HK1231008B - Method for performing a high speed centrifugation to small volume samples - Google Patents

Description

Method for high-speed centrifugation of small sample volumes

Background Art

Conventional centrifuges are too large and inefficient for processing small volumes of liquid samples. They also fail to include certain features that are desirable when processing small sample volumes.

Incorporation by reference

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

Summary of the Invention

It will be appreciated that implementations of the present disclosure may be adapted to have one or more of the features described herein.

In one non-limiting example, an automated system for separating one or more components in a biological fluid is provided. The system may include: (a) a centrifuge comprising one or more buckets configured to receive a container to perform the separation of the one or more components in the fluid sample; and (b) the container, wherein the container comprises one or more shaped features that complement the shaped features of the bucket.

It should be understood that embodiments herein may be adapted to have one or more of the following features. In one non-limiting example, the system may have one or more buckets, the buckets being swinging buckets 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. Alternatively, the system may have a plurality of swinging buckets spaced radially symmetrically on the centrifuge. Alternatively, the fluid sample is a biological fluid. Alternatively, the biological fluid is blood. Alternatively, the container is configured to contain 100uL or less of sample fluid. Alternatively, the container is configured to contain 50uL or less of sample fluid. Alternatively, the container is configured to contain 25uL or less of sample fluid. Alternatively, the container is closed on one end and open on an opposite end. Alternatively, the container is a centrifuge vessel. Alternatively, the centrifuge vessel has a rounded end having one or more internal nubs. Optionally, the system includes an extraction tip having one or more shaped features that are complementary to the shaped features of the centrifuge vessel and are configured to fit within the centrifuge vessel. Optionally, the shaped features of the bucket include one or more shelves, and the protruding portion of the container is configured to rest on the one or more shelves. Optionally, the bucket is configured to accommodate a plurality of containers having different configurations, and wherein the shaped features of the bucket include a plurality of shelves, wherein a first container having a first configuration is configured to rest on a first shelf, and a second container having a second configuration is configured to rest on a second shelf.

In another embodiment described herein, a compact high-speed centrifuge is provided, comprising a centrifuge body; a motor for rotating the centrifuge body; and a detector integrated with the motor and configured to determine at least a 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 embodiments herein may be adapted to have one or more of the following features. 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 speed. Optionally, the detector has a first surface for detecting one type of encoder information and a second surface for detecting another type of encoder information. Optionally, the first surface and the second surface face different directions. Optionally, the first surface and the second surface face the same direction. Optionally, the motor includes multiple detectors for determining rotational position. Optionally, the motor also includes a first encoder disk that provides first type encoder information and a second encoder disk that provides second type encoder information. Optionally, the motor also 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 first type encoder information and second type 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 an integrated encoder assembly is described in the context of a centrifuge, the motor may also be suitable for use in other scenarios where it is desirable to integrate position and/or speed detector features into the motor.

In another embodiment described 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; using the first type of encoder to determine the rotational position of a rotating part of the motor, and using the second type of encoder to determine the rotational speed of the rotating part of the motor.

It should be understood that embodiments herein may be adapted to have one or more of the following features. 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 compact high-speed centrifuge for use with sample containers is provided. The centrifuge may include: a first portion comprising a thermally insulating material; a second portion comprising a thermally conductive material; wherein the container is arranged such that the container is located in an area having the thermally insulating material; wherein the thermally conductive material is configured to direct heat away from the container.

In another embodiment described herein, a compact 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; an active cooling unit for minimizing heat transfer to the sample; wherein the container is arranged so that the container is located in an area with reduced thermal exposure; the active cooling unit is configured to cool the drive mechanism; wherein the stator is coaxially positioned within a rotor of a motor in the drive mechanism.

In another embodiment described herein, a compact 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 described herein, a compact 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 configured to move under centrifugal force to a position that minimizes unbalanced rotation of the centrifuge body in the event of an uneven load in a sample holder of the centrifuge.

In another embodiment described herein, a compact 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 configured to support the centrifuge during operation.

In another embodiment described herein, a compact 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 configured to support the centrifuge during operation, wherein at least a portion of the air bearing is part of the centrifuge housing.

In another embodiment described herein, a compact 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 for detecting a rate change of force outside a predetermined force condition range.

It should be understood that embodiments herein may be adapted to have one or more of the following features. In one non-limiting example, the centrifuge vessel holder pivots inwardly toward the central axis of the centrifuge rotor under centrifugal force. Optionally, the centrifuge vessel holder forms a surface flush with the rotor body to minimize aerodynamic drag. Optionally, the centrifuge vessel holder is configured to retract downward under centrifugal force. Optionally, electrical connections to cooling elements of the centrifuge body are not interrupted, even when such elements are in operation during centrifugal operation.

In another embodiment described herein, a compact 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, wherein the centrifuge body extends downward to cover at least a portion of the drive mechanism; wherein the drive mechanism includes a stator and a rotor; and wherein the rotor is concentric with respect to the stator.

In another embodiment described herein, a compact 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, wherein the centrifuge body extends downward to cover at least a portion of the drive mechanism; wherein the drive mechanism includes a stator and a rotor; and wherein the stator is concentric with the rotor.

In another embodiment described herein, a compact 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 one or more swing-out holders located on the centrifuge body for containing centrifuge vessels. The swing-out holders or the sample containers have a maximum dimension of no more than about 10 mm.

In another embodiment described herein, a compact 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 one or more swing-out holders located on the centrifuge body for containing centrifuge vessels. The swing-out holders move from a first orientation to a second orientation that is more horizontal than the first orientation during centrifugation.

In another embodiment described herein, a compact 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 one or more swing-out holders located on the centrifuge body for containing centrifuge vessels. The sample container has a width greater than a length.

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

In another embodiment, a compact high-speed centrifuge for use with low-capacity sample containers is provided, the centrifuge comprising a centrifuge rotor; a motor for rotating the centrifuge rotor; a plurality of buckets coupled to the centrifuge rotor; and at least one magnetic device located on the buckets, the magnetic device being positioned to couple the buckets to a stationary portion of the centrifuge when the buckets are in a stationary position.

It should be understood that the embodiments herein may be adapted to have one or more of the following features. In a non-limiting example, the rotor includes at least an optical encoder and a Hall effect sensor to determine the rotational position. Optionally, the rotor includes at least an optical encoder and a Hall effect sensor to determine at least the rotational position and the rotational speed. Optionally, a first encoder disk is included and the first encoder disk provides a first type of encoder information, while a second encoder disk provides a second type of encoder information. Optionally, the first encoder disk providing optical encoder information and the second encoder disk providing magnetic encoder information are coupled to the motor. Optionally, the bucket is configured to accommodate a vessel for holding a sample volume of no more than 70uL. Optionally, the bucket is configured to accommodate a vessel for holding a sample volume of no more than 80uL. Optionally, the bucket is configured to accommodate a vessel for holding a sample volume of no more than 90uL. Optionally, the bucket is configured to accommodate a vessel for holding a sample volume of no more than 100uL. Optionally, the bucket is configured to accommodate a vessel for holding a sample volume of no more than 150uL. Optionally, each of the buckets has an L-shaped configuration. Optionally, a centrifuge housing is provided and is sized to cover at least a portion of the side of the centrifuge rotor. Optionally, the housing includes a plurality of cutouts to allow air to enter when the centrifuge body rotates.

In another non-limiting example, a method is provided, comprising providing a motor coupled to a centrifuge body; determining the rotational speed of the rotating portion of the motor using an encoder on the centrifuge body; and maintaining the bucket on the centrifuge body using at least one magnet in the bucket when the centrifuge is in a stopped condition. Optionally, the bucket is configured to hold a vessel having a sample chamber no larger than 100 uL. Optionally, the method comprises using a thermally conductive material configured to direct heat away from the container. Optionally, the method comprises using an active cooling unit for minimizing heat transfer to the sample, wherein the container is arranged so that the container is located in an area where heat exposure is reduced; the active cooling unit is configured to cool the drive mechanism. Optionally, the method comprises using an automatic balancing weight coupled to the centrifuge body, wherein such a weight is configured to move under centrifugal force to a position that minimizes unbalanced rotation of the centrifuge body in the event of an uneven load in a sample holder of the centrifuge. Optionally, the method includes using at least one air bearing configured to support the centrifuge during operation. Optionally, the method includes using at least one air bearing configured to support the centrifuge during operation, wherein at least a portion of the air bearing is part of the centrifuge housing. Optionally, the method includes using a force detector configured to detect a rate of change in force outside a predetermined force condition range. Optionally, the centrifuge vessel holder pivots inwardly toward the central axis of the centrifuge rotor under centrifugal force. Optionally, the centrifuge vessel holder forms a surface flush with the rotor body to minimize aerodynamic drag. Optionally, the centrifuge vessel holder is configured to retract downward under centrifugal force. Optionally, the electrical connection to the centrifuge body cooling element is not interrupted, even if such element is in operation during centrifugal operation. Optionally, the centrifuge vessel holder moves from a first orientation to a second orientation that is more horizontal than the first orientation during centrifugal operation.

It should be understood that the embodiments in the present disclosure provide a method comprising at least one technical feature from any one of the other embodiments herein. Alternatively, a method may comprise at least any two technical features from any one of the other embodiments herein.

Optionally, a device may include at least any one technical feature from any of the other embodiments herein. Optionally, a device may include at least any two technical features from any of the other embodiments herein. Optionally, a system may include at least any one technical feature from any of the other embodiments herein. Optionally, a system may include at least any two technical features from any of the other embodiments herein.

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

BRIEF DESCRIPTION OF THE DRAWINGS

1 to 3 show various views of an embodiment of a centrifuge described herein.

4-5 show various views of an embodiment of a centrifuge described herein.

6-8 show various views of an embodiment of a vessel holder as described herein.

9-12 illustrate various embodiments of the centrifuge described herein.

13-16 show various views of an embodiment of a centrifuge having thermal control features as described herein.

17A-17G illustrate various embodiments of apparatus and methods for position and/or velocity control as described herein.

18A-18C illustrate various embodiments of the self-balancing features described herein.

19-20 illustrate various embodiments of apparatus and methods as described herein.

21 shows a schematic diagram of one embodiment of an integrated system having a sample processing component, a pre-processing component, and an analysis component.

Figure 22 shows yet another embodiment of an apparatus as described herein.

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 invention as claimed. It should be noted that as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a material" may include mixtures of materials, reference to "a compound" may include a plurality of compounds, and so forth. The references cited herein are hereby incorporated by reference in their entirety, except to the extent they conflict with the teachings expressly set forth in this specification.

In this specification and in the claims that follow, reference will be made to several terms that shall be defined to have the following meanings:

"Optional" or "optionally" means that the subsequently described circumstance may or may not occur, such that the description includes instances where the circumstance occurs and instances where the circumstance does not occur. For example, if a device optionally includes a feature for a sample collection well, this means that the sample collection well may or may not be present, and thus the description includes both configurations in which the device has a sample collection well and configurations in which the sample collection well is not present.

centrifuge

Figure 1, Figure 2 and Figure 3 show the scale perspective (Figure 1 - side view, Figure 2 - front view, Figure 3 - rear view) of the centrifuge that can be integrated into the system. The centrifuge can include an electric motor that can rotate the rotor at 15,000 rpm. The shape of one type of centrifuge rotor is a bit like a fan blade installed on the motor main shaft on a vertical plane. The sample fixing element (tip) is maintained and an element with a ridge or shelf is provided and is attached to the rotor. The end of the tip located on the distal side of the motor shaft rests on the ridge or shelf and the ridge or shelf provides support during centrifugation so that the sample cannot escape. The tip can also be further supported by a mechanical stop in the rotor at its proximal end. This tip can be provided so that the force generated during centrifugation will not cause the tip to cut off the soft vinyl cover. The tip can be inserted and removed by a standard pick-and-place mechanism, but is preferably inserted and removed by a pipette. The rotor is a single acrylic block (or other material block) whose shape is set to minimize vibration and noise during centrifuge operation. The shape of the rotor is (optionally) set so that when it is oriented at a specific angle to the vertical, other movable components in the instrument can move through the centrifuge. The sample holding element is centrifugally balanced by blocks on opposite sides of the rotor so that the center of inertia is axial relative to the motor. The centrifuge motor can provide position data to a computer, which can then control the rotor's static position (usually vertical before and after centrifugation).

According to published standards (DIN 58933-1; for the United States, CLSI standard H07-A3 "Procedure for Determining Packed Cell Volume by the Microhematocrit Method"; approved standard - 3rd edition), in order to minimize the centrifugation time (without generating too much mechanical stress during centrifugation), convenient rotor sizes are in the range of about 5-10 cm, rotating at about 10,000-20,000 rpm, thus providing a time of about 5 minutes for packing of red blood cells.

In some embodiments, the centrifuge can be a horizontally oriented centrifuge with a swinging bucket design. In some preferred embodiments, the rotation axis of the centrifuge is vertical. In alternative embodiments, the rotation axis can be horizontal or at any angle. The centrifuge can be capable of rotating two or more vessels simultaneously and can be designed to be fully integrated into an automated system using a computer-controlled pipette. In some embodiments, the bottom of the vessel can be closed. The swinging bucket design can allow the centrifugal vessel to be passively oriented in a vertical position when stopped and to rotate outward to a fixed angle when rotating. In some embodiments, the swinging bucket can allow the centrifugal vessel to rotate outward to a horizontal orientation. Or they can rotate outward to any angle between a vertical position and a horizontal position (for example, about 15 degrees, 30 degrees, 45 degrees, 60 degrees or 75 degrees from a vertical plane). A centrifuge with a swinging bucket design can meet the position accuracy and repeatability requirements of a robotic system that employs several positioning systems.

A computer-based control system can use position information from an optical encoder to rotate the rotor at a controlled low speed. Since appropriate motors can be designed for high-speed performance, there is no need to use position feedback alone to maintain an accurate static position. In some embodiments, a cam combined with a solenoid-actuated lever can be used to achieve a very accurate and stable stop at a fixed number of positions. Using a separate control system and feedback from a Hall effect sensor built into the motor, the speed of the high-speed rotor can be controlled very accurately.

Because several sensitive instruments must function simultaneously within an assay instrument system, the centrifuge design preferably minimizes or reduces vibration. The rotor can be aerodynamically designed with a smooth exterior that completely encloses the bucket when it is in its horizontal position. Additionally, vibration damping can be employed at various locations within the housing design. It should be understood that any of the embodiments shown in Figures 1-3 can be configured to incorporate any of the other features described herein.

rotor

The centrifuge rotor can be a component of the system that can hold one or more centrifugal vessels and rotate them. The axis of rotation can be vertical, and therefore the rotor itself can be positioned horizontally. However, in alternative embodiments, different axis of rotation and rotor positions can be adopted. There are two components called buckets, which are symmetrically positioned on either side of the rotor holding the centrifugal vessels. Alternative configurations are possible, in which the buckets are oriented to be radially symmetrical, for example, three buckets are oriented at 120 degrees. Any number of buckets can be provided, including but not limited to 1, 2, 3, 4, 5, 6, 7, 8 or more buckets. The buckets can be evenly spaced apart from each other. For example, if n buckets are provided, where n is an integer, the buckets can be spaced apart by about 360/n degrees. In other embodiments, the buckets do not need to be evenly spaced apart or radially symmetrical around each other.

When the rotor is stationary, these buckets may be passively lowered under the influence of gravity to position the vessels vertically and make them accessible to the pipette. Figure 4 shows an example of a stationary rotor in which the buckets are vertical. In some embodiments, the buckets can be passively lowered to a predetermined angle, which may or may not be vertical. When the rotor rotates, the buckets are forced by centrifugal force into an almost horizontal position or a predetermined angle. Figure 5 shows an example of a rotor at a certain speed in which the buckets are at a small angle to the horizontal plane. There may be physical hard stops for both the vertical and horizontal positions to enforce their accuracy and position repeatability.

The rotor can be aerodynamically designed with a disk shape and as few physical features as possible to minimize vibrations caused by air turbulence. To achieve this, the outer geometry of the bucket can be precisely matched to the outer geometry of the rotor so that when the rotor is rotating and the bucket can be forced to level, the bucket and rotor are perfectly aligned.

To facilitate plasma extraction, the rotor can be angled downward, toward the ground, relative to the horizontal. This allows for a fixed angle of rotation of the bucket, since the angle of the bucket can be matched to the angle of the rotor. The resulting precipitate from this configuration can be angled relative to the vessel when it is positioned vertically. Plasma can be drawn from the top of the centrifuge vessel using a narrow extraction tip. By positioning the extraction tip near the bottom of the slope created by the angled precipitate, the final volume of plasma can be extracted more efficiently without disturbing the sensitive buffy coat.

A variety of tube designs can be accommodated in the bucket of the device. In some embodiments, the various tube designs can be closed-end. Some tube designs are shaped like conventional centrifuge tubes with a tapered bottom. Other tube designs can be cylindrical. Tubes with a lower height to cross-sectional area ratio can be beneficial for cell processing. Tubes with a large ratio (>10:1) can be suitable for accurate measurement of hematocrit and other imaging requirements. However, any height to cross-sectional area ratio can be used. The bucket can be made of any of several plastics (polystyrene, polypropylene) or any other material discussed elsewhere in this article. The bucket can have a capacity ranging from a few microliters to about 1 milliliter. A "pick and place" mechanism can be used to insert and remove the tubes into and from the centrifuge.

control system

Due to the rotation and positioning requirements of the centrifuge equipment, a dual control system can be used. In order to make the rotor index to a specific rotation orientation, a position-based control system can be implemented. In some embodiments, the control system can adopt a PID (proportional integral differential) control system. Other feedback control systems known in the art can be adopted. Position feedback for a position controller can be provided by a high-resolution optical encoder. In order to make the centrifuge run at a low to high speed, a speed controller can be implemented while adopting a PID control system that is adjusted for speed control. The rotation rate feedback for a speed controller can be provided by a group of simple Hall effect sensors placed on the motor shaft. During one cycle of each motor shaft rotation, each sensor can generate a square wave.

Stop agency

In order to position the rotor consistently and securely in a specific position, a physical stop mechanism can be employed in some embodiments herein. In one embodiment, the stop mechanism can utilize a cam coupled to the rotor in conjunction with a solenoid-actuated lever. The cam can be shaped like a disk having several "C"-shaped notches machined around the circumference. To position the centrifuge rotor, its rotational speed can first be reduced to a maximum of 30 RPM. In other embodiments, the rotational speed can be reduced to any other amount, including but not limited to approximately 5 rpm, 10 rpm, 15 rpm, 20 rpm, 25 rpm, 35 rpm, 40 rpm, or 50 rpm. Once the speed is slow enough, the lever can be actuated. Located at the end of the lever is a cam follower that can slide along the circumference of the cam with minimal friction. Once the cam follower reaches the center of a specific notch in the cam, the force of the solenoid-actuated lever can overcome the force of the motor and can stop the rotor. At that time, the motor can be electronically braked, and in combination with the stop mechanism, the rotational position can be maintained indefinitely and very accurately and securely.

Centrifuge bucket(s)

A centrifuge swing bucket can be configured to accommodate different types of centrifuge tubes. In a preferred embodiment, each tube type can have a collar or flange at its upper (open) end. This collar or flange feature can rest on the upper end of the bucket and support the tube during centrifugation. As shown in Figures 6, 7, and 8, conical and cylindrical tubes of various lengths and volumes can be accommodated. Figures 6, 7, and 8 provide examples of buckets, and other bucket designs can be used. For example, Figure 6 shows an example of a bucket configuration. The bucket can have side portions that mate with the centrifuge and allow the bucket to swing freely. The bucket can have a closed bottom and an opening at its top. Figure 7 shows an example of a centrifuge vessel that mates with the bucket. As previously mentioned, the bucket can be shaped to accommodate centrifuge vessels of various configurations. The centrifuge vessel can have one or more protruding members that can rest on the bucket. The centrifuge vessel can be shaped with one or more features that mate with the centrifuge bucket. The features can be shaped features of the vessel or one or more protrusions. Figure 8 shows an example of another centrifuge vessel that mates with the bucket. As previously described, the bucket may have one or more shaped features that may allow different configurations of centrifuge vessels to mate with the bucket. It should be understood that any embodiment of the centrifuge in Figures 4-8 may be configured with any other features described in this disclosure.

Centrifuge tubes and sample extraction techniques

The centrifuge tube and extraction tip can be provided individually and can be mated together to extract the material after centrifugation. The centrifuge tube and extraction tip can be designed to handle complex processes in automated systems. Any dimensions are provided by way of example only, and other dimensions with the same or different proportions can be used.

The system can do one or more of the following:

1. Rapidly process small blood samples (usually 5–50uL)

2. Accurately and precisely measure hematocrit

3. Efficiently remove plasma

4. Efficiently resuspend formed elements (red blood cells and white blood cells)

5. Concentrated white blood cells (after labeling with fluorescent antibodies and fixation and lysis of red blood cells)

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

Overview of Centrifuge Vessels and Extraction Tips

Customized vessels and advanced technology can be used to operate the centrifuge, so as to meet the multiple constraints placed on the system. The centrifugal vessel can be a tube with a bottom closure designed to rotate in the centrifuge. In some embodiments, the centrifugal vessel can be the vessel shown in Figure 7, or can have one or more features shown in Figure 7. It can have several unique features supporting the desired functions of a wide range, and the functions include hematocrit measurement, RBC lysis, sediment resuspension and efficient plasma extraction. Extraction tip can be designed to be inserted into the centrifugal vessel, for accurate fluid extraction and sediment resuspension. In some embodiments, extraction tip can be the advanced technology shown in Figure 6, or can have one or more features shown in Figure 6. Discussed herein the exemplary description of extraction tip and it can be learned in U.S. application serial numbers 13/355,458 and 13/244,947, the full text of the application being incorporated herein by reference for all purposes.

Centrifuge vessels

In one embodiment, a centrifuge vessel can be designed to handle two separate usage scenarios, each associated with a different anticoagulant and whole blood volume.

The first use case may require sedimentation of 40 uL of whole blood with heparin, recovery of the maximum volume of plasma, and measurement of the hematocrit using computer vision. In the case of a hematocrit of 60% or less, the required or preferred plasma volume may be approximately 40 uL*40%=16 uL.

In some embodiments, it will not be possible to recover 100% of the plasma because the buffy coat must not be disturbed and therefore a minimum distance must be maintained between the bottom of the tip and the top of the sediment. This minimum distance can be determined experimentally, but the volume (V) sacrificed as a function of the required safety distance (d) can be estimated using the following formula: V(d) = d*π1.25mm2. For example, for a hematocrit of 60%, the volume sacrificed can be 1.23uL for a required safety distance of 0.25mm. This volume can be reduced by reducing the inner diameter of the hematocrit portion of the centrifuge vessel. However, since in some embodiments this narrow portion must completely accommodate the outer diameter of the extraction tip (which may not be less than 1.5mm), the existing size of the centrifuge vessel may be close to the minimum value.

In some embodiments, along with plasma extraction, it may also be necessary to use computer vision to measure the hematocrit. To facilitate this process, the total height of a given volume of hematocrit can be maximized by minimizing the inner diameter of the narrow portion of the vessel. By maximizing the height, the relationship between the change in hematocrit volume and the physical change in column height can be optimized, thereby increasing the number of pixels available for measurement. The height of the narrow portion of the vessel can also be long enough to accommodate a worst-case scenario of 80% hematocrit, while still leaving a small portion of plasma at the top of the column to allow efficient extraction. Thus, 40uL*80%=32uL can be the volume capacity required for accurate hematocrit measurement. The volume of the narrow portion of the designed tip can be approximately 35.3uL, which can allow for some volume of plasma to remain even in the worst-case scenario.

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

Sedimentation of whole blood

·Plasma extraction

Resuspend the pellet in lysis buffer and stain

Sedimentation of remaining white blood cells (WBCs)

Remove the supernatant

Resuspend WBCs

Completely extract WBC suspension

In order to make the sediment of packing resuspend fully, experiment has shown that, can physically disturb this sediment with the tip that can arrive the bottom of the vessel that comprises sediment fully.The preferred geometry of the vessel bottom that is used for resuspending seems to be hemispherical shape, similar to standard commercial PCR tube.In other embodiments, other vessel bottom shapes can be used.Centrifugal vessel together with extraction tip can be designed for by complying with these geometrical shape requirements and also allow extraction tip to contact described bottom physically and promote resuspending process simultaneously.

During manual resuspension experiments, it was noted that physical contact between the bottom of the vessel and the bottom of the tip can create a seal that prevents fluid from moving. A slight spacing can be used to completely disturb the sediment while allowing fluid to flow. To facilitate this process in a robotic system, physical features can be added to the bottom of the centrifugal vessel. In some embodiments, the feature can include four small hemispherical nubs placed around the perimeter of the bottom portion of the vessel. When the extraction tip is fully inserted into the vessel and allowed to make physical contact, the end of the tip can rest on the nubs, and the fluid is allowed to flow freely between the nubs. This may result in a small amount of volume being lost in the gap (~0.25uL).

During the lysis process, in some implementations, the maximum expected fluid volume is 60 uL, which, together with the 25 uL displaced by the extraction tip, may require a total volume capacity of 85 uL. A design with a current maximum volume of 100 uL may exceed this requirement. Other aspects of the second use scenario require similar or already discussed tip characteristics.

The upper geometry of the centrifugal vessel can be designed to cooperate with the pipette mouth. Any pipette mouth described in other places of this paper or known in the art can be used. The external geometry of the upper portion of the vessel can be accurately matched with the external geometry of the reaction tip, when the front mouth and cartridge can be designed to surround the reaction tip. In some embodiments, very small ridges can circumscribe the inner surface of the upper portion. This ridge can be a visual marker of maximum fluid height, which is intended to promote the automatic error detection using a computer vision system.

In some embodiments, the distance from the bottom of the fully mated mouth to the top of the maximum fluid line is 2.5 mm. This distance is 1.5 mm less than the recommended distance of 4 mm that extraction tips adhere to. This reduced distance may be influenced by the need to minimize the length of the extraction tip while adhering to the minimum volume requirement. The reason for this reduced distance stems from the specific use of the vessel. Since in some implementations, fluid may only be exchanged with the vessel from the top, the maximum fluid it will have when mated with the mouth is the maximum amount of whole blood expected at any given time (40 uL). The height of this fluid may be much lower than the bottom of the mouth. Another concern is that at other times, the volume of fluid in the vessel may be much greater than this and soak the walls up to the height of the mouth. In some embodiments, the fluid will be as high as those heights at which the vessel is used to ensure that the meniscus of any fluid contained in the vessel does not exceed the maximum fluid height, even when the total volume is less than the specified maximum amount. In other embodiments, other features may be provided to keep the fluid contained in the vessel.

Any dimensions, sizes, volumes or distances provided herein are provided by way of example only. Any other dimensions, sizes, volumes or distances may be utilized, which may or may not be proportional to the amounts mentioned herein.

During the process of exchanging fluids and inserting and removing advanced technology rapidly, centrifugal vessel may be subject to some forces. If vessel is unconstrained, then these forces may be strong enough to lift vessel from centrifuge bucket or otherwise remove. In order to prevent movement, vessel should be fixed in some way. In order to achieve this, the small ring outside the bottom of external vessel has been added. This ring can easily cooperate with the compliant mechanical feature on the bucket. As long as the holding force of the small piece is greater than the force experienced during the fluid manipulation but less than the frictional force when cooperating with the mouth, this problem is solved.

Extraction tip

Extraction tip can be designed to be connected with centrifugal vessel, thereby extracting plasma efficiently and making the cell of precipitation resuspend.When needed, its total length (for example, 34.5mm) can be accurately matched with the total length of another blood tip including but not limited to those blood tips described in U.S. Serial No. 12/244,723 (incorporated herein by reference), but can be long enough to physically contact the bottom of centrifugal vessel.In some embodiments, the ability of contact vessel bottom may be needed, both for resuspending process and for complete recovery of leukocyte suspension.

The volume of the extraction tip required can be determined by the maximum volume expected to be drawn from the centrifuge vessel at any given time. In some embodiments, this volume can be approximately 60uL, which can be less than the maximum capacity of the tip, 85uL. In some embodiments, a tip having a volume larger than the required volume can be provided. As with the centrifuge vessel, an internal feature on the interior of the upper portion of the circumscribed tip can be used to mark the height of this maximum volume. The distance between the maximum volume line and the top of the mating nozzle can be 4.5mm, which can be considered a safe distance to prevent nozzle contamination. Any sufficient distance sufficient to prevent nozzle contamination can be used.

A centrifuge can be used to sediment the precipitated LDL-cholesterol. Imaging can be used to verify that the supernatant is clear, indicating complete removal of the precipitate.

In one example, plasma can be diluted into a mixture of dextran sulfate (25 mg/dL) and magnesium sulfate (100 mM), and can then be incubated for 1 minute to precipitate LDL-cholesterol. The reaction product can be drawn into a tube of a centrifuge, then capped and spun at 3000 rpm for three minutes. Images of the initial reaction mixture taken before centrifugation (showing a white precipitate), after centrifugation (showing a clear supernatant), and images of the LDL-cholesterol precipitate taken (after removing the cap) are respectively as shown in U.S. application serial numbers 13/355,458 and 13/244,947 and are incorporated herein by reference in their entirety for all purposes.

Other examples of centrifuges that may be employed in the present invention are described in U.S. Patent Nos. 5,693,233, 5,578,269, 6,599,476, and U.S. Patent Publication Nos. 2004/0230400, 2009/0305392, and 2010/0047790, the entire contents of which are incorporated by reference for all purposes.

Example Scenario

Many variations of protocols can be used for centrifugation and processing. For example, a typical protocol for using a centrifuge to process and concentrate white blood cells for cell counting may include one or more of the following steps. The steps below may be provided in a different order, or other steps may be substituted for any of the steps below:

1. Receive 10uL of blood anticoagulated with anticoagulant (pipette the blood into the bottom of the centrifuge bucket)

2. Sediment the red blood cells and white blood cells by centrifugation (<5 min x 10000 g).

3. Measuring Hematocrit by Imaging

4. Slowly remove plasma by drawing it into a pipette (4 uL, corresponding to the worst case scenario [60% hematocrit]) without disturbing the cell pellet.

5. Resuspend the pellet after adding 20 uL of an appropriate mixture of up to five fluorescently labeled antibodies dissolved in buffered saline.

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) with the white blood cell fixation reagent (formaldehyde).

8. Add 30uL of Lysis/Fixation Reagent (total reaction volume is approximately 60uL).

9. Incubate at 37°C for 15 minutes.

10. Sediment the leukocytes by centrifugation (10,000 g).

11. Remove the hemolyzed product from the supernatant.

12. Resuspend the leukocytes by adding buffer (isotonic buffered saline).

13. Measure volume accurately.

14. Deliver the sample to the cytometer.

The steps may include receiving a sample. The sample may be a body fluid, such as blood, or any other sample described elsewhere herein. The sample may be a small volume, such as any volume measurement described elsewhere herein. In some cases, the sample may have an anticoagulant.

In one embodiment, a separation step may occur. For example, a density-based separation may occur. Such separation may occur via centrifugation, magnetic separation, lysis, or any other separation technique known in the art. In some embodiments, the sample may be blood, and red blood cells and white blood cells may be separated.

In one embodiment, measurements can be performed. In some cases, measurements can be performed via imaging or any other detection mechanism described elsewhere herein. For example, the hematocrit of a separated blood sample can be measured by imaging. Imaging can be performed via a digital camera or any other image capture device described herein.

In one embodiment, one or more components of a sample can be removed. For example, if a sample is separated into a solid component and a liquid component, the liquid component can be moved. Plasma can be removed from a blood sample. In some cases, liquid components such as plasma can be removed via a pipette. The liquid component can be removed without disturbing the solid component. Imaging can assist in removing the liquid component or any other selected component of the sample. For example, imaging can be used to determine where the plasma is located and can assist in the placement of a pipette to remove the plasma.

In some embodiments, reagents or other materials may be added to the sample. For example, solids in the sample may be resuspended. Labels may be added to the material. One or more incubation steps may occur. In some cases, lysis reagents and/or fixatives may be added. Additional separation steps and/or resuspension steps may occur. Dilution and/or concentration steps may occur as needed.

The volume of a sample can be measured. In some cases, the volume of a sample can be measured in an accurate and/or precise manner. The volume of a sample can be measured in a system having a low coefficient of variation, such as the coefficient of variation values described elsewhere herein. In some cases, imaging can be used to measure the volume of a sample. An image of the sample can be captured and the volume of the sample can be calculated based on the image.

The sample can be delivered to a desired process. For example, the sample can be delivered for cell counting.

In another example, a typical scheme for nucleic acid purification that may or may not utilize a centrifuge may include one or more of the following steps. The system can support DNA/RNA extraction so that the nucleic acid template is delivered to the exponential amplification reaction for detection. The process can be designed to extract nucleic acid from a variety of samples, including but not limited to whole blood, serum, virus transport culture medium, human and animal tissue samples, food samples, and bacterial cultures. The process can be fully automated and can extract DNA/RNA in a consistent and quantitative manner. The steps hereinafter may be provided in different orders, or any of the steps hereinafter may be replaced by other steps:

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

2. Surface loading. The sample of cracking can be exposed to a functionalized surface (typically the form of a packed bed of microbeads), such as, but not limited to, a resin support filled in a chromatographic analysis column, magnetic beads mixed with a sample in a batch mode, a sample pumped through a suspended resin in a fluidized bed mode, and a sample pumped through a closed channel in a tangential flow mode on the surface. The surface can be functionalized to bind nucleic acids (e.g., DNA, RNA, DNA/RNA hybrids) in the presence of a lysis buffer. Surface types can include silicon dioxide and ion exchange functional groups, such as diethylaminoethanol (DEAE). The mixture of cracking can be exposed to a surface and nucleic acid binders.

3. Washing. Wash the solid surface with a saline solution, such as a 0-2 M sodium chloride and ethanol (20-80% v/v) solution at a pH of 7.0-7.5. The washing can be achieved in the same manner as the loading.

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

The system can adopt many variations of these schemes or other schemes.Such schemes can be used in conjunction with any scheme or method described herein or use instead of it.

In some embodiments, it is important to be able to reclaim the cells accumulated and concentrated by centrifugation for cell counting. In some embodiments, this can be achieved by using a pipetting device. Liquid (typically a mixture of isotonic buffered saline, a lysing agent, a lysing agent and a fixative, or a mixture of labeled antibodies in a buffer) can be distributed to a centrifuge bucket and repeatedly drawn on and resuspended. The tip of the pipette can be forced to enter the accumulated cells to facilitate the process. Image analysis assists the process by objectively verifying that all cells have been resuspended.

Use pipettes and centrifuges to process samples before analysis

According to an embodiment of the present invention, the system can have pipetting capabilities, pick-and-place capabilities, and centrifugation capabilities. Such capabilities can enable the efficient execution of almost any type of sample pretreatment and complex assay procedures using very small volumes of sample.

Specifically, the system can support the separation of formed elements (red blood cells and white blood cells) from plasma. The system can also support the resuspension of formed elements. In some embodiments, the system can support the concentration of white blood cells from fixed and hemolyzed blood. The system can also support the lysis of cells to release nucleic acids. In some embodiments, the system can support the purification and concentration of nucleic acids by filtering through a tip piled with (usually beaded) solid phase reagents (e.g., silica). The system can also allow elution of purified nucleic acids after solid phase extraction. The system can also support the removal and collection of precipitates (e.g., LDL-cholesterol precipitated using polyethylene glycol).

In some embodiments, the system can support affinity purification. Small molecules such as vitamin-D and serotonin can be absorbed onto beaded (particle) hydrophobic substrates, and then eluted using organic solvents. Antigen can be provided on a substrate coated with an antibody and eluted with acid. The same method can be used to concentrate analytes found at low concentrations, such as thromboxane-B2 and 6-keto-prostaglandin F1α. Antigen can be provided on a substrate coated with an antibody or an aptamer and then eluted.

In some embodiments, the system can support chemical modification of the analyte prior to measurement. For example, to measure serotonin (5-hydroxytryptamine), it may be necessary to convert the analyte into a derivative (such as an acetylated form) using a reagent (such as acetic anhydride). This may be done to produce a form of the analyte that can be recognized by an antibody.

Can use pipette to move liquid (vacuum suction and pumping).Pipette may be limited to relatively low positive and negative pressure (about 0.1-2.0 atmospheric pressure).When needed, centrifuge can be used to produce much higher pressure to force liquid to pass through beaded solid phase medium.For example, use under the speed of 10000rpm, the rotor of radius is 5cm, can generate the power of about 5000xg (about 7 atmospheric pressures), it is enough to force liquid to pass through resistive media such as packed bed.Can use other centrifuge designs and configurations discussed in various places of this paper or known in the art.

Hematocrit measurements can be made using very small volumes of blood. For example, inexpensive digital cameras can capture good images of small objects, even when the contrast is poor. Utilizing this capability, the system of the present invention can support automated hematocrit measurements using very small volumes of blood.

For example, 1 uL of blood can be drawn into a microliter glass capillary. The capillary can then be sealed with a curable adhesive and then subjected to centrifugation at 10,000 x g for 5 minutes. The accumulated cell volume can be easily measured, and the plasma meniscus (indicated by the arrow) may also be visible, so the hematocrit can be accurately measured. This can enable the system to not waste a relatively large volume of blood to perform this measurement. In some embodiments, the camera can be used "as is" without operating a microscope to obtain a larger image. In other embodiments, a microscope or other optical techniques can be used to amplify the image. In one implementation, a digital camera is used to determine the hematocrit without additional light interference, and the hematocrit measured is the same as the hematocrit determined by the conventional microhematocrit laboratory method that requires many microliters of sample. In some embodiments, the length of the sample column and the length of the column of accumulated red blood cells can be measured very accurately (+/-<0.05mm). Assuming that the blood sample column can be approximately 10-20 mm, the standard deviation of the hematocrit can be much better than the 1% match obtained by standard laboratory methods.

The system can support the measurement of erythrocyte sedimentation rate (ESR). ESR can be measured by leveraging the digital camera's ability to measure very small distances and rates of change in distance. In one example, three blood samples (15 μL) were drawn into the "reaction 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 measurement accuracy can be estimated 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 example, when this measurement accuracy is related to the distance traveled in one hour, it is determined to be 0.038 mm or <2% CV. Therefore, ESR can be accurately measured by this method. Another method for determining ESR is to measure the maximum slope of the distance versus time relationship.

centrifuge

With reference now to Figures 9 to 11, further embodiments of the centrifuge will now be described. According to some embodiments of the present invention, a system may include one or more centrifuges. One or more centrifuges may be included in an apparatus in the system. For example, one or more centrifuges may be provided within an apparatus housing. A module may have one or more centrifuges. A centrifuge may be provided in one, two or more modules of the apparatus. The centrifuge may be supported by a module support structure or may be contained within a module housing. The centrifuge may have a form factor that is compact, flat, and takes up only a small footprint. In some embodiments, the centrifuge may be miniaturized for point-of-service applications, but still capable of rotating at high speeds equal to or exceeding about 10,000 rpm and capable of withstanding gravitational accelerations of up to about 1,200 m/s ² or greater.

In some embodiments, a centrifuge can be configured to receive one or more samples. A centrifuge can be used to separate and/or purify materials of varying densities. Examples of such materials can include viruses, bacteria, cells, proteins, environmental components, or other components. A centrifuge can be used to concentrate cells and/or particles for subsequent measurement.

In some embodiments, a centrifuge may have one or more cavities configured to receive a sample. A cavity may be configured to receive a sample directly within the cavity, such that the sample can contact the cavity walls. Alternatively, a cavity may be configured to receive a sample vessel that may contain a sample therein. Any description of a cavity herein may apply to any configuration that can receive and/or contain a sample or sample container. For example, a cavity may include an indentation in a material, a scoop-shaped structure, a protrusion with a hollow interior, or a member configured to interconnect with a sample container. Any description of a cavity may also include configurations that may or may not have a concave surface or inner surface. Examples of sample vessels may include any vessel or tip design described elsewhere herein. A sample vessel may have an inner surface and an outer surface. A sample vessel may have at least one open end configured to receive a sample. The open end may be closable or sealable. The sample vessel may have a closed end. The sample vessel may be a nozzle of a fluid handling device that can function as a centrifuge, rotating a fluid within the nozzle, tip, or another vessel attached to such a nozzle.

In some embodiments, a centrifuge can have 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 8 or more, 10 or more, 12 or more, 15 or more, 20 or more, 30 or more, or 50 or more cavities configured to receive samples or sample vessels.

In some embodiments, the centrifuge can be configured to accept small sample volumes. In some embodiments, the cavity and/or sample vessel may be configured to accommodate a sample volume of 1000 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 μL or less, 500 nL or less, 300 nL or less, 100 nL or less, 50 nL or less, 10 nL or less, 1 nL 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, centrifuge can have a capping, and the capping can include the sample in the centrifuge. The capping can prevent the sample from atomizing and/or evaporating. Centrifuge can alternatively have a film, oil (e.g., mineral oil), wax or gel, which can include the sample in the centrifuge and/or prevent it from atomizing and/or evaporating. Film, oil, wax or gel can be provided as a layer on the sample in the cavity and/or sample vessel that can be included in the centrifuge.

Centrifuge can be configured to rotate around the axis of rotation. Centrifuge may be able to rotate with any rpm. For example, the rotational speed of centrifuge can be up to 100rpm, 1000rpm, 2000rpm, 3000rpm, 5000rpm, 7000rpm, 10000rpm, 12000rpm, 15000rpm, 17000rpm, 20000rpm, 25000rpm, 30000rpm, 40000rpm, 50000rpm, 70000rpm or 100000rpm. At some time points, centrifuge can remain stationary, and at other time points, centrifuge can rotate. Static centrifuge does not rotate. Centrifuge can be configured to rotate with variable speed. In some embodiments, centrifuge can be controlled to rotate with the speed of expectation. In some embodiments, the rate of change of rotational speed can be variable and/or controllable.

In some embodiments, the rotation axis can be vertical. Alternatively, the rotation axis can be horizontal, or can have any angle (for example, about 15, 30, 45, 60 or 75 degrees) between vertical and horizontal. In some embodiments, the rotation axis can be in a fixed direction. Alternatively, the rotation axis can change during the use of equipment. When the centrifuge is rotating, the rotation axis angle can change or may not change.

In some embodiments, the centrifuge may include a base. In some embodiments, the base includes a centrifuge rotor. The base may have a top surface and a bottom surface. The base may be configured to rotate about an axis of rotation. The axis of rotation may be orthogonal to the top surface and/or bottom surface of the base. In some embodiments, the top surface and/or bottom surface of the base may be flat or curved. The top surface and bottom surface may or may not be substantially parallel to each other.

In some embodiments, the base can have a circular shape. The base can have any other shape, including but not limited to an oval, triangular, quadrilateral, pentagonal, hexagonal, or octagonal shape.

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

Centrifuge can have any size. For example, centrifuge can have about 200cm or ^less , 150cm or less, ^100cm or less, ^90cm or less, ^80cm or less, 70cm or less, ^60cm or less, ^50cm or less, ^40cm or less, ^30cm or less, ^20cm or less, ^10cm or less, ^5cm or ^less , or ^1cm or less footprint. Centrifuge can have about 5cm or less, 4cm or less, ^3cm or less, 2.5cm or less, 2cm or less, 1.75cm or less, 1.5cm or less, 1cm or less, 0.75cm or less, 0.5cm or less, or 0.1cm or less height. In some embodiments, the maximum dimension of the centrifuge can be about 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 configured to receive a drive mechanism. The drive mechanism may be a motor or any other mechanism capable of rotating the centrifuge about an axis of rotation. The drive mechanism may be a brushless motor comprising a brushless motor rotor and a brushless motor stator. The brushless motor may be an induction motor. The brushless motor rotor may surround the brushless motor stator. The rotor may be configured to rotate about the axis of rotation relative to the stator.

The base may be connected to or incorporated into the brushless motor rotor, which may cause the base to rotate relative to the stator. The base may be attached to the rotor or may be integral with the rotor. The base may rotate relative to the stator, and a plane orthogonal to the motor's rotational axis may be coplanar with a plane orthogonal to the base's rotational axis. For example, the base may have a plane orthogonal to the base's rotational axis that passes substantially between the base's upper and lower surfaces. The motor may have a plane orthogonal to the motor's rotational axis that passes substantially through the motor's center. The base plane and the motor plane may be substantially coplanar. The motor plane may pass between the base's upper and lower surfaces.

The brushless motor assembly may include a motor rotor and a stator. The motor assembly may include electronic components. The integration of the brushless motor into the motor rotor assembly can reduce the overall size of the centrifuge assembly. In some embodiments, the motor assembly does not extend beyond the base height. In other embodiments, the height of the motor assembly is no more than 1.5 times the base height, 2 times the base height, 2.5 times the base height, 3 times the base height, 4 times the base height, or 5 times the base height. The motor rotor may be surrounded by the base so that the motor rotor is not exposed outside the base.

The motor assembly can affect the rotation of the centrifuge without the need for a spindle/shaft assembly.The rotor can surround the stator, and the stator can be electrically connected to a controller and/or power supply.

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

The centrifuge can be configured to receive sample vessels, and can be configured to allow the sample vessel to be in a first orientation when the base is stationary and to allow the sample vessel to be in a second orientation when the base rotates. The first orientation can be a vertical orientation, and the second orientation can be a horizontal orientation. The sample vessel can have any orientation, wherein the sample vessel can be greater than and/or equal to about 0 degree, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, 75 degrees, 80 degrees, 85 degrees or 90 degrees from the vertical plane. In some embodiments, the first orientation can be closer to vertical than the second orientation. Alternatively, no matter the base is stationary or rotating, the sample vessel can have the same orientation. The orientation of the vessel may depend on or may not depend on the speed at which the base rotates.

9 shows a non-limiting example of a centrifuge according to one embodiment of the present invention. The centrifuge may include a base 3600 having a bottom surface 3602 and/or a top surface 3604. The base may include one, two, or more wings 3610a, 3610b.

The wings can be configured to fold over an axis extending through the base. In some embodiments, the axis can form a secant through the base. The axis extending through the base can be a folding axis, which can be formed by one or more pivot points 3620. The wings can comprise the entire portion of the base on one side of the axis. The entire base can fold over to form the wings. In some embodiments, the central portion 3606 of the base may intersect the axis of rotation, while the wings do not. The central portion of the base may be closer to the axis of rotation than the wings. The central portion of the base can be configured to receive a drive mechanism 3630. The drive mechanism can be a motor or any other mechanism capable of causing the base to rotate, and is discussed in further detail elsewhere herein. In some embodiments, the wings may occupy an area that is approximately 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% or more of the base's footprint.

In some embodiments, a plurality of folding axes may be provided through the base. The folding axes may be parallel to one another. Alternatively, some of the folding axes may be orthogonal to one another or at any other angle relative to one another. The folding axes may extend through the lower surface of the base, the upper surface of the base, or between the lower and upper surfaces of the base. In some embodiments, the folding axes may extend through the base closer to the lower surface of the base or closer to the upper surface of the base. In some embodiments, the pivot point may be located at or closer to the lower surface of the base or the upper surface of the base.

One, two, three, four, five, six, or more cavities may be provided in the wing. For example, the wing may be configured to receive one, two, or more samples or sample vessels. Each wing may be capable of receiving the same number of vessels or a different number of vessels. The wing may include cavities configured to receive sample vessels, wherein the sample vessels are oriented in a first orientation when the base is stationary and are configured to be oriented in a second orientation when the base is rotated.

In some embodiments, the wings can be configured to be angled relative to the center portion of the base. For example, the wings can be between 90 and 180 degrees from the center portion of the base. For example, when the base is stationary, the wings can be vertically oriented. When oriented vertically, the wings can be 90 degrees from the center portion of the base. When the base rotates, the wings can be horizontally oriented. When oriented horizontally, the wings can be 180 degrees from the center portion of the base. When the base rotates, the wings can extend from the base to form a substantially uninterrupted surface. For example, when the base rotates, the wings can extend to form a substantially continuous surface of the bottom surface and/or top surface of the base. The wings can be configured to fold downward relative to the center portion of the base.

The pivot point of the wing can include one or more pivot pins 3622. The pivot pins can extend through a portion of the wing and a portion of the central portion of the base. In some embodiments, the wing and the central portion of the base can have interlocking features 3624, 3626 that prevent the wing from sliding laterally relative to the central portion of the base.

The wing can have a center of gravity 3680 that is positioned lower than the fold axis and/or pivot point 3620. When the base is stationary, the wing's center of gravity can be positioned lower than the axis extending through the base. When the base is rotated, the wing's center of gravity can be positioned lower than the axis extending through the base.

The wings can be formed from two or more different materials having different densities. Alternatively, the wings can be formed from a single material. In one example, the wings can have a lightweight wing cover 3640 and a heavy wing base 3645. In some embodiments, the wing cover can be formed from a material having a lower density than the wing base. For example, the wing cover can be formed from plastic, while the wing base is formed from metal, such as steel, tungsten, aluminum, copper, brass, iron, gold, silver, titanium, or any combination or alloy thereof. The heavier wing base can help provide the wing's center of mass below the fold axis and/or pivot point.

The wing cover and wing base can be connected by any mechanism known in the art. For example, fasteners 3650 can be provided, or adhesives, welding, interlocking features, clamps, hook and loop fasteners, or any other mechanism can be used. The wing can optionally include an insert 3655. The insert can be formed of a heavier material than the wing cover. The insert can help position the wing center of mass below the fold axis and/or pivot point.

One or more cavities 3670 can be provided within the wing cover or wing base, or any combination thereof. In some embodiments, the cavity can be configured to accommodate multiple sample vessel configurations. The cavity can have an inner surface. At least a portion of the inner surface can contact the sample vessel. In one example, the cavity can have one or more shelves or inner surface features that can allow a first sample vessel having a first configuration to fit within the cavity, and a second sample vessel having a second configuration to fit within the cavity. The first sample vessel and the second sample vessel having different configurations can contact different portions of the inner surface of the cavity.

The centrifuge can be configured to engage a fluid handling device. For example, the centrifuge can be configured to connect to a pipette or other fluid handling device. In some embodiments, a watertight seal can be formed between the centrifuge and the fluid handling device. The centrifuge can be engaged with the fluid handling device and configured to receive samples dispensed from the fluid handling device. The centrifuge can be engaged with the fluid handling device and configured to receive sample vessels from the fluid handling device. The centrifuge can be engaged with the fluid handling device and allow the fluid handling device to pick up or aspirate samples from the centrifuge. The centrifuge can be engaged with the fluid handling device and allow the fluid handling device to pick up sample vessels.

The sample vessel can be configured to engage with a fluid handling device. For example, the sample vessel can be configured to connect to a pipette or other fluid handling device. In some embodiments, a watertight seal can be formed between the sample vessel and the fluid handling device. The sample vessel can engage with the fluid handling device and be configured to receive a sample dispensed from the fluid handling device. The sample vessel can engage with the fluid handling device and allow the fluid handling device to pick up or aspirate a sample from the sample vessel.

The sample vessel can be configured to extend out of the centrifuge wings. In some embodiments, the centrifuge base can be configured to allow the sample vessel to extend out of the centrifuge wings when the wings are folded, and to allow the wings to pivot between a folded state and an extended state.

10 shows a non-limiting example of a centrifuge according to another embodiment of the present invention. The centrifuge may include a base 3700 having a bottom surface 3702 and/or a top surface 3704. The base may include one, two, or more buckets 3710a, 3710b.

The bucket can be configured to pivot about a bucket pivot axis extending through the base. In some embodiments, the axis can form a secant line through the base. The bucket can be configured to pivot about a rotation point 3720. The base can be configured to receive a drive mechanism. In one example, the drive mechanism can be a motor, such as a brushless motor. The drive mechanism can include a rotor 3730 and a stator 3735. The rotor can optionally be a brushless motor rotor, and the stator can optionally be a brushless motor stator. The drive mechanism can be any other mechanism that can cause the base to rotate and can be discussed in further detail elsewhere herein.

In some embodiments, multiple axes of rotation of the bucket can be provided through the base. The axes can be parallel to each other. Alternatively, some of the axes can be orthogonal to each other or at any other angle relative to each other. The bucket axis of rotation can extend through the lower surface of the base, the upper surface of the base, or between the lower and upper surfaces of the base. In some embodiments, the bucket axis of rotation can extend through the base closer to the lower surface of the base or closer to the upper surface of the base. In some embodiments, the rotation point can be 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 in the bucket. For example, the bucket may be configured to receive one, two, or more samples or sample vessels 3740. Each bucket may be capable of receiving the same number of vessels or a different number of vessels. The bucket may include cavities configured to receive sample vessels, wherein the sample vessels are oriented in a first orientation when the base is stationary and are configured to be oriented in a second orientation when the base is rotated.

In some embodiments, the bucket can be configured to be angled relative to the base. For example, the bucket can be between 0 and 90 degrees from the base. For example, the bucket can be oriented vertically when the base is stationary. The bucket can be positioned upwardly over the top surface of the centrifuge base when the base is stationary. When the base is stationary, at least a portion of the sample vessel can extend beyond the top surface of the base. The wings can be 90 degrees to the center portion of the base when oriented vertically. When the base rotates, the bucket can be oriented horizontally. When oriented horizontally, the bucket can be 0 degrees to the base. When the base rotates, the bucket can retract into the base, thereby forming a substantially uninterrupted top surface and/or bottom surface. For example, when the base rotates, the bucket can retract, thereby forming a substantially continuous surface of the bottom surface and/or top surface of the base. The bucket can be configured to pivot upward relative to the base. The bucket can be configured so that at least a portion of the bucket can pivot upward over the top surface of the base.

The bucket's point of rotation may include one or more pivot pins. The pivot pins may extend through the bucket and the base. In some embodiments, the bucket may be positioned between portions of the base that prevent the bucket from sliding laterally relative to the base.

The bucket can have a center of mass 3750 that is positioned below the rotation point 3720. When the base is stationary, the center of mass of the bucket can be positioned below the rotation point. When the base is rotating, the center of mass of the bucket can be positioned below the rotation point.

The bucket may be formed from two or more different materials with different densities. Alternatively, the bucket may be formed from a single material. In one example, the bucket may have a main body 3715 and an internal insert 3717. In some embodiments, the main body may be formed from a material with a lower density than the insert. For example, the main body may be formed from plastic, while the insert may be formed from a metal, such as tungsten, steel, aluminum, copper, brass, iron, gold, silver, titanium, or any combination or alloy thereof. The heavier insert may help position the bucket's center of mass below the rotation point. The bucket material may include a higher density material and a lower density material, with the higher density material positioned below the rotation point. The bucket's center of mass may be positioned such that when the centrifuge is stationary, the bucket naturally swings, with the open end facing upward and the heavier end facing downward. The bucket's center of mass may be positioned such that when the centrifuge is rotating at a certain speed, the bucket naturally retracts. The bucket may retract when the speed reaches a predetermined speed, which may include any speed or any speed mentioned elsewhere.

One or more cavities may be provided within the bucket. In some embodiments, the cavity may be configured to accommodate multiple sample vessel configurations. The cavity may have an inner surface. At least a portion of the inner surface may contact the sample vessel. In one example, the cavity may have one or more shelves or inner surface features that allow a first sample vessel having a first configuration to fit within the cavity and a second sample vessel having a second configuration to fit within the cavity. The first sample vessel and the second sample vessel having different configurations may contact different portions of the inner surface of the cavity. Although the embodiments in Figures 9-11 show centrifuge vessels having a high aspect ratio in height to width, it will be understood that embodiments in which the height is equal to or less than the width may also be used in alternative embodiments.

As previously mentioned, a centrifuge can be configured to interface with a fluid handling device. For example, a centrifuge can be configured to connect to a pipette or other fluid handling device. A centrifuge can be configured to receive a sample dispensed by a fluid handling device, or to provide a sample to be aspirated by a fluid handling device. A centrifuge can be configured to receive or provide a sample vessel.

As previously mentioned, the sample vessel can be configured to engage with a fluid handling device. For example, the sample vessel can be configured to connect to a pipette or other fluid handling device.

The sample vessel can be configured to extend out of the bucket. In some embodiments, the centrifuge base can be configured to allow the sample vessel to extend out of the bucket when the bucket is provided in a retracted state, and to allow the bucket to pivot between the retracted state and the protruding state. The sample vessel extending out of the top surface of the centrifuge can allow for easier transfer of samples or sample vessels to and/or from the centrifuge. In some embodiments, the bucket can be configured to retract into the rotor, thereby creating a compact assembly and reducing drag during operation, and having additional benefits such as reduced noise and heat generation and requiring lower power.

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

In some embodiments, the ball bearings can be placed in sealed/enclosed tracks within the rotor. This configuration is useful for dynamically balancing centrifuge rotors, particularly when simultaneously centrifuging samples of varying volumes. In some embodiments, the ball bearings can be external to the motor, making the overall system more robust and compact.

The passage can surround the centrifuge base. In some embodiments, the passage can surround the base along the circumference of the centrifuge base. In some embodiments, the passage can be at or closer to the upper surface of the centrifuge base or the lower surface of the centrifuge base. In some cases, the passage can be equidistant for the upper surface and lower surface of the centrifuge base. The ball bearing can slide along the circumference of the centrifuge base. In some embodiments, the passage can surround the base at a distance from the axis of rotation. The passage can form a circle, wherein the axis of rotation is at the basic center of the circle.

Figure 11 illustrates an additional non-limiting example of a centrifuge provided according to another embodiment of the present invention. The centrifuge may include a base 3800 having a bottom surface 3802 and/or a top surface 3804. The base may include one, two, or more buckets 3810a, 3810b. The bucket may be connected to a module frame 3820, which may be connected to the base. Alternatively, the bucket may be directly connected to the base. The bucket may also be attached to a counterweight 3830.

The module frame may be connected to the base. The module frame may be connected to the base at a boundary, which boundary may form a continuous or substantially continuous surface with the base. Portions of the top, bottom, and/or side surfaces of the base may form a continuous or substantially continuous surface with the module frame.

The bucket can be configured to pivot about a bucket pivot that extends through the base and/or module frame. In some embodiments, the shaft can form a secant through the base. The bucket can be configured to pivot about the bucket pivot 3840. The base can be configured to receive a drive mechanism. In one example, the drive mechanism can be a motor, such as a brushless motor. The drive mechanism can include a rotor 3850 and a stator 3855. In some embodiments, the rotor can be a brushless motor rotor, and the stator can be a brushless motor stator. The drive mechanism can be any other mechanism that can cause the base to rotate and can be discussed in further detail elsewhere herein.

In some embodiments, multiple rotation axes of the bucket may be provided through the base. The axes may be parallel to each other. Alternatively, some of the axes may be orthogonal to each other or at any other angle relative to each other. The bucket rotation axis may extend through the lower surface of the base, the upper surface of the base, or between the lower and upper surfaces of the base. In some embodiments, the bucket rotation axis may extend through the base closer to the lower surface of the base or closer to the upper surface of the base. In some embodiments, the bucket pivot may be at or closer to the lower surface of the base or the upper surface of the base. The bucket pivot may be at or closer to the lower surface of the module frame or the upper surface of the module frame.

One, two, three, four, or more cavities may be provided in the bucket. For example, the bucket may be configured to receive one, two, or more samples or sample vessels. Each bucket may be capable of receiving the same number of vessels or a different number of vessels. The bucket may include cavities configured to receive sample vessels, wherein the sample vessels are oriented in a first orientation when the base is stationary and are configured to be oriented in a second orientation when the base is rotated.

In some embodiments, the bucket can be configured to be angled relative to the base. For example, the bucket can be between 0 and 90 degrees from the base. For example, the bucket can be oriented vertically when the base is stationary. The bucket can be positioned upwardly over the top surface of the centrifuge base when the base is stationary. When the base is stationary, at least a portion of the sample vessel can extend beyond the top surface of the base. The wings can be 90 degrees to the center portion of the base when oriented vertically. When the base rotates, the bucket can be oriented horizontally. When the base is oriented horizontally, the bucket can be 0 degrees to the base. When the base rotates, the bucket can retract into the base and/or frame module, thereby forming a substantially uninterrupted top surface and/or bottom surface. For example, when the base rotates, the bucket can retract, thereby forming a substantially continuous surface with the bottom surface and/or top surface of the base and/or frame module. The bucket can be configured to pivot upward relative to the base and/or frame module. The bucket may be configured such that at least a portion of the bucket may be pivoted upwardly over a top surface of the base and/or frame module.

The bucket can be locked in multiple positions to support the unloading and picking up of centrifuge tubes, as well as to draw and distribute liquids into and out of the centrifuge vessel when the centrifuge vessel is in the centrifuge bucket. One technology to achieve this is one or more motors that drive a rotor in contact with the centrifuge rotor to finely position and/or lock the rotor. Another method can be to use a cam (CAM) shape formed on the rotor without the need for an additional motor or rotor. An accessory from a pipette, such as a centrifuge tip attached to a pipette nozzle, can press down on the cam shape on the rotor. This force on the cam surface can cause the rotor to rotate to the desired locking position. The continuous application of this force can enable the rotor to be firmly held in the desired position. Multiple such cam shapes can be added to the rotor to support multiple locking positions. When the rotor is held by one pipette nozzle/tip, another pipette nozzle/tip can be connected to the centrifuge bucket to unload or pick up the centrifuge vessel or perform other functions, such as drawing or distributing the centrifuge vessel from the centrifuge bucket. It should be understood that this cam feature may be adapted for use with any of the embodiments mentioned in this disclosure.

The bucket pivot may include one or more pivot pins. The pivot pins may extend through the bucket and the base and/or frame module. In some embodiments, the bucket may be positioned between portions of the base and/or frame module that prevent the bucket from sliding laterally relative to the base.

The bucket can be attached to a counterweight. The counterweight can be configured to move when the base begins to rotate, thereby causing the bucket to pivot, typically from a completely vertical position to a non-vertical position for use during centrifugation. When the base begins to rotate, the counterweight can be caused to move by the centrifugal force applied to the counterweight. The counterweight can be configured to move away from the axis of rotation when the base begins to rotate at a threshold speed. In some embodiments, the counterweight can move in a linear direction or path. Alternatively, the counterweight can move along a curved path or any other path. The bucket can be attached to the counterweight at a counterweight pivot point 3860. One or more pivot pins or protrusions can be used that allow the bucket to rotate relative to the counterweight. In some embodiments, the counterweight can move along a horizontal linear path, causing the bucket to pivot up or down. The counterweight can move in a linear direction orthogonal to the centrifuge's axis of rotation. This means that the bucket does not extend outward below the bottom surface of the centrifuge rotor. In some embodiments, this allows the overall height of the centrifuge design to be reduced when the device is in operation.

It will also be appreciated that the force required to move the bucket from the rest configuration to the operating configuration is selected so that there is sufficient centrifugal force so that any sample within the centrifuge vessel does not spill or be expelled from the vessel when the bucket changes orientation. Typically, the centrifuge vessel may be an open-top vessel that is not sealed and thus cannot contain spillage from a vessel that is oriented in the wrong direction.

The counterweight can be positioned between portions of the module frame and/or base. The module frame and/or base can be configured to prevent the counterweight from sliding out of the base. The module and/or base can restrict the path of the counterweight. The path of the counterweight can be constrained to a straight line. One or more guide pins 3870 can be provided to restrict the path of the counterweight. In some embodiments, the guide pins can extend through the frame module and/or base as well as the counterweight.

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

One or more cavities can be provided within the bucket. In some embodiments, the cavity can be configured to accommodate multiple sample vessel configurations. The cavity can have an inner surface. At least a portion of the inner surface can contact the sample vessel. In one example, the cavity can have one or more shelves or inner surface features that can allow a first sample vessel having a first configuration to fit within the cavity and a second sample vessel having a second configuration to fit within the cavity. The first sample vessel and the second sample vessel having different configurations can contact different portions of the inner surface of the cavity.

As previously mentioned, a centrifuge can be configured to interface with a fluid handling device. For example, a centrifuge can be configured to connect to a pipette or other fluid handling device. A centrifuge can be configured to receive a sample dispensed by a fluid handling device, or to provide a sample to be aspirated by a fluid handling device. A centrifuge can be configured to receive or provide a sample vessel.

As previously mentioned, the sample vessel can be configured to engage with a fluid handling device. For example, the sample vessel can be configured to connect to a pipette or other fluid handling device.

The sample vessel can be configured to extend beyond the bucket. In some embodiments, the centrifuge base and/or module frame can be configured to allow the sample vessel to extend beyond the bucket when the bucket is provided in a retracted state, and to allow the bucket to pivot between the retracted state and the protruding state. The sample vessel extending beyond the top surface of the centrifuge can allow for easier transfer of samples or sample vessels to and/or from the centrifuge.

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

The passage can surround the centrifuge base. In some embodiments, the passage can surround the base along the circumference of the centrifuge base. In some embodiments, the passage can be at or closer to the upper surface of the centrifuge base or the lower surface of the centrifuge base. In some cases, the passage can be equidistant for the upper surface and lower surface of the centrifuge base. The ball bearing can slide along the circumference of the centrifuge base. In some embodiments, the passage can surround the base at a distance from the axis of rotation. The passage can form a circle, wherein the axis of rotation is at the basic center of the circle.

Other examples of centrifuge configurations known in the art can be used, including various swinging bucket configurations. See, for example, U.S. Patent No. 7,422,554, which is hereby incorporated by reference in its entirety for all purposes. For example, the bucket can swing downward instead of upward. The bucket can swing to the side instead of projecting upward or downward.

The centrifuge can be enclosed in a housing or shell. In some embodiments, the centrifuge can be fully enclosed in the housing. Alternatively, the centrifuge can have one or more open sections. The housing can include a removable portion that allows fluid handling equipment or other automated equipment to approach the centrifuge. Fluid handling equipment and/or other automated equipment can provide a sample, take a sample, provide a sample vessel, or take a sample vessel in the centrifuge. Such access can be permitted at the top, side, and/or bottom of the centrifuge.

The sample can be dispensed and/or picked up from the cavity. The sample can be dispensed and/or picked up using a fluid handling system. The fluid handling system can be a pipette as described elsewhere herein, or any other fluid handling system known in the art. The sample can be dispensed and/or picked up using a tip having any of the configurations described elsewhere herein. The dispensing and/or aspiration of the sample can be automated.

In some embodiments, the sample vessel can be provided to the centrifuge or removed from the centrifuge. The sample vessel can be inserted into the centrifuge or removed from the centrifuge using equipment in an automated process. The sample vessel can extend from the surface of the centrifuge, which can simplify automated picking and/or retrieval. The sample may have been provided in the sample vessel. Alternatively, the sample can be distributed and/or picked up from the sample vessel. The sample can be distributed and/or picked up from the sample vessel using a fluid handling system.

In some embodiments, a tip from a fluid handling system may be at least partially inserted into a sample vessel and/or cavity. The tip may be insertable and removable from the sample vessel and/or cavity. In some embodiments, the sample vessel and tip may be a centrifugal vessel and centrifugal tip as previously described, or may have any other vessel or tip configuration. In some embodiments, a container may be placed in a centrifuge rotor. This configuration may provide certain advantages compared to conventional tips and/or vessels. In some embodiments, a container may be patterned with one or more channels having a specialized geometry so that the products of the centrifugal process are automatically separated into separate compartments. One such embodiment may be a container with a tapered channel that terminates in a compartment separated by a narrow opening. Supernatant (e.g., plasma from blood) may be forced into the compartment by centrifugal force, while red blood cells remain in the main channel. The container may be more complex, having several channels and/or compartments. The channels may be isolated or connected.

In some embodiments, one or more cameras can be placed in the centrifuge rotor so that it can image the contents of the centrifuge vessel as the rotor rotates. The camera image can be analyzed and/or transmitted in real time, for example, by using a wireless communication method. This method can be used to track sedimentation rate/cell accumulation - such as for ESR (erythrocyte sedimentation rate) determination, in which the sedimentation speed of RBC (red blood cells) is measured. In some embodiments, one or more cameras can be positioned outside the rotor, and the camera can image the contents of the centrifuge vessel as the rotor rotates. This can be achieved by using a stroboscopic illumination source that is synchronized with the camera and the rotating rotor. Real-time imaging of the contents of the centrifuge vessel as the rotor rotates allows the rotor to be stopped after the centrifugation process is completed, thereby saving time and potentially preventing excessive accumulation and/or excessive separation of the contents.

As shown in Figure 12, some embodiments can include window or opening 3825 on the centrifugal vessel holder to allow observation of the sample contained therein. This may relate to a camera or other detector, which can visualize the sample in the vessel by window or opening 3825. Alternatively, some embodiments can provide window or opening 3825 to allow an illumination source to radiate onto the sample being processed. Some embodiments can include detectors such as cameras in the centrifuge, such as but not limited to the detector integrated into the centrifuge rotor, to image the sample therein. This can be useful, because if the camera is in the reference frame identical with the sample, the movement of any blood component in the sample can be more easily visualized. Of course, it is not excluded that detectors such as but not limited to cameras are in the embodiment of the reference frame different from the sample being moved. Non-visual detectors are not excluded yet, as long as they detect the movement of the blood component in the vessel.

In some embodiments, the present invention can further comprise a window or opening 3827 having the same size as window or opening 3825 or a different size. When the centrifuge vessel is maintained in the centrifuge, this window or opening 3827 allows the sample fluid in the vessel to be illuminated. Alternatively, some embodiments can use the same opening for both illumination and observation. Some embodiments have the visualization through a window or opening and the illumination through another group of windows or openings that may or may not be relative to the first group of windows or openings. For any embodiment herein, it should be understood that the window or opening can comprise the optically transparent material covering such a window or opening.

Thermal Control

Centrifugation can sometimes cause undesirable changes in sample temperature due, at least in part, to the heat generated by the centrifugation operation. One source of heat during centrifugation is waste heat from the centrifuge's drive motor and/or drive mechanism. This waste heat can be particularly problematic if several samples are processed sequentially in the same centrifuge, and the heat from each operation accumulates over that time period, potentially raising the sample temperature beyond an acceptable range.

To prevent such waste heat or other sources of thermal energy from undesirably changing the sample temperature, efforts may be made to insulate, actively cool, and/or configure the system to direct the undesirable thermal energy away from the sample.

In one embodiment, because motor can be integrated in the centrifuge, so such integration can benefit from the effort in order to solve the heat dissipation problem relevant to motor, centrifuge rotor, bucket, vessel and/or sample.The method for solving this type of heat dissipation problem can comprise and carry out one or more of the following simultaneously or sequentially: cooling, thermal isolation and/or maintenance cooling.Some embodiments may relate to the active technology of processing heat dissipation problem.Some embodiments may relate to passive technology, such as but not limited to the centrifuge component thermal isolation that will be connected to the heat source associated with centrifuge.

Some embodiments can use heat-conducting materials such as, but not limited to, thermal tape to change the heat transfer curve of centrifuge.In a non-limiting example, the tape can be configured to guide heat away from the heat-sensitive area that will have a thermal impact on the sample on the centrifuge. The thermal tape is designed to provide a preferential heat transfer path between the heating component and the radiator or other cooling device (for example, fan, heat spreader, etc.). The thermal tape can be a viscous pressure-sensitive adhesive loaded with a thermally conductive ceramic filter, and the filter does not need a thermal curing cycle to form a combination to many substrates. This can be used alone or in combination with any other thermal solution described herein.

Some embodiments can use active coolers such as but not limited to Peltier (Peltier) heater/cooler to cool one or more of the sample and/or the aforementioned centrifuge assembly. Active cooler can directly contact with the target surface being cooled. Some embodiments can attach active radiator or Peltier heater/cooler to a bucket or a holder that holds a centrifugal vessel. Alternatively, active cooler can be close to the target surface but not in direct contact with it. For example, active radiator or Peltier heater/cooler can be attached to a centrifuge housing, and this centrifuge housing and the centrifuge keep the part of sample close.

Some embodiments may include structures located outside the centrifuge housing to assist in convection cooling. Some embodiments may involve adding fins or air moving structures to the centrifuge rotor and/or other moving parts of the centrifuge. Some embodiments may attach fins or air moving structures to a stationary portion of the housing near the rotor. Such fins may be used to radiate any excess heat and/or to assist in convection.

As seen in Figure 12, some embodiments can use non-thermal conductive materials to change the heat transfer curve. In an effort to insulate the sample from (one or more) heat sources, some embodiments can change some metal materials to plastic materials or other solid materials with low thermal conductivity. Some embodiments can isolate the sample from foam or other types of insulating materials to prevent undesirable heat transfer. Some embodiments can have a centrifuge rotor that is entirely made of low thermal conductivity material. Some embodiments can only have parts of the centrifuge rotor made of low thermal conductivity material. As seen in Figure 12, some embodiments can only replace selected parts with thermal insulation materials, such as but not limited to replacing frame portion 3820.

13A , some embodiments may use one or more external cooling devices 400, such as fans or air conditioning sources, to minimize sample heating during centrifugation using convection of cooled or uncooled air or gas. As shown in FIG13A , some embodiments may use more than one cooling device 400 at different locations and/or orientations relative to the centrifuge housing 402 to direct convection flow on the centrifuge.

In addition, as seen in Figure 13A, some embodiments can have an active thermal device 410, such as but not limited to a Peltier effect radiator, attached to one or more components of the centrifuge system (such as, but not limited to, the centrifuge housing 402). Figure 13A shows that the stationary housing 402 can have an active thermal device 410, such as a Peltier effect radiator 410, positioned at one or more locations on the housing 402. Some embodiments can replace the Peltier effect radiator 410 or use conventional passive radiators in combination therewith. By way of example and not limitation, some positions indicating that there are active thermal devices 410 in Figure 13A can have those units replaced or enhanced by passive radiators.

In one embodiment, a Peltier effect heat sink can use electricity to achieve extremely low temperatures. One embodiment can connect the Peltier effect heat sink to the motor circuit with a wire. Of course, other configurations for powering the heat sink are not excluded. Because the opposite side of the heat sink is heated during operation, it is desirable to position the heat sink near a duct, vent, heat spreader, heat radiating fins, heat radiating pins, or other elements for absorbing excess heat from the cooling side of the heat sink. Some embodiments can use a thermally conductive motor mount to absorb heat away from internal components. One such embodiment can include a fan with aluminum stator blades brazed to an aluminum motor mount. The motor can fit tightly with the housing and be coated with a "heat transfer compound" to provide a preferred thermal path for directing heat away from the motor. This will improve the heat transfer from the motor to the cooling fins.

Although Figure 13A shows that the thermal regulation element can be placed on the housing or other non-moving part of the centrifuge system, it should be understood that similar (one or more) active thermal devices or passive thermal devices can also be installed on the internal components and/or moving components of the centrifuge system. For non-limiting example, Figure 13B shows that the motor, centrifuge rotor 404, bucket, vessel and/or surface in contact with the sample can also be configured to be under the thermal control of (one or more) devices 410. Figure 13B shows that the active thermal device 410 can be located on the circumferential side surface of the centrifuge rotor 404. Alternatively, the active thermal device 410 can be located on the top surface of the centrifuge rotor 404. Alternatively, the active thermal device 410 can be located on the lower surface of the centrifuge rotor 404. Alternatively, the active thermal device 410 can be located on the shield, housing or end shield of the rotor 412. By way of example and not limitation, some positions indicated in Figure 13B with active thermal devices 410 can have those units replaced or enhanced by passive radiators.

With reference now to Figures 14A-14B, some embodiments may involve venting the housing around the centrifuge rotor to improve convective airflow. This may involve placing holes, cutouts, or shaped openings in the housing and/or the centrifuge rotor to allow air flow. A vent 450 may be formed in a housing 452 surrounding a portion of the centrifuge motor. The size and/or position of the vent 450 may be set to allow greater convective cooling of the motor elements of the centrifuge. In this non-limiting example, the size of the larger opening 454 is set to accommodate an encoder ring reader. It should be understood that, in addition to (one or more vents), the embodiments in Figures 14A-14B may also include any one of the active thermal elements or passive thermal elements described in Figures 13A-13B. Based on the position information provided by the various configurations described in this disclosure, some embodiments of the centrifuge may be configured to drive and/or brake the centrifuge so that the centrifuge stops at a specific position specified by a user and/or device (such as, but not limited to, a programmable processor).

Figure 15 shows another embodiment, wherein vent 460 can be formed in the housing 462 near the centrifuge rotor or even be formed within the centrifuge rotor itself.The vent 460 in this embodiment can be positioned to be positioned at below the rotating part of the centrifuge rotor (for ease of illustration and not shown).Other embodiments can have the vent 460 of larger or smaller number.Other embodiments can have the vent 460 of other shapes, described other shapes such as but not limited to square, rectangle, ellipse, triangle, trapezoid, parallelogram, pentagon, hexagon, octagon, any other shape or the single combination or multiple combinations of aforementioned shapes.Some embodiments can have a plurality of vents 460, and these vents all have the same shape.The vent 460 that some embodiments have can have at least one shape that is different from the vent of the shape of at least another vent 460.

Referring now to Figures 16A-16D, yet other embodiments can position the thermal control element 500 on the rotating and/or non-rotating components of the centrifuge to support greater convective heat transfer. Figure 16A shows a thermal control element 500 in the shape of an airfoil on the outer radial surface of the centrifuge housing 501. The airfoil can have a planar configuration. Alternatively, some embodiments of the thermal control element 500 can be a projection in the shape of a sheath 502. Some embodiments can incorporate one or more of these structural features. These structural features can be used as passive thermal control devices or active thermal control devices.

In some embodiments, the cross-sectional shape of the fins can be circular, crescent-shaped, teardrop-shaped, square, rectangular, triangular, polygonal, or any other shape. The cross-sectional shape of the fins can be the same or different along the longitudinal length of the fins. For example, in some embodiments, the fins can have a generally cylindrical shape; in other embodiments, the fins can have a pyramidal (including truncated pyramidal) or cone (including truncated cone) shape. In still other embodiments, the surface of the fins (e.g., sheath-fins) can be curved along the longitudinal length of the fins. Non-limiting examples of the surface profile of a curved fin (e.g., sheath-fin) include a hyperbola, a quadratic curve, a polynomial curve with an order higher than two, an arc, or a combination thereof. In some embodiments, the fins are solid structures, while in other embodiments, the fins can be hollow. In some embodiments, the fins can be partially hollow and partially solid. Hollow fins can allow for efficient heat transfer while further reducing the amount of material required to make the heat sink, thereby further reducing production costs. Alternatively or additionally, the pattern formed by the fins can be interrupted by channels along the perimeter of the heat sink to provide additional openings to the interior of the heat sink and increase airflow to the internal fins. The resulting channels can have any pattern, such as a commonly used cross-rasp, herringbone, or wavy pattern. In some embodiments, the fins can be coupled together at their bases (or other connection areas) to form a connected network of fins, such as, but not limited to, multiple columns or rows. Some fins can be connected to form a permeable network of connected fins.

Figure 16 B shows an embodiment with fins 510 on the inner radial portion of the centrifuge. Figure 16 C shows fins 520 on the downside of the centrifuge rotor. Figure 16 D shows a further embodiment in which the fins 530 on the circumferential portion of the rotor can be optionally shaped and/or directed for use with a shaped housing 540 so that air is drawn into the housing, thereby helping to cool the components therein when the centrifuge rotor rotates. Of course, some embodiments can combine one, two, three or all of the above-mentioned components with other cooling elements to maximize the cooling potential of the system. The embodiments in Figures 16 B-16 D can have various thermal control devices that are coupled to the moving part or stationary part of the centrifuge.

In yet another embodiment, an internal fan-cooled electric motor (in layman's terms, a fan-cooled motor) can be used as a self-cooling electric motor. In one embodiment, a fan-cooled motor features an axial fan attached to the motor rotor (typically on the opposite end from the output shaft) that rotates with the motor to provide increased airflow to the internal and external components of the motor to aid in cooling.

In another embodiment, water cooling can be used to cool the housing of the motor. In one non-limiting example, a small centrifugal pump can be built outside the shaft with a reservoir of pre-cooled water that circulates around the motor housing. Other active liquid cooling techniques or passive liquid cooling techniques can also be used. These techniques can be used to cool a portion of the motor housing. Some embodiments can be used to cool only the side walls of the motor housing. Some embodiments can cool the entire housing. Some embodiments can cool only the end portion(s) of the housing, such as but not limited to the portion with the closest access to the sample.

In further embodiments, significantly reducing the winding resistance can be used to reduce the heat generated by the motor. This may involve using a motor with fewer windings to improve motor performance and, in turn, reduce the heat output from the motor itself. It is also possible to change the number of poles and magnets to improve motor performance. In this way, the motor assembly can be selected to reduce heat dissipation issues, such as by using a motor with lower heat output for normal operating conditions of a centrifuge.

Centrifuge position control

With reference now to Figure 17A-Figure 17D, the improvement to the position control system of centrifuge rotor will now be described.In one embodiment, can use various encoder discs or structures such as but not limited to encoder ring 600 to more accurately control and/or detect the position of centrifuge rotor 604, and programmable processor can calculate where the fixture on centrifuge rotor 6604 is positioned based on this position.In such embodiment, accurate information relevant to the position of centrifuge rotor 604 will allow pipette or sample handling system to accurately engage such vessel when centrifuge vessel is removed from centrifuge without using "parking" system, so that it is always positioned at a specific position when centrifuge rotor 604 stops.

Figure 17 A shows an embodiment of an encoder ring 600 used together with a detector 602 for reading encoder position. The encoder ring 600 will rotate together with the centrifuge rotor 604 so that the encoder ring 600 will provide position information of the centrifuge rotor 604 and any features thereon. In one embodiment, the encoder ring 600 can have a pattern thereon and be configured to be used together with the optical detector 602. In one embodiment, the ring 600 can be made of glass or plastic, with a transparent area and an opaque area. Some embodiments can use a reflective pattern on the ring 600. The encoder ring 600 can be configured to detect each different angle of the encoder ring. The ring 600 can be an absolute encoder or an incremental encoder.

Figure 17 B shows another embodiment, and wherein encoder ring 610 is integrated as the part for centrifuge rotor 604, such as being integrated along the circumference of the rotor.Detector 612 is directed for use with integrated encoder ring 610.This detector can be used individually or in combination with other position detection systems.Alternatively, some embodiments can use a system for high-accuracy position sensing, and use another system for high-speed rate sensing.Encoder ring 610 can also reduce overall centrifuge height from the movement below centrifuge rotor 604, and this is because detector 612 and encoder ring no longer take the vertical space below the centrifuge rotor 604.

In any embodiments herein, the centrifuge rotor 604 is hollow to allow components to be positioned within the rotor 604 during operation of the centrifuge. In one embodiment, the entire centrifuge vessel is contained within the outline of the centrifuge rotor when the centrifuge is in operation.

Figure 17 C shows a further embodiment, wherein in the process of manufacturing motor, motor 622 can be incorporated into encoder ring or device 620 in motor 622.Encoder 620 can be read by the detector in motor 622 or read by the detector positioned at motor 622 outside, to determine the shaft angle position of motor.Such integrated encoder and motor configuration can be used in centrifuge and be used in other system components such as pipette in sample handling system of accurate position control that is little and expecting because of motor form factor.By way of example and not limitation, incremental encoder can be used on induction motor type servomotor, and absolute encoder can be used in permanent magnet brushless motor.In one embodiment, housing 628 (shown with dotted lines) can be used for the encoder part of enclosing motor.

Figure 17 D shows another embodiment, wherein uses other encoder technologies such as but not limited to conductive coding and/or magnetic encoding to replace other encoder technologies such as but not limited to optical encoders or detect rotor position together with it.(one or more) magnetic encoder readers 650 and/or 652 can be positioned at various locations to detect centrifuge rotor position. Other position detection technologies can be used to replace encoder technology described herein or be used in combination with it. In some embodiments as described herein, these capabilities can be integrated into the equipment.

In some embodiments, the centrifuge can be controlled by a plurality of sensors. Alternatively, some embodiments can use a separate sensor for speed and position. Some embodiments can use the same sensor for the two. By way of example and not limitation, the embodiment with more than a sensor can be configured to have a sensor for fine position control and a sensor for speed control. In this way, higher centrifuge speed can be realized without the need to by means of more complicated sensor, such as but not limited to 40000rpm, because each type can be optimized for its specific purpose, such as high-accuracy position control during low speed and speed control during high speed. A programmable processor can be used to determine when to transform the control based on a sensor or another sensor to the centrifuge rotation. Alternatively, data from two types of sensors can be used during all time domains to provide accurate position and speed control.

Should be understood that, in the system that can not carry out accurate control, the system using the stopper can be used to ensure the final static position (it is known) of the centrifuge rotor.Other embodiments can use alignment guide rails, sheaths, cams and/or other mechanisms to move the centrifuge rotor to a known position so that the sample processing system can accurately engage the centrifuge vessels on the rotor.According to the understanding that the centrifuge has stopped where, the pipette can be transferred to the vessel.Some embodiments of the centrifuge also can have guide rails, to guide the pipette to the desired position or use the pipette to move it to the correct position before the centrifuge rotor engages any sample containing vessel installed on the centrifuge.

As shown in Figures 17A-17D, the centerpiece of the centrifuge can have a single bearing, optionally with two bearings that are pressed 660 together, to improve stability during rotation and especially for improving bearing life. As shown in Figures 17A-17D, multiple bearings can be positioned to distribute the load more evenly than when using only a single bearing. Of course, other numbers and/or types of bearings are not excluded.

In some embodiments described herein, it will be appreciated that the motor may be enhanced with position and/or speed sensing capabilities integrated directly into the motor. In a non-limiting example, some embodiments may implement position and/or speed sensing by adding hardware. In one embodiment, rotational position and/or speed sensing may be configured for one or more rotating parts of the motor or a rotating element attached to the motor.

Possibilities for hardware integration with the motor include, but are not limited to, 1) (one or more) optical encoders (for position (relative and/or absolute) and/or speed sensing) and/or 2) (one or more) Hall effect sensors (for position (relative) and/or speed 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, the Hall effect sensor(s) can be used to detect the position of a permanent magnet in a brushless DC electric motor.

Some embodiments may combine multiple types of detector hardware, such as, but not limited to, both (one or more) Hall effect sensors and (one or more) optical encoders in the same motor. Alternatively, some embodiments may have multiple sensors of the same type in a motor. Of course, other types of position and/or speed detection hardware are not excluded from the embodiments herein or from use in combination with optical or magnetic encoders.

For non-limiting example, at least some embodiments of the sensors and/or encoders herein can be performed at speeds of up to 12,000 RPM (at least 1,800 counts per revolution) for position sensing. Alternatively, at least some embodiments of the sensors and/or encoders herein can be performed at speeds of up to 10,000 RPM (at least 1,600 counts per revolution) for position sensing. In one embodiment, the encoder has an index that is constantly aligned with the motor assembly in each centrifuge for absolute positioning. Some embodiments may use absolute encoders, such as, but not limited to, multi-bit Gray code encoders and/or single-track Gray encoders, to obtain absolute position. Some embodiments may use sinusoidal wave encoders. Encoder technology may include, but is not limited to, conductive tracks, optical tracks (including reflective versions), and magnetically encoded tracks sensed by Hall effect sensors or magnetoresistive sensors.

In either configuration (sensor or encoder), at least some embodiments herein may be configured such that the overall height (excluding the output shaft) is at or below 13 mm, while the diameter will remain below 35 mm. Optionally, some embodiments may have an overall height of approximately 10 mm or less and a diameter of 30 mm or less. In some embodiments, the hardware is designed such that the integration of position sensing hardware and/or speed sensing hardware does not change the external motor housing size relative to the same motor without the sensing hardware. Optionally, the Hall effect sensor(s) may be mounted in the stator slot(s) of the motor to minimize the size change.

Alternatively, some alternative embodiments may use firmware and/or software that detects the position and/or speed of the rotor without 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 herein may be used in combination for position and/or speed sensing.

Referring now to FIG17E , another embodiment of a centrifuge having a magnetic sensor is shown, such as, but not limited to, a Hall effect sensor assembly 630 that can be integrated directly into the motor assembly or located external to the motor but as part of the centrifuge assembly. FIG17E shows an exploded view showing a Hall effect detector 632 and an encoder portion 634. Arrow 636 indicates that the assembly 630 can be inserted into the centrifuge housing in the direction shown. By way of non-limiting example, the assembly 630 is shown with three detectors 632, but it should be understood that other numbers of detectors can be used. The assembly 630 is also shown with all detectors in the same plane. It should be understood that some embodiments can have detectors located in different planes, including but not limited to detectors located above and below the Hall effect encoder portion 634. By way of non-limiting example, the encoder portion includes multiple magnets and/or multiple other magnetic field generating or interfering components that can be detected by the Hall effect detectors 632.

Referring now to FIG. 17F , a perspective view of one embodiment of a motor with integrated position and/or speed sensing is shown. For ease of illustration, some motor components are not shown in this embodiment to provide a clearer view of the encoder assembly used with the motor. This encoder embodiment can be used to detect shaft position and/or rotor position. In this non-limiting example, a detector 670 is used in conjunction with an encoder disk 672 and a Hall-effect encoder disk 674. Detector 670 can have a first surface for detecting optical encoder information and a second surface for detecting magnetic encoder information. In one non-limiting example, detector 670 can have a first surface 680 for detecting a first type of encoder information, such as, but not limited to, optical encoder information, and a second surface 682 for detecting a second type of encoder information, such as, but not limited to, magnetic encoder information. Optionally, some embodiments can have both the first and second types of encoder information be of the same type, such as, but not limited to, both optical or both magnetic. In such a configuration, the resolutions of the at least two encoder types can optionally differ, with one encoder type providing better low-speed resolution for position control and one encoder type providing better high-speed resolution for speed control. This may also be the case when different types of encoder information are used, such as one optical and one magnetic.Of course, embodiments using even more sensors 670 or more than two types of encoder information are not excluded.

Still referring to Figure 17F, a magnetic assembly 676 can be mounted in a disk 674. These components can all be configured to rotate with the motor shaft 678. The motor housing H can extend to cover all, some, or none of these encoder assemblies. Optionally, some embodiments may combine at least two encoder types onto a single rotating element, such as, but not limited to, an encoder disk. In one such configuration, a single disk on the shaft can include both a magnetic encoder assembly and an optical encoder assembly. By way of non-limiting example, the outer portion of the ring can have an area for the optical encoder while the inner portion has the magnetic assembly, or vice versa. Optionally, both are located on the same portion of the ring. Alternatively, one type of encoder type can be located on a planar surface while the other assembly is located on the side of the disk. Of course, embodiments using more than two types of encoder information on a single rotating assembly are not excluded. By way of example and not limitation, embodiments using a single detector 670 can also simplify manufacturing by having a single wiring harness attached to the detector 670, thereby simplifying wire management.

Figure 17 G shows another type of motor that can be configured to include one or more encoder assemblies disclosed herein. Some embodiments can use a rotor 640 and a stator 642 in the motor design. Alternatively, some embodiments can use a stator 644, a rotor 640 and a stator 642 for increased torque. Any embodiment in these embodiments can be configured to have the encoder assembly shown in this article. Some embodiments can directly attach or integrate encoder elements such as, but not limited to, optical encoder discs or magnetic encoder discs to the stator or rotor. It should be understood that the motor can be suitable for use with other encoder hardware or other encoder technologies. As seen in Figure 17G, the embodiment of this motor can be configured to be fitted in the motor housing inside shown in Figure 17 A-Figure 17E so that the centrifuge body rotates.

Automatic balancing

With reference now to Figure 18A, some embodiments herein can be configured to use the automatic balancing mechanism on the rotor to minimize rotor vibration, and not all fixtures contain samples. One embodiment can use automatic balancing elements 700 such as but not limited to microbeads, spheres or counterweights to automatically balance the centrifuge rotor, and this may be useful for compensating for the different sample volumes in different buckets. Some embodiments can be loaded into some centrifuge fixtures when there is no bucket. Automatic balancing element 700 can be in channel 710 (covered or uncovered) to allow the automatic balancing element to reach a steady-state position, which minimizes the rotational instability of the rotor during operation to the greatest extent possible. In some embodiments, some embodiments can have channels formed in certain discrete segments, rather than having channels continuous along the circumference, with the discrete segments having automatic balancing elements that will only stay in their specific discrete channel segments.

As shown in Figure 18B, some embodiments may include a fixed feature 720 that only releases the automatic balancing element 700 to move freely once the minimum rotational speed is reached and centrifugal force or other forces release the automatic balancing element so that it can move. When sufficient speed is reached, feature 720 may be moved as indicated by arrow 722. This movement releases the automatic balancing element 700 to move to a position that balances the load on the centrifuge. In this way, the automatic balancing element 700 is not able to move freely at a slower speed. This can help minimize noise and rotational instability that may be caused by the automatic balancing element 700 being able to easily roll to a non-optimal equilibrium position at a slower speed.

In one embodiment, the weight of the automatic balancing element 700 can be selected to be at least about half of the total maximum weight of all sample containers and samples that can be used with the centrifuge. In another embodiment, the weight of the automatic balancing element 700 can be selected to be at least about 40% of the total maximum weight of all sample containers and samples that can be used with the centrifuge. In yet another embodiment, the weight of the automatic balancing element 700 can be selected to be at least about 30% of the total maximum weight of all sample containers and samples that can be used with the centrifuge. Of course, other weights are not excluded.

18C , further embodiments may position the automatic balancing element 700 in a plurality of separate zones 730 on the rotating portion of the centrifuge. In one embodiment, the zones 730 may be connected to one another so that the automatic balancing element 700 can move between zones. Alternatively, some embodiments may isolate each of the zones 730 from one another so that the automatic balancing element 730 cannot move from one zone 730 to another.

Non-mechanical bearing(s)

In further embodiments, some systems may be configured to not have mechanical bearings but instead use non-mechanical bearings, such as, but not limited to, air bearings 720. Air bearings may generate less heat, which can reduce the time required for centrifugation. Alternatively, they may support longer centrifugation times without the heat losses that may be caused by the heat associated with mechanical bearings. Air bearings are available from suppliers such as, but not limited to, New Way Air Bearings of Aston, Pennsylvania, USA. Of course, some embodiments may combine the use of both air bearings and mechanical bearings in the same device.

19B shows another embodiment in which one air bearing is annular 722 and another air bearing 724 is configured to oppose the sidewall of the centrifuge rotor. By way of non-limiting example, the air bearing 724 can be shaped in a continuous or discontinuous manner to support the centrifuge rotor.

Fault detection sensor

Referring now to Figure 20, another embodiment of centrifuge equipment will now be described. Figure 20 is a cross-sectional perspective view illustrating a centrifuge rotor 800 such as, but not limited to, a centrifuge disc, which rotates as indicated by arrow 802 in a non-rotating housing 804. The centrifuge may include a detector 810, such as, but not limited to, an accelerometer installed on the centrifuge, to detect unexpected force changes during the operation of the centrifuge. In one embodiment, the detector 810 is installed to the outside of the centrifuge housing to detect whether an error occurs. The detector 810 may be used to detect an early indication of the abnormal instability in the operation of the centrifuge. If these signs of instability are detected in the abnormal rate of change of the force experienced by the centrifuge, the centrifuge may select to slow down or stop operation before catastrophic equipment failure, such as by a programmable processor. Some embodiments may trigger other actions, such as alarms or warnings, based on the detection of the rate of change or force outside the threshold range.

Figure 20 also shows other features discussed herein, incorporated into this embodiment. For example, and not limitation, air bearings 722 and/or 724 can be incorporated into this embodiment of the device for use together. (One or more) vibration dampers 816 can also be used to isolate the vibration from the centrifuge to avoid being transferred to other elements outside the centrifuge housing. Figure 20 also shows that thermal insulation areas 820, 822 and/or 824 can be used to minimize the heat transfer from the motor 830 to the other parts of the centrifuge rotor.

Should be understood that the embodiment among Figure 20 can be configured for described any rotor and/or vessel holder configuration, and described configuration includes but is not limited to those configurations shown in Figure 1 to Figure 12.The vessel holder that some embodiments have can extend to the upper plane of this rotor or above the surface when centrifuge rotor is stationary for the most part.Alternatively, some embodiments can have the vessel holder that extends to the plane of this rotor or below the surface when centrifuge rotor is stationary.For those embodiments in which the vessel holder extends to the plane of centrifuge rotor or below the surface, housing 804 can be configured to have shaping cutout to allow clearance when vessel holder and/or vessel rotate in the downwardly extending position.Alternatively, some embodiments can install rotor 800 higher and/or whole motor higher, to provide enough clearance for vessel holder and/or vessel when they rotate in the downwardly extending position.

By way of non-limiting example, the centrifuge can have a footprint of approximately 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 can have one or more dimensions (e.g., width, length, height) of 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 embodiment in FIG. 20 also illustrates a rotor/stator configuration where, for at least some embodiments herein, the stator is coaxially mounted within the rotor, where the rotor includes centrifuge disks connected to or integrally formed with the rotor of the motor.

Figure 20 also shows that, for at least some embodiments herein, a housing 804 that is molded to at least the circumference of the centrifuge disc of the enclosed rotor 800 can provide a controlled area in which the centrifuge disc can rotate. The rotating parts in this embodiment can include the centrifuge disc of the encoder wheel 600, the rotor 800, and the rotor portion of the motor. In some embodiments, the housing 804 can serve as an end shield to keep the vibratory motion of the motor within the housing, because a damper 816 can be mounted to the housing 804 to provide isolation therein. There can be bearings 830 and 832 that can mount the rotating part thereon. Alternatively, some embodiments can be configured to use only a single bearing. Alternatively, some embodiments can be configured to use multiple bearings. Some embodiments can use the motor in Figures 17F to 17G to power the centrifuge in Figure 20. Alternatively, a centrifuge with one or more features described herein can be mounted on a system in Figure 21 having an overhead sample processing system as shown in the figure or similar to the system shown in Figure 21. Optionally, such a centrifuge may be mounted on a common mounting plate, common platform, or common frame with the other components 912, 914, or 916 and all components available for use with the overhead sample processing system.

It should also be understood that the embodiment of FIG. 20 may also be configured to include features from other figures herein, such as, but not limited to, the self-balancing features of FIG. 18A-18C .

Service point system

With reference now to Figure 21, it should be understood that the process described herein can be performed using automation technology.Automation can be used in an integrated automation system.In some embodiments, this automation can be in a single instrument, which has multiple functional components and is surrounded by a common housing.The processing techniques and methods for sedimentation measurement can be preset.Alternatively, the processing techniques and methods can be based on a scheme or a procedure that can be dynamically changed in the mode described in U.S. Patent Application Serial Nos. 13/355,458 and 13/244,947 as needed, and these two applications are incorporated herein by reference for all purposes.

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

As seen in Figure 21, the control by processor 902 can allow pipette system 904 to obtain blood sample from cartridge 910 and move this sample to one of assembly 912,914 or 916. Such movement can relate to sample being distributed in the removable vessel in cartridge 910 and then this removable vessel is transported to one of assembly 912,914 or 916. Alternatively, blood sample is distributed directly to the container that has been installed on one of assembly 912,914 or 916. In a non-limiting example, one of these assemblies 912,914 or 916 can be a centrifuge with imaging configuration to allow illumination and visualization to the sample in the container. Other assemblies 912,914 or 916 perform other analyses, measure or detection functions.

In a non-limiting example, the sample vessel in the centrifuge, such as one of these assemblies 912, 914 or 916, can be moved to another (or alternatively, another position or device) in assembly 912, 914 or 916 by one or more manipulators, for further processing sample and/or sample vessel. Some embodiments can use pipette system 904 to engage sample vessel to move it from assembly 912, 914 or 916 to another position in the system. In a non-limiting example, this may be useful for moving the sample vessel to an analysis station (such as, but not limited to, imaging) and then moving the vessel back to the centrifuge for further processing. In an embodiment, this can be accomplished using other sample handling systems in pipette system 904 or the device. In one non-limiting example, moving vessels, tips, etc. from cartridge 910 to one of components 912, 914, or 916 and then to another position in the system (or vice versa) can also be accomplished using pipette system 904 or other sample handling systems in the device. It should also be understood that in some embodiments, pipette system 904 can be used to rotate a centrifuge rotor to an appropriate position so that (one or more) vessels can be loaded and/or unloaded from a known position. In such embodiments, pipette system 904 can engage a centrifuge rotor or other features using tips, nozzles, or other pipette features that can rotate the rotor until the rotation is moved to the desired orientation.

With reference now to Figure 22, further embodiments of the centrifuge 1000 will now be described. Figure 22 shows an exploded perspective view of the centrifuge 1000 having a cover plate 1010 coupled to a rotatable frame 1020 during operation. In this non-limiting example, the rotatable frame 1020 can have an automatic balancing element 700, which in this embodiment can be a channel 1030 with a plurality of weighted spheres 1032 therein. Alternatively, some embodiments can have the automatic balancing element 700 in the cover plate 1010, the shaft 1060, or other rotating parts of the centrifuge. Alternatively, other automatic balancing features currently known or to be developed in the future can be incorporated into the rotatable frame 1020, the cover plate 1010, the shaft 1060, or other rotating parts of the centrifuge 100.

As seen in this non-limiting example, there may be one or more sample vessel holders such as a bucket 1040, which are attached to a hinge or other attachment that allows the bucket 1040 to swing as indicated by arrow 1050 when the motor shaft 1060 rotates the centrifuge disk. As seen in this embodiment, the bucket 1040 may have (one or more) windows or (one or more) viewing portions 1042 that allow viewing of the sample vessel contained therein. Alternatively, some embodiments may not have windows. Some embodiments may also have a bucket 1040 designed with a weighted portion 1044 that will bias the bucket toward returning to a vertical or substantially vertical orientation. Some embodiments may bias the bucket 1040 slightly away from vertical. There may be a coupling device such as, but not limited to, a magnet 1062 (either in direct contact with or spaced apart from the bucket in the rest position) to assist in having a consistent resting position so that any vessel in the bucket 1040 can be easily loaded or unloaded. In some embodiments, the bucket 1040 may have ferrous portions and/or magnets thereon to assist in engaging with a coupling device, such as magnet 1062. Alternatively, some embodiments may have magnets in the bucket 1040 or in both the bucket 1040 and the shaft 1060. Some embodiments may have magnets in the bucket 1040 and shaft 1060 that are not directly aligned, such as one magnet along the longer portion of the bucket and another magnet at the "foot" of the bucket 1040.

Although only two buckets are shown in FIG. 22 , it should be understood that embodiments with multiple buckets are not precluded. Optionally, when bucket 1040 is in the rotated position, at least a portion of the bucket can fill cavity 1070 in cover plate 1010 to create a portion that is flush with the plane of the cover plate, thereby reducing drag. Optionally, only about 90% or less of the cavity is filled by bucket 1040 in the rotated position. Optionally, only about 80% or less of the cavity is filled by bucket 1040 in the rotated position. Optionally, only about 70% or less of the cavity is filled by bucket 1040 in the rotated position.

As seen in this embodiment of Figure 22, when the centrifuge assembly is assembled and lowered into the housing 1100 as shown by arrow 1102, the cover plate 1010 can be substantially flush with the top of the housing 1100. In some embodiments, a position sensor 1110 such as, but not limited to, a Hall sensor can be used to sense an indicator 1112 on the rotating part of the centrifuge. This may be useful for determining the stationary position of the rotating part so that the sample processing device can accurately engage the bucket 1040. Optical detection technology, electromagnetic detection technology, and/or other detection technology can be used for position detection. Alternatively, some embodiments can incorporate position sensing into the motor and/or motor shaft. It should be understood that, for ease of assembly or other reasons, some embodiments can integrate the parts described herein into fewer individual parts. It should be understood that the centrifuge herein can use any motor as described herein (including those with encoders).

Figures 22 and 23 also show that some embodiments can have ventilation features, such as, but not limited to, ventilation ports 1120 in the sides and/or bottom of the housing 1100. As seen in the side cross-sectional view in Figure 23, the rotation of the centrifuge disc will draw air into the housing 1110 to help cool the centrifuge. As the centrifuge disc rotates as indicated by arrows 1130, air can be drawn in. Some embodiments can have ports 1120 only on the side walls of the housing 1110. Alternatively, some embodiments can have ports only in the bottom of the housing 1110. Alternatively, some embodiments can have openings in both. Figure 23 shows that the interior of the housing can have a shaped bottom portion to assist in directing the airflow into the housing 1110. Optionally, some embodiments can mount the housing 1110 on elastic mountings, shock absorbing members, etc. to minimize any vibration transmission from the centrifuge to any other part of the device. 23 , the centrifuge disks 1150 define a gap 1160 that is 10% or less of the diameter of the disks 1150. Alternatively, the centrifuge disks 1150 define a gap 1160 that is 5% or less of the diameter of the disks 1150. This allows for a fit that minimizes the desired air flow around the centrifuge disks. Alternatively, other embodiments may have cutouts over a larger portion of the housing 1100, with cutouts at fewer locations (or smaller cutouts at more locations) to provide the desired level of cooling.

All of the aforementioned embodiments can be integrated into a single housing 920 and configured for desktop or small footprint floor mounting. In one example, a small footprint floor mounting system can occupy a floor area of approximately 4 m ² or less. In one example, a small footprint floor mounting system can occupy a floor area of approximately 3 m ² or less. In one example, a small footprint floor mounting system can occupy a floor area of approximately 2 m ² or less. In one example, a small footprint floor mounting system can occupy a floor area of approximately 1 m ² or less. In some embodiments, the instrument footprint can be less than or equal to about ^4m2 , ^3m2 , 2.5m2, ^2m2 , ^1.5m2 , ^1m2 , ^0.75m2 , ^0.5m2 , ^0.3m2 , ^0.2m2 , 0.1m2, 0.08m2, 0.05m2 ^{, 0.03m2} , ^100cm2 , ^80cm2 , ^70cm2 , ^60cm2 , ^50cm2 , ^40cm2 , ^30cm2 , ^{20cm2 , 15cm2} , 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 ^{, the} entire contents of which are incorporated herein by reference for all purposes. This embodiment may be configured for use with any module or system described in those patent applications.

By way of non-limiting example, the centrifuge can have a footprint of approximately 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 can have one or more dimensions (e.g., width, length, height) of 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 reference to certain specific embodiments thereof, it will be understood by those skilled in the art that various adaptations, changes, modifications, substitutions, deletions, or additions may be made to the procedures and protocols without departing from the spirit and scope of the present invention. For example, with respect to any of the above-described 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 centrifuge a sample in an initial phase, and then position the sample in a filter that then removes the formed blood components to complete the separation. Although the present invention is described in the context of centrifugation, other accelerated separation techniques may also be suitable for use in the systems herein. It should also be understood that although the present invention is described in the context of blood samples, the technology herein may also be configured to be applicable to other samples (biological samples or other samples). Any embodiment herein may be configured to have an encoder and/or sensor as described in this disclosure. Any embodiment herein may be configured to have a position detection device as described in this disclosure. Any embodiment herein may be configured to have an automatic stop feature as described in this disclosure. Any embodiment herein may be configured to have (one or more) thermal control features as described in this disclosure.

Alternatively, at least one embodiment can use a variable speed centrifuge. Utilize feedback, such as but not limited to the imaging of the position of (one or more) interfaces in the sample, the speed of the centrifuge can be changed so that the compaction curve and time become linear (until compaction fully), and extract ESR data from the speed curve of the centrifuge rather than the sedimentation rate curve. In such a system, one or more processors can be used to carry out feedback control to have a linear compaction curve, also record the speed curve of the centrifuge simultaneously. According to which interface has been tracked, the sedimentation rate data are calculated based on the centrifuge speed. In a non-limiting example, use higher centrifuge speed to keep a linear curve when compaction approaches completion.

In addition, those skilled in the art will recognize that any embodiment of the present invention can be applicable to collecting sample fluid from humans, animals or other subjects. Optionally, the volume of blood used for sedimentation testing can 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 nL or less, 250 nL or less, 100 nL or less, 50 nL or less, 20 nL or less, 10 nL or less, 5 nL or less, or 1 nL or less.

In addition, concentration, quantity and other numerical data can be presented in range format herein. It should be understood that such range format is used only for the sake of convenience and brevity, and should be flexibly interpreted as not only including the numerical value clearly listed as the limit of the range, but also including all individual numerical values or subranges contained within the range, as if each numerical value and subrange were clearly listed. For example, the size range of about 1 nm to about 200 nm should be interpreted as not only including the clearly listed limits of about 1 nm and about 200 nm, but also including individual sizes such as 2 nm, 3 nm, 4 nm and subranges such as 10 nm to 50 nm, 20 nm to 100 nm.

The publications discussed or referenced herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publications by virtue of prior invention. In addition, the dates of the publications provided may differ from the actual publication dates, which may need to be independently confirmed. All publications mentioned herein are incorporated herein by reference to disclose and describe the structures and/or methods associated with the referenced publications. The following applications are also incorporated herein by reference for all purposes: U.S. Patent Application Serial Nos. 13/355,458, 13/244,947, 13/769,820, 61/852,489, 61/930432, filed July 18, 2012, entitled “Rapid Measurement of Formed Blood Component Sedimentation Rate from Small No. 61/673,037, filed on January 22, 2014; U.S. Provisional Application Serial No. 61/930,462, filed on January 22, 2014; U.S. Patents 8,380,541, 8,088,593; U.S. Patent Publication No. 2012/0309636; U.S. Patent Application Serial No. 61/676,178, filed on July 26, 2012; PCT/US2012/57155, filed on September 25, 2012; U.S. Application Serial No. 13/244,946, filed on September 26, 2011; U.S. Patent Application 13/244,949, filed on September 26, 2011; and U.S. Application Serial No. 61/673,245, filed on September 26, 2011; and a patent application entitled “High No. 61/673,245, filed July 25, 2012, entitled “High Speed, Compact Centrifuge for Use with Small Sample Volumes,” U.S. Provisional Application Serial No. 61/675,758, filed September 27, 2012, entitled “High Speed, Compact Centrifuge for Use with Small Sample Volumes,” and U.S. Provisional Application Serial No. 61/675,758, filed September 27, 2012, entitled “High Speed, Compact Centrifuge for Use with Small Sample Volumes.” No. 61/706,753, filed on July 26, 2012; U.S. Patent Nos. 8,380,541 and 8,088,593; U.S. Patent Publication No. 2012/0309636; U.S. Patent Application Serial No. 61/676,178, filed on July 26, 2012; PCT/US2012/57155, filed on September 25, 2012; U.S. Application Serial No. 13/244,946, filed on September 26, 2011; U.S. Patent Application 13/244,949, filed on September 26, 2011; and U.S. Application Serial No. 61/673,245, filed on September 26, 2011.

While the above is a complete description of preferred embodiments of the present invention, various alternatives, modifications, and equivalents are possible. Therefore, the scope of the present invention should not be determined by reference to the above description, but rather by reference to the appended claims, along with their full scope of equivalents. Any feature, whether preferred or not, may be combined with any other feature, whether preferred or not. The appended claims should not be interpreted as containing means-plus-function limitations unless such a limitation is expressly recited in a given claim using the phrase "means for...". It should be understood that the meanings of "a," "an," and "the," as used in the description herein and throughout the claims that follow, include plural references unless the context clearly dictates otherwise. Additionally, the meaning of "in," as used in the description herein and throughout the claims that follow, includes "in" and "on," unless the context clearly dictates otherwise. Finally, the meanings of "and" and "or," as used in the description herein and throughout the claims that follow, include both conjunctive and disjunctive meanings and are used interchangeably unless the context clearly dictates otherwise. Thus, in contexts where the terms "and" or "or" are used, use of such conjunctions does not exclude the meaning of "and/or" unless the context clearly dictates otherwise.

This document contains material that is subject to copyright protection. For example, all drawings shown herein are subject to copyright protection. The copyright owner (herein the applicant) has no objection to the facsimile reproduction of the patent document and disclosure as it appears in the U.S. Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights. The following notice applies: Copyright 2012-2014 Theranos Corporation.

Claims (6)

1. A method for high-speed centrifugation of small-volume samples, comprising: A motor is provided coupled to a centrifuge rotor, the motor being used to rotate the centrifuge rotor; The rotational speed of the rotating part of the motor is determined using an encoder on the centrifuge rotor; When the centrifuge is stopped, the scoop is held on the stationary part of the centrifuge using at least one magnet in the scoop, wherein the scoop is coupled to the centrifuge rotor and is configured to hold a container having a sample chamber of no more than 100 μL. 2. The method of claim 1, further comprising using a thermally conductive material configured to conduct heat in a direction away from the container. 3. The method of claim 1, further comprising using an active cooling unit to minimize heat transfer to the sample, wherein the container is arranged such that the container is located in a region where heat exposure is reduced; the active cooling unit is configured to cool the drive mechanism. 4. The method of claim 1, further comprising using an automatic balancing weight coupled to the centrifuge rotor, wherein the automatic balancing weight is configured to move under centrifugal force to a position that minimizes the unbalanced rotation of the centrifuge rotor in the event of uneven load distribution in the sample holder of the centrifuge. 5. The method of claim 1, further comprising using at least one air bearing configured to support the centrifuge during operation. 6. The method of claim 1, further comprising using at least one air bearing configured to support the centrifuge in operation, wherein at least a portion of the air bearing is part of the centrifuge housing.