including any appended claims), unless the context requires otherwise, the word "comprise" and variations such as "comprises" and the illustrative "comprising" will be understood to mean including the specified integer or step. or group of integers or steps, but does not exclude the inclusion of any other integer or step or group of integers or steps.

Figure References

01 Actuation component Actuation component

02 Fluidic Channels Fluidic Channels

03 Actuation Area Actuation Area

04 Injection Pump injection pump Symbol injection pump symbol

05 In-Line Pump Symbol Inline pump symbol

06 On/Off Valve Or Variable Flow Valve Symbol Switch valve or variable flow valve symbol

07 One Way Valve Symbol One Way Valve Symbol

08 Actuation Area Actuation Area

09 Inline Pump Inline pump

10 Fluidic Channels Fluidic Channels

11 Injection Pump injection pump

12 On/Off Valve Or Variable Flow Valve On/Off Valve Or Variable Flow Valve

13 In-line pump actuated on opposite actuation cycle to other Inline Pump

Inline pumps actuated on opposite actuation cycles to other inline pumps

14 Actuation Area Actuation area

15 Fluidic Channels Fluidic Channels

16 On/Off Valve Or Variable Flow Valve On/Off Valve Or Variable Flow Valve

17 In-Line Pump Inline pump

18 Injection Pump injection pump

19 Actuation Area Actuation area

20 Fluidic Channels Fluidic Channels

21 In-Line Pump

22 On/Off Valve Or Variable Flow Valve On/Off Valve Or Variable Flow Valve

23 Stream of fluid stream

24 Stream of fluid stream

25 Stream crossover/intersection point

26 Injector pump and two valves in same Actuation Area Injector pump and two valves in same Actuation Area

27 Injector pump and two valves in same Actuation Area Injector pump and two valves in same Actuation Area

28 Inline Pump Inline pump

29 Inline Pump and two valves in same Actuation Area Inline Pump and two valves in same Actuation Area

30 Stream of fluid

31 Stream crossover/intersection point Stream exchange/intersection point

32 Stream of fluid

33 Actuation Area Actuation area

34 One Way Valves

35 Membrane stop valve

36 Deformable Membrane Deformable membrane

37 Inlet Fluid flow Inlet fluid flow

38 Outlet Fluid flow outlet fluid flow

39 Inlet port with Applied force

40 Deformable Layer Deformable layer

41 Debubbler Debubbler

42 Vent With Check valve Exhaust port with check valve

43 In-Line Pump

44 Iniection Pump injection pump

45 Gas gas

46 Semi-permeable Membrane Or Vent Semi-permeable membrane or vent

47 Fluid flow Fluid flow

48 Gas flow from pressure gradient Gas flow caused by pressure gradient

49 Substrate base

50 Vent exhaust port

51 Inlet Port entrance

52 Fluidic Channel Fluidic Channel

53 Chamber cavity

54 Fluidic Channel Fluidic Channel

55 Layered Device

56 Vent exhaust port

57 Vent Chamber exhaust cavity

58 Semi-permeable Membrane Or Vent Semi-permeable membrane or vent

59 Gas Bubble Bubble

60 Regulating valve Regulating valve

61 Venting chamber Exhaust cavity

62 Deformable Membrane Deformable membrane

63 Semi-permeable Membrane Or Vent Semi-permeable membrane or vent

64 Fluid chamber flow cavity

65 Air passage

66 Deformable structure Deformable structure

67 One-way Valve Check valve

68 Semi-permeable Membranes Semi-permeable membrane

69 Pressure Relief Valve

70 Fluid Reservoir Fluid Tank

71 Fluidic Channels Fluidic Channels

72 Semi-permeable membrane Semi-permeable membrane

73 Gas Flow Path Gas flow path

74 Fluid Flow Path Fluid flow path

75 One Way Valves

76 Applied pressure gradient Applied pressure gradient

77 Fluid Flow in pump chamber The fluid flow in the pump chamber

78 Semi-permeable Membrane Semi-permeable membrane

79 Applied pressure gradient Applied pressure gradient

80 Fluid Flow Fluid flow

81 Semi-permeable membrane Semi-permeable membrane

82 Conductive Material Conductive material

83 Hole in substrate layer The hole in the substrate layer

84 Deformable Actuation Structure Deformable Actuation Structure

85 Fluid flow direction Fluid flow direction

86 Semi-permeable membrane Semi-permeable membrane

87 Deformable Actuation Structure Deformable Actuation Structure

88 Pressure Relief Valve

89 Actuation direction of deformable structure Deformable structure actuation direction

90 Actuation volume Actuation volume

91 Fluid Pumping Chamber Fluid pumping chamber

92 Inlet port entrance

93 Inline Pump Inline pump

94 Debubbler Debubbler

95 Detection chamber Detection chamber

96 Direction Of Fluid Flow Fluid flow direction

97 Pressure relief structures

98 Fluidic Channels Fluidic Channels

99 In-line Pump Inline pump

100 One Way Valve Check Valve

101 Sample introduction with one way valve

102 Actuation Area Actuation area

103 Debubbler Debubbler

104 One way valve pressure relief valve

105 Split flow Mixer

106 Detection Chambers

107 Pressure relief structure Decompression structure

108 Sample introduction Port with semi-permeable membrane

109 Air return

110 Multi-layer fluidic device Multi-layer fluidic device

111 Inline Pump Inline pump

112 Inline Pump Inline pump

113 One-way valves Check valve

114 Fluid storage well Fluid storage tank

115 Fluid storage well Fluid storage tank

116 Debubbler Debubbler

117 Detection chambers Detection chamber

118 Fluid pressure relief structures

119 Fluid storage well Fluid storage tank

120 Inline Pump Inline pump

121 Injection Chamber injection cavity

122 Actuation stop valve Actuation stop valve

123 Inline Pump Inline pump

124 Fluid storage well Fluid storage tank

125 One-way valves

126 Fluidic Card Fluidic Card

127 Pressure chamber Pressure chamber

128 On-card Pumps Card on the pump

129 Instrument Valves

130 Pressurization port

131 External valve interface External valve interface

132 Valve interface port Valve interface port

133 Gasket Washer

201 Ball Or Roller Bearing ball bearing or roller bearing

202 Flexible Wall Flexible Wall

203 Rigid Substrate rigid substrate

204 Fluidic Channel Fluidic Channel

205 Elastomer material Elastomer material

206 Non-deformable substrate Non-deformable substrate

207 Deformable material Deformable material

208 Fluidic Channel Or Chamber Fluidic Channel Or Chamber

209 Direction Of Applied Force The direction of the applied force

210 Deformable Material Deformable material

211 Fluidic Channels Fluidic Channels

212 Deformable Material Deformable material

213 Substrate base

214 Deformable Material Deformable material

215 Substrate With Suitable Restrictions Or contoured surface Substrate With Suitable Restrictions Or contoured surface

216 Flowing Fluid Flowing Fluid

217 Fluidic Channel Fluidic Channel

218 Bearing bearing

219 Direction Of Movement And Flow Movement and flow direction

220 Linear pumping zone Linear pumping zone

221 Radial pumping zone Radial pumping zone

222 Valve Locations Valve Location

223 Inlet/Outlet Ports entry/exit port

224 Radial Pumps radial pump

225 Fluidic Channel Fluidic Channel

226 Rod Like Driving Mechanism

227 Spherical Objects spherical objects

228 Rotating Housing

229 Rotating Platform(Wobble Board)

230 Rotating Cams On Rod Structure Rotating Cams On Rod Structure

231 Rotating Wiper

232 Rotating Housings

233 Fixing Pins

234 Spherical Objects spherical objects

235 Drive Gears

236 Drive GearsIMotor drive gear/motor

237 Solid Fixing Base Solid fixed base

238 Drive Rods/Bearings Drive Rods/Bearings

301 Transmissive Windows Transmission window

302 Photon Pathways

303 Fluidic Device

304 Detection Channel detection channel

305 Individual Substrate Layers Each base layer

306 Reflective Layer or Coating Reflective layer or coating

307 Cut-Out or Void In Layer Cut or void in layer

308 Reflective Layers or Coatings reflective layer or coating

309 Individual Substrate Layers Each base layer

310 Individual Substrate Layers Each base layer

311 Reflective Layers or Coatings reflective layer or coating

312 Reflective Layer or Coating Reflective layer or coating

313 Individual Substrate Layers Each base layer

314 Void or Fluidic Channel Void or Fluidic Channel

315 Individual Substrate Layers Each base layer

316 Void or Fluidic Channel Void or Fluidic Channel

317 Photon Pathways

318 Reflective Layers or Coatings reflective layer or coating

319 Concave Structure concave structure

320 Concave Structure concave structure

321 Reflective Layers or Coatings reflective layer or coating

322 Photon Pathways

323 Void or Fluidic Channel Void or Fluidic Channel

324 Individual Substrate Layers Each base layer

325 Convex Structure Convex structure

326 Individual Substrate Layers Each base layer

327 Concave-Planar Structure concave flat structure

328 Reflective Layers or Coatings reflective layer or coating

329 Photon Pathways

330 Void or Fluidic Channel Void or Fluidic Channel

331 Plano-Convex Structure Plano-convex structure

332 Void, Refractive Inclusion or Fluidic Channel Void, Refractive Inclusion or Fluidic Channel

333 Convex Structures Convex structure

334 Concave Structures concave structure

335 Photon Pathways

336 Fluidic Device

337 Void or Fluidic Channel Void or Fluidic Channel

338 Light Fiber or Wave Guide Fiber or Wave Guide

339 Fluidic Device

340 End Of Fiber Optic Bundle

341 Fiber Optic Bundle Drawn Into Smaller Diameter Reduced to a smaller diameter fiber bundle

342 Prismatic Structure-Reflective or Refractive Prismatic Structure-Reflective or Refractive

343 Photon Pathways

344 Reflective Surface reflective surface

345 Reflective Surfaces reflective surface

346 Photon Pathways

347 Direction Of Fluidic Flow Fluid flow direction

348 Fluidic Device

349 Collimating Surface Structures Collimating Surface Structures

350 Fluidic Device

351 Photon Pathways

352 Fluidic Channel Fluidic Channel

353 Collimating Surface Structures Collimating Surface Structures

354 Reflective Surfaces reflective surface

355 Fluidic Device

356 Fluidic Channel Fluidic Channel

357 Collimating Surface Structures Collimating Surface Structures

358 Reflective Surfaces reflective surface

359 Photon Pathway

360 Photon Pathways

361 Device Layer device layer

362 Collimating Surface Structures Collimating Surface Structures

363 Collimated Transmitted Radiation Collimated transmitted radiation

364 Random Incident Radiation Random Incident Radiation

365 Collimating Surface Structures Collimating Surface Structures

366 Reflective Surfaces reflective surface

367 Refractive/Reflective Prismatics Refractive/Reflective Prismatic

368 Reflective Surface structures Reflective surface structures

369 Surface Lens Structures Surface Lens Structures

370 Fresnel Lens Structures Fresnel Lens Structures

371 Fluidic Channel Fluidic Channel

372 Photon Pathways

373 Fluidic Channel Fluidic Channel

374 Surface Collimating Structures Surface collimating structure

375 Reflective Layer or Coating Reflective layer or coating

376 Surface Lens Structures lens structure surface

377 Particles Of Interest In Fluidic Channel Related particles in the fluidic channel

378 Representation Of A Fluidic Device

379 Photon Transparent Region Light transparent region

380 Photon Transparent Region With Photon Conditioning Element

381 External Wave Guide External waveguide

382 Internal Wave Guide Internal waveguide

383 Photon Pathways

384 Preformed Channel Preformed Channel

385 Fluidic Device

386 Suitable Tool Suitable Tool

387 Refractive Material Refractive material

388 Cured And Formed Refractive Wave Guide Cured and Formed Refractive Wave Guide

389 Preformed Wave Guides Preformed Waveguide

390 Partially Complete Fluidic Substrate Partially Complete Fluidic Substrate

391 Containment Layer

392 Completed Fluidic Device Completed fluidic device

393 Wave Guides In Situ

401 Fluidic Channels Fluidic Channels

402 Fluidic Channels Fluidic Channels

403 Fluidic Channels Fluidic Channels

404 Waveguide Waveguide

405 Transmission Port transmission port

406 Waveguide Waveguide

407 Fluidic Channels Fluidic Channels

408 Fluidic Channels Fluidic Channels

409 Fluidic Channels Fluidic Channels

410 Waveguide Waveguide

411 Prismatic Structure Prismatic structure

412 Angular reflective surfaces Angled reflective surfaces

Claims (15)

1. fluid handling structure comprises:

Realize the activation zone that the fluid in this structure of control flows; With

In this activation zone greater than one actuated components;

Wherein this activation zone is arranged to trigger or to control said actuated components greater than;

Wherein, said fluid handling structure comprises a deformable films and a pellicle, and said pellicle allows gas to pass through, and liquid phase to impermeable through said pellicle;

Wherein, said fluid handling structure is a micro-fluidic structure, and

Wherein geometry is used to limit and flows to or passage or chamber that outflow is communicated with said pellicle fluid, and to separate the fluid media (medium) that mixes, wherein said geometry is one or more control valves; Wherein, only when the pressure reduction that traverses this valve that need be used to open this control valve exceeded, said control valve passed through fluid.

2. structure as claimed in claim 1; Wherein said activation zone comprises the controller that flows in order to the fluid in the control device, wherein said controller adopts pneumatically, electromagnetic ground, mechanically, hydraulically, utilize acoustically or utilize the piezoelectricity mode and operate.

3. structure as claimed in claim 1, wherein said actuated components comprises one or more: injection pump, pump in upright arrangement; Close/open valve or variable flow valve, check valve and other fluid handling structure or their combination.

4. structure as claimed in claim 1, wherein the part activation zone comprises removable or deformable material at least; Wherein said deformable material constitutes and is arranged as under the condition of exerting pressure and changes shape; Can change shape to another predetermined geometry from predetermined geometry; And then through using, remove and/or the excitation of reversing returning to reservation shape, manual, heat, electricity, the machinery input, pneumatic, hydraulic pressure, magnetic or their combination that wherein said excitation comprises.

5. structure as claimed in claim 1, wherein said actuated components comprises: at least two pumps in upright arrangement on the relative stroke that is applied by same activation zone, operating provide pump action thus on the forward circulation of activation zone and recycled back.

6. structure as claimed in claim 1, wherein a plurality of fluid passages intersect.

7. structure as claimed in claim 1, wherein a plurality of close/open valves or vario valve are associated with the fluid passage, and each valve constitutes and be arranged as sequential activation, produce pump action when therefore being triggered by single activation zone.

8. structure as claimed in claim 1 wherein also comprises:

In order to control the mobile additional activation zone of fluid in the said structure;

At least one actuated components in said additional activation zone; With

The mutual fluid of wherein said activation zone and said additional activation zone is communicated with; And

Wherein said additional activation zone is arranged to trigger or to control each additional actuated components.

9. structure as claimed in claim 1, wherein said control valve is formed by the deformable layer of separating two fluid handling structures.

10. structure as claimed in claim 1, wherein:

In order to realize the mobile activation zone of fluid in the said structure of control;

In fluid cavity or the passage at least one;

Form the pellicle at least one border of said fluid cavity or passage, said pellicle arrange with allow the control fluid through and flow to said fluid cavity or passage, the fluid that promotes thus, limit or stop in said fluid cavity or the passage is mobile.

11. structure as claimed in claim 10 wherein also comprises: second pellicle that forms second border of said fluid cavity or passage.

12. the fluid network of many interconnection, wherein at least one in the fluid network comprises the fluid network according to each formation among the claim 1-11.

13. fluid network as claimed in claim 12 also comprises controller, said controller comprises the external device (ED) that constitutes and be configured to be used for be communicated with at least one fluid network fluid.

14. like claim 12 or 13 described fluid networks, wherein said controller comprises dismountable card, said card comprises the pneumatic interconnection that configurable and said at least one fluid network links to each other.

15. like claim 12 or 13 described fluid networks, wherein said controller constitutes and arranges to provide to the shared control action that is present in a plurality of actuated components in the fluid network.

Images