HK1210737B - High speed, compact centrifuge for use with small sample volumes - Google Patents

Description

High-speed mini centrifuge for small sample volumes

Technical Field

The present disclosure relates to a high-speed miniature centrifuge for small sample volumes.

Background Art

Conventional centrifuges are too large and inefficient for centrifuging small volumes of liquid specimens. They also lack the specific configurations needed to handle small sample volumes.

Introductory clause

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

Summary of the Invention

It should be understood that embodiments of the present invention may be adapted to have one or more of the configurations described herein.

In a non-limiting example, an automated system is provided for separating one or more components in a biological fluid. The system may include: (a) a centrifuge having one or more centrifuge buckets configured to receive a container to produce the described separation effect on one or more components in a liquid sample; and (b) the container including one or more shaped structures complementary in shape to a shaped structure of the centrifuge bucket.

It should be understood that the examples herein may be suitable for having one or more of the following configurations. In a non-limiting example, the system may include one or more floats that are in or near a vertical position when the centrifuge is stationary and in or near a horizontal position when the centrifuge is rotating. Optionally, the system may include multiple floats positioned radially symmetrically on the centrifuge. Optionally, the liquid sample is a biological fluid. Optionally, the biological fluid is blood. Optionally, the container is designed to hold 100uL or less of sample liquid. Optionally, the container is designed to hold 50uL or less of sample liquid. Optionally, the container is designed to hold 25uL or less of sample liquid. Optionally, one end of the container is closed and the other end is open. Optionally, the container is a centrifuge container. Optionally, the centrifuge container has a rounded end with one or more inner tubercles. Optionally, the system includes an extraction pipette tip having one or more molding structures that complement a molding structure of the centrifuge container and is designed to be integrated with the centrifuge container. Optionally, the molding structure of the centrifuge bucket includes one or more shelves, and a protrusion of the container is designed to be placed on the shelf. Optionally, the centrifuge bucket is designed to accommodate multiple containers with different designs, wherein the molding structure of the centrifuge bucket includes multiple shelves, a first container with a first design is designed to be placed on a first shelf, and a second container with a second design is designed to be placed on a second shelf.

In yet another example described herein, a small high-speed centrifuge is provided that includes a centrifuge body; a motor for rotating the centrifuge body; and a detector integrated into the motor and designed to determine at least one rotational position of a rotating portion of the motor, wherein the detector uses at least two different types of encoder information to determine the rotational position.

It should be understood that the examples herein may be suitable for one or more of the following configurations. In one non-limiting example, the detector uses at least an optical encoder and Hall effect technology to determine rotational position. Optionally, the detector uses at least an optical encoder and Hall effect technology to determine at least rotational position and rotational rate. Optionally, the detector includes a first surface that directly detects one type of encoder information and a second surface that directly detects another type of encoder information. Optionally, the first surface and the second surface are located in different orientations. Optionally, the first surface and the second surface are located in the same orientation. Optionally, the motor includes multiple detectors for determining rotational position. Optionally, the motor includes a first encoder disk that provides a first type of encoder information and a second encoder disk that provides a second type of encoder information. Optionally, the motor includes a first encoder disk that provides optical encoder information and a second encoder disk that provides magnetic encoder information. Optionally, the motor includes an encoder disk that provides both the first type of encoder information and the second type of encoder information. Optionally, the motor includes an encoder disk that provides both optical encoder information and magnetic encoder information. It should be understood that while the motor with integrated encoder components is described in the context of a centrifuge, the motor may also be suitable for use in other situations where it is desirable to have position and/or velocity detector structures integrated with the motor.

In yet another example herein, a method is provided comprising: providing a motor; integrating a first type of encoder into the motor; integrating a second type of encoder into the motor; determining the rotational position of a rotating portion of the motor using the first type of encoder, and determining the rotational rate of the rotating portion of the motor using the second type of encoder.

It should be understood that the examples herein may be adapted to have one or more of the following configurations. In one non-limiting example, the first type of encoder provides optical encoder information. Alternatively, the first type of encoder provides magnetic encoder information. Alternatively, the first type of encoder provides Hall effect encoder information. Alternatively, the first type of encoder and the second type of encoder provide different types of encoder information.

In another embodiment described herein, a small high-speed centrifuge for use with sample containers is provided. The centrifuge may include a first portion comprised of a thermally insulating material; a second portion comprised of a thermally conductive material; wherein the container is arranged to be located within the region of the thermally insulating material; and wherein the thermally conductive material is configured to conduct heat away from the container.

In another embodiment, a small high-speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body; and an active cooling unit for reducing heat transfer to the sample; wherein the container is arranged to be located in an area with less heat exposure; the active cooling unit is used to cool the drive mechanism; and wherein the stator of the drive mechanism is located within a coaxial motor rotor.

In another embodiment, a small high-speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge body, a drive mechanism for rotating the centrifuge body, and a position detector for determining the rotational position of the centrifuge body.

In another embodiment, a small high-speed centrifuge for use with sample containers is provided. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body; and an automatic balancing weight coupled to the centrifuge body, wherein the weight is designed to move to a position under the action of centrifugal force to reduce uneven rotation of the centrifuge body when the centrifuge sample rack is unevenly loaded.

In another embodiment, a small high-speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge body, a drive mechanism for rotating the centrifuge body, and at least one air bearing designed to operably support the centrifuge.

In another embodiment, a small high-speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge housing; a centrifuge body; a drive mechanism for rotating the centrifuge body; and at least one air bearing designed to operably support the centrifuge, wherein at least a portion of the air bearing is part of the centrifuge housing.

In another embodiment, a small high-speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge housing; a centrifuge body; a drive mechanism for rotating the centrifuge body; and a force detector configured to detect a force change exceeding a predetermined external force condition.

It should be understood that the examples herein are suitable for having one or more of the following configurations. In a non-limiting example, the centrifugal container holder is directed inwardly toward a central axis of the centrifugal rotor under the action of centrifugal force. Alternatively, the centrifugal container holder forms a flush surface with the rotor body to reduce aerodynamic drag. Alternatively, the centrifugal container holder is designed to retract downwards under the action of centrifugal force. Alternatively, the electrical connection of the centrifugal body cooling element will not be cut off, although these elements are in motion during centrifugal operation.

In another embodiment, a small high-speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body, wherein the centrifuge body extends downwardly over at least a portion of the drive mechanism; wherein the drive mechanism includes a stator and a rotor, and the rotor is concentric with the stator.

In another embodiment, a small high-speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body, wherein the centrifuge body extends downwardly over at least a portion of the drive mechanism; wherein the drive mechanism includes a stator and a rotor; and the stator and the rotor are concentric.

In another embodiment, a small high-speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body; and one or more floating bucket racks located on the centrifuge body for holding a centrifuge container. A maximum dimension of the floating bucket rack or the sample container does not exceed 10 mm.

In another embodiment, a small high-speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body; and one or more floating bucket racks located on the centrifuge body for holding a centrifuge container. During operation of the centrifuge, the floating bucket racks move from a first position to a second position that is more horizontal than the first position.

In another embodiment, a small high-speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body; and one or more floating bucket racks located on the centrifuge body for holding a centrifuge container. The width of the sample container is greater than a length of the sample container.

In another embodiment, a small high-speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge body and a drive mechanism for rotating the centrifuge body.

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

BRIEF DESCRIPTION OF THE DRAWINGS

Figures 1-3 show different views of an example of the centrifuge described.

Figures 4-5 show different views of an example of the centrifuge described.

6-8 show different views of the described container rack example.

Figures 9-12 show various examples of a centrifuge as described.

13-16 show different views of the described example centrifuge with a temperature control configuration.

17A-17G illustrate various examples of apparatus and methods described for controlling position and/or velocity.

18A-18C show different examples of the described self-balancing configurations.

19A-19B and 20 show various examples of the described apparatus and methods.

FIG21 shows a schematic diagram of an example of an integrated system having sample processing, pre-processing, and analysis components.

DETAILED DESCRIPTION

It should be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the subject matter of the claims. It should be noted that, unless the context clearly indicates otherwise, the singular forms "a," "an," and "the" used in the specification and the appended claims include plural concepts. Thus, for example, the concept of "a material" may include a mixture of several materials; the concept of "an ingredient" may include multiple ingredients, and so on. Unless otherwise expressly stated in the specification, the references cited herein are fully incorporated herein.

In the following specification and claims, some terms will be used and have the following meanings:

"Optional" or "optionally" means that the subsequently described situation may or may not occur, so the description includes both situations where the situation occurs and situations where it does not occur. For example, a device "optionally" includes a structure as a sample collection hole, which means that the sample collection hole may or may not exist, so the description includes both devices with and without the sample collection hole.

centrifuge

Figures 1, 2, and 3 show perspective views of the dimensions of a centrifuge that may be integrated into the system (Figure 1 - side view, Figure 2 - front view, Figure 3 - rear view). The centrifuge may contain an electric motor capable of driving the rotor at 15,000 rpm. One type of centrifuge rotor is shaped like fan blades suspended in a vertical plane from the motor shaft. Affixed to the rotor is a member that may receive sample-receiving elements (tips) and provide a ledge or shelf upon which the ends of the tips distal to the motor shaft may rest, providing support during centrifugation to prevent sample leakage. The tips may be further supported at their proximal ends by a mechanical stop within the rotor. This stop can be provided so that the centrifugal forces generated during centrifugation do not cause the tips to penetrate the flexible nylon cap. Tips may be inserted and removed using a standard pick-and-place mechanism, but a pipette is preferred. The rotor is a single piece of plastic (or other material) shaped to reduce vibration and noise during centrifuge operation. The rotor is (optionally) shaped so that other movable parts within the device can move through the centrifuge when it is at a specific angle to the vertical plane. The sample retention element is centrifugally balanced by chip masses on opposite sides of the rotor so that the center of rotational inertia is axially relative to the motor. The centrifuge motor may provide position data to a computer, which may then control the rotor's static position (typically vertical before and after centrifugation).

According to published standards (DIN 58933-1; U.S. CLSI standard H07-A3: "Procedure for Determining Packed Cell Volume by the Microhematocrit Method"; Approved Standard - 3rd Edition), to reduce centrifugation time (and not generate excessive mechanical stress during centrifugation), the rotor is suitably sized in the range of approximately 5-10 cm, rotating at 10,000-20,000 rpm, giving a packed red blood cell time of approximately 5 minutes.

In some embodiments, a centrifuge may be a horizontal centrifuge with a floating bucket design. In some preferred embodiments, the centrifuge axis of rotation is vertical. In other embodiments, the axis of rotation may be horizontal or at any angle. The centrifuge may be capable of spinning two or more containers simultaneously and may be designed to be fully integrated into an automated system using computer-controlled pipetting. In some embodiments, the containers may be bottom-enclosed. The floating bucket design may allow the centrifuge container to be passively oriented in a vertical position when centrifugation is stopped and to rotate out at a fixed angle during rotation. In some embodiments, the floating bucket may allow the centrifuge container to be rotated out in a horizontal orientation. Alternatively, they may be rotated out at any angle between vertical and horizontal (for example, approximately 15, 30, 45, 60, or 75 degrees from vertical). Centrifuges with a floating bucket design may require an automated system using a number of positioning systems to meet positioning accuracy and repeatability requirements.

A computer control system may use position information from an optical encoder to rotate the rotor at controlled low speeds. Because a suitable motor may be designed for high-speed rotation, accurate static position cannot be maintained using position feedback alone. In some cases, a cam combined with an electromagnetically driven lever may be used to achieve very accurate and stable stops at a fixed number of positions. Using a different control system and feedback information from a Hall effect sensor built into the motor, the rotor's speed can be well controlled at high speeds.

Because a large number of sensitive devices within the detection system must function simultaneously, the centrifuge design must first effectively reduce or minimize vibration. The rotor may be aerodynamically designed to have a smooth outer surface—completely enclosed when the centrifuge buckets are in a horizontal position. Furthermore, the housing design may utilize multiple vibration damping features. It should be understood that any of the examples in Figures 1-3 may incorporate any of the other structures described herein.

rotor

A centrifuge rotor may be part of a system that may contain and rotate the centrifuge container. The shaft may be vertical so that the rotor itself may be in a horizontal position. In other instances, different shaft and rotor positions may be used. Two known centrifuge buckets are symmetrically placed on either side of the rotor that contains the centrifuge container. Or the centrifuge buckets may be designed to be radially symmetrically distributed, for example, three centrifuge buckets are each placed at 120 degrees. Any number of centrifuge buckets may be provided, including but not limited to 1, 2, 3, 4, 5, 6, 7, 8 or more. The spacing between these centrifuge buckets may be equal. For example, n centrifuge buckets are provided, where n is the number of centrifuge buckets, and the spatial distance between each centrifuge bucket is 360/n degrees. In other instances, the centrifuge buckets do not need to be equidistant or radially symmetrical.

When the rotor is stationary, the buckets may passively droop due to gravity, just like a vertically placed container, allowing easy access for the pipette. Figure 4 shows a demonstration of a rotor in a stationary state with vertical buckets. In some instances, the buckets may passively droop to a predetermined angle, which may or may not be vertical. When the rotor rotates, the buckets are forced to an approximately horizontal position or a predetermined angle by centrifugal force. Figure 5 shows a demonstration of a rotor with buckets at a small angle to the horizontal at a certain speed. When enforcing accuracy and position repeatability, both the vertical and horizontal positions may be physically difficult to stop.

To reduce vibrations caused by air turbulence, the rotor may be a dish-shaped aerodynamic design with as little physical structure as possible. To achieve this, the outer geometry of the centrifuge bucket may be precisely matched to the geometry of the rotor, so that when the rotor is rotating and the centrifuge bucket is forced to a horizontal position, the centrifuge bucket and the rotor may be completely aligned.

To perform plasma extraction, the rotor may be angled toward the ground and away from the horizontal. Because the bucket angle may match the rotor angle, this may force the bucket to rotate at a fixed angle. The resulting pellet from such a centrifugation may be angled relative to the vertical container. A narrow extraction tip may be used to aspirate plasma from the upper portion of the centrifuge container. By placing the extraction tip at the bottom of the angled pellet slope, the final plasma volume can be aspirated more efficiently without disturbing the sensitive white blood cell layer.

A variety of tube designs may be accommodated within the centrifuge bucket of the device. In some instances, the different tube designs may be closed at the ends. Some are designed to resemble traditional conical-bottom centrifuge tubes. Other tube designs may be cylindrical. Tubes with a low height to cross-sectional area ratio may be more suitable for processing cells. Tubes with a high ratio (>10:1) may be suitable for accurately measuring hematocrit and other imaging needs. Otherwise, any height to cross-sectional area ratio may be used. The centrifuge bucket may be made of any of several plastics (polystyrene, polypropylene), or any other material discussed elsewhere. The capacity of the centrifuge bucket ranges from a few microliters to approximately 1 ml. The tube is inserted into and removed from the centrifuge via a "lift and release" mechanism.

control system

Given the rotation and positioning requirements of the centrifugal device, a dual control system may be used. In order to direct the rotor to a specified rotational position, a position-dependent control system may be installed. In some instances, the control system may use a PID (proportional-integral-differential) control system. Feedback control systems known in other technologies may also be used. Position feedback for the position controller may be provided by a high-resolution optical encoder. In order to run the centrifuge from low speed to high speed, a speed controller may be installed and the speed control adjusted using a PID control system. Speed feedback for the speed controller may be provided by a set of simple Hall effect sensors mounted on the motor shaft. Each sensor may generate a square wave for each rotation of the motor shaft.

Suspension mechanism

To continuously and securely hold the rotor in a specific position, a physical stop mechanism may be used in some instances. In one example, this stop mechanism may utilize a cam coupled into the rotor with an electromagnetically actuated lever. The cam may be shaped like a C-shaped disc with machine-cut grooves along its edge. To position the centrifuge rotor, its rotational speed may first be reduced to below 30 rpm. In other examples, the speed may be reduced to any other value, including but not limited to 5 rpm, 10 rpm, 15 rpm, 20 rpm, 25 rpm, 35 rpm, 40 rpm, or 50 rpm. Once the speed is sufficiently low, the lever can be actuated. The lever terminates in a cam follower that slides along the outer edge of the cam with minimal friction. Once the cam follower reaches the center of a specific groove in the cam, the electromagnetic lever actuation force overcomes the motor power and stops the rotor's rotation. At that point, the motor can be electrically braked, and when used in conjunction with the stop mechanism, a rotational position can be very accurately and securely maintained indefinitely.

Centrifuge bucket

The centrifuge float may be designed to accommodate different types of centrifuge tubes. In a preferred embodiment, these different tube types may include an annular rim or flange at their upper (open) end. This annular rim or flange may be located at the upper end of the centrifuge bucket and provide support for the tube during centrifugation. As shown in Figures 6, 7, and 8, conical and cylindrical tubes of varying lengths and capacities may be accommodated. Figures 6, 7, and 8 provide examples of centrifuge buckets and other centrifuge bucket designs that may be used. For example, Figure 6 shows an example of a centrifuge bucket design. The centrifuge bucket may include side portions that engage with the centrifuge and allow the bucket to swing freely. The centrifuge bucket may be closed at the bottom and open at the top. Figure 7 shows an example of a centrifuge container that engages with the centrifuge bucket. As mentioned above, the centrifuge bucket may be molded to accommodate different centrifuge container designs. The centrifuge container may include one or more protrusions that may rest on the centrifuge bucket. The centrifuge container may be molded with one or more structures that may engage with the centrifuge bucket. Such structures may be a molded structure of the container or one or more protrusions. What Fig. 8 showed is another centrifugal container demonstration that may be closely connected with centrifugal bucket.As previously mentioned, this centrifugal bucket may have one or more molding structures to allow the centrifugal containers of different designs to engage with it.It should be understood that among Fig. 4-8, any one centrifuge example all may contain other any structure described by the present invention.

Centrifuge tubes and sample extraction techniques

The centrifuge tube and extraction tip may be provided separately and may be joined together for extraction of material after centrifugation. The centrifuge tube and extraction tip may be designed to handle complex processes in an automated system. Any dimensions are provided by way of example only, and other dimensions of the same or different proportions may be used.

The system may do one or more of the following:

1. Rapidly process small volume blood specimens (usually 5-50uL)

2. Accurate and precise measurement of hematocrit

3. Effectively remove plasma

4. Efficient resuspension of formed elements (red blood cells and white blood cells)

5. Concentrated white blood cells (after fluorescent antibody labeling and red blood cell fixation and lysis)

6. Optical Confirmation of Red Blood Cell Lysis and White Blood Cell Recovery

Overview of Centrifuge Vessels and Extraction Tips

A custom centrifuge container and pipette tip may be used for the centrifugation operation to meet the various constraints imposed by the system. The centrifuge container may be a closed-bottom test tube designed for rotation within the centrifuge. In some instances, the centrifuge container may be the container depicted in FIG. 116 , or may have one or more of the configurations depicted in FIG. 116 . It may have many unique configurations capable of performing a wide range of desired functions, including hematocrit measurement, RBC lysis, pellet resuspension, and efficient plasma extraction. The extraction tip may be designed to be inserted into the centrifuge container for precise liquid extraction and pellet resuspension. In some instances, the extraction tip may be the tip depicted in FIG. 117 , or may have one or more of the configurations depicted in FIG. Typical specifications for extraction tips are discussed herein and may also be found in U.S. application serial numbers 13/355,458 and 13/244,947 , which are incorporated herein by reference in their entirety for all purposes.

Centrifuge container

In one example, the centrifuge container may be designed to handle two different applications, each associated with a different anticoagulation and whole blood volume.

The first application scenario may require sedimentation of 40 uL of whole blood with heparin, reconstitution of the maximum volume of plasma, and measurement of the hematocrit using machine vision. At a hematocrit of 60% or less, the required or preferred plasma volume may be approximately 40 uL*40%=16 uL.

In some cases, 100% plasma reconstitution is not possible due to the inability to disrupt the buffy coat, necessitating a minimum distance between the tip of the pipette and the pellet. This minimum distance can be determined empirically, but the volume sacrificed (V) as a function of the required safety distance (d) can be estimated using the following formula: V(d) = d * π1.25 ^mm² . For example, if a 0.25 mm safety distance is required, the volume sacrificed at a hematocrit of 60% would be 1.23 uL. This volume can be reduced by reducing the inner diameter of the hematocrit portion of the centrifuge container. However, because in some cases, the narrow portion must fully fit within the outer diameter of the extraction tip, which may be no less than 1.5 mm, the existing dimensions of the centrifuge container may already approach this minimum value.

In addition to plasma extraction, some instances may also require the use of computer vision to measure hematocrit. To perform this operation, the total height of a given hematocrit volume may be maximized by reducing the inner diameter of the narrow portion of the container. By maximizing the height, the relationship between the volumetric change in hematocrit and the physical change in sediment height may be optimized, thereby increasing the number of pixels used for measurement purposes. The height of the narrow portion of the container may also be sufficient to accommodate a worst-case hematocrit of 80%, where a small amount of plasma may still remain above the sediment for effective extraction. Therefore, 40uL * 80% = 32uL may be the volume required to accurately measure hematocrit. The designed capacity of the narrow portion of the pipette tip may be approximately 35.3uL, allowing for some residual plasma volume even in the worst-case scenario.

The second use case is more common and may require one, more, or all of the following:

Whole blood sedimentation

Plasma extraction

The pellet was resuspended in lysis buffer and stained

Retain white blood cells (WBCs) sediment

Remove the supernatant

Resuspension of WBCs

Completely extract WBC suspension

To completely resuspend a packed pellet, experiments have shown that it is possible to physically disrupt the pellet using a pipette tip that fully contacts the bottom of the container containing the pellet. The preferred geometry of the resuspension container bottom appears to be a hemispherical shape similar to that of a standard commercially available PCR tube. Other container bottom shapes may also be used in other embodiments. The centrifuge tube, along with the extraction tip, may be designed to perform resuspension operations by adhering to these geometric requirements and allowing the extraction tip to physically contact the container bottom.

During manual resuspension experiments, we noticed that the physical contact between the bottom of the centrifuge container and the tip of the pipette tip can create a sealing effect that inhibits liquid movement. To completely break up the pellet while allowing liquid to flow, a very small gap may be used. To perform this operation in an automated system, a physical structure may be added to the bottom of the centrifuge tube. In some embodiments, this structure may consist of four small hemispherical nodules placed along the circumference of the container bottom. When the extraction tip is fully inserted into the container and allowed to make physical contact, the tip of the tip may rest on the nodules, allowing liquid to flow freely between the nodules. This may result in a small amount of volume loss (~0.25 uL) between the gaps.

In a lysis operation, some projects may expect a maximum liquid volume of 60 uL, which, combined with the 25 uL displaced by the extraction tip, may require a total volume of 85 uL. A current design with a maximum volume of 100 uL may exceed this requirement. Other aspects of the second use case require similar or already discussed tip features.

The geometry of the centrifuge container's upper portion may be designed to engage a pipette nozzle. Any pipette nozzle described elsewhere or known elsewhere may be used. The outer geometry of the container's upper portion may precisely match a reaction tip, around which current nozzles and cartridges may be designed. In some embodiments, a small ridge may be defined on the inner surface of the upper portion. This ridge may be a visible marker of maximum liquid height, allowing for automated error detection using computer vision systems.

In some embodiments, the distance from the bottom of the fully engaged nozzle to the upper limit of the maximum liquid level is 2.5 mm. This distance is 1.5 mm shorter than the recommended 4 mm distance for the extraction tip. This shortened distance may be due to the need to reduce the length of the extraction tip while adhering to minimum volume requirements. The explanation for this reduced distance is the specific use of the container. In some designs, since the liquid in the container can only be changed from above, the maximum amount of liquid it can contain when the nozzle is engaged is the maximum expected whole blood volume at any given time (40 uL). This liquid level may be just below the bottom of the nozzle. Another concern is that, at other times, the container may contain more liquid than this, filling the entire nozzle height. In some embodiments, the use of the container is relied upon to ensure that the meniscus of any liquid contained within the container does not exceed the maximum liquid level, even if the total volume is less than the specified maximum capacity. In other embodiments, additional structures may be provided to retain liquid within the container.

Any dimensions, sizes, capacities, or distances provided herein are for exemplary purposes only. Any other dimensions, sizes, capacities, or distances may be used and may or may not be proportional to the values set forth herein.

During the operation of changing liquids and quickly inserting or removing the pipette tip, the centrifuge container may be subjected to some external forces. If the container is not fixed, these external forces may be enough to lift the container or move it away from the centrifuge bucket. In order to prevent movement, the container should be fixed in some way. To achieve this purpose, a small ring is added that is restricted around the outside of the bottom of the container. This small ring can easily be engaged with a flexible mechanical structure on the centrifuge bucket. When connected to the nozzle, this problem is solved as long as the external force retained by the nodule is greater than the external force it is subjected to during liquid operations and less than the friction when connected to the nozzle.

Extraction tips

The extraction tip may be designed to interact with the centrifuge container, effectively extract plasma, and resuspend the pelleted cells. When designed, its overall length (e.g., 34.5 mm) may closely match the length of another blood tip, including but not limited to those described in U.S. Serial No. 12/244,723 (incorporated herein by reference), but may be long enough to physically contact the bottom of the centrifuge container. Some embodiments may require the ability to contact the bottom of the container, both for resuspension and for complete reconstitution of the leukocyte suspension.

The required capacity of the extraction tip may be determined by the maximum volume desired to be extracted from the centrifuge container at any given time. In some instances, this capacity may be 60uL, which is less than the tip's maximum volume of 85uL. In some instances, a tip larger than the required capacity may be provided. When used with the centrifuge container, a structure constrained inside the upper portion of the tip may be used to mark the height of this maximum capacity. The distance between this maximum capacity marking and the top of the engagement nozzle may be 4.5mm, which may be considered a safe distance to prevent nozzle contamination. Any distance sufficient to prevent nozzle contamination may be used.

The centrifuge may be used to pellet the LDL-cholesterol. Imaging may be used to demonstrate that the supernatant is colorless, indicating complete pelleting.

In one demonstration, plasma may be diluted into a mixture of (1:10) dextran sulfate sodium (25 mg/dL) and magnesium sulfate (100 mM) and then incubated for 1 minute to precipitate LDL-cholesterol. The reaction product may be aspirated into the centrifuge tube, capped, and centrifuged at 3000 rpm for 3 minutes. Figures 119, 120, and 121 are images of the original reaction mixture before centrifugation (showing a white precipitate), after centrifugation (showing a colorless supernatant), and the LDL-cholesterol precipitate (after removing the cap), respectively.

Another example of a centrifuge that may be used in the present invention is described in US Pat. Nos. 5,693,233, 5,578,269, 6,599,476 and US Patent Publication Nos. 2004/0230400, 2009/0305392, and 2010/0047790, which are incorporated herein by reference in their entirety for all purposes.

Operating procedure demonstration

Many different protocols may be used for centrifugation and sample processing. For example, a typical protocol for centrifuging and concentrating white blood cells for cytometry analysis may include one or more of the following steps. The following steps may be provided in a different order, or other steps may be substituted for any of the following steps:

1. Receive 10uL of whole blood containing an anticoagulant (use a pipette to inject the blood into the bottom of the centrifuge bucket)

2. Centrifuge to pellet red blood cells and white blood cells (<5 minutes x 10,000g)

3. Measuring Hematocrit by Imaging

4. Use the pipette to slowly remove the plasma (4uL in the worst case, [hematocrit 60%]) without disturbing the cell pellet.

5. Add 20uL of a buffered saline solution containing up to 5 fluorescently labeled antibodies to the pellet for re-suspending

6. Incubate at 37°C for 15 minutes

7. Prepare the lysis/fixation reagent by mixing the red blood cell lysis solution (ammonium chloride/potassium bicarbonate) and the white blood cell fixative (formalin)

8. Add 30uL of lysis/fixation reagent (total reaction volume is 60uL)

9. Incubate at 37°C for 15 minutes

10. Centrifuge to pellet leukocytes (10,000 g)

11. Remove the lysis supernatant

12. Add buffer (isotonic buffered saline) to resuspend the white blood cells

13. Accurately measure capacity

14. Send the sample to the cell counter

The steps may include receiving a sample. The sample may be a bodily fluid, such as blood, or any other sample described elsewhere. The sample may be in a small volume, such as any of the measured volumes described elsewhere. In some cases, the sample may contain an anticoagulant.

A separation step may occur. For example, a density-based separation step may occur. This separation may be performed by centrifugation, magnetic separation, lysis, or any other known separation technique. In some embodiments, the sample may be blood, in which red blood cells and white blood cells may be separated.

A measurement may be performed. In some cases, the measurement may be performed by imaging, or any other detection mechanism described elsewhere. For example, the hematocrit of a fractionated blood sample may be measured by imaging. Imaging may be performed using a digital camera or any other image acquisition device described herein.

One or more components of a sample may be removed. For example, if the sample is separated into solid and liquid components, the liquid component may be removed. The plasma portion of a blood sample may be removed. In some cases, the liquid portion, such as plasma, may be removed using a pipette. The liquid component may be removed without disturbing its solid portion. Imaging may aid in the removal of the liquid component, or any other selected component of the sample. For example, imaging may be used to determine where the plasma is located and may help position the pipette to remove the plasma.

In some instances, a reagent or other substance may be added to the sample. For example, the solid portion of the sample may be resuspended. A labeled substance may be added. One or more incubation steps may occur. In some cases, a lysis and/or fixation reagent may be added. Additional separation and/or resuspension steps may occur. Dilution and/or concentration steps may also be performed, if necessary.

The volume of the sample may be measured. In some cases, the volume of the sample may be measured in a precise and/or accurate manner. The volume of the sample may be measured within a system of variables with low correlation coefficients, such as the correlation coefficients described elsewhere. In some cases, the volume of the sample may be measured using imaging techniques. An image of the sample may be collected, and the volume of the sample may be calculated from the image.

The sample can be sent for a desired procedure. For example, the sample may be sent for a cell count.

In another embodiment, a routine protocol for nucleic acid purification, which may or may not utilize a centrifuge, may include one or more of the following steps. The system may perform DNA/RNA extraction and deliver nucleic acid template for exponential amplification for detection. The protocol may be designed to extract nucleic acids from various samples, including but not limited to whole blood, serum, viral transcripts, human or animal tissue specimens, food samples, and bacterial cultures. The procedure may be fully automated or may extract DNA/RNA in a continuous and quantitative manner. The following steps may be provided in a different order, or other steps may be substituted for any of the following steps:

1. Sample lysis. The cells in the sample may be lysed using a chaotropic salt buffer. The chaotropic salt buffer may include one or more of the following: a chaotropic salt, such as but not limited to 3-6 M guanidine hydrochloride or guanidine thiocyanate, sodium dodecyl sulfate (SDS) typically at a concentration of 0.1-5% v/v, ethylenediaminetetraacetic acid (EDTA) typically at a concentration of 1-5 mM, lysozyme typically at a concentration of 1 mg/ml, proteinase K typically at a concentration of 1 mg/ml; and a buffer set at a pH of 7-7.5, such as HEPES. In some instances, the sample may be incubated in the buffer at a temperature typically of 20-95°C for 0-30 minutes. Isopropanol (50%-100% v/v) may be added to the mixture after lysis.

2. Surface loading. The lysed sample may be exposed to a functionalized surface (commonly in the form of a bead-filled layer), such as, but not limited to, a resin-supported chromatographic column, magnetic beads mixed with the sample in various forms, the sample is pumped into and through a suspended resin in a liquid layer mode, or the sample is pumped into a closed pipe and passed through the surface in a tangential flow mode. The surface may be functionalized so that it can bind to nucleic acids (such as DNA, RNA, DNA/RNA hybrids) in the presence of the lysis buffer. Types of surfaces may include silica, and ion exchange functional groups such as diethylaminoethanol (DEAE). The lysis mixture may be exposed to the surface and the nucleic acid binding site.

3. Washing. The solid surface is rinsed with a salt solution, such as 0-2 M sodium chloride at pH 7.0-7.5 and 20-80% v/v ethanol. This rinsing process can be completed in the same operation as the sample addition.

4. Elution. Nucleic acids can be eluted from the surface by exposing the surface to water or a pH 7-9 buffer. Elution can be performed in the same operation as sample loading.

Many variations of these protocols or other protocols may be used with the system. These protocols may be used in conjunction with, or in place of, any protocol or method described herein.

In some instances, it is very important to be able to recover cells that have been compressed and concentrated by centrifugation and use them for cell counting. In some instances, this may be accomplished using the pipette device. A liquid (usually a plasma-buffered saline solution, a lysis solution, a lysis-fixation mixture, or a buffered mixture containing labeled antibodies) is added to the centrifuge bucket and repeatedly aspirated. The pipette tip may be forced into the packed cells to perform this operation. Image analysis assists this operation by objectively demonstrating that all cells have been resuspended.

Sample processing prior to analysis using pipettes and centrifuges

In accordance with one embodiment of the present invention, the system may have pipetting, pick-and-place, and centrifugation functions that may be able to efficiently perform nearly any type of sample pre-processing and complex assays using very small amounts of sample.

In particular, the system may be capable of separating the visible components (red and white blood cells) from plasma. The system may also be capable of resuspending the visible components. In some instances, the system may be capable of concentrating white blood cells from fixed and lysed blood. The system may also be capable of lysing cells to release nucleic acids. In some instances, the system may be capable of purifying and concentrating nucleic acids by filtering the sample through a pipette tip filled with a solid-phase reagent (e.g., silica, typically beads). The system may also allow for elution of purified nucleic acids after solid-phase extraction. The system may also be capable of removing or collecting precipitates (e.g., LDL-cholesterol precipitates obtained using polyethylene glycol).

In some cases, the system may also be capable of affinity purification. Small molecules such as vitamin D and serotonin can be adsorbed onto hydrophobic materials coating beads (particles) and then eluted using organic solvents. Antigens can be presented onto antibody-coated materials and eluted with acid. The same approach can be used to concentrate low-concentration analytes such as thromboxane B2 and 6-keto-prostaglandin F1α. Antigens can be presented onto antibody- or aptamer-coated materials and then eluted.

In some instances, the system may be able to chemically modify the assay substrate prior to testing. For example, to test for serotonin (pentahydropyramine), the assay substrate may be converted to a derivative (such as an acetylated form) using a reagent (such as anhydrous acetic acid). This process may produce a form of the assay substrate that is recognized by an antibody.

Liquid may be removed using the pipette (vacuum suction and aspiration). The pipette may be limited to relatively low positive and negative pressure states (approximately 0.1-2.0 atmospheres). When external forces are required to drive the liquid through the solid phase medium filled with balls, a centrifuge may be used to generate relatively high pressures. For example, using a rotor with a radius of 5 cm, the centrifugal force generated at a speed of 10,000 rpm is approximately 5,000 x g (approximately 7 atmospheres), which is sufficient to drive the liquid through a resistive medium such as a compression layer. Any other centrifuge design and structure discussed or known elsewhere may be used.

It's possible to measure hematocrit using a small amount of whole blood. For example, inexpensive digital cameras can capture good images of small objects even when the contrast is poor. Leveraging this capability, the system being developed could potentially be used to automatically measure hematocrit using a small amount of whole blood.

For example, 1 μL of whole blood can be drawn into a glass capillary tube with a microcap. The capillary tube can then be sealed with a removable adhesive and centrifuged at 10,000 x g for 5 minutes. The packed cell volume can be easily measured, and the plasma meniscus (arrow) can be visible, allowing the hematocrit to be accurately determined. This may enable the system to avoid wasting a relatively large blood sample volume to perform this measurement. In some instances, the camera can be used for "basic imaging" without the need for a microscope to produce a larger image. In other instances, a microscope or other optical technology can be used to magnify the image. In one approach, the digital camera can be used to determine the hematocrit without the need for other optical technology; the measured hematocrit is comparable to that obtained using a traditional microhematocrit laboratory method that requires a few microliters of sample. In some instances, the length of the sample column and the length of the packed red cell pellet can be measured with great precision (+/- <0.05 mm). Assuming that the blood specimen column is likely to be approximately 10-20 mm, the standard deviation of the hematocrit matches the data obtained by standard laboratory methods to much better than 1%.

This system may be capable of measuring erythrocyte sedimentation rate (ESR). The digital camera's ability to measure minute distances and the rate of change of distance can be exploited to measure ESR. In a demonstration, three blood samples (15 μL) were aspirated into a "reactive tip." Images were captured at two-minute intervals over an hour. Image analysis was used to measure the movement of the interface between red blood cells and plasma.

The accuracy of the measurement can be assessed by fitting the data to a polynomial function and calculating the standard deviation of the difference between the data and the fitted curve (for all samples). In this demonstration, the accuracy was determined to be 0.038 mm or <2% CV when the relevant distance was moved over one hour. Therefore, ESR can be accurately measured using this method. Another method for determining ESR is to measure the maximum slope of the distance vs. time curve.

centrifuge

Now referring to Figures 9 to 11, more centrifuge examples will be described here. Consistent with some examples in the invention, a system may include one or more centrifuges. An apparatus in the system may include one or more centrifuges. For example, one or more centrifuges may be provided in an apparatus housing. A module may be equipped with one or more centrifuges. One, two, or more modules of an apparatus may be equipped with a centrifuge. The centrifuge may be supported by a module support structure or may be located within a module frame. The centrifuge may have a size characteristic that is compact, flat and requires only a small footprint. In some examples, the centrifuge may be miniaturized to suit point-of-service applications, but still maintain high-speed rotation performance equal to or greater than 10,000 rpm and be able to withstand accelerations of approximately 1,200 m/s ² or more.

In some instances, a centrifuge may be designed to hold one or more samples. A centrifuge may be used to separate and/or purify substances of varying densities. Examples of these substances may include viruses, bacteria, cells, proteins, environmental components, or other components. A centrifuge may also be used to concentrate cells and/or particles for further measurement.

In some embodiments, a centrifuge may have one or more cavities that may be designed to receive a sample. The cavity may be designed to receive the sample directly within the cavity, such that the sample may contact the cavity wall. Alternatively, the cavity may be designed to receive a sample container that may contain a sample. Any description herein of a centrifuge cavity may apply to any design that may receive and/or contain a sample or sample container. For example, a centrifuge cavity may include a groove within a material, a barrel-shaped form, a hollow protrusion, or various designs that interconnect with a sample container. Any description of a centrifuge cavity may also include designs that may or may not include concave surfaces or internal surfaces. Examples of sample containers may include any container or pipette tip designs described elsewhere. A sample container may have an interior surface and an exterior surface. A sample container may have at least one open port for receiving a sample. The open port may be closable or sealable. The sample container may have a closed port. The sample container may be a nozzle of a liquid handling device, which may function similarly to a centrifuge, centrifuging liquid within the nozzle, within a pipette tip, or other container associated with the nozzle.

In some embodiments, the centrifuge may have one or more, two or more, three or more, four or more, five or more, six or more, eight or more, 10 or more, 12 or more, 15 or more, 20 or more, 30 or more, or 50 or more centrifuge chambers designed to hold a sample or sample container.

In some embodiments, the centrifuge may be designed to handle a small sample volume. In some embodiments, the centrifuge chamber and/or sample container may be designed to hold a sample volume of 1,000 μL or less, 500 μL or less, 250 μL or less, 200 μL or less, 175 μL or less, 150 μL or less, 100 μL or less, 80 μL or less, 70 μL or less, 60 μL or less, 50 μL or less, 30 μL or less, 20 μL or less, 15 μL or less, 10 μL or less, 8 μL or less, 5 μL or less, 1 nL or less, 500 nL or less, 300 nL or less, 100 nL or less, 50 nL or less, 10 nL or less, 1 pL or less, 500 pL or less, 100 pL or less, 50 pL or less, 10 pL or less, 5 pL or less, or 1 pL or less.

In some embodiments, the centrifuge may include a lid to contain the sample within the centrifuge. The lid may prevent the sample from atomizing and/or evaporating. The centrifuge may optionally include a film, oil (e.g., mineral oil), wax, or gel to contain the sample within the centrifuge and/or prevent the sample from atomizing and/or evaporating. The film, oil (e.g., mineral oil), wax, or gel may be provided as a layer covering a sample that may be contained within the centrifuge chamber and/or sample container.

A centrifuge may be designed to rotate around an axis of rotation. A centrifuge may be capable of rotating at any number of speeds per minute. For example, a centrifuge may rotate to a rate of 100 rpm, 1000 rpm, 2000 rpm, 3000 rpm, 5000 rpm, 7000 rpm, 10000 rpm, 12000 rpm, 15000 rpm, 17000 rpm, 20000 rpm, 25000 rpm, 30000 rpm, 40000 rpm, 50000 rpm, 70000 rpm, or 100000 rpm. At some points in time, a centrifuge may remain stationary, while at other points in time, the centrifuge may be in a rotating state. A centrifuge in a stationary state does not rotate. A centrifuge may be designed to rotate at different speeds. In some instances, the centrifuge may be controlled to rotate at a desired speed. In some instances, the frequency of change in the speed may be different and/or controllable.

In some embodiments, the rotation axis may be vertical. Alternatively, the rotation axis may be horizontal, or may be any angle between horizontal and vertical (e.g., approximately 15 degrees, 30 degrees, 45 degrees, 60 degrees, or 75 degrees). In some embodiments, the rotation axis may be located in a fixed orientation. Alternatively, the rotation axis may vary during use of a device. The rotation axis angle may or may not vary as the centrifuge rotates.

In some embodiments, a centrifuge may include a base. In some embodiments, the base contains the centrifuge rotor. The base may have an upper surface and a bottom surface. The base may be designed to rotate along a rotation axis. The rotation axis may be perpendicular to the upper surface and/or bottom surface of the base. In some embodiments, the upper surface and/or bottom surface of the base may be flat or curved. The upper surface and bottom surface of the base may or may not be substantially parallel to each other.

In some embodiments, the base may have a circular shape. The base may have any other shape, including but not limited to an oval, triangle, quadrilateral, pentagon, hexagon or octagon.

The base may have a height and one or more outer edge dimensions (e.g., diameter, width, or length). The base height may be parallel to the axis of rotation. The outer edge may be perpendicular to the axis of rotation. The base outer edge may be greater than the height. The base outer edge may be greater than 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 8 or more, 10 or more, 15 or more, or 20 or more times the base height.

The centrifuge may be of any size. For example, the area occupied by the centrifuge may be approximately 200 ^cm or less, 150 ^cm or less, 100 ^cm or less, 90 ^cm or less, 80 ^cm or less, 70 ^cm or less, 60 ^cm or less, ⁵⁰ cm or less, 40 ^cm or less, 30 ^cm or less, ²⁰ cm or less, 10 cm or less, ⁵ cm or less, or ^{1 cm} or less. The centrifuge height may be approximately 5 cm or less, 4 cm or less, 3 cm or less, 2.5 cm or less, 2 cm or less, 1.75 cm or less, 1.5 cm or less, 1 cm or less, 0.75 cm or less, 0.5 cm or less, or 0.1 cm or less. In some embodiments, the maximum outer dimension of the centrifuge may be approximately 15 cm or less, 10 cm or less, 9 cm or less, 8 cm or less, 7 cm or less, 6 cm or less, 5 cm or less, 4 cm or less, 3 cm or less, 2 cm or less, or 1 cm or less.

The centrifuge base may be designed to receive a drive mechanism. A drive mechanism may be a motor or any other mechanism capable of rotating the centrifuge along a rotational axis. The drive mechanism may be a brushless motor, which may include a brushless motor rotor and a brushless motor stator. The brushless motor may be an induction motor. The brushless motor rotor may surround a brushless motor stator. The rotor may be designed to rotate about a stator as the rotational axis.

The base may be connected to the brushless motor rotor or used in combination with the brushless motor rotor, which may allow the base to rotate around the stator. The base may be attached to the rotor or may be integrated with the rotor. The base may rotate around the stator, and a plane perpendicular to the motor's rotational axis may be coplanar with a plane perpendicular to the base's rotational axis. For example, the base may have a plane perpendicular to the base's rotational axis that passes roughly between the base's upper and lower surfaces. The motor may have a plane perpendicular to the motor's rotational axis that passes roughly through the center of the motor. The base plane and the motor plane may be roughly coplanar. The motor plane may pass between the upper and lower surfaces of the base.

A brushless motor assembly may include a motor rotor and a stator. The motor assembly may also include electronic components. Integrating a brushless motor into the motor rotor assembly may reduce the overall size of the centrifuge assembly. In some embodiments, the motor assembly does not exceed the height of the base. In other embodiments, the height of the motor assembly is no greater than 1.5 times, 2 times, 2.5 times, 3 times, 4 times, or 5 times the height of the base. The motor rotor may be surrounded by the base such that the motor rotor is not exposed outside the base.

The motor assembly may effect rotation of the centrifuge without a shuttle/spindle assembly. The rotor may surround the stator, which may be electrically connected to a controller and/or power supply.

In some instances, the centrifugal chamber may be designed to have a first orientation when the base is stationary and a second orientation when the base is rotating. The first orientation may be vertical, while a second orientation may be horizontal. The centrifugal chamber may have any orientation, wherein the angle of the centrifugal chamber to the vertical direction and/or the rotation axis may be greater than and/or equal to 0 degrees, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, 75 degrees, 80 degrees, 85 degrees, or 90 degrees. In some instances, the first orientation may be closer to vertical than the second orientation. The first orientation may be closer to parallel to the rotation axis than the second orientation. Alternatively, the centrifugal chamber may have the same orientation regardless of whether the base is stationary or rotating. The orientation of the centrifugal chamber may or may not depend on the rotation speed of the base.

The centrifuge may be designed to hold a sample container, and may be designed so that the sample container is in a first orientation when the base is stationary and in a second orientation when the base is rotating. The first orientation may be vertical, and the second orientation may be horizontal. The sample container may be in any orientation, and the angle from vertical may be greater than and/or equal to 0 degrees, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, 75 degrees, 80 degrees, 85 degrees, or 90 degrees. In some instances, the first orientation may be closer to vertical than the second orientation. Alternatively, the sample container may remain in the same orientation regardless of whether the base is stationary or rotating. The orientation of the container may or may not depend on the rotational speed of the base.

Figure 9 shows a non-limiting example of a centrifuge consistent with the description of the invention. The centrifuge may include a base 3600 having a bottom surface 3602 and/or an upper surface 3604. The base may include one, two, or more base wings 3610a, 3610b.

A base wing may be designed to fold over an axis extending through the base. In some instances, the axis may intersect tangentially with the base. An axis extending from the base may be a folding axis, which may be formed by one or more pivot points 3620. A base wing may comprise an entire portion of the base on one side of the central axis. The entire base may fold to form the base wing. In some instances, a central portion 3606 of the base may transverse the axis of rotation, while the base wing does not. The central portion of the base may be closer to the axis of rotation than the base wing. The central portion of the base may be designed to receive a drive mechanism 3630. This drive mechanism may be a motor or any other mechanism capable of rotating the base, and may be described in detail below. In some instances, the area occupied by a base wing may be 2%, 5%, 10%, 15%, 20%, 25%, 30%, 40%, or more of the area occupied by the base.

In some embodiments, a plurality of folding axes may be provided through the base. These folding axes may be parallel to one another. Alternatively, some of the folding axes may be perpendicular to one another or at any angle to one another. A folding axis may extend from the lower surface, the upper surface, or between the upper and lower surfaces of the base. In some embodiments, the folding axes may extend closer to the lower surface of the base or closer to the upper surface of the base. In some embodiments, a pivot point may be located at or closer to a lower surface of the base or an upper surface of the base.

A base wing may provide one, two, three, four, five, six, or more cavities. For example, a base wing may be designed to hold one, two, or more samples or sample containers. Each base wing may be capable of holding the same number of containers or a different number of containers. The base wing may contain a cavity designed to hold a sample container, wherein the sample container may be positioned in a first orientation when the base is stationary and in a second orientation when the base is rotated.

In some embodiments, the base wings may be designed to be at an angle to the center portion of the base. For example, the base wings may be at an angle of between 90 and 180 degrees to the center portion of the base. For example, when the base is stationary, the base wings may be vertical. In the vertical orientation, the base wings may be 90 degrees from the center portion of the base. When the base rotates, the base wings may be horizontal. In the horizontal orientation, the base wings may be 180 degrees from the center portion of the base. When the base rotates, the base wings may extend from the base to form a generally continuous plane. For example, when the base rotates, the base wings may extend to form a generally continuous lower surface and/or upper surface of the base. The base wings may be designed to fold downward relative to the center portion of the base.

The pivot point for a base wing may include one or more pivot pins 3622. A pivot pin may extend through a portion of the base wing and a portion of the base center. In some embodiments, the base wing and base center may have interlocking structures 3624, 3626 that prevent the base wing from sliding relative to the base center.

A base wing may have a center of gravity 3680 located below the fold axis and/or pivot point 3620. When the base is stationary, the center of gravity of the base wing may be located below the rotation axis extending through the base. When the base is rotating, the center of gravity of the base wing may be located below the rotation axis extending through the base.

The base wing may be made of two or more different materials of different densities. Alternatively, the base wing may be made of a single material. In one demonstration, the base wing may have a lightweight base wing cap 3640 and a heavier base wing base 3645. In some instances, the base wing cap may be made of a lower density material than the base wing base. For example, the base wing cap may be made of plastic and the base wing base may be made of metal, such as steel, tungsten, aluminum, copper, brass, iron, gold, silver, titanium, or any combination or alloy. A heavier base wing base may assist in providing a base wing center of mass below a fold axis and/or pivot point.

The base wing cap and base wing base may be connected by any known mechanism. For example, a latch 3650 may be provided, or bonding, welding, snap-fit structures, clamps, hook and loop fasteners, or any other mechanism may be used. The base wing may optionally include an insert 3655. The insert may be made of a heavier material than the base wing cap. The insert may assist in providing a base wing center of mass below a folding axis and/or pivot point.

One or more cavities 3670 may be provided within the base wing cap, the base wing base, or any combination. In some instances, a cavity may be designed to receive multiple sample container structures. The cavity may have an inner surface. At least a portion of the inner surface may contact a sample container. In one embodiment, the cavity may have one or more shelves or inner surface structures that may allow a first sample container having a first design to fully mate with the cavity, while a second sample container having a second design also fully mates with the cavity. The first and second sample containers having different designs may contact different portions of the inner surface of the cavity.

The centrifuge may be designed to be connected to a liquid handling device. For example, the centrifuge may be designed to be connected to a pipette or other liquid handling device. In some instances, a water-tight structure may be formed between the centrifuge and the liquid handling device. The centrifuge may be connected to the liquid handling device and designed to receive a sample distributed from the liquid handling device. The centrifuge may be connected to the liquid handling device and designed to receive a sample container from the liquid handling device. The centrifuge may be connected to the liquid handling device and allow the liquid handling device to extract or aspirate a sample from the centrifuge. The centrifuge may be connected to the liquid handling device and allow the liquid handling device to extract a sample container.

A sample container may be designed to interface with the liquid handling device. For example, the sample container may be designed to connect to a pipette or other liquid handling device. In some embodiments, a watertight seal may be formed between the sample container and the liquid handling device. The sample container may interface with the liquid handling device and be designed to receive a sample dispensed by the liquid handling device. The sample container may interface with the liquid handling device and allow the liquid handling device to extract or aspirate a sample from the sample container.

A sample container may be designed to extend from a centrifugal wing. In some instances, the centrifugal base may be designed to allow the sample container to extend from the centrifugal wing when the centrifugal wing is in a folded state, and to allow the base wing to pivot between a folded state and an extended state.

Figure 10 shows a non-limiting example of a centrifuge consistent with another embodiment of the invention. The centrifuge may include a base 3700 having a lower surface 3702 and/or an upper surface 3704. The base may contain one, two, or more centrifuge buckets 3710a, 3710b.

A centrifuge bucket may be designed to rotate about a centrifuge bucket pivot extending from the base. In some instances, the pivot may intersect tangentially with the base. The centrifuge bucket may be designed to rotate about a pivot point 3720. The base may be designed to receive a drive mechanism. In one embodiment, the drive mechanism may be a motor, such as a brushless motor. The drive mechanism may include a rotor 3730 and a stator 3735. The rotor may optionally be a brushless motor rotor, and the stator may optionally be a brushless motor stator. The drive mechanism may be any other mechanism capable of rotating the base, and may be discussed further elsewhere.

In some instances, a large number of centrifuge bucket rotation axes may be provided through the base. These rotation axes may be parallel to each other. Alternatively, some rotation axes may be perpendicular to each other, or at any angle to each other. A centrifuge bucket rotation axis may extend through a lower surface, an upper surface, or between the upper and lower surfaces of the base. In some instances, the centrifuge bucket rotation axis may extend out from the base and be positioned closer to the lower surface of the base, or closer to the upper surface of the base. In some instances, a rotation point may be located at or closer to the lower surface of the base or the upper surface of the base.

One, two, three, four, or more cavities may be provided within a centrifuge bucket. For example, a centrifuge bucket may be designed to hold one, two, or more samples or sample containers 3740. Each centrifuge bucket may be capable of holding the same number of containers, or a different number of containers. The centrifuge bucket may contain a cavity for receiving a sample container, wherein the sample container is in a first orientation when the base is stationary and in a second orientation when the base is rotated.

In some embodiments, the centrifuge bucket may be designed to be at an angle to the base. For example, the angle between the centrifuge bucket and the base may be between 0 and 90 degrees. For example, when the base is stationary, the centrifuge bucket may be in a vertical orientation. When the base is stationary, the centrifuge bucket may be placed upwardly beyond the upper surface of the centrifuge base. When the base is stationary, at least a portion of the sample container may extend beyond the upper surface of the base. In a vertical orientation, the base wings may be at 90 degrees to the center portion of the base. When the base rotates, the centrifuge bucket may be in a horizontal orientation. In a horizontal orientation, the centrifuge bucket may be at a 0-degree angle to the base. When the base rotates, the centrifuge bucket may retract into the base to form a substantially continuous upper surface and/or lower surface. For example, when the base rotates, the centrifuge bucket may contract so that the lower surface and/or upper surface of the base form a continuous plane. The centrifuge bucket may be designed to move upward about a pivot relative to the base. The bucket may be designed so that at least a portion of the bucket may be pivotally movable upwardly beyond the upper surface of the base.

The rotation point of a centrifuge bucket may include one or more pivot pins. The pivot pins may extend through the centrifuge bucket and the base. In some instances, the centrifuge bucket may be positioned between different portions of the base, which may prevent the centrifuge bucket from sliding sideways relative to the base.

A centrifuge bucket may have a center of mass 3750 that is located lower than the rotation point 3720. When the base is stationary, the center of mass of the centrifuge bucket may be located lower than the rotation point. When the base is rotating, the center of mass of the centrifuge bucket may be located lower than the rotation point.

The centrifuge bucket may be made of two or more different materials with different densities. Alternatively, the centrifuge bucket may be made of a single material. In one embodiment, the centrifuge bucket may include a main body 3715 and an insert 3717. In some instances, the main body may be made of a material with a lower density than the insert. For example, the main body may be made of plastic, while the insert is made of a metal material such as tungsten, steel, aluminum, copper, brass, iron, gold, silver, titanium, or any combination or alloy. A heavier insert may help provide the centrifuge bucket's center of mass below the rotation point. The centrifuge bucket material may include a high-density material and a low-density material, with the high-density material positioned below the rotation point. When the centrifuge is stationary, the centrifuge bucket's center of gravity may be positioned such that the bucket naturally hangs with its opening facing upward and its heavier end facing downward. When the centrifuge is rotating at a certain speed, the centrifuge bucket's center of gravity may be positioned such that the bucket naturally retracts. The centrifuge bucket may retract when the centrifuge is rotating at a predetermined speed, which may include any speed, or any speed mentioned elsewhere.

One or more cavities may be provided within the centrifuge bucket. In some instances, a cavity may be designed to receive multiple sample container structures. The cavity may have an inner surface. At least a portion of the inner surface may contact a sample container. In one demonstration, the cavity may have one or more shelves or inner surface structures, allowing a first sample container having a first design to completely match the interior of the cavity, and a second sample container having a second design to also completely match the cavity. The first and second sample containers having different designs may contact different portions of the inner surface of the cavity. Although the examples in Figures 9-11 show containers having a high aspect ratio, i.e., the ratio of height to width, it should be understood that containers having a height equal to or less than the width may also be used in other instances.

As previously mentioned, the centrifuge may be designed to interface with a liquid handling device. For example, the centrifuge may be designed to connect to a pipette or other liquid handling device. The centrifuge may be designed to receive a sample dispensed by the liquid handling device, or to provide a sample for aspirating by the liquid handling device. The centrifuge may be designed to receive or provide a sample container.

As mentioned above, a sample container may be designed to be connected to the liquid handling device. For example, the sample container may be designed to be connected to a pipette or other liquid handling device.

A sample container may be designed to extend out of a centrifuge bucket. In some instances, the centrifuge base may be designed to allow the sample container to extend out of the centrifuge bucket when the centrifuge bucket is provided in a retracted state, and to allow the centrifuge bucket to pivot between the retracted and extended states. The sample container may extend from the upper surface of the centrifuge and may allow the sample or sample container to be transferred into and/or out of the centrifuge more easily. In some instances, the centrifuge bucket may be designed to retract into the rotor, forming a small combination and reducing the pulling during operation, with some additional benefits such as reducing noise and heat generation, and reducing power requirements.

In some embodiments, the centrifuge base may include one or more pipes or other similar structures, such as grooves, conduits, or channels. Any description of a pipe may also apply to any similar structure. The pipe may contain one or more ball bearings. These ball bearings may slide through the pipe. The pipe may be open, closed, or partially open. The pipe may be designed to prevent the ball bearings from sliding out of the pipe.

In some cases, the ball bearings may be located within the rotor within a sealed or enclosed track. These designs help maintain the dynamic balance of the centrifuge rotor, particularly when centrifuging samples of varying sizes simultaneously. In other cases, the ball bearings may be located outside the motor, making the entire system more robust and compact.

The conduit may encircle the centrifuge base. In some instances, the conduit may encircle the perimeter of the centrifuge base. In some instances, the conduit may be located at or near the upper surface of the centrifuge base, or the lower surface of the centrifuge. In some instances, the conduit may be equidistant from both the upper and lower surfaces of the centrifuge base. The ball bearing may slide along the perimeter of the centrifuge base. In some instances, the conduit may encircle the base at a distance from the axis of rotation. The conduit may form a circle approximately centered on the axis of rotation.

FIG11 shows an additional non-limiting example of a centrifuge consistent with another embodiment of the invention. The centrifuge may include a base 3800 having a lower surface 3802 and/or an upper surface 3804. The base may contain one, two, or more centrifuge buckets 3810a, 3810b. A centrifuge bucket may be connected to a modular frame 3820 that is connected to the base. Alternatively, the centrifuge bucket may be directly connected to the base. The centrifuge bucket may also be attached to a weight 3830.

A modular frame may be connected to a base. The modular frame may be connected to the base at a boundary, thereby forming a continuous or substantially continuous plane with the base. The upper surface, lower surface, and/or a portion of the side surface of the base may form a continuous or substantially continuous plane with the modular frame.

A centrifuge bucket may be designed to rotate about a centrifuge bucket pivot extending from the base and/or module frame. In some instances, the pivot may intersect tangentially with the base. The centrifuge bucket may be designed to rotate about the centrifuge bucket pivot 3840. The base may be designed to receive a drive mechanism. In one example, the drive mechanism may be a motor, such as a brushless motor. The drive mechanism may include a rotor 3850 and a stator 3855. In some instances, the rotor may be a brushless motor rotor and the stator may be a brushless motor stator. The drive mechanism may be any other mechanism capable of rotating the base and may be discussed further elsewhere.

In some instances, a large number of centrifuge bucket rotating shafts may be provided through the base. These rotating shafts may be parallel to each other. Alternatively, some rotating shafts may be perpendicular to each other, or at any angle to each other. The centrifuge bucket rotating shaft may extend through the lower surface, upper surface, or between the upper and lower surfaces of the base. In some instances, the centrifuge bucket rotating shaft may extend out of the base to a position closer to the lower surface of the base, or closer to the upper surface of the base. In some instances, the centrifuge bucket shaft pivot may be located at or closer to the lower surface or upper surface of the base. A centrifuge bucket shaft pivot may be located at or closer to the lower surface of the module frame or the upper surface of the module frame.

One, two, three, four, or more cavities may be provided within a centrifuge bucket. For example, a centrifuge bucket may be designed to hold one, two, or more samples or sample containers. Each centrifuge bucket may be capable of holding the same number of containers, or a different number of containers. The centrifuge bucket may include a cavity for receiving a sample container, wherein the sample container is positioned in a first orientation when the base is stationary and in a second orientation when the base is rotated.

In some embodiments, the centrifuge bucket may be designed to form an angle with respect to the base. For example, the angle between the centrifuge bucket and the base may be between 0 and 90 degrees. For example, when the base is stationary, the centrifuge bucket may be in a vertical orientation. When the base is stationary, the centrifuge bucket may be positioned upwardly beyond the upper surface of the centrifuge base. When the base is stationary, at least a portion of the sample container may extend beyond the upper surface of the centrifuge base. In a vertical orientation, the base wings may be at a 90-degree angle to the center of the base. When the base is rotating, the centrifuge bucket may be in a horizontal orientation. In a horizontal orientation, the centrifuge bucket may form a 0-degree angle with the base. The centrifuge bucket may retract into the base and/or module frame to form a substantially continuous upper and/or lower surface when the base rotates. For example, when the base rotates, the centrifuge bucket may retract to form a substantially continuous plane with the lower and/or upper surfaces of the base and/or module frame. The centrifuge bucket may be designed to rotate upward relative to the base and/or module frame. The centrifuge bucket may be designed so that at least one portion may be rotated upwardly beyond the upper surface of the base and/or the module frame.

The centrifuge bucket may be locked at multiple locations to ensure the release and extraction of centrifuge tubes, and to enable aspiration of liquid from one centrifuge container or dispensing of liquid into another centrifuge container while the centrifuge container is within the centrifuge bucket. One technique for accomplishing this is to use one or more motors to drive rollers into contact with the centrifuge rotor to precisely position and/or lock the rotor. Another technique may use a cam (CAM) shape molded into the rotor, without the need for an additional motor or roller. An attachment from the pipette, such as a centrifuge tip attached to a pipette nozzle, may be pressed against the rotor cam. This external force applied to the cam surface may induce the rotor to rotate to the desired locking position. Continuing to apply this external force may rigidly hold the rotor in the desired position. Multiple similar cam shapes may be added to the rotor to enable multiple locking locations. While the rotor is held in one position by a pipette nozzle or tip, other pipette nozzles or tips may engage with the centrifuge bucket to release or extract a centrifuge container or perform other functions, such as aspirating or dispensing from a centrifuge container within the centrifuge bucket. It should be understood that the cam structure is applicable to any embodiment mentioned in this application.

A centrifuge bucket pivot may include one or more pivot pins. A pivot pin may extend through the centrifuge bucket and the base and/or module frame. In some embodiments, the centrifuge bucket may be positioned between the base and/or module frame to prevent the centrifuge bucket from sliding relative to the base.

The centrifuge bucket may be attached to a weight. When the base begins to rotate, the weight may be designed to move, causing the bucket to pivot, typically from a fully vertical position to a non-vertical position used during centrifugation. When the base begins to rotate, the weight may be moved by the centrifugal force acting upon it. The weight may be designed to move away from the rotation axis when the base begins to rotate at a starting speed. In some instances, the weight may move along a linear direction or path. Alternatively, the weight may move along a curved or other path. The bucket may be attached to the weight at its pivot point. One or more pivot pins or protrusions may be used, allowing the bucket to rotate with the weight. In some instances, the weight may move along a horizontal linear path, causing the bucket to rotate upward or downward. The weight may move in a linear direction perpendicular to the centrifuge axis of rotation. This means that the bucket does not extend below the lower surface of the centrifuge axis of rotation. In some instances, this can reduce the overall height of the centrifuge design while the device is in operation.

It should also be understood that the external force required to centrifuge the centrifuge bucket from a rest state to an operating state is selected so that there is sufficient centrifugal force to prevent the sample in a centrifuge container from spilling or being ejected from the container when the centrifuge bucket changes orientation. Typically, the centrifuge container may be an unsealed container with an open top, so that there cannot be any reverse spillage from the container.

The weight may be located between a module frame and/or a base portion. The module frame and/or base may be designed to prevent the weight from sliding out of the base. The module and/or base may limit the weight's path of movement. The weight's path may be limited to a linear direction. One or more locating pins 3870 may be provided to limit the weight's path of movement. In some instances, the locating pin may pass through the frame module and/or base and the weight.

A biasing force may be provided to the weight. The biasing force may be provided by a spring 3880, elastic force, air mechanism, hydraulic mechanism, or any other mechanism. When the base is stationary, the biasing force may maintain the weight in a first position; and when the centrifuge rotates at the starting speed, the centrifugal force generated by the rotation of the centrifuge may move the weight to a second position. When the centrifuge returns to a stationary state, or the rotation speed drops below a predetermined speed, the weight may return to the first position. When the weight is in the first position, the centrifuge bucket may have a first orientation; and when the weight is in the second position, the centrifuge bucket may be in a second orientation. For example, when the weight is in the first position, the centrifuge bucket may be in a vertical orientation; and when the weight is in the second position, the centrifuge bucket may be in a horizontal orientation. The first position of the weight may be closer to the axis of rotation than the second position.

One or more cavities may be provided within the centrifuge bucket. In some instances, a cavity may be designed to accommodate multiple sample container designs. The cavity may have an inner surface. At least a portion of the inner surface may contact a sample container. In one embodiment, the cavity may have one or more shelves or inner surface structures that allow a first sample container having a first design to fully fit within the cavity, while a second sample container having a second design also fully fits within the cavity. The first and second sample containers having different designs may contact different portions of the cavity inner surface.

As previously mentioned, the centrifuge may be designed to interface with a liquid handling device. For example, the centrifuge may be designed to connect to a pipette or other liquid handling device. The centrifuge may be designed to receive a sample dispensed by the liquid handling device, or to provide a sample for the liquid handling device to aspirate. The centrifuge may be designed to receive or provide a sample container.

As mentioned above, a sample container may be designed to be connected to the liquid handling device. For example, the sample container may be designed to be connected to a pipette or other liquid handling device.

A sample container may be designed to extend from a centrifuge bucket. In some embodiments, the centrifuge base and/or module frame may be designed to allow the sample container to extend from the centrifuge bucket when the centrifuge bucket is in a retracted position and to allow the centrifuge bucket to pivot between retracted and extended positions. Extending the sample container from the top surface of the centrifuge may facilitate transfer of samples or sample containers into and/or out of the centrifuge.

In some embodiments, the centrifuge base may include one or more pipes, or other similar structures, such as grooves, conduits, or channels. Any description of a pipe may also apply to any similar structure. The pipe may contain one or more ball bearings. The ball bearings may slide through the pipe. The pipe may be open, closed, or partially open. The pipe may be designed to prevent the ball bearings from sliding out of the pipe.

The conduit may encircle the centrifuge base. In some instances, the conduit may encircle the perimeter of the centrifuge base. In some instances, the conduit may be located at or near the upper surface of the centrifuge base, or the lower surface of the centrifuge. In some instances, the conduit may be equidistant from both the upper and lower surfaces of the centrifuge base. The ball bearing may slide along the perimeter of the centrifuge base. In some instances, the conduit may encircle the base at a distance from the axis of rotation. The conduit may form a circle approximately centered on the axis of rotation.

Other known centrifuge designs, including various floating bucket designs, may also be used. See U.S. Patent No. 7,422,554, which is incorporated herein by reference in its entirety for all purposes. For example, the centrifuge bucket may swing downward instead of upward. The centrifuge bucket may swing out from the side instead of up and down.

The centrifuge may be enclosed in a housing or dark box. In some instances, the centrifuge may be completely enclosed in the housing. Alternatively, the centrifuge may have one or more open areas. The housing may include a removable portion that allows a liquid handling device or other automated device to access the interior of the centrifuge. The liquid handling device and/or other automated device may provide a sample into the centrifuge, obtain a sample, provide a sample container, or obtain a sample container. This may be accessed through the top, side, and/or bottom of the centrifuge.

A sample may be dispensed into and/or extracted from the centrifuge chamber. The sample may be dispensed and/or extracted using a liquid handling system. The liquid handling system may be a pipette as described elsewhere, or any other known liquid handling system. The sample may be dispensed and/or extracted using any of the pipette tip designs described elsewhere. Dispensing and/or extracting a sample may be automated.

In some embodiments, a sample container may be provided to or removed from a centrifuge. The sample container may be inserted into or removed from a centrifuge in an automated manner using a device. The sample container may extend from the surface of the centrifuge, which may simplify the process of automated extraction and/or recovery. A sample may already be provided in the sample container. Alternatively, a sample may be dispensed into and/or extracted from the sample container. The sample may be dispensed into and/or extracted from the sample container using a liquid handling system.

In some examples, a pipette tip from a liquid handling system may be at least partially inserted into the sample container and/or cavity. The pipette tip may be inserted and removed from the sample container and/or cavity. In some examples, the sample container and pipette tip may be centrifugal containers and centrifugal tips as described above, or any other container or tip design. In some examples, a cuvette may be placed within a centrifuge rotor. This design may offer certain advantages over conventional pipette tips and/or containers. In some examples, the cuvette may be combined with one or more channels to form a specific geometry that automatically separates the centrifuged product into separate compartments. A similar example may be a cuvette with a tapered channel that terminates in a compartment separated by a narrow opening. Supernatant (e.g., plasma separated from blood) may be centrifugally drawn into the compartment, while red blood cells remain in the main channel. The cuvette may be more complexly configured with multiple channels and/or compartments. These channels may be separate or connected.

In some embodiments, one or more cameras may be placed inside the centrifuge rotor so that as the rotor rotates, the cameras can image the contents of the centrifuge container. These images can be analyzed and/or communicated in real time using a method such as wireless communication. This method can be used to track sedimentation rate or cell sedimentation rate, such as in an ESR (erythrocyte sedimentation rate) test, which measures the sedimentation rate of RBCs. In some embodiments, one or more cameras may be placed outside the centrifuge rotor so that as the rotor rotates, the cameras can image the contents of the centrifuge container. This function can be achieved using a stroboscopic illumination source synchronized with the cameras and the rotating rotor. Real-time imaging of the contents of the centrifuge container as the rotor rotates may allow the rotor to be stopped after the centrifugation process is completed, saving time and potentially preventing over-sedimentation and/or over-separation of the contents.

As shown in Figure 12, some embodiments may have a window or opening on the centrifugal container rack to allow observation of the contained sample. This may involve a camera or other monitor that may observe the sample in the container through the window or opening 3825. Alternatively, some embodiments may provide a window or opening 3825 to allow an illumination light source to illuminate the sample being processed. Some embodiments may be in the centrifuge, such as but not limited to being integrated into the centrifuge rotor, including a camera-like monitor to image the sample. Its advantage is that if the camera is located in the same reference frame as the sample, the movement of any blood components in the sample can be more easily seen. Of course, it is not excluded that the monitor, such as but not limited to the camera, is in a different reference frame from the moving sample. Non-optical monitors are also not excluded as long as they can monitor the movement of blood components in the container.

Some examples may also contain a corresponding window or opening 3827 that is the same or different in size from the window or opening 3825. This window or opening 3827 allows the liquid sample in the centrifugal container to be illuminated while the container is retained in the centrifuge. Alternatively, some examples may use the same opening to illuminate and observe simultaneously. Some examples may observe through one window or opening and illuminate through another window or opening, which may or may not be relative to the first window or opening. For any example herein, it should be understood that the window or opening may comprise an optically transparent material covering these windows or openings.

Temperature control

Centrifuges can sometimes cause undesirable changes in sample temperature, at least in part due to heat generated during the centrifugation process. One source of heat generated during centrifugation is waste heat from the drive motor and/or centrifuge drive mechanism. This waste heat problem is exacerbated if several samples are processed sequentially in the same centrifuge. Heat generated by each step accumulates over the operating time and can unnecessarily raise sample temperatures beyond acceptable limits.

To prevent such waste heat or other sources of thermal energy from unnecessarily changing the sample temperature, efforts may be made to isolate the waste heat, actively cool it, and/or remove the unnecessary thermal energy from the sample.

In one embodiment, since the motor may be integrated into the centrifuge, such integration may be beneficial in minimizing heat issues associated with the motor, centrifuge rotor, centrifuge bucket, container, and/or sample. Methods for resolving similar heat issues may include implementing one or more of the following measures simultaneously or sequentially: cooling, insulation, and/or maintaining cooling. Some embodiments may involve active techniques to address heat issues. Some embodiments may involve passive techniques, such as, but not limited to, insulating the portion of the centrifuge that is in contact with the heat source associated with the centrifuge.

Some embodiments may use thermally conductive materials, such as but not limited to thermally conductive tape, to change the heat transfer characteristics of the centrifuge. In a non-limiting example, such tape may be designed to conduct heat directly away from heat-sensitive areas of the centrifuge that have a thermal impact on the sample. Thermally conductive tape is designed to provide a preferential heat transfer path between heat-generating parts and heat-absorbing or other cooling devices (such as fans, radiators, etc.). Thermally conductive tape may be a pressure-sensitive adhesive filled with ceramic fillers with thermally conductive properties that can be bonded to many substances without the need for a thermal curing cycle. It may be used alone or in combination with any other heat transfer method described herein.

Some embodiments may use an active cooler, such as but not limited to a Peltier heater/cooler, to cool the sample and/or one or more of the centrifuge components mentioned above. The active cooler may be in direct contact with the target surface to be cooled. Some embodiments may attach a heat sink or Peltier heater/cooler to the centrifuge bucket or the rack on which the centrifuge container is placed. Alternatively, the active cooler may be near the target surface rather than in direct contact with it. For example, an active heat sink or Peltier heater/cooler may be attached to a centrifuge housing that is close to the portion of the centrifuge that holds the sample.

Some embodiments may include structures mounted on the centrifuge housing to assist with convective heat dissipation. Some embodiments may involve adding fins or air flow structures to the centrifuge rotor and/or other moving parts of the centrifuge. Some embodiments may attach fins or air flow structures to a fixed portion of the housing located near the rotor. These fins may be used to dissipate any waste heat or assist with convection.

As shown in Figure 12, some examples may use non-thermal conductive materials to change the thermal conductivity. In order to isolate the sample from the heat source as much as possible, some examples may replace some metal materials with plastic or other hard materials with low thermal conductivity. Some examples may use foam or other types of thermal insulation to isolate the sample from unnecessary heat conduction. Some examples may contain a centrifuge rotor made entirely of low thermal conductivity materials. Some examples may only have a portion of the centrifuge rotor made of low thermal conductivity materials. As shown in Figure 12, some examples may only replace selected parts with thermal insulation materials, such as but not limited to frame portion 3820.

Referring now to FIG13A , some embodiments may utilize one or more external cooling devices 400, such as heat sinks or air conditioning sources utilizing cooled or uncooled air or gas, to reduce sample temperature rise during centrifugation. As shown in FIG13A , some embodiments may utilize more than one refrigeration device 400 at various locations and/or orientations within the centrifuge housing to provide direct convective cooling of the centrifuge.

As also shown in FIG13A , some embodiments may include an active temperature control device 410, such as, but not limited to, a Peltier effect heat sink, attached to one or more components of the centrifuge system, such as, but not limited to, the centrifuge housing 402. FIG13A shows the housing 402 in a static state, and may include active temperature control devices 410, such as, but not limited to, Peltier effect heat sinks 410, at one or more locations. Some embodiments may use conventional passive heat sinks in place of, or in conjunction with, the Peltier effect heat sink 410. By way of example and not limitation, some locations shown in FIG13A as containing active temperature control devices 410 may also have those components replaced or augmented by passive heat sinks.

In one embodiment, the Peltier effect heat sink may use electricity to achieve a relatively low temperature. In another embodiment, the Peltier effect heat sink may be connected to the motor circuit via wires. Of course, other designs for providing electrical power to the heat sink are not excluded. Because the other end of the heat sink will become hot during operation, it is necessary to place the heat sink near a duct, exhaust vent, heat sink, fin heat sink or other element to direct the waste heat away from the low-temperature end of the heat sink. Some embodiments may use a thermally conductive motor base to draw heat away from its internal structure. A similar embodiment may include a fan with aluminum stator blades brazed to an aluminum motor base. A motor may be securely mounted in the housing and affixed with "heat transfer compound" to provide a preferred thermal path to conduct heat generated by the motor. This will improve the heat transfer effect from the motor to the cooling fin.

Although FIG13A shows that the thermal regulation element may be placed on the housing or other inactive part of the centrifuge system, it should be understood that similar active or passive heat dissipation devices may also be installed on the interior and/or active parts of the centrifuge system. As an example and not limited to this, FIG13B shows that the motor, centrifuge rotor 404, centrifuge bucket, container, and/or sample contact surface may also be designed to be under the control of temperature control device 410. FIG13B shows that the active temperature control device 410 may be placed on the side wall surface surrounding the centrifuge rotor 404. Alternatively, the active temperature control device 410 may be placed on the upper surface of the centrifuge rotor 404. Alternatively, the active temperature control device 410 may be placed on the lower surface of the centrifuge rotor 404. Alternatively, the active temperature control device 410 may be placed on a motor cover, housing or shield 412. By way of example and not limitation, some of the locations indicated in FIG. 13B as containing active temperature control devices 410 may have those elements replaced or augmented by passive heat sinks.

Referring now to Figures 14A-14B , some embodiments may involve venting the housing surrounding the centrifuge rotor to enhance airflow. This may involve punching, hollowing, or molding openings in the housing and/or the centrifuge rotor to allow for airflow. Exhaust holes 450 may be formed in the housing 452 surrounding the centrifuge rotor. The exhaust holes 450 may be sized and/or positioned to allow for enhanced convective cooling of the centrifuge's motor components. In the present non-limiting example, the larger opening 454 is intended to accommodate an encoder ring reader. It should be understood that, in addition to the exhaust holes, the embodiments shown in Figures 14A-14B may also include any of the active or passive heat dissipation elements described in Figures 13A-13B . Based on position information provided by the various designs described herein, some centrifuge embodiments may be designed to activate and/or deactivate centrifugation, such that the centrifuge is brought to rest at a specific position specified by a user and/or a device such as, but not limited to, a programmed processor.

FIG15 shows another example in which vent holes 460 are provided on a housing 462 near the centrifuge rotor or even within the centrifuge rotor itself. The vent holes 460 in the example shown here may be positioned below the rotating portion of the centrifuge rotor (not shown for ease of illustration). Other examples may include a greater or lesser number of vent holes 460. Other examples may include vent holes 460 of other shapes, such as, but not limited to, square, rectangular, oval, triangle, rhombus, parallelogram, pentagon, hexagon, octagon, any other shape, or a combination of one or more of the aforementioned shapes. Some examples may include vent holes 460 of uniform shape. Some examples may include at least one vent hole 460 that is a different shape from the other vent holes 460.

Referring now to Figures 16A-16B, or in other embodiments, a temperature control element 500 may be mounted on the rotating and/or non-rotating portions of the centrifuge to promote greater convective heat transfer. Figure 16 shows a sheet-like temperature control element 500 on a radially outer surface of the centrifuge housing 501. The temperature control sheet may be a flat design. Alternatively, some embodiments of the temperature control element 500 may be a pin-shaped protrusion 502. Some embodiments may combine one or more of these structural configurations. These can be used as passive or active temperature control devices.

In some instances, the cross-sectional shape of a heat sink may be circular, crescent-shaped, teardrop-shaped, square, rectangular, triangular, polygonal, or any other shape. The cross-sectional shape of the heat sink may be uniform or non-uniform along the long axis. For example, in some instances, the heat sink may have a common cylindrical shape; in other instances, the heat sink may be pyramidal (including a truncated pyramid) or conical (including a truncated conical). In still other instances, the surface of the heat sink (e.g., the cross-sectional shape of the heat sink may be uniform or non-uniform along the long axis) may be curved along the long axis. Non-limiting examples of surface features of a curved heat sink (e.g., the cross-sectional shape of the heat sink may be uniform or non-uniform along the long axis) include hyperbolas, quadratic curves, polynomial curves above binomial, circular arcs, or combinations of these curves. In some instances, the heat sink is a solid structure; in other instances, the heat sink may be hollow. In some instances, the heat sink may be partially hollow and partially solid. When it is necessary to further reduce the amount of heat absorbing material used, hollow heat sinks may allow for efficient heat transfer and further reduce the cost of the product. Alternatively or additionally, a pattern formed by the heat sink may be broken by pipes around the periphery of the heat sink to provide additional openings to the interior of the heat sink and increase the airflow to the interior of the heat sink. The constituent pipes may be of any pattern, with common ones being transverse, herringbone, or wavy. In some instances, the heat sinks may be interconnected at the base (or other connection areas) to form a connected heat dissipation network, such as but not limited to multiple horizontal or vertical rows. Some may be connected to form a heat dissipation filter.

Figure 16B shows an example of a centrifuge with fins 510 on the inner radial portion. Figure 16C shows the fins 520 at the bottom of the centrifuge rotor. Figure 16D shows a further example in which the fins 530 on the periphery of the rotor may be selectively shaped and/or positioned to be used in conjunction with a shaped housing 540 that allows air to be drawn into the housing to assist in cooling the structure as the centrifuge rotor rotates. Of course, some examples may combine one, two, three, or all of the above designs with other cooling elements to maximize the potential refrigeration of the system. The examples of Figures 16B-16D may have various temperature control devices connected to the active or stationary parts of the centrifuge.

In another example, an internally air-cooled electric motor (commonly known as an air-cooled motor) may be used as a self-cooling electric motor. In one example, the air-cooled motor is equipped with an axial flow fan attached to the motor rotor (usually located on the opposite side of the output shaft) and rotates with the motor to provide more airflow to the parts inside and outside the motor that need to be cooled.

In another example, water cooling may be used to cool the motor housing. In one non-limiting example, a small centrifugal pump may be built into the output shaft, with a pre-cooled water reservoir surrounding the motor housing. Other active or passive liquid cooling techniques may also be used. These techniques may be used to cool a portion of the motor housing. Some examples may only cool the sidewalls of the motor housing. Some examples may cool the entire housing. Some examples may only cool the end portions of the housing, such as, but not limited to, the passageway closest to the sample.

In a further example, significantly reduced winding resistance could be used to reduce the heat generated by the motor. This could involve using a motor with fewer windings to improve motor performance and correspondingly reduce the heat generated by the motor itself. Changing the number of poles and magnets could also be selected to improve motor performance. In this way, motor components could be selected to reduce heat generation issues, such as using a motor with lower heat output for normal centrifuge operation.

Centrifugal position control

Referring now to Figures 17A-17D, improvements to the centrifuge rotor position control system will be described. In one embodiment, various encoder disks or structures, such as, but not limited to, encoder ring 600, may be used to more accurately control and/or monitor the position of the centrifuge rotor 604. A programmed processor in the encoder can calculate where a sample rack on the centrifuge rotor 604 is located. In this embodiment, when it is necessary to remove such a container from the centrifuge, accurate information about the position of the centrifuge rotor 604 allows a pipette or sample handling system to accurately engage the centrifuge container without having to use a "parking" system to keep the centrifuge rotor 604 in a specific position after stopping centrifugation.

Figure 17A shows an example of an encoder ring 600 used in conjunction with a detector 602 for interpreting encoder position. The encoder ring 600 will rotate with the centrifuge rotor 604 so that the encoder ring 600 will provide position information for the centrifuge rotor 604 and any configuration thereon. In one embodiment, the encoder ring 600 may have a pattern and be designed to be used in conjunction with an optical detector 602. In one embodiment, the encoder ring 600 may be made of glass or plastic material with light-transmitting and light-opaque areas. Some embodiments may use a reflective device on the encoder ring 600. By design, the encoder ring 600 may be designed to detect every exact angle of itself. The encoder ring 600 may be an absolute encoder or an incremental encoder.

What Figure 17 B showed is another example, wherein this encoder 610 is integrated as a part of centrifugal rotor 604, for example, around the outside of this rotor. A detector 612 is oriented so that it is used together with this integrated encoder 610. This mode can be used alone or in combination with other position detection systems. Alternatively, some examples may use a system for high-accuracy positioning perception; and another system for high-speed perception. When this detector 612 and encoder ring no longer occupy the vertical space below the centrifugal rotor 604, removing encoder ring 610 from below the centrifugal rotor 604 can also reduce the overall height of the centrifuge.

In any embodiment herein, the centrifuge rotor 604 is hollow to allow some components to be placed inside the rotor 604 during operation of the centrifuge. In one embodiment, the entire centrifuge container is contained within the outer frame of the centrifuge rotor when the centrifuge is in operation.

FIG17C shows a further example in which the motor 622 may have an encoder ring or encoder device 620 incorporated therein when the motor is manufactured. The encoder 620 may be interpreted by a detector located inside the motor 622, or by a detector located outside the motor 622 to determine the angular position of the motor shaft of the motor. Such an integrated encoder and motor design may be used in centrifuges and other system components, such as a pipette in a sample processing system, where a small size motor is required for accurate position control. By way of example and not limitation, incremental encoders may be used for servo motors of the induction motor type, while absolute encoders may be used for permanent magnetic brushless motors. In one example, a housing 628 (shown in phantom) may be used to enclose the encoder portion of the motor.

Figure 17 B also shows another example, wherein other encoder technologies, such as but not limited to conduction and/or magnetic encoding technology are used to replace other encoder technologies such as but not limited to optical encoders, or used together with them to detect rotor position. This magnetic encoder reader 650 and/or 652 may be placed in different positions to detect the position of this centrifugal rotor. Other position detection technologies may be used to replace the encoder technology described herein, or be used in combination with it. In some examples described herein, these functions can be integrated into the device.

Alternatively, some instances may use separate sensors to sense speed and position respectively. Some instances may use the same sensor to sense both. By way of demonstration but not limited thereto, the instance containing more than one sensor may be designed to be used for fine position control and for rate control. In this case, the centrifuge may obtain higher centrifugal speeds, such as but not limited to 40,000 rpm, without having to adopt more complex sensors, because each type can be optimized for its special purpose, such as high-accuracy position control during low speed and speed control during high speed. A programmed processor may be used to determine when to control conversion of the centrifugal rotor according to one or another sensor information. Alternatively, throughout the entire time period, the data derived from two types of sensors can be used to provide accurate position control and speed control.

It should be understood that in systems that cannot provide accurate position control, a system of stop stations can be used to ensure that the final resting position of the centrifuge rotor is known. Other examples may use line indicators, pins, cams and/or other mechanisms to move the centrifuge rotor to a known position so that a sample processing system can accurately dock with the centrifuge container on the rotor. After knowing where the centrifuge stopped, the pipette can approach the container. Some centrifuge examples may also be equipped with a guide to guide the pipette to the desired position, or use the pipette to move the centrifuge rotor to the correct position before docking with any container containing a sample placed on the centrifuge.

As shown in Figures 17A-17D , the center portion of a centrifuge may have a single bearing, or alternatively, may have two bearings 660 compressed together to increase stability during rotation, particularly to increase bearing life. As shown in Figures 17A-17D , multiple bearings may be positioned to provide a more balanced load-bearing configuration than would be possible with a single bearing. Other numbers and/or types of bearings are contemplated.

In some of the examples described herein, it should be understood that integrating position and/or velocity sensing functionality directly into the motor may improve motor performance. In a non-limiting example, some examples may achieve position and/or velocity sensing through additional hardware. In one example, rotational position and/or velocity sensing may be designed for one or more rotating parts of the motor or a rotating element attached to the motor.

Hardware that may be integrated into the motor includes, but is not limited to, 1) an optical encoder (for position (relative or absolute) and/or velocity sensing) and/or 2) a Hall effect sensor (for position (relative) and/or velocity sensing). A Hall effect sensor is a semiconductor device in which the flow of electrons is affected by a magnetic field perpendicular to the direction of the current. In one non-limiting example, a Hall effect sensor can be used to detect the position of a permanent magnet in a brushless DC motor.

Some embodiments may combine multiple types of sensor hardware, such as, but not limited to, Hall Effect sensors and optical encoders in the same motor. Alternatively, some embodiments may include multiple sensors of the same type in a motor. Of course, the embodiments herein do not exclude the use of other types of position and/or velocity sensing hardware, or the use of optical or magnetic encoders in conjunction with the motor.

As a non-limiting example, the sensors and/or encoders of at least some instances can operate at speeds of up to 12,000 rpm with a position sensing resolution of at least 1,800 CPR. Alternatively, the sensors and/or encoders of at least some instances can operate at speeds of up to 10,000 rpm with a position sensing resolution of at least 1,600 CPR. In one embodiment, the encoder contains an index aligned identically to the motor assembled into each centrifuge for absolute positioning. Some instances may use absolute encoders, such as, but not limited to, multi-bit Gray code encoders and/or single-track Gray code encoders for absolute positioning. Some instances may use sinusoidal wave encoders, and encoder technology may include, but is not limited to, conductive tracks, optical tracks (including reflective cases), and magnetically encoded tracks, which are sensed by Hall effect sensors or magnetoresistive sensors.

In any design (sensor or encoder), at least some embodiments herein may be designed such that the overall height (excluding the output shaft) is equal to or less than 13 mm, and the diameter may be less than 35 mm. Alternatively, some embodiments may have an overall height of less than 10 mm and a diameter of less than 30 mm. In some embodiments, the hardware design integrating position and/or velocity sensing hardware does not change the external dimensions of the motor housing relative to the same motor without the sensing hardware. Alternatively, one embodiment may place the Hall effect sensors within the stator slots of the motor to minimize the size change.

Alternatively, other implementations may use firmware and/or software to detect the rotor position and/or velocity without requiring additional hardware. Examples may include monitoring back EMF, tracking impedance, or using other techniques for sensorless motor control. One or more of the techniques described here may be used in combination for position and/or velocity sensing.

Referring now to FIG. 17 , another example centrifuge with a magnetic sensor, such as, but not limited to, a Hall-effect sensor assembly 630, is shown. This assembly may be integrated directly into the motor assembly or located externally to the motor but still part of the centrifuge assembly. FIG. 17E shows an exploded view of a Hall-effect sensor 632 and an encoder section 634. Arrow 636 indicates that the assembly 630 can be inserted into the centrifuge housing in the indicated direction. As a non-limiting example, the assembly 630 is shown with three sensors 632, but it should be understood that other numbers of sensors may be used. The assembly 630 is also shown with all sensors located in the same plane, but it should be understood that in some embodiments, the sensors may be located in different planes, including, but not limited to, sensors above and below the Hall-effect encoder 634. As a non-limiting example, the encoder section contains a plurality of magnets and/or other magnetic field generating or interfering components that may be detected by the Hall-effect sensors 632.

Referring now to FIG. 17F , a perspective view of an example motor with integrated position and/or speed sensing is shown. For ease of illustration, some components of the motor are not shown in this example to provide a clearer view of the encoder used with the motor. This example encoder can be used to detect the position of the output shaft and/or the position of the rotor. In this non-limiting example, a detector 670 is used in conjunction with an encoder 672 and a Hall-effect encoder disk 674. The detector 670 may have a first surface directed to detect optical encoder information and a second surface directed to detect magnetic encoder information. In a non-limiting example, the detector 670 may have a first surface 680 directed to detect a first type of encoder information, such as, but not limited to, optical encoder information, and a second surface 682 directed to detect a second type of encoder information, such as, but not limited to, magnetic encoder information. Optionally, in some examples, the first and second types of encoder information may be of the same type, such as, but not limited to, both optical or both magnetic. In such a design, at least two encoder types may selectively differ in resolution, with one type providing better low-speed resolution for position control and one type providing better high-speed resolution for rate control. This also applies to the use of different encoder types (e.g., one optical and one magnetic). However, the use of more sensors 670 or more than two types of encoder types is not excluded.

With further reference to Figure 17E , the magnetic portion 676 may be housed within the disc 674. These components may all be designed to rotate with the motor shaft 678. The motor housing H may extend to cover all, some, or none of these encoder components. Optionally, some embodiments may combine at least two encoder types onto a single rotating component, such as, but not limited to, an encoder disc. In such a design, a single disc on the output shaft may include both magnetic and optical encoder components. By way of non-limiting example, an outer portion of the encoder ring may contain an area for the optical encoder, while an inner portion may contain the magnetic component, or vice versa. Optionally, both may be located on the same portion of the encoder ring. Optionally, one encoder type may be located on a flat surface, while the other component may be located on an outer surface of the disc. Of course, embodiments utilizing more than two encoder types on a single rotating component are not excluded. By way of non-limiting example, embodiments utilizing a single detector 670 may also simplify operation by attaching a single wiring harness to the detector 670, thereby simplifying wire management.

Figure 17 G shows another type of motor, and it can be designed to include one or more encoder assembly accessories shown here.Some instances may use a rotor 640 and a stator 642 in the motor design.Selectively, some instances may use a stator 644, rotor 640 and stator 642 to increase torsion.Any one of these instances may be designed to have this encoder assembly accessories shown here.Some instances may be such as, but not limited to, that optical encoder disc or magnetic encoder disc directly attach or be integrated into this stator or rotor with this encoder element.It should be understood that this motor may be suitable for using other encoder hardware or other encoder technologies.As shown in Figure 17 G, this motor instance can be designed to fully mate with the motor housing inside shown in Figure 17 A-E to rotate this centrifugal body.

Automatic balancing

Referring to Figure 18A, some embodiments herein may be designed to utilize an automatic balancing mechanism on the rotor to reduce rotor vibration when not all sample racks contain samples. One embodiment may utilize automatic balancing elements 700 to automatically balance the centrifuge rotor, such as, but not limited to, balls, spheres, or weights; and this may be used to compensate for different sample volumes in different centrifuge buckets. Some embodiments may not have centrifuge buckets in some of the centrifuge racks when loading samples. The automatic balancing element 700 may be placed within a tube 710 (covered or exposed) to allow the automatic balancing element to achieve a stable resting position, minimizing rotational instability of the rotor during operation. Some embodiments do not have a continuous tube around the periphery, but may instead have tubes that contain automatic balancing elements in the form of discrete segments, which can only remain within their designated discrete segments of the tube.

Optionally, as shown in FIG18B , some embodiments may include a retaining structure 720 that releases the self-balancing element 700 for free movement only when a minimum rotational speed is reached and centrifugal force or other external forces are applied. When a sufficient rotational speed is reached, the structure 720 may move in the direction indicated by arrow 722. This movement releases the self-balancing element 700 and causes it to move to a position that balances the centrifuge's load. In this manner, the self-balancing element 700 does not move freely at lower speeds. This can help reduce noise and rotational instability, because without this retaining structure, the self-balancing element 700 would easily roll into an unbalanced position at lower rotational speeds, causing rotational instability.

In one example, the weight of the automatic balancing element 700 may be selected to be at least half of the maximum combined weight of all sample containers and samples that can be used with the centrifuge. In another example, the weight of the automatic balancing element 700 may be selected to be at least 40% of the maximum combined weight of all sample containers and samples that can be used with the centrifuge. In still another example, the weight of the automatic balancing element 700 may be selected to be at least 30% of the maximum combined weight of all sample containers and samples that can be used with the centrifuge. Other weight values are of course not excluded.

Referring now to FIG. 18C , a further embodiment may include automatic balancing elements 700 in a plurality of separate zones 730 on a rotating portion of the centrifuge. In one embodiment, the zones 730 may be interconnected so that the automatic balancing element 700 can be moved from one zone to another. Alternatively, some embodiments may separate each zone 730 from the others so that the automatic balancing element 700 cannot move from one zone 730 to another.

Non-mechanical bearings

In a further embodiment, some systems may be designed to not include mechanical bearings, but instead use non-mechanical bearings, such as, but not limited to, air bearings 720. Such air bearings may generate less heat, which may reduce the time required for centrifugation. Alternatively, they may be able to be centrifuged for longer periods without the thermal damage that may result from the increased heat generation associated with mechanical bearings. Air bearings are available from retailers such as, but not limited to, New Way Air Bearings of Aston, PA, USA. Of course, some embodiments may use a combination of air bearings and mechanical bearings in the same device.

19B shows another example in which one of the air bearings is annular 722, while the other air bearings 724 are designed to be located on the opposite sidewall of the centrifuge rotor. By way of non-limiting example, the air bearings 724 may be shaped in a continuous or discontinuous manner to support the centrifuge rotor.

Fault detection sensor

Referring now to FIG. 20 , another example of a centrifuge apparatus will be described. FIG. 20 is a cross-sectional perspective view showing a centrifuge rotor 800, such as, but not limited to, a centrifuge disk, rotating in the direction indicated by arrow 802 within a non-rotating housing 804. The centrifuge may include a detector 810, such as, but not limited to, an accelerometer positioned on the centrifuge, to detect unwanted changes in external forces during centrifugation. In one example, the detector 810 is positioned outside the centrifuge housing to detect any errors. The detector 810 can be used to detect unusual signs of instability during centrifugation. If these signs of instability are detected as unusual rates of change in centrifuge forces, the centrifuge may be slowed or halted, such as by a programmed processor, before catastrophic equipment failure occurs. Some examples may trigger other actions, such as prompts or warnings, based on a detected rate of change or external force exceeding a threshold range.

FIG20 also shows some other structures discussed and incorporated into the present embodiment. For example, but not limited to, air bearings 722 and/or 724 may be used with this embodiment of the apparatus. Shock absorbers 816 may also be used to isolate vibrations originating from the centrifuge from being transmitted to other components outside the centrifuge housing. FIG20 also shows that temperature isolation regions 820, 822, and/or 824 may be used to reduce heat transfer from the motor 830 to other parts of the centrifuge rotor.

It should be understood that the example in Figure 20 may be designed for use with any of the described rotor and/or container rack centrifuge devices, including but not limited to the examples shown in Figures 1-12. Some examples may have most of the container racks that extend above the upper plane or surface of the centrifuge rotor when the centrifuge rotor is stationary. Alternatively, some examples may have the container racks that extend below the plane or surface of the rotor when the centrifuge rotor is stationary. For those container rack examples that extend from below the plane or surface of the centrifuge rotor, the housing 804 may be designed to have a molded opening to allow the container rack and/or container to be extended downwardly and rotated to provide sufficient clearance. Alternatively, some examples may mount the rotor 800 and/or the entire motor higher to provide sufficient clearance for the container rack and/or container when extended downwardly and rotated.

By way of non-limiting example, the centrifuge may have a footprint less than or equal to 0.1 ^mm2 , 0.5 ^mm2 , 1 ^mm2 , 3 ^mm2 , 5 ^mm2 , 7 ^mm2 , 10 ^mm2 , 15 ^mm2 , ^{20 mm2 ,} 25 mm2, 30 ^mm2 , 40 ^mm2 , 50 ^mm2 , 60 ^mm2 , 70 ^mm2 , 80 ^mm2 , 90 ^mm2 , 100 ^mm2 , 125 ^mm2 , 150 ^mm2 , 200 ^mm2 , 250 ^mm2 , 300 ^mm2 , 500 ^mm2 , or up to 750 ^mm2 . The cytometer may have one or more dimensions (e.g., width, length, and height) that is less than or equal to 0.05 mm, 0.1 mm, 0.5 mm, 0.7 mm, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 15 mm, 17 mm, 20 mm, 25 mm, 30 mm, 40 mm, 50 mm, 60 mm, 70 mm, 80 mm, 100 mm, 150 mm, 200 mm, 300 mm, 500 mm, or 750 mm.

The example of FIG. 20 also illustrates, in at least some embodiments, a rotor/stator centrifuge design in which the stator is coaxially mounted within the rotor, wherein the rotor includes centrifugal disks that are connected to or integrally formed with the motor rotor.

The example of FIG. 20 also shows that, in at least some embodiments, a housing 804 shaped to encompass at least the outer perimeter of the rotor's centrifugal disk 800 can provide a control area within which the centrifugal disk can rotate. The rotating components of this embodiment can include the encoder wheel 600, the rotor centrifugal disk 800, and the rotor portion of the motor. In some embodiments, the housing 804 can serve as a shield to contain motor vibrations within the housing, as a shock absorber 816 can be mounted to the housing 804 to provide vibration isolation. Bearings 830 and 832 can also be provided to mount the rotating components. Alternatively, some embodiments may be designed to utilize only a single bearing. Alternatively, some embodiments may be designed to utilize multiple bearings. Some embodiments may utilize the motor shown in FIG. 7F or FIG. 17G to power the centrifuge shown in FIG. Alternatively, a centrifuge incorporating one or more of the structures described herein can be installed in a system as shown in FIG. 21 , which includes an upper sample processing system similar to that shown in FIG. 21 . Alternatively, such a centrifuge may be mounted on a common mounting plate, common platform, or common frame as the other components 912, 014, or 916 and all available components of the suspended sample processing system.

It should also be understood that the example shown in FIG. 20 may also include configurations from other structures herein, such as, but not limited to, the self-balancing device shown in FIGs. 18A-18C.

Key points of service system

With reference now to Figure 21, it should be understood that the processing procedure described herein may use automation technology.This automation process may be used in an integrated automation system.In some instances, it may be positioned at a single device that contains many functional components and is surrounded by a common shell.The processing technology and method that are used for sedimentation determination can be preset.Selectively, it may be formulated according to operating procedure or program, and by the mode described in U.S. Patent Application Serial No. 13/355,458 and 13/244,947, it is dynamically changed in due time, and both are fully incorporated into this paper for all purposes in form of reference.

In a non-limiting example shown in FIG21 , an integrated device 900 may be provided with a programmed processor 902 that can be used to control various components of the device. For example, in one embodiment, the processor 902 may control a single or multiple pipette systems 904 that move along the X-Y and Z axes as indicated by arrows 906 and 908. The same processor or a different processor may also control other components 912, 914, or 916 within the device. In one embodiment, the components 912, 914, or 916 include a centrifuge.

As shown in Figure 21, being controlled by the processor 902 may allow the pipette system 904 to obtain a blood sample from the dark box 910 and move the sample to one of the component parts 912, 914 or 916. Such movement may involve dispensing the sample into a removable container within the dark box 910, which is then transferred to one of the component parts 912, 914 or 916. Alternatively, the blood sample is dispensed directly into a container that has been installed on one of the component parts 912, 914 or 916. In a non-limiting example, one of the component parts 912, 914 or 916 may be a centrifuge with an imaging design that allows the sample in the container to be illuminated and observed. Other component parts 912, 914 or 916 perform other analysis, testing or monitoring functions.

In a non-limiting example, a sample container within a centrifuge, such as one of the components 912, 914, or 916, may be moved by one or more manipulators from one of the components 912, 914, or 916 to another component 912, 914, or 916 (or optionally to another location or device) for further processing of the sample and/or sample container. Some embodiments may use the pipette system 904 to engage the sample container and move it from one of the components 912, 914, or 916 to another location in the system. In a non-limiting example, it may be useful to move the sample container to an analysis station (such as, but not limited to, imaging) and then return the container to the centrifuge for further processing. In some embodiments, this operation may be performed using the pipette system 904 or other liquid handling system in the device. In a non-limiting example, the operation of moving a container, tip, or the like from the dark box 910 to one of the components 912, 914, or 916 or other locations in the system (or vice versa) can also be accomplished using the pipette system 904 or other liquid handling systems in the device. It should also be understood that in some examples, the pipette system 904 can be used to rotate a centrifuge rotor into an appropriate position so that containers can be loaded and/or unloaded at a known location. In such an example, the pipette system 904 may use a tip, nozzle, or other pipette configuration to engage the centrifuge rotor or other structure that can rotate the rotor until it is rotated to a desired orientation.

All of the aforementioned structures may be integrated into a single housing 920 and designed for use in a desktop or small-footprint system. In one example, a small-footprint system may occupy an area of approximately 4 ^m² or less. In one example, the small-footprint system may occupy an area of approximately 3 ^m² or less. In one example, the small-footprint system may occupy an area of approximately 2 ^m² or less. In one example, the small-footprint system may occupy an area of approximately 1 ^m² or less. In some examples, the footprint of the apparatus may be less than or equal to ^4m2 , ^3m2 , 2.5m2 ^{, 2m2} , 1.5m2, ^1m2 , ^0.75m2 , ^0.5m2 , ^0.3m2 , ^0.2m2 , 0.1m2, ^0.08m2 , 0.05m2, ^0.03m2 , ^100cm2 , ^80cm2 , ^70cm2 , ^60cm2 , ^50cm2 , ^40cm2 , ^30cm2 , ^20cm2 , ^15cm2 , or ^10cm2 . Some suitable systems in a point of service setting are described in U.S. patent application serial numbers 13/355,458 and 13 ^/ 244,947, ^both of which are incorporated herein by reference in ^their entirety for all purposes. This embodiment may be designed for use with any of the modes or systems described within these patent applications.

By way of non-limiting example, the centrifuge footprint may be less than or equal to 0.1 ^mm2 , 0.5 ^mm2 , 1 ^mm2 , 3 ^mm2 , 5 ^mm2 , 7 ^mm2 , 10 ^mm2 , ^{15 mm2 ,} 20 ^mm2 , 25 ^mm2 , 30 mm2, 40 ^mm2 , 50 ^mm2 , 60 ^mm2 , 70 ^mm2 , 80 ^mm2 , 90 ^mm2 , 100 ^mm2 , 125 ^mm2 , 150 ^mm2 , 200 ^mm2 , 250 ^mm2 , 300 ^mm2 , 500 ^mm2 , or up to 750 ^mm2 . The cytometer may have one or more dimensions (e.g., width, length, and height) less than or equal to 0.05 mm, 0.1 mm, 0.5 mm, 0.7 mm, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 15 mm, 17 mm, 20 mm, 25 mm, 30 mm, 40 mm, 50 mm, 60 mm, 70 mm, 80 mm, 100 mm, 150 mm, 200 mm, 300 mm, 500 mm, or 750 mm.

Although the present invention has been described and illustrated with respect to certain specific embodiments, those skilled in the art will recognize that various variations, modifications, alterations, substitutions, deletions, or additions to steps and procedures may be made without departing from the spirit and scope of the present invention. For example, with respect to any of the above embodiments, it should be understood that other techniques for plasma separation may be used in conjunction with, or in place of, centrifugation. For example, one embodiment may initially centrifuge the sample, and then the sample may be placed in a filter to remove visible blood components to complete the separation process. Although this embodiment is described in the context of centrifugation, other accelerated separation techniques may also be applicable to this system. It should be understood that although this embodiment is described in the context of blood specimens, the technology herein may also be designed for use with other samples (biological or otherwise). Any of the embodiments herein may be designed with the encoders and/or sensors described herein. Any of the embodiments herein may be designed with the position detection devices described herein. Any of the embodiments herein may be designed with the automatic stop mechanisms described herein. Any of the embodiments herein may be designed with the temperature control mechanisms described herein.

Alternatively, at least one embodiment may use a variable speed centrifuge. Through feedback, such as but not limited to imaging the position of the sample interface, the centrifugal speed can be changed to maintain a linear relationship between the packing curve and time (until complete compaction), and the ESR data is extracted from the centrifugal speed data rather than from the sedimentation rate curve. In such a system, one or more processors can be used to feedback control the centrifuge so that it has a linear packing curve, and the centrifugal speed data is also recorded. Depending on which interface is tracked and recorded, the sedimentation rate data is calculated based on the centrifugal speed. In a non-limiting example, as the packing process nears completion, the system uses a higher centrifugal speed to maintain a linear curve.

Furthermore, those skilled in the art will appreciate that any of the embodiments of the present invention can be used to collect body fluid samples from humans, animals, or other research subjects. Optionally, the blood volume for the erythrocyte sedimentation rate test may be 1 mL or less, 500 μL or less, 300 μL or less, 250 μL or less, 200 μL or less, 170 μL or less, 150 μL or less, 125 μL or less, 100 μL or less, 75 μL or less, 50 μL or less, 25 μL or less, 20 μL or less, 15 μL or less, 10 μL or less, 5 μL or less, 3 μL or less, 1 μL or less, 500 μL or less, 250 nL or less, 100 nL or less, 50 nL or less, 20 nL or less, 10 nL or less, or 1 nL or less.

In addition, concentrations, amounts, and other numerical data may be displayed in a range format. It should be understood that this range format is used only for convenience and brevity and should be interpreted flexibly to include not only the explicitly listed range limits, but also all individual values or sub-ranges contained within the range, as if each value and sub-range were explicitly listed. For example, a size range of approximately 1 nm to 20 nm should be interpreted to include not only the explicitly listed limits of 1 nm and 20 nm, but also individual sizes such as 2 nm, 3 nm, and 4 nm, as well as sub-ranges such as 10 nm to 50 nm, 20 nm to 100 nm, and so on.

The publications discussed or referenced herein are provided only as of the date of filing of this application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate the prior invention of similar publications. Furthermore, the dates provided for publications may differ from the actual publication dates, which may require independent confirmation. All publications mentioned herein are incorporated herein by reference for the purpose of illustrating and describing the structures and/or methods to which the referenced publications relate. The following applications are incorporated herein by reference in their entirety for all purposes: U.S. patent application serial numbers 13/355,458 and 13/244,947; U.S. provisional application serial number 61/673,245, titled: "High-speed miniature centrifuge for small sample volumes," filed July 18, 2012. U.S. Provisional Application Serial No. 61/675,758, entitled "High-Speed Microcentrifuge for Small Sample Volumes," filed July 25, 2012; and U.S. Provisional Application Serial No. 61/706,753, entitled "High-Speed Microcentrifuge for Small Sample Volumes," filed September 27, 2012; U.S. Patents 8,380,541, 8,088,593; U.S. Patent No. 2012/0309636; U.S. Patent Application Serial No. 61/676,178, filed July 26, 2012; PCT/US2012/57155, filed September 25, 2012; U.S. application serial No. 13/244,946, filed September 26, 2012; U.S. patent application 13/244,949, filed September 26, 2011; and U.S. application serial No. 61/673,245, filed September 26, 2011.

While the above fully describes the preferred embodiments of the present invention, various alternatives, modifications, and equivalents are possible. Therefore, the scope of the present invention should be determined not with reference to the above description, but rather with reference to the appended claims along with their full scope of equivalents. Any structure, whether intended or not, may be combined with any other structure, whether intended or not. The appended claims should not be interpreted as including a "mean-plus-function" limitation unless such a limitation is expressly recited in a given claim using the phrase "meaning." It should be understood that, as used in this specification and throughout the claims that follow, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. It should also be understood that, as used in this specification and throughout the claims that follow, the meaning of "in" includes "in" and "on," unless the context clearly dictates otherwise. Finally, as used in this specification and throughout the claims that follow, the meanings of "and" and "or" include both conjunction and disjunction and are intended to be used interchangeably unless the context clearly dictates otherwise. Therefore, when "and" or "or" is used in the context, this conjunction does not exclude the meaning of "and/or" unless the context clearly indicates otherwise.

This document contains material that is subject to copyright protection. For example, all graphics displayed herein are copyrighted material. The copyright owner (herein, applicant) has no objection to the facsimile reproduction of the patented material and invention, as it appears in the U.S. Patent and Trademark Office records or records, but otherwise reserves all copyright rights whatsoever. The following notice shall apply: Copyright 2012-2013, Theranos, Inc.

Claims (17)

1. A small high-speed centrifuge, the centrifuge being used for low-volume sample containers, the centrifuge comprising: Centrifugal rotor; A motor used to rotate the centrifugal rotor; A detector integrated into a motor is designed to detect at least one rotational position of a rotating part of the motor, wherein the detector uses information from at least two different types of encoders to detect said rotational position. The detector has a first surface oriented to detect one type of encoder information and a second surface oriented to detect another type of encoder information. 2. The small high-speed centrifuge as described in claim 1, wherein the detector uses at least one optical encoder technique and one Hall effect technique to determine the rotational position. 3. The small high-speed centrifuge as described in claim 1, wherein the detector uses at least optical encoder technology and Hall effect technology, and is used at least to determine the rotational position and rotational speed. 4. The small high-speed centrifuge as described in claim 1, wherein the first surface and the second surface are located in different directions. 5. The small high-speed centrifuge as described in claim 1, wherein the first surface and the second surface are located in the same direction. 6. The small high-speed centrifuge as described in claim 1, comprising multiple detectors for detecting rotational position. 7. The small high-speed centrifuge as described in claim 1 further includes a first encoder disk providing encoder information of a first type and a second encoder disk providing encoder information of a second type. 8. The small high-speed centrifuge of claim 1 further includes a first encoder disk that provides optical encoder information and a second encoder disk that provides magnetic encoder information. 9. The small high-speed centrifuge as described in claim 1 further includes an encoder disk that provides both the first type of encoder information and the second type of encoder information. 10. The small high-speed centrifuge as described in claim 1 further includes an encoder disk that provides both optical encoder information and magnetic encoder information. 11. The small high-speed centrifuge as described in claim 1, further comprising: Centrifuge casing, the shape of which is used to surround at least the circumferential boundary of the centrifugal rotor; A first air bearing is configured to operably support the bottom surface of the centrifugal rotor, wherein at least a portion of the first air bearing is defined by the centrifuge housing; and A second air bearing is configured to operably support the side surface of the centrifugal rotor, wherein at least a portion of the second air bearing is defined by the centrifuge housing. 12. A method for manufacturing a small high-speed centrifuge, comprising: Motors are provided; The detector is integrated into the motor; The first type of encoder is integrated into the motor, and the first type of encoder is on the first surface of the detector; The second type of encoder is integrated into the motor, and the second type of encoder is on the second surface of the detector; Using the detector, the rotational position of a rotating part in the motor is determined using the encoder of the first type; Using the same detector, the second type of encoder is used to determine the rotational speed of the rotating part in the motor. 13. The method of claim 12, wherein the first type of encoder provides optical encoder information. 14. The method of claim 12, wherein the first type of encoder provides magnetic encoder information. 15. The method of claim 12, wherein the first type of encoder provides Hall effect encoder information. 16. The method of claim 12, wherein the first type of encoder and the second type of encoder provide encoder information of different types. 17. A small high-speed centrifuge, said centrifuge for use with sample containers, the centrifuge comprising: Centrifuge body; The driving mechanism for rotating the centrifuge body; and A position detector is used to determine the rotational position of the centrifuge body, wherein the position detector is integrated with the drive mechanism and uses information from at least two different types of encoders to determine the rotational position. The detector has a first surface oriented to detect one type of encoder information and a second surface oriented to detect another type of encoder information.