CN106102921B - Method for high-speed centrifugation of small volume samples - Google Patents

Abstract

In one non-limiting example, there is provided an automated system for separating one or more components in a biological fluid, wherein the system comprises: (a) a centrifuge comprising a one or more scoops to effect said separation of one or more components in a fluid sample; and (b) said container, wherein said container includes one or more shaping features that are The shape characteristics of the bucket are complementary.

Description

Method for high-speed centrifugation of small volume samples

Background technique

Traditional centrifuges are oversized and inefficient for handling small volumes of liquid samples. They also fail to include certain features that are desirable when dealing with small sample volumes.

incorporated by reference

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

SUMMARY OF THE INVENTION

It will be appreciated that embodiments 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 including one or more buckets configured to receive a container to effect said separation of one or more components in a fluid sample; and (b) said A container, wherein the container includes one or more shaping features that are complementary to the shaping features of the bucket.

It should be understood that the 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 that are oscillating buckets that are in or near a vertical position when the centrifuge is stationary and The centrifuge is rotated at or near a horizontal position. Optionally, the system may have a plurality of oscillating buckets spaced radially symmetrically on the centrifuge. Optionally, the fluid sample is a biological fluid. Optionally, the biological fluid is blood. Optionally, the container is configured to contain 100 uL or less of sample fluid. Optionally, the container is configured to contain 50 uL or less of sample fluid. Optionally, the container is configured to contain 25uL or less of sample fluid. Optionally, the container is closed on one end and open on the opposite end. Optionally, the container is a centrifuge vessel. Optionally, the centrifuge vessel has a rounded end with one or more internal nubs. Optionally, the system includes an extraction tip having one or more shaped features complementary to the shaped features of the centrifuge vessel and configured to fit within the centrifuge vessel. Optionally, the shaped features of the bucket include one or more shelves on which the protruding portion of the container is configured to rest. Optionally, the bucket is configured to receive a plurality of containers having different configurations, and wherein the shaping feature of the bucket includes a plurality of shelves, wherein the first container having the first configuration is configured to rest On the first shelf, and a second container having a second configuration is configured to rest on the second shelf.

In yet another embodiment described herein, there is provided a compact high-speed centrifuge comprising a centrifuge body; a motor for rotating the centrifuge body; and a detector associated with the motor Integrated 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 the embodiments herein may be adapted to have one or more of the following features. In one non-limiting example, the detector uses at least optical encoders and Hall effect techniques to determine rotational position. Optionally, the detector uses at least an optical encoder and Hall effect technology to determine at least the 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 in different directions. Optionally, the first surface and the second surface face the same direction. Optionally, the motor includes a plurality of detectors for determining rotational position. Optionally, the motor further includes a first encoder disc providing first type of encoder information and a second encoder disc providing second type of encoder information. Optionally, optionally, the motor further includes a first encoder disk providing optical encoder information and a second encoder disk providing magnetic encoder information. Optionally, the motor includes an encoder disc providing first type of encoder information and second type of encoder information. Optionally, the motor includes an encoder disk that provides both optical encoder information and magnetic encoder information. It will be appreciated that although the motor with integrated encoder assembly is described in the context of a centrifuge, the motor may also be adapted for use in other scenarios where it is desirable to integrate position and/or velocity detector features into the motor .

In yet another embodiment described herein, there is provided a method comprising: providing a motor; integrating a first type encoder into the motor; integrating a second type encoder into the motor; The first type of encoder is used to determine the rotational position of the rotating part of the motor, and the second type of encoder is used to determine the rotational speed of the rotating part of the motor.

It should be understood that the 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. Optionally, the first type encoder provides magnetic encoder information. Optionally, the first type encoder provides Hall effect encoder information. Optionally, the first type encoder and the second type encoder provide different types of encoder information.

In another embodiment described herein, a compact high-speed centrifuge for use with a sample container is provided. The centrifuge may comprise: a first portion comprising a thermally insulating material; a second portion comprising a thermally conductive material; wherein the receptacle is arranged such that the receptacle is located in an area with thermally insulating material; wherein the thermally conductive material is configured Used to direct heat away from the container.

In another embodiment described herein, a compact high-speed centrifuge for use with a sample container is provided. The centrifuge may comprise 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 such that the container is located at having a region where thermal exposure is reduced; 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 a rotational position of the centrifuge body.

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 self-balancing weight coupled to the centrifuge body, wherein such weight is configured to move under centrifugal force To a position that minimizes unbalanced rotation of the centrifuge body with uneven loading in the 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 in 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 in operation, wherein the centrifuge 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 rate changes of forces outside a predetermined force condition range.

It should be understood that the 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 downwardly under centrifugal force. Optionally, wherein the electrical connection to the cooling elements of the centrifuge body is not interrupted, even if such elements are in operation during the centrifugation 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 body; a drive mechanism for rotating the centrifuge body, wherein the centrifuge body extends downwardly to cover at least a portion of the drive mechanism; wherein the drive mechanism includes a stator and a rotor; wherein the rotor is concentric with respect to the stator.

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, wherein the centrifuge body extends downwardly to cover at least a portion of the drive mechanism; wherein the drive mechanism includes a stator and a rotor; wherein the stator is concentric with respect to the rotor.

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; one or more oscillating holders on the centrifuge body for containing the centrifuge vessel; wherein the The maximum dimension of the swing holder or the sample container does not exceed about 10 mm.

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; one or more oscillating holders on the centrifuge body for containing the centrifuge vessel; wherein the The oscillating fixture moves from a first orientation to a second orientation that is more horizontal than the first orientation during centrifugation operations.

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; one or more oscillating holders on the centrifuge body for containing the centrifuge vessel; wherein the The width of the sample container is greater than the length of the sample container.

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 and a drive mechanism for rotating the centrifuge body.

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

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

In another non-limiting example, there is provided a method comprising providing a motor coupled to a centrifuge body; determining a rotational speed of the rotating portion of the motor using an encoder on the centrifuge body; and at least one magnet in the bucket is used to hold the bucket on the centrifuge body when the centrifuge is in a stopped condition. Optionally, the bucket is configured to hold a vessel having a sample chamber of no greater than 100 uL. Optionally, the method includes using a thermally conductive material configured to direct heat in a direction away from the container. Optionally, the method uses an active cooling unit for minimizing heat transfer to the sample, wherein the vessel is arranged such that the vessel is located in an area where thermal exposure is reduced; the active cooling unit is configured to cool the drive mechanism. Optionally, the method includes using a self-balancing counterweight coupled to the centrifuge body, wherein such counterweight is configured to move under centrifugal force such that there are inhomogeneities in the sample holder of the centrifuge. The position where the unbalanced rotation of the centrifuge body is minimal under the condition of the load. Optionally, the method includes using at least one air bearing configured to support the centrifuge in operation. Optionally, the method includes 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. Optionally, the method includes using a force detector configured to detect a change in rate of force outside a predetermined range of force conditions. Optionally, the centrifuge vessel holder pivots inwardly towards 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 downwardly under centrifugal force. Optionally, electrical connections to cooling elements of the centrifuge body are not interrupted, even if such elements are in operation during centrifugation operations. Optionally, the centrifuge vessel holder is moved from a first orientation to a second orientation that is more horizontal than the first orientation during a centrifugation operation.

It will be appreciated that embodiments in the present disclosure provide a method comprising at least one technical feature from any of the other embodiments herein. Optionally, a method may include at least any two technical features from any of the other embodiments herein.

Optionally, a device may include at least any one of the technical features 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 of the technical features 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.

Description of drawings

1-3 show various views of embodiments of the centrifuge described herein.

4-5 show various views of embodiments of the 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 centrifuges described herein.

13-16 illustrate 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 the apparatus and method as described herein.

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

Figure 22 shows yet another embodiment of a device as described herein.

Detailed ways

It is to 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 may 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 a mixture of materials, reference to "a compound" may include multiple compounds, and the like. References cited herein are hereby incorporated by reference in their entirety, unless 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 which shall be defined as having the following meanings:

"Optional" or "optionally" means that the subsequently described circumstance may or may not occur, such that the description includes instances in which the circumstance occurs and instances in which it does not. For example, if a device optionally includes features for sample collection wells, this means that sample collection wells may or may not be present, and thus the description includes both structures in which the device possesses sample acquisition wells and in which no sample is present The structure of the acquisition wells.

centrifuge

Figures 1, 2 and 3 show perspective perspectives of a centrifuge that can be integrated into the system (Figure 1 - Side View, Figure 2 - Front View, Figure 3 - Back View). The centrifuge may contain an electric motor capable of rotating the rotor at 15000 rpm. One type of centrifuge rotor is shaped somewhat like a fan blade mounted vertically on the main shaft of a motor. The element that holds the sample holding element (tip) and provides a rib or shelf on which the end of the tip distal to the motor shaft rests and which provides a rib or shelf is attached to the rotor. The plate provides support during centrifugation so that the sample cannot escape. The tip may also be further supported by a mechanical stop in the rotor at its proximal end. Such a tip may be provided so that the forces generated during centrifugation do not cause the tip to sever 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 block of acrylic (or other material) shaped to minimize vibration and noise during centrifuge operation. The rotor is (optionally) shaped so that other movable components in the instrument can move past the centrifuge when it is oriented at a certain angle from the vertical. The sample holding element is centrifugally balanced by blocks on opposite sides of the rotor so that the center of the moment of inertia is axial with respect to the motor. The centrifuge motor can provide position data to a computer, which in turn can control the rotor's rest position (usually vertical before and after centrifugation).

In order to minimize centrifugation time (during Without generating too much mechanical stress), convenient dimensions of the rotor are in the range of about 5-10 cm, rotating at about 10000-20000 rpm, providing about 5 min of time to pack red blood cells.

In some embodiments, the centrifuge may be a horizontally oriented centrifuge with an oscillating bucket design. In some preferred embodiments, the axis of rotation of the centrifuge is vertical. In alternative embodiments, the axis of rotation may be horizontal or at any angle. Centrifuges can be capable of spinning two or more vessels simultaneously, and can be designed to be fully integrated into automated systems employing computer-controlled pipettes. In some embodiments, the bottom of the vessel may be closed. The swinging bucket design can allow the centrifuge vessel to be passively oriented in a vertical position when stopped and swiveled out to a fixed angle when rotated. In some embodiments, the swinging bucket may allow the centrifuge vessel to be rotated outward to a horizontal orientation. Or they can be rotated out to any angle between the vertical and horizontal positions (eg, about 15, 30, 45, 60, or 75 degrees from the vertical). A centrifuge with an oscillating bucket design can meet the positional accuracy and repeatability requirements of robotic systems that employ several positioning systems.

A computer-based control system can use the position information from the optical encoder to rotate the rotor at a controlled low speed. Position feedback alone does not need to be used to maintain an accurate static position as the motor can be designed for high speed performance. In some embodiments, a cam in combination with a solenoid-actuated lever can be employed to achieve very accurate and stable stops at a fixed number of positions. Using a separate control system and feedback from Hall-effect sensors built into the motor, the speed of the high-speed rotor can be controlled very accurately.

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

rotor

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

When the rotor is stationary, these buckets may be passively lowered by gravity to position the vessels vertically and make them accessible to pipettes. Figure 4 shows an example of a stationary rotor where the bucket is vertical. In some embodiments, the bucket can be passively lowered to a predetermined angle, which may or may not be vertical. As the rotor rotates, the bucket is forced into an almost horizontal position or predetermined angle by centrifugal force. Figure 5 shows an example of a rotor at a speed where the bucket is at a small angle to the horizontal. There may be physical hard stops for both 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 in order 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 the bucket and rotor can be perfectly aligned when the rotor is rotating and the bucket can be forced to level.

To facilitate plasma extraction, the rotor may be angled relative to the horizontal downward toward the ground. Since the angle of the bucket can be matched to the angle of the rotor, this enables a fixed angle of rotation of the bucket. The resulting pellet from such a configuration may be angled relative to the vessel when the vessel is placed upright. Plasma can be aspirated from the top of the centrifuge vessel using a narrow extraction tip. By placing 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.

Various tube designs can be accommodated in the bucket of the appliance. In some embodiments, various tube designs may be closed-ended. Some tube designs are shaped like conventional centrifuge tubes with tapered bottoms. Other tube designs may be cylindrical. Tubes with lower height to cross-sectional area ratios can facilitate cell processing. Tubes with large ratios (>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 from any of several plastics (polystyrene, polypropylene) or any other material discussed elsewhere herein. Scoops can have volumes ranging from a few microliters to about 1 milliliter. Tubes can be inserted into and removed from the centrifuge using a "pick and place" mechanism.

Control System

Due to the rotation and positioning requirements of the centrifuge equipment, a dual control system approach can be used. To index the rotor to a specific rotational orientation, a position-based control system can be implemented. In some embodiments, the control system may employ a PID (Proportional Integral Derivative) control system. Other feedback control systems known in the art may be employed. Position feedback to the position controller can be provided by a high-resolution optical encoder. To run the centrifuge at low to high speeds, a speed controller can be implemented, with a PID control system tuned for speed control. Rotation rate feedback for the speed controller can be provided by a set of simple Hall effect sensors placed on the motor shaft. Each sensor can generate a square wave during one cycle of each motor shaft rotation.

stop agency

To consistently and securely position the rotor in a particular location, a physical stop mechanism may be employed in some embodiments herein. In one embodiment, the stop mechanism may use a cam coupled to the rotor in conjunction with a solenoid actuated lever. The cam can be shaped like a disc with a number of "C" shaped notches machined around the perimeter. To position the centrifuge rotor, first spin it down to a maximum of 30 RPM. In other embodiments, the rotational speed may be reduced to any other amount, including but not limited to about 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. 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 particular slot in the cam, the force of the solenoid actuating the lever can overcome the force of the motor and the rotor can be stopped. At that time, the motor can be braked electronically, and in combination with a stop mechanism, it is possible to maintain the rotational position very accurately and securely indefinitely.

(one or more) centrifuge buckets

The centrifuge pendulum bucket can be configured to accommodate different types of centrifuge tubes. In preferred embodiments, various tube types may have collars or flanges at their upper (open) ends. 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 may be employed. For example, Figure 6 shows an example of a bucket configuration. The bucket may have side portions that cooperate with the centrifuge and allow the bucket to swing freely. The bucket may have a closed bottom and an opening at its top end. Figure 7 shows an example of a centrifuge vessel mated with a bucket. As previously mentioned, the buckets can be shaped to receive centrifuge vessels of various configurations. The centrifuge vessel may have one or more protruding members that may rest on the bucket. The centrifuge vessel can be shaped with one or more features that can mate with the centrifuge bucket. The feature may be a shaped feature of the vessel or one or more projections. Figure 8 shows an example of another centrifuge vessel that can be mated with a bucket. As previously described, the bucket may have one or more contouring features that may allow different configurations of centrifuge vessels to fit with the bucket. It should be understood that any of the embodiments of the centrifuges of FIGS. 4-8 may be configured with any of the 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 material after centrifugation. Centrifuge tubes and extraction tips 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 may be used.

A system may implement one or more of the following:

1. Rapid processing of small blood samples (usually 5–50uL)

2. Accurate and precise measurement of hematocrit

3. Efficient removal of plasma

4. Efficiently resuspension of formed components (red and white blood cells)

5. Concentration of leukocytes (after labeling with fluorescent antibodies and fixation and lysis of erythrocytes)

6. Optical Confirmation of RBC Lysis and Leukocyte Recovery

Overview of Centrifuge Vessels and Extraction Tips

The centrifuge can be operated using custom vessels and tips to meet the various constraints placed on the system. A centrifuge vessel can be a closed bottom tube designed to be spun in a centrifuge. In some embodiments, the centrifuge vessel may be the vessel shown in FIG. 7 , or may have one or more of the features shown in FIG. 7 . It may have several unique features that support a wide range of desired functions, including hematocrit measurement, RBC lysis, pellet resuspension, and efficient plasma extraction. Extraction tips can be designed to be inserted into centrifuge vessels for precise fluid extraction and sediment resuspension. In some embodiments, the extraction tip may be the tip shown in FIG. 6 , or may have one or more of the features shown in FIG. 6 . Exemplary illustrations of extraction tips are discussed herein and can be found in US Application Serial Nos. 13/355,458 and 13/244,947, the entire contents of which are hereby incorporated by reference for all purposes.

centrifuge vessel

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

A first usage scenario might entail precipitation of 40uL of whole blood with heparin, recovery of the maximum volume of plasma, and measurement of hematocrit using computer vision. In the case of a hematocrit of 60% or less, the desired or preferred plasma volume may be approximately 40uL*40%=16uL.

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 pellet. 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 formula: V(d)=d*π1.25mm2. For example, for a hematocrit of 60%, the sacrificed volume may be 1.23uL for the 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 the narrow portion must fully accommodate the outer diameter of the extraction tip (which may be no less than 1.5 mm), the existing dimensions of the centrifuge vessel may be close to a minimum.

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

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

· Pellet whole blood

· Plasma extraction

Resuspend the pellet in lysis buffer and stain

· Pellet remaining white blood cells (WBCs)

·Remove the supernatant

· Resuspend the WBC

· Complete extraction of WBC suspension

In order to completely resuspend the packed sediment, experiments have shown that the sediment can be physically disturbed with a tip that can fully reach the bottom of the vessel containing the sediment. The preferred geometry of the vessel bottom for resuspension appears to be a hemispherical shape, similar to standard commercial PCR tubes. In other embodiments, other vessel bottom shapes may be used. The centrifuge vessel along with the extraction tip can be designed to facilitate the resuspension process by adhering to these geometrical requirements while also allowing the extraction tip to physically contact the bottom.

During manual resuspension experiments, note that physical contact between the bottom of the vessel and the bottom of the tip can create a seal that prevents fluid movement. Small spacing can be used in order to completely disturb the sediment while allowing fluid flow. To facilitate this process in robotic systems, physical features can be added to the bottom of the centrifuge vessel. In some embodiments, the feature may 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 tip of the tip can rest on the nubs and fluid is allowed to flow freely between the nubs. This may result in a small volume loss (~0.25uL) in the gap.

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 the current maximum volume of 100uL may exceed this requirement. Other aspects of the second usage scenario require similar or already discussed cutting-edge features.

The upper geometry of the centrifuge vessel can be designed to fit the pipette nozzle. Any pipette tip described elsewhere herein or known in the art can be used. The outer geometry of the upper part of the vessel can be precisely matched to the outer geometry of the reaction tip around which both the mouth and the cartridge can now be designed. In some embodiments, very small ridges may circumscribe the inner surface of the upper portion. The ridge can be a visual marker of maximum fluid height, which is intended to facilitate automatic error detection using computer vision systems.

In some embodiments, the distance from the bottom of the fully fitted mouth to the top of the maximum fluid line is 2.5 mm. This distance is 1.5mm less than the recommended distance of 4mm adhered to by the extraction tip. This reduced distance may be influenced by the need to minimize the length of the extraction tip while adhering to minimum volume requirements. The reason for this reduced distance stems from the specific use of the vessel. Since in some implementations fluid may be exchanged with the vessel only from the top, the maximum fluid it will have when mated with the mouth is the maximum volume of whole blood (40 uL) expected at any given time. The height of this fluid may be well below 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 wet the walls up to the height of the mouth. In some embodiments, the fluid will reach those heights at which the vessel is used to ensure that the meniscus of any fluid contained within the vessel does not exceed the maximum fluid height even if the total volume is less than the specified maximum. In other embodiments, other features may be provided to keep the fluid contained within the vessel.

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

During the process of exchanging fluids and rapidly inserting and removing the tip, the centrifuge vessel may experience some force. If the vessel is not restrained, these forces will likely be strong enough to lift or otherwise remove the vessel from the centrifuge bucket. To prevent movement, the vessel should be secured in some way. To achieve this, a small ring on the outside of the bottom of the outer vessel was added. The ring can easily mate with compliant mechanical features on the bucket. This problem is solved as long as the nub's retention force is greater than the force experienced during fluid manipulation but less than the frictional force when mating with the mouth.

extraction tip

Extraction tips can be designed to interface with centrifuge vessels to efficiently extract plasma and resuspend pelleted cells. If desired, its overall length (eg, 34.5 mm) can be exactly the same as that of another blood tip including, but not limited to, those described in US Serial No. 12/244,723 (incorporated herein by reference) match, but can be long enough to physically touch the bottom of the centrifuge vessel. In some embodiments, the ability to contact the bottom of the vessel may be required, both for the resuspension process and for complete recovery of the leukocyte suspension.

The volume of 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, the volume may be about 60 uL, which may be less than the tip's maximum capacity of 85 uL. In some embodiments, a tip with a larger volume than desired may be provided. As with centrifuge vessels, the height of this maximum volume can be marked using internal features on the interior of the upper portion of the circumscribed tip. The distance between the maximum volume line and the top of the fitted mouth may be 4.5mm, which can be considered a safe distance to prevent mouth contamination. Any sufficient distance to prevent mouth contamination can be used.

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

In one example, plasma can be diluted into a mixture of dextran sulfate (25 mg/dL) and magnesium sulfate (100 mM), and incubation can be followed for 1 minute to precipitate LDL-cholesterol. The reaction product can be pipetted into a centrifuge tube, then capped and spun at 3000 rpm for three minutes. Images of the initial reaction mixture before centrifugation (white precipitate shown), after centrifugation (clear supernatant shown), and LDL-cholesterol precipitate (after cap removal), respectively As shown in US Application Serial Nos. 13/355,458 and 13/244,947 and 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 US Patent Nos. 5,693,233, 5,578,269, 6,599,476 and US Patent Publication Nos. 2004/0230400, 2009/0305392 and 2010/0047790, the entire contents of which are hereby incorporated by reference for all purposes Incorporated by reference.

Example scenario

Many variants of the protocol can be used for centrifugation and processing. For example, a typical protocol using a centrifuge to process and concentrate leukocytes for cytometry 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 injects blood into bottom of centrifuge bucket)

2. Pellet erythrocytes and leukocytes by centrifugation (<5min x 10000g).

3. Measurement of hematocrit by imaging

4. Remove plasma slowly by pipetting plasma into a pipette (4 uL, corresponding to worst case scenario [60% hematocrit]) without disturbing the cell pellet.

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

6. Incubate at 37C for 15 minutes.

7. Prepare lysis/fixation reagent by mixing erythrocyte lysis solution (ammonium chloride/potassium bicarbonate) with leukocyte fixation reagent (formaldehyde).

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

9. Incubate at 37C for 15 minutes.

10. Pellet leukocytes by centrifugation (10000 g).

11. Remove the supernatant hemolysate.

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 can be a body fluid, such as blood, or any other sample described elsewhere herein. The sample can be a small volume, such as any of the volume measurements described elsewhere herein. In some cases, the sample may have an anticoagulant.

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

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

In one embodiment, one or more components of the sample can be removed. For example, if the 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. Liquid components can be removed without disturbing solid components. Imaging can help remove liquid components or any other selected components of the sample. For example, imaging can be used to determine where the plasma is located and can aid placement of a pipette to remove the plasma.

In some embodiments, reagents or other materials can be added to the sample. For example, the solid portion of the sample can be resuspended. Marks can be added to materials. One or more incubation steps can occur. In some cases, lysis reagents and/or immobilization reagents may be added. Additional separation steps and/or resuspension steps may occur. Dilution and/or concentration steps can occur as desired.

The volume of the sample can be measured. In some cases, the volume of the sample can be measured in a precise and/or accurate manner. The volume of the sample can be measured in a system with 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 the sample. An image of the sample can be captured and the volume of the sample can be calculated from the image.

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

In another example, a typical protocol 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 to deliver nucleic acid templates to exponential amplification reactions for detection. The process can be designed to extract nucleic acids from a variety of samples including, but not limited to, whole blood, serum, viral delivery media, human and animal tissue samples, food samples, and bacterial cultures. The process can be fully automated and enables DNA/RNA extraction in a consistent and quantitative manner. The steps below may be provided in a different order, or other steps may be substituted for any of the steps below:

1. Sample lysis. A chaotropic salt buffer can be used to lyse cells in a sample. The chaotropic salt buffer may include one or more of the following: chaotropic salts such as, but not limited to, 3-6M guanidine hydrochloride or guanidine thiocyanate; ten at typical concentrations of 0.1-5% v/v Sodium Dialkyl Sulfonate (SDS); Ethylenediaminetetraacetic Acid (EDTA) at a typical concentration of 1-5 mM; Lysozyme at a typical concentration of 1 mg/mL; Proteinase-K at a typical concentration of 1 mg/mL; And the pH can be set at 7-7.5 using buffers such as HEPES. In some embodiments, the sample can be incubated in 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 cleavage.

2. Surface loading. The cleaved sample can be exposed to a functionalized surface (usually in the form of a packed bed of microbeads) such as, but not limited to, a resin support packed in a chromatographic column, magnetic beads mixed with the sample in a batch fashion, The fluidized bed mode pumps the sample through the suspended resin and the sample through the closed channel in tangential flow on the surface. The surface can be functionalized to bind nucleic acids (eg, DNA, RNA, DNA/RNA hybrids) in the presence of a lysis buffer. Surface types may include silica and ion exchange functional groups such as diethylaminoethanol (DEAE). The lysed mixture can be exposed to the surface and nucleic acid conjugates.

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

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

Systems can employ many variations of these or other schemes. Such protocols can be used in conjunction with or in place of any of the protocols or methods described herein.

In some embodiments, it is important to be able to recover cells packed and concentrated by centrifugation for cell counting. In some embodiments, this can be accomplished using a pipetting device. Liquid (usually isotonic buffered saline, lysing agent, a mixture of lysing agent and fixative, or a mixture of labeled antibodies in buffer) can be dispensed into a centrifuge bucket and pipetted and resuspended repeatedly. The tip of the pipette can be forced into the stacked cells to facilitate this process. Image analysis aids this process by objectively verifying that all cells have been resuspended.

Use pipettes and centrifuges to process samples prior to analysis

According to embodiments of the present invention, the system may have pipetting capabilities, pick-and-place capabilities, and centrifugation capabilities. Such capabilities may enable efficient performance of virtually any type of sample pretreatment and complex assay procedures with very small volumes of sample.

Specifically, the system can support the separation of formed components (red and white blood cells) from plasma. The system can also support resuspension of formed components. In some embodiments, the system can support the concentration of leukocytes from fixed and hemolyzed blood. The system can also support lysis of cells to release nucleic acids. In some embodiments, the system can support nucleic acid purification and concentration by filtration through tips packed with (usually beaded) solid phase reagents (eg, silica). The system can also allow for elution of purified nucleic acids after solid phase extraction. The system can also support the removal and collection of precipitates (eg, LDL-cholesterol precipitated with polyethylene glycol).

In some embodiments, the system can support affinity purification. Small molecules such as vitamin-D and serotonin can be absorbed onto beaded (granular) hydrophobic substrates, followed by elution using organic solvents. Antigen can be provided on an antibody-coated substrate 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. Antigens can be provided on an antibody or aptamer-coated substrate and then eluted.

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

A pipette can be used to move liquids (vacuum and pump). Pipettes may be limited by relatively low positive and negative pressures (approximately 0.1–2.0 atmospheres). When needed, a centrifuge can be used to generate much higher pressures to force the liquid through the beaded solid phase medium. For example, using a rotor with a radius of 5 cm at a speed of 10000 rpm, a force of about 5000 x g (about 7 atmospheres) can be generated, which is sufficient to force a liquid through a resistive medium such as a packed bed. Any centrifuge design and configuration discussed elsewhere herein or known in the art may be used.

Hematocrit measurements using very small volumes of blood can occur. For example, inexpensive digital cameras can take good images of small objects, even when contrast is poor. Using this capability, the system of the present invention can support automated measurement of hematocrit with 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 curable adhesive and then subjected to centrifugation at 10000 x g for 5 minutes. Packed cell volume can be easily measured, and the plasma meniscus (indicated by arrow) may also be visible, so hematocrit can be accurately measured. This may enable the system to perform this measurement without wasting a relatively large volume of blood. In some embodiments, the camera can be used "as is" without manipulating the microscope to obtain larger images. In other embodiments, microscopy or other optical techniques can be used to magnify the image. In one implementation, hematocrit is determined using a digital camera without additional optical interference, and the measured hematocrit is comparable to that determined by conventional micro-hematocrit laboratory methods requiring many microliters of sample the same hematocrit. In some embodiments, the length of the column of the sample as well as the length of the column of packed red blood cells can be measured very accurately (+/-<0.05mm). Given that the blood sample column can be about 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 taking advantage of the ability of a digital camera to measure very small distances and rates of distance change. In one example, three blood samples (15uL) were pipetted into a "reaction tip". Images are captured within an hour at two-minute intervals. Image analysis was used to measure the movement of the interface between red blood cells and plasma.

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, this measurement accuracy was determined to be 0.038mm or <2% CV when it was related to the distance moved in one hour. 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

Referring now to Figures 9 to 11, still further embodiments of the centrifuge will now be described. According to some embodiments of the invention, the system may include one or more centrifuges. One or more centrifuges may be included in the equipment in the system. For example, one or more centrifuges may be provided within the device housing. A module may have one or more centrifuges. There may be centrifuges in one, two or more modules of the apparatus. The centrifuge may be supported by the module support structure, or may be contained within the module housing. Centrifuges can have form factors that are compact, flat, and occupy only a small footprint. In some embodiments, the centrifuge can 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 1200 m/s ² or more.

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

In some embodiments, the centrifuge may have one or more chambers configurable to receive a sample. The cavity can be configured to receive the sample directly within the cavity such that the sample can contact the cavity walls. Alternatively, the 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, the cavity may include a gap in the material, a scoop shape, a protrusion with a hollow interior, a member configured to interconnect with a sample container. Any description of a cavity may also include configurations that may or may not have a concave or inner surface. Examples of sample vessels may include any vessel or tip design described elsewhere herein. The sample vessel can have an inner surface and an outer surface. The 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 can have closed ends. The sample vessel may be the mouth of a fluid handling device, which may act as a centrifuge to spin fluid within the mouth, tip, or another vessel attached to such a mouth.

In some embodiments, the centrifuge may have 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more , 8 or more, 10 or more, 12 or more, 15 or more, 20 or more, 30 or more, or 50 or more A cavity configured to receive a sample or sample vessel.

In some embodiments, the centrifuge may be configured to accept small volumes of samples. In some embodiments, the cavity and/or sample vessel can be configured to receive 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 Lesser, 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 Smaller, 10 pL or less, 5 pL or less, or 1 pL or less sample volume.

In some embodiments, the centrifuge can have a lid that can contain the sample within the centrifuge. Caps prevent sample fogging and/or evaporation. The centrifuge can optionally have a membrane, oil (eg, mineral oil), wax, or gel that can contain the sample within the centrifuge and/or prevent it from atomizing and/or evaporating. Membranes, oils, waxes or gels can be provided as a layer over the sample that can be contained within the chamber of the centrifuge and/or the sample vessel.

The centrifuge may be configured to rotate about an axis of rotation. The centrifuge may be able to spin at any rpm. For example, the spin rate of the centrifuge can be as high as 100rpm, 1000rpm, 2000rpm, 3000rpm, 5000rpm, 7000rpm, 10000rpm, 12000rpm, 15000rpm, 17000rpm, 20000rpm, 25000rpm, 30000rpm, 40000rpm, 50000rpm, 70000rpm, or 100000rpm. At some points in time, the centrifuge may remain stationary, while at other points in time, the centrifuge may be rotated. A stationary centrifuge does not spin. The centrifuge can be configured to spin at a variable rate. In some embodiments, the centrifuge can be controlled to spin at a desired rate. In some embodiments, the rate of change of rotational speed may be variable and/or controllable.

In some embodiments, the axis of rotation may be vertical. Alternatively, the axis of rotation may be horizontal, or may have any angle between vertical and horizontal (eg, about 15, 30, 45, 60 or 75 degrees). In some embodiments, the axis of rotation may be in a fixed orientation. Alternatively, the axis of rotation may vary during use of the device. While the centrifuge is spinning, the rotation axis angle may or may not change.

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

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

The base may have a height and one or more lateral dimensions (eg, diameter, width, or length). The height of the base can be parallel to the axis of rotation. The lateral dimension can be perpendicular to the axis of rotation. The lateral dimension of the base may be greater than the height. The lateral dimension of the base can 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 than the height , 15 times or more, or 20 times or more.

Centrifuges can be of any size. For example, a centrifuge can have a ^diameter of about ²⁰⁰ cm or less, 150 cm or less, 100 ^cm or less, 90 ^cm or less, 80 ^cm or less, 70 ^cm or less, 60 ^cm or less, 50 cm ² or less, 40 cm ² or less, 30 cm ² or less, 20 cm ² or less, 10 cm ² or less, 5 cm ² or less, or 1 cm ² or less footprint. The centrifuge may have a size of about 5 cm or less, 4 cm or less, 3 cm or less, 2.5 cm or less, 2 cm or less, 1.75 cm or less, 1.5 cm or less, 1 cm or less, 0.75 cm or less, 0.5cm or less, or 0.1cm or less in 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 the drive mechanism. The drive mechanism may be a motor, or any other mechanism that enables the centrifuge to rotate about the axis of rotation. The drive mechanism may be a brushless motor, which may include a brushless motor rotor and a brushless motor stator. The brushless motor may be an induction motor. The brushless motor rotor may surround the brushless motor stator. The rotor may be configured to rotate about the axis of rotation with respect to the stator.

The base may be attached to or may incorporate a brushless motor rotor, which may cause the base to rotate with respect to the stator. The base may be attached to the rotor, or may be integral with the rotor. The base may be rotatable with respect to the stator, and a plane orthogonal to the axis of rotation of the motor may be coplanar with a plane orthogonal to the axis of rotation of the base. For example, the base may have a plane orthogonal to the axis of rotation of the base, the plane passing substantially between the upper and lower surfaces of the base. The motor may have a plane orthogonal to the axis of rotation of the motor, the plane passing substantially through the center of the motor. The base plane and the motor plane may be substantially coplanar. The motor plane may pass between the upper and lower surfaces of the base.

The brushless motor assembly may include a 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 height of the base. In other embodiments, the height of the motor assembly is no greater than 1.5 times the height of the base, 2 times the height of the base, 2.5 times the height of the base, 3 times the height of the base, 4 times the height of the base or the base 5 times the height. The motor rotor may be surrounded by the base such 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 main shaft/shaft assembly. The rotor may surround the stator, which may be electrically connected to a controller and/or a power source.

In some embodiments, the cavity may be configured to have a first orientation when the base is stationary and a second orientation when the base is rotated. The first orientation may be a vertical orientation and the second orientation may be a horizontal orientation. The cavity can have any orientation, wherein the cavity can be at 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. In some embodiments, the first orientation may be closer to vertical than the second orientation. The first orientation may be closer to parallel with the axis of rotation than the second orientation. Alternatively, the cavity may have the same orientation whether the base is stationary or rotating. The orientation of the cavity may or may not depend on the speed at which the base is rotated.

The centrifuge may be configured to receive a sample vessel, and may be configured to have the sample vessel in a first orientation when the base is stationary and a second orientation when the base is rotating. The first orientation may be a vertical orientation and the second orientation may be a horizontal orientation. The sample vessel can have any orientation, wherein the sample vessel can be at 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 from the vertical , 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, 75 degrees, 80 degrees, 85 degrees, or 90 degrees. In some embodiments, the first orientation may be closer to vertical than the second orientation. Alternatively, the sample vessel may have the same orientation whether the base is stationary or rotating. The orientation of the vessel may or may not depend on the speed at which the base is rotated.

Figure 9 shows one non-limiting example of a centrifuge provided in accordance with 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 may be configured to fold on a shaft extending through the base. In some embodiments, the shaft may form a secant line through the base. The shaft extending through the base may be a fold shaft, which may be formed by one or more pivot points 3620. The wings may comprise the entire portion of the base on one side of the shaft. Entire parts of the base can be folded to form wings. In some embodiments, the central portion 3606 of the base may intersect the axis of rotation while the wings do not intersect the axis of rotation. The central portion of the base may be closer to the axis of rotation than the wings. The central portion of the base may be configured to receive the drive mechanism 3630. The drive mechanism can be a motor, or any other mechanism that can cause the base to rotate, and is discussed in further detail elsewhere herein. In some embodiments, the wings may have a footprint of about 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% or more of the base footprint area.

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

1, 2, 3, 4, 5, 6 or more cavities may be provided in the wings. For example, the wings may be configured to receive one, two or more samples or sample vessels. Each wing may be able to receive the same number of vessels or a different number of vessels. The wings may include a cavity configured to receive a sample vessel, wherein the sample vessel faces a first orientation when the base is at rest, and is configured to face a second orientation when the base is rotated.

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

The pivot points of the wings may include one or more pivot pins 3622. The pivot pin can extend through a portion of the wings and a portion of the center portion of the base. In some embodiments, the wings and the central portion of the base can have interlocking features 3624, 3626 that prevent lateral sliding of the wings relative to the central portion of the base.

The wings may have a center of gravity 3680 positioned below the folding axis and/or pivot point 3620. When the base is at rest, the center of gravity of the wings may be positioned lower than the axis extending through the base. As the base rotates, the center of gravity of the wings may be positioned lower than the axis extending through the base.

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

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

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

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

The sample vessel can be configured for engagement with the fluid handling device. For example, the sample vessel may be configured for connection to a pipette or other fluid handling device. In some embodiments, a watertight seal may be formed between the sample vessel and the fluid handling device. A sample vessel is engageable with the fluid handling device and configured to receive a sample dispensed from the fluid handling device. The sample vessel can be engaged with the fluid handling device and allow the fluid handling device to pick up or aspirate the sample from the sample vessel.

The sample vessel may be configured to extend beyond 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 the collapsed and extended states.

Figure 10 shows one non-limiting example of a centrifuge provided in accordance with 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 contain one, two or more buckets 3710a, 3710b.

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

In some embodiments, multiple axes of rotation of the buckets through the base may be provided. 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 point of rotation may be at or nearer the lower surface of the base or the upper surface of the base.

1, 2, 3, 4 or more cavities are available in the bucket. For example, a bucket may be configured to receive one, two or more samples or sample vessels 3740. Each bucket may be able to receive the same number of utensils or a different number of utensils. The bucket may include a cavity configured to receive a sample vessel, wherein the sample vessel faces a first orientation when the base is at rest, and is configured to face a second orientation when the base is rotated.

In some embodiments, the bucket may be configured to be angled relative to the base. For example, the bucket may be between 0 and 90 degrees of the base. For example, the bucket may be vertically oriented when the base is at rest. The bucket may be positioned upward over the top surface of the centrifuge base when the base is stationary. At least a portion of the sample vessel may extend beyond the top surface of the base when the base is at rest. The wings may be 90 degrees from the central portion of the base when oriented vertically. The bucket may be oriented horizontally when the base is rotated. The bucket can be 0 degrees from the base when oriented horizontally. When the base is rotated, the bucket can be retracted into the base to form a substantially uninterrupted top and/or bottom surface. For example, as the base rotates, the bucket can be retracted to form a substantially continuous surface of the bottom surface and/or top surface of the base. The bucket may be configured to pivot upwardly relative to the base. The bucket can be configured such that at least a portion of the bucket can pivot upwardly past the top surface of the base.

The rotation point of the bucket may include one or more pivot pins. The pivot pin can extend through the bucket and 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 may have a center of mass 3750 positioned below the rotation point 3720. When the base is stationary, the center of mass of the bucket may be positioned below the point of rotation. As the base rotates, the center of mass of the bucket can be positioned below the point of rotation.

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 body 3715 and an inner insert 3717. In some embodiments, the body may be formed of a material having a lower density than the insert. For example, the body may be formed from plastic and the insert from metal, such as tungsten, steel, aluminum, copper, brass, iron, gold, silver, titanium, or any combination or alloy thereof. A heavier insert helps provide the bucket centroid below the swivel point. The bucket material may include a higher density material and a lower density material, where the higher density material is positioned below the rotation point. The centroid of the bucket can be positioned so that when the centrifuge is stationary the bucket naturally swings with the open end up and the heavier end down. The center of mass of the bucket can be positioned so that the bucket naturally retracts when the centrifuge rotates at a certain speed. The bucket may be retracted when the speed is at 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 receive multiple sample vessel configurations. The cavity may 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 interior 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 fit in 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 should be understood that alternative embodiments may also use embodiments with a height equal to or less than the width.

As previously described, the centrifuge may be configured for engagement with fluid handling equipment. For example, a centrifuge may be configured to connect to a pipette or other fluid handling device. The centrifuge may be configured to receive a sample dispensed by the fluid handling device, or to provide a sample to be drawn by the fluid handling device. The centrifuge can be configured to receive or provide sample vessels.

As previously mentioned, the sample vessel can be configured for engagement with a fluid handling device. For example, the sample vessel may be configured for connection to a pipette or other fluid handling device.

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

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

In some embodiments, ball bearings may be placed in a sealed/closed track within the rotor. This configuration is useful for dynamically balancing centrifuge rotors, especially when centrifuging samples of different volumes at the same time. In some embodiments, the ball bearings may be external to the motor, thereby making the overall system more robust and compact.

The channel can surround the centrifuge base. In some embodiments, the channel may surround the centrifuge base along the perimeter of the base. In some embodiments, the channel may be at or nearer the upper surface of the centrifuge base or the lower surface of the centrifuge base. In some cases, the channels may be equidistant from the upper and lower surfaces of the centrifuge base. Ball bearings slide along the perimeter of the centrifuge base. In some embodiments, the channel may surround the base at a distance from the axis of rotation. The channels may form a circle with the axis of rotation at the substantial center of the circle.

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

The module frame can be attached to the base. The module frame may be connected to the base at a boundary that may form a continuous or substantially continuous surface with the base. A portion of the top, bottom and/or side surfaces of the base may form a continuous or substantially continuous surface with the module frame.

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

In some embodiments, multiple axes of rotation of the buckets through the base may be provided. 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 nearer the lower surface of the base or the upper surface of the base. The bucket pivot may be at or nearer the lower surface of the module frame or the upper surface of the module frame.

1, 2, 3, 4 or more cavities are available in the bucket. For example, a bucket may be configured to receive one, two or more samples or sample vessels. Each bucket may be able to receive the same number of utensils or a different number of utensils. The bucket may include a cavity configured to receive a sample vessel, wherein the sample vessel faces a first orientation when the base is at rest, and is configured to face a second orientation when the base is rotated.

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

The buckets are lockable in multiple positions to support unloading and picking up centrifuge tubes, as well as drawing and dispensing liquids into and out of centrifuge vessels when the centrifuge vessels are in the centrifuge buckets. One technique for accomplishing this is one or more motors that drive a runner in contact with the centrifuge rotor to finely position and/or lock the rotor. Another approach could be to use a cam (CAM) shape formed on the rotor without the need for an additional motor or runner. Accessories from the pipette, such as the centrifuge tip attached to the pipette nozzle, can be pressed down onto the cam shape on the rotor. This force on the cam surface can cause the rotor to rotate to the desired locked position. Continued application of this force can enable the rotor to be held securely in the desired position. Multiple such cam shapes can be added to the rotor to support multiple lock positions. While the rotor is held by one pipette nozzle/tip, the other pipette nozzle/tip can interface with the centrifuge bucket to unload or pick up centrifuge dishes or perform other functions, such as removing from the centrifuge bucket centrifuge dish for pipetting or dispensing. 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 pin 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 may be attached to the counterweight. The counterweight may be configured to move when the base begins to rotate, thereby pivoting the bucket, typically from a fully 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 exerted on the counterweight. The counterweight may be configured to move away from the axis of rotation when the base begins to rotate at the threshold speed. In some embodiments, the counterweight can move in a linear direction or path. Alternatively, the counterweight may move along a curved path or any other path. The bucket may be attached to the counterweight at the counterweight pivot point 3860. One or more pivot pins or projections may be used that allow the bucket to rotate relative to the counterweight. In some embodiments, the counterweight can move along a horizontal straight path, causing the bucket to pivot up or down. The counterweight can move in a linear direction orthogonal to the axis of rotation of the centrifuge. This indicates that the buckets do not extend outward below the bottom surface of the centrifuge rotor. In some embodiments, this enables the overall height of the centrifuge design to be reduced when the apparatus 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 drain out of the vessel when the bucket changes orientation. Typically, centrifuge vessels may be open-top vessels that are not sealed and thus cannot contain spillage from vessels oriented in the wrong direction.

Counterweights may be located between portions of the module frame and/or base. The module frame and/or the base may be configured to prevent the counterweight from sliding out of the base. Modules and/or bases may limit the path of the counterweight. The path of the counterweight can be restricted to a straight line. One or more guide pins 3870 may be provided that may limit the path of the counterweight. In some embodiments, guide pins may pass through the frame module and/or base and counterweight.

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

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

As previously described, the centrifuge may be configured for engagement with fluid handling equipment. For example, a centrifuge may be configured to connect to a pipette or other fluid handling device. The centrifuge may be configured to receive a sample dispensed by the fluid handling device, or to provide a sample to be drawn by the fluid handling device. The centrifuge can be configured to receive or provide sample vessels.

As previously mentioned, the sample vessel can be configured for engagement with a fluid handling device. For example, the sample vessel may be configured for connection to a pipette or other fluid handling device.

The sample vessel may be configured to extend out of the bucket. In some embodiments, the centrifuge base and/or the module frame may be configured to allow the sample vessel to extend out of the bucket when the bucket is provided in the retracted state, and to allow the bucket to be in one of the retracted and protruding states pivot between. A sample vessel extending beyond the top surface of the centrifuge may 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 channels may also apply to any similar structure. The channel may contain one or more ball bearings. Ball bearings slide through the channel. The channel can be open, closed or partially open. The channel may be configured to prevent the ball bearing from falling out of the channel.

The channel can surround the centrifuge base. In some embodiments, the channel may surround the centrifuge base along the perimeter of the base. In some embodiments, the channel may be at or nearer the upper surface of the centrifuge base or the lower surface of the centrifuge base. In some cases, the channels may be equidistant from the upper and lower surfaces of the centrifuge base. Ball bearings slide along the perimeter of the centrifuge base. In some embodiments, the channel may surround the base at a distance from the axis of rotation. The channels may form a circle with the axis of rotation at the substantial center of the circle.

Other examples of centrifuge configurations known in the art may be used, including various oscillating bucket configurations. See, eg, US Patent No. 7,422,554, which is hereby incorporated by reference in its entirety for all purposes. For example, the bucket can swing down instead of up. The bucket can swing to bulge sideways instead of up or down.

The centrifuge can be enclosed in a housing or housing. In some embodiments, the centrifuge may be completely enclosed within the housing. Alternatively, the centrifuge may have one or more open sections. The housing may include movable portions that may allow fluid handling equipment or other automated equipment to access the centrifuge. The fluid handling equipment and/or other automated equipment may provide the sample, take the sample, provide the sample vessel, or take the sample vessel in the centrifuge. Such access may be permitted at the top, side and/or bottom of the centrifuge.

Samples can be dispensed and/or picked up from the chamber. Samples can be dispensed and/or picked up using a fluid handling system. The fluid handling system may be a pipette as described elsewhere herein, or any other fluid handling system known in the art. Samples can be dispensed and/or picked up using tips having any of the configurations described elsewhere herein. Dispensing and/or aspiration of samples can be automated.

In some embodiments, the sample vessel can be provided to or removed from the centrifuge. Sample vessels can be inserted into or removed from the centrifuge using the device in an automated process. Sample vessels 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 dispensed and/or picked up from the sample vessel. The sample can be dispensed and/or picked up from the sample vessel using the fluid handling system.

In some embodiments, the tip from the fluid handling system can be inserted at least partially into the 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 can be a centrifuge vessel and centrifuge tip as previously described, or have any other vessel or tip configuration. In some embodiments, the cuvette may be placed in the centrifuge rotor. This configuration may provide certain advantages over conventional tips and/or vessels. In some embodiments, the cuvette can be patterned with one or more channels with specialized geometries such that the products of the centrifugation process are automatically separated into separate compartments. One such embodiment may be a cuvette with a tapered channel terminating in a compartment separated by a narrow opening. The supernatant (eg, plasma from blood) can be forced into the compartment by centrifugal force, while the red blood cells remain in the main channel. The cuvette can be more complex, with several channels and/or compartments. Channels can 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. Camera images may be analyzed and/or transmitted in real time, eg, by using wireless communication methods. This method can be used to track sedimentation rate/cell accumulation - such as for ESR (erythrocyte sedimentation rate) assays, where the rate of RBC (red blood cell) sedimentation is measured. In some embodiments, one or more cameras can be positioned outside the rotor that can image the contents of the centrifuge vessel as the rotor rotates. This can be achieved by using a stroboscopic illumination source that is timed synchronously with the camera and the rotating rotor. Real-time imaging of the contents of the centrifuge dish while the rotor is spinning may allow the rotor to be stopped after the centrifugation process is complete, saving time and potentially preventing excessive accumulation and/or excessive separation of the contents.

As seen in Figure 12, some embodiments may include windows or openings 3825 on the centrifuge vessel holder to allow viewing of the sample contained therein. This may involve a camera or other detector that can visualize the sample in the vessel through the window or opening 3825. Optionally, some embodiments may provide a window or opening 3825 to allow the illumination source to radiate onto the sample being processed. Some embodiments may include detectors, such as cameras, in the centrifuge, such as, but not limited to, detectors integrated into the centrifuge rotor to image samples therein. This can be beneficial because the movement of any blood components in the sample can be more easily visualized if the camera is in the same frame of reference as the sample. Of course, embodiments in which detectors, such as, but not limited to, cameras, are in a different frame of reference than the moving sample are not excluded. Non-visual detectors are also not excluded, as long as they detect the movement of blood components in the vessel.

Some embodiments may also include a corresponding window or opening 3827 that is the same size as the window or opening 3825 or a different size. This window or opening 3827 allows illumination of the sample fluid within the centrifuge vessel when the centrifuge vessel remains in the centrifuge. Optionally, some embodiments may use the same opening for both illumination and viewing. Some embodiments have visualization through one window or opening and illumination through another set of windows or openings that may or may not be opposite the first set of windows or openings. As with any of the embodiments herein, it should be understood that the window or opening may comprise an optically transparent material covering such window or opening.

thermal control

Centrifugation can sometimes result in undesired changes in sample temperature due, at least in part, to the heat generated by the centrifugation operation. One source of heat during centrifugation operations is waste heat from the drive motor and/or drive mechanism of the centrifuge. This waste heat can be especially problematic if several samples are processed sequentially in the same centrifuge, and heat from each operation builds up during that time period, which can undesirably raise the sample temperature to outside the acceptable range.

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

In one embodiment, because the motor may be integrated into the centrifuge, such integration may benefit from efforts to address heat dissipation issues associated with the motor, centrifuge rotor, bucket, vessel, and/or sample. Methods for addressing such heat dissipation problems may include performing one or more of the following: cooling, thermal isolation, and/or maintaining cooling, either concurrently or sequentially. Some implementations may involve active techniques to deal with thermal issues. Some embodiments may involve passive techniques, such as, but not limited to, thermal isolation of centrifuge components connected to heat sources associated with the centrifuge.

Some embodiments may use thermally conductive materials, such as, but not limited to, heat tape, to alter the heat transfer curve of the centrifuge. In one non-limiting example, the belt may be configured to direct heat away from heat sensitive areas on the centrifuge that will have a thermal effect on the sample. The heat strips are designed to provide a preferential heat transfer path between heat generating components and a heat sink or other cooling device (eg, fan, heat spreader, etc.). The tape may be a viscous pressure sensitive adhesive loaded with a thermally conductive ceramic filter that does not require a heat cure cycle to form bonds to many substrates. This can be used alone or in combination with any of the other thermal solutions described herein.

Some embodiments may use an active cooler, such as, but not limited to, a Peltier heater/cooler, to cool the sample and/or one or more of the aforementioned centrifuge components. Active coolers can be in direct contact with the target surface being cooled. Some embodiments may attach an active heat sink or Peltier heater/cooler to a bucket or holder that holds the centrifuge vessel. Alternatively, the active cooler may be in close proximity to, but not in direct contact with, the target surface. For example, an active radiator or Peltier heater/cooler can be attached to the centrifuge housing in close proximity to the portion of the centrifuge that holds the sample.

Some embodiments may install structures outside the centrifuge housing to assist in convective 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 can be used to radiate any waste heat and/or to assist convection.

As seen in Figure 12, some embodiments may use non-thermally conductive materials to alter the heat transfer curve. In an effort to insulate the sample from the heat source(s), some embodiments may change some metallic materials to plastic materials or other solid materials with low thermal conductivity. Some embodiments may isolate the sample from foam or other types of insulating materials to prevent undesired heat transfer. Some embodiments may have centrifuge rotors made entirely of low thermal conductivity materials. Some embodiments may only have portions of the centrifuge rotor made of low thermal conductivity materials. As seen in FIG. 12, some embodiments may replace only selected portions, such as but not limited to replacing frame portion 3820, with thermally insulating material.

Referring now to Figure 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 seen in Figure 13A, some embodiments may use more than one cooling device 400 at different locations and/or in different orientations with respect to the centrifuge housing 402 to direct convective flow over the centrifuge.

Also seen in Figure 13A, some embodiments may have active thermal devices 410 attached to one or more components of the centrifuge system, such as, but not limited to, the centrifuge housing 402, such as, but not limited to, Peltier heat dissipation device. FIG. 13A shows that a stationary housing 402 may have active thermal devices 410 , such as Peltier effect heat sinks 410 , positioned at one or more locations on the housing 402 . Some embodiments may use conventional passive heat sinks in place of or in combination with Peltier effect heat sink 410 . By way of example and not limitation, some locations indicated in FIG. 13A with active thermal devices 410 may have those cells replaced or augmented by passive heat sinks.

In one embodiment, a Peltier effect heat sink can use electricity to achieve extremely low temperatures. One embodiment may wire the Peltier effect heat sink into the motor circuit. Of course, other configurations for powering the radiator are not excluded. Since the opposite sides of the heat sink are heated during operation, it is desirable to locate the heat sink in ducts, vents, heat spreaders, heat radiation fins, heat radiation pins, or cooling for drawing waste heat away from the heat sink other components on the side. Some embodiments may use thermally conductive motor mounts to draw heat away from internal components. One such embodiment may include a fan with aluminum stator blades brazed to an aluminum motor mount. The motor may be tightly fitted with the housing and coated with a "heat transfer compound" to provide a preferred thermal path for directing heat away from the motor. This will improve heat transfer from the motor to the cooling fins.

Although FIG. 13A shows that thermal conditioning elements may be placed on the housing or other non-moving part of the centrifuge system, it should be understood that similar active thermal device(s) or passive thermal device(s) may also be mounted on On internal and/or moving components of the centrifuge system. By way of non-limiting example, FIG. 13B shows that the motor, centrifuge rotor 404 , buckets, utensils and/or surfaces in contact with the sample may also be configured to be under thermal control of the device(s) 410 . FIG. 13B shows that active thermal devices 410 may be located on the perimeter side surfaces of centrifuge rotor 404 . Alternatively, active thermal device 410 may be located on the top surface of centrifuge rotor 404 . Alternatively, active thermal device 410 may be located on the underside surface of centrifuge rotor 404 . Alternatively, the active thermal device 410 may be located on the shroud, housing or end shield of the rotor 412 . By way of example and not limitation, some locations indicated in FIG. 13B with active thermal devices 410 may have those cells replaced or augmented by passive heat sinks.

Referring 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, cuts or shaped openings in the housing and/or centrifuge rotor to allow air flow. A vent hole 450 may be formed in the housing 452 surrounding a portion of the centrifuge motor. The gauge vent 450 can be sized and/or positioned to allow for greater convective cooling of the motor elements of the centrifuge. In this non-limiting example, the larger opening 454 is sized to accommodate the encoder ring reader. It should be understood that, in addition to (one or more vent holes), the embodiments of Figures 14A-14B may also include any of the active thermal elements or passive thermal elements described in Figures 13A-13B. Based on the location information provided by the various configurations described in this disclosure, some embodiments of a centrifuge may be configured to drive and/or brake the centrifuge so that the centrifuge is used by a user and/or equipment such as But it is not limited to the specific position specified by the programmable processor).

Figure 15 shows yet another embodiment in which vents 460 may be formed in housing 462 adjacent to the centrifuge rotor or even within the centrifuge rotor itself. The vent holes 460 in this embodiment may be positioned below the rotating portion of the centrifuge rotor (not shown for ease of illustration). Other embodiments may have a larger or smaller number of vent holes 460 . Other embodiments may have vents 460 in other shapes such as, but not limited to, square, rectangle, oval, triangle, trapezoid, parallelogram, pentagon, hexagon, octagon, any other shape, or A single combination or multiple combinations of the foregoing shapes. Some embodiments may have multiple vent holes 460, which all have the same shape. Some embodiments may have vent holes 460 with at least one vent hole having a shape different from the shape of at least one other vent hole 460 therein.

Referring now to Figures 16A-16D, yet other embodiments may position thermal control elements 500 on rotating and/or non-rotating parts of the centrifuge to support greater convective heat transfer. FIG. 16A shows a thermal control element 500 in the shape of a fin on the outer radial surface of the centrifuge housing 501 . The fins may have a planar configuration. Alternatively, some embodiments of thermal control element 500 may be projections in the shape of sheath 502 . Some embodiments may 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 may be circular, crescent, teardrop, square, rectangular, triangular, polygonal, or any other shape. The cross-sectional shapes of the fins may or may not be the same 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 the shape of a pyramid (including truncated pyramids) or a cone (including truncated pyramids). In still other embodiments, the surfaces of the fins (eg, sheath-fins) may be curved along the longitudinal length of the fins. Non-limiting examples of surface profiles of curved fins (eg, sheath-fins) include hyperbolas, quadratic curves, polynomial curves with degrees higher than two, circular arcs, or combinations thereof. In some embodiments, the fins are solid structures, but in other embodiments, the fins may be hollow. In some embodiments, the fins may be partially hollow and partially solid. Hollow fins can allow for efficient heat transfer while further reducing the amount of material to be used to make the heat sink, further reducing production costs. Alternatively or additionally, the pattern formed by the fins may 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 interior fins. The resulting channels can have any pattern, such as a generally cross-grained, fish ridge or wavy pattern. In some embodiments, the fins may be coupled together at their bases (or other connection regions) to form a connected network of fins, such as, but not limited to, multiple columns or rows. Some of the fins can be connected to form a permeable network of connected fins.

Figure 16B shows an embodiment with fins 510 on the inner radial portion of the centrifuge. Figure 16C shows the fins 520 on the underside of the centrifuge rotor. Figure 16D shows a still further embodiment in which the fins 530 on the circumferential portion of the rotor can be optionally shaped and/or oriented for use with a shaped housing 540 to draw air into the housing, This helps cool the components in the centrifuge rotor as it spins. Of course, some embodiments may combine one, two, three, or all of the above-described components with other cooling elements to maximize the cooling potential of the system. The embodiments in Figures 16B-16D may have various thermal control devices coupled to moving or stationary parts 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 (usually on the opposite end as the output shaft) that rotates with the motor to provide increased access to Airflow for auxiliary cooling of the internal and external components of the motor.

In another embodiment, water cooling may be used to cool the housing of the motor. In one non-limiting example, a small centrifugal pump can be built off the shaft with a reservoir of pre-cooled water circulating around the motor housing. Other active liquid cooling techniques or passive liquid cooling techniques may also be used. These techniques can be used to cool a portion of the motor housing. Some embodiments may be used to cool only the side walls of the motor housing. Some embodiments may cool the entire housing. Some embodiments may 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 still further embodiments, significantly reducing the winding resistance can be used to reduce the heat being generated by the motor. This may involve using a motor with fewer windings to improve motor performance and in turn reduce heat output from the motor itself. There is also an option to vary the number of poles and magnets to improve motor performance. In this way, the motor assembly can be selected to reduce heat dissipation problems, such as by using a motor with a lower heat output for normal operating conditions of the centrifuge.

Centrifuge position control

Referring now to Figures 17A-17D, improvements to the position control system of the centrifuge rotor will now be described. In one embodiment, various encoder disks or structures, such as, but not limited to, encoder ring 600 may be used to more accurately control and/or detect the position of centrifuge rotor 604 from which a programmable processor may calculate centrifuge Where to locate the retainer on the machine rotor 6604. In such an embodiment, accurate information about the position of the centrifuge rotor 604 would allow the pipette or sample handling system to engage accurately when removing the centrifuge vessel from the centrifuge without the use of a "parking" system Such a vessel is always positioned in a specific position when the centrifuge rotor 604 is stopped.

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

Figure 17B shows another embodiment in which the encoder ring 610 is integrated as part of the centrifuge rotor 604, such as along a portion of the circumference of the rotor's circumference. Detector 612 is oriented for use with integrated encoder ring 610 . The detector can be used alone or in combination with other position detection systems. Alternatively, some embodiments may use one system for high accuracy position sensing and another system for high speed velocity sensing. The movement of the encoder ring 610 from below the centrifuge rotor 604 may also reduce the overall centrifuge height because the detector 612 and encoder ring no longer occupy vertical space below the centrifuge rotor 604 .

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

Figure 17C shows a still further embodiment in which the motor 622 may incorporate an encoder ring or device 620 into the motor 622 during the manufacture of the motor. The encoder 620 may be read by a detector within the motor 622 or by a detector located external to the motor 622 to determine the shaft angular position of the motor. Such an integrated encoder and motor configuration can be used in centrifuges and other system components such as pipettes in sample processing systems where accurate position control is desired due to the small motor form factor. By way of example and not limitation, incremental encoders may be used in induction motor type servo motors, while absolute encoders may be used in permanent magnet brushless motors. In one embodiment, a housing 628 (shown in phantom) may be used to enclose the encoder portion of the motor.

Figure 17D shows yet another embodiment in which other encoder technologies such as, but not limited to, conductive and/or magnetic encoding are used in place of or in conjunction with other encoder technologies such as, but not limited to, optical encoders to detect rotor position . Magnetic encoder reader(s) 650 and/or 652 may be positioned at various locations to detect centrifuge rotor position. Other position detection techniques may be used in place of or in combination with the encoder techniques described herein. In some embodiments as described herein, these capabilities may be integrated into the device.

Alternatively, some embodiments may use separate sensors for speed and position. Some embodiments may use the same sensor for both. By way of example and not limitation, embodiments with more than one sensor may be configured with one sensor for fine position control and one sensor for speed control. In this way, higher centrifuge speeds, such as but not limited to 40,000 rpm, can be achieved without resorting to more complex sensors, since each type can be optimized for its specific purpose, such as low speeds High accuracy position control at high speed and speed control at higher speed. A programmable processor may be used to determine when to transition control of centrifuge rotation based on one sensor or another. Optionally, data from both types of sensors can be used during all time domains to provide accurate position and velocity control.

It will be appreciated that in systems where accurate control is not possible, a system using stops can be used to ensure the final rest position of the centrifuge rotor (which is known). Other embodiments may use alignment 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 vessel on the rotor. With knowledge of where the centrifuge has stopped, the pipette can go to the vessel. Some embodiments of the centrifuge may also have guides to guide the pipette to a desired location or use the pipette to move the pipette to the correct location before the centrifuge rotor engages any sample containing vessel mounted on the centrifuge.

As seen in Figures 17A-17D, the central part of the centrifuge may have a single bearing, optionally two bearings pressed 660 together, to improve stability during rotation and in particular to increase bearing life. As seen in Figures 17A-17D, multiple bearings can be positioned to distribute the load more evenly than if only a single bearing was used. Of course, other numbers and/or types of bearings are not excluded.

In some embodiments described herein, it should be understood that a motor may be enhanced with position and/or velocity sensing capabilities integrated directly into the motor. In one non-limiting example, some embodiments may implement position and/or velocity 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 rotating elements attached to the motor.

Possibilities for hardware integration with motors include, but are not limited to 1) (one or more) optical encoders (for position (relative and/or absolute) and/or velocity sensing) and/or 2) (one or more) Multiple) Hall effect sensors (for position (relative) and/or velocity sensing). Hall effect sensors are semiconductor devices in which the flow of electrons is affected by a magnetic field perpendicular to the direction of the current flow. In one non-limiting example, Hall effect sensor(s) may be used to detect the position of a permanent magnet in a brushless DC electric motor.

Some embodiments may incorporate multiple types of detector hardware, such as, but not limited to, both Hall effect sensor(s) and optical encoder(s) in the same motor. Optionally, some embodiments may have multiple sensors of the same type in the motor. Of course, other types of position and/or velocity detection hardware are not excluded from the embodiments herein or used in conjunction with optical or magnetic encoders.

By way of non-limiting example, at least some embodiments of the sensors and/or encoders herein can perform at speeds up to 12000 RPM (at least 1800 counts per revolution) for position sensing. Optionally, at least some embodiments of the sensors and/or encoders herein can perform at speeds 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 in constant alignment 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 positions. Some implementations may use a sine wave encoder. Encoder technologies may include, but are not limited to, conductive tracks, optical tracks (including reflective versions), and magnetically encoded tracks sensed by Hall-effect sensors or magnetoresistive sensors.

With 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 13mm, while the diameter will remain below 35mm. Alternatively, some embodiments may have an overall height of about 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 velocity sensing hardware does not change the external motor housing size relative to the same motor without the sensing hardware. Optionally, Hall effect sensor(s) can be mounted in the stator slot(s) of the motor to minimize size changes.

Optionally, 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 velocity sensing.

Referring now to FIG. 17E, another embodiment of a centrifuge having a magnetic sensor such as, but not limited to, may be directly integrated into the motor assembly or external to the motor but as part of the centrifuge assembly is shown. The Hall Effect Sensor Assembly 630. Figure 17E shows an exploded view showing Hall effect detector 632 and encoder portion 634. Arrow 636 shows that assembly 630 can be inserted into the centrifuge housing in the orientation as shown. By way of non-limiting example, the assembly 630 is shown with three detectors 632, although it should be understood that other numbers of detectors may be used. Assembly 630 is also shown with all detectors on the same plane. It should be appreciated that some embodiments may have detectors located on 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 a plurality of magnets and/or a plurality of other magnetic field generating or disturbing components that can be detected by the Hall effect detector 632 .

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

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

17G illustrates yet another type of motor that may be configured to include one or more of the encoder assemblies disclosed herein. Some embodiments may use one rotor 640 and one stator 642 in the motor design. Optionally, some embodiments may use a stator 644, a rotor 640, and a stator 642 for increased torque. Any of these embodiments may be configured with the encoder assembly shown herein. Some embodiments may attach or integrate encoder elements, such as, but not limited to, optical encoder disks or magnetic encoder disks directly to the stator or rotor. It should be understood that the motor may be adapted for use with other encoder hardware or other encoder technologies. As seen in Figure 17G, an embodiment of the motor may be configured to fit inside the motor housing shown in Figures 17A-17E to rotate the centrifuge body.

auto balance

Referring now to Figure 18A, some embodiments herein may be configured to use an automatic balancing mechanism on the rotor to minimize rotor vibration, not all holders contain samples. One embodiment may use self-balancing elements 700 such as, but not limited to, beads, spheres, or weights to self-balance the centrifuge rotor, and this may be useful to compensate for different sample volumes in different buckets. Some embodiments can be loaded in some centrifuge holders without a bucket. The auto-balancing element 700 may be in the channel 710 (covered or uncovered) to allow the auto-balancing element to reach a steady state position that minimizes rotational instability of the rotor during operation. In some embodiments, rather than having channels that are continuous along the perimeter of the circumference, some embodiments may have channels formed in certain discrete sections that will only stay in their specific discrete channel sections Automatic balancing element in .

Optionally, as seen in Figure 18B, some embodiments may include a securing feature 720 that only releases the self-balancing element 700 once a minimum rotational speed is reached and centrifugal or other forces release the self-balancing element for movement. into free movement. When sufficient speed is reached, feature 720 may move as indicated by arrow 722 . This movement releases the self-balancing element 700 to move to a position that balances the load on the centrifuge. In this way, the self-balancing element 700 cannot move freely at slower speeds. This can help minimize noise and rotational instability that may result from the ease with which the self-balancing element 700 can roll to a non-optimal balance position at slower speeds.

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

Referring now to Figure 18C, still further embodiments may have the self-balancing element 700 located in a plurality of separate regions 730 on the rotating portion of the centrifuge. In one embodiment, the regions 730 can be connected to each other such that the self-balancing element 700 can move between the regions. Optionally, some embodiments may isolate each of the regions 730 from each other so that the self-balancing element 730 does not move from one region 730 to another.

(one or more) non-mechanical bearings

In still further embodiments, some systems may be configured not to have mechanical bearings but to 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 the centrifuge. Or it can support longer centrifugation times without 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 use both air bearings and mechanical bearings in the same device.

Figure 19B shows yet another embodiment in which one air bearing is annular 722 and the other air bearing 724 is configured to oppose the side wall 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, yet another embodiment of a centrifuge apparatus will now be described. FIG. 20 is a cutaway perspective view showing a centrifuge rotor 800 , such as, but not limited to, a centrifuge disk, rotating as indicated by arrow 802 within a non-rotating housing 804 . The centrifuge may include a detector 810, such as, but not limited to, an accelerometer or the like mounted on the centrifuge to detect undesired force changes during operation of the centrifuge. In one embodiment, a detector 810 is mounted to the exterior of the centrifuge housing to detect if an error has occurred. Detector 810 may be used to detect early indications of abnormal instability in centrifuge operation. If these signs of instability are detected in the abnormal rate of change of force experienced by the centrifuge, the centrifuge may choose to slow down or stop operation, such as by means of a programmable processor, prior to catastrophic equipment failure. Some embodiments may trigger other actions, such as alarms or warnings, based on detection of a rate of change or force outside a threshold range.

Figure 20 also illustrates other features discussed herein that are incorporated into this embodiment. By way of example and not limitation, air bearings 722 and/or 724 may be incorporated for use with this embodiment of the apparatus. Vibration damper(s) 816 may also be used to isolate vibrations from the centrifuge from being transmitted to other elements outside the centrifuge housing. Figure 20 also shows that thermally insulating regions 820, 822, and/or 824 may be used to minimize heat transfer from motor 830 to other parts of the centrifuge rotor.

It should be understood that the embodiment in FIG. 20 may be configured for use with any of the rotor and/or vessel holder configurations described, including but not limited to those shown in FIGS. 1-12 . Some embodiments have vessel holders that can extend mostly above the upper plane or surface of the centrifuge rotor when the rotor is stationary. Optionally, some embodiments may have vessel holders that extend below the plane or surface of the centrifuge rotor when the rotor is stationary. For those embodiments in which the vessel holder extends below the plane or surface of the centrifuge rotor, the housing 804 may be configured with a shaped cutout to allow for spare when the vessel holder and/or vessel are rotated in the downwardly extended position gap. Optionally, some embodiments may mount the rotor 800 higher and/or mount the entire motor higher to provide sufficient clearance for the vessel holder and/or vessel as it rotates in the downwardly extended position .

By way of non-limiting example, a centrifuge may have a diameter of approximately less than or equal to 0.1 mm ² , 0.5 mm ² , 1 mm ² , 3 mm ² , 5 mm ² , 7 mm ² , 10 mm ² , 15 mm ² , 20 mm ² , 25 mm ² , 30 mm ² , 40mm ² , 50mm ² , 60mm ² , 70mm ² , 80mm ² , 90mm ² , 100mm ² , 125mm ² , 150mm ² , 200mm ² , 250mm ² , 300mm ² , 500mm ² or up to 750mm ² footprint. Cell counters can have less than or equal to 0.05mm, 0.1mm, 0.5mm, 0.7mm, 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 15mm, 17mm, 20mm , 25mm, 30mm, 40mm, 50mm, 60mm, 70mm, 80mm, 100mm, 150mm, 200mm, 300mm, 500mm, or 750mm in one or more dimensions (eg, width, length, height).

The embodiment in FIG. 20 also shows a rotor/stator configuration, for at least some embodiments herein, wherein the stator is coaxially mounted within the rotor, wherein the rotor includes a centrifuge disk attached to or integrally formed with the rotor of the motor .

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

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

point of service system

Referring now to Figure 21, it should be understood that the processes described herein may be performed using automated techniques. Automated processing can be used in an integrated automation system. In some embodiments, this automated process may be in a single instrument that has multiple functional components therein and is surrounded by a common housing. Processing techniques and methods for settlement measurements can be preset. Alternatively, the processing techniques and methods can be based on protocols or protocols that can be dynamically changed as needed in the manner described in US Patent Application Serial Nos. 13/355,458 and 13/244,947, which are incorporated by reference for all purposes Incorporated here.

In one non-limiting example as shown in Figure 21, the 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 may control a single or multiple pipette systems 904 that are movable in the X-Y and Z directions as indicated by arrows 906 and 908. The same or different processors may 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 FIG. 21 , control by processor 902 may allow pipette system 904 to obtain a blood sample from cartridge 910 and move the sample to one of assemblies 912 , 914 or 916 . Such movement would involve dispensing the sample into a removable vessel in cartridge 910 and then transporting the removable vessel to one of assemblies 912 , 914 or 916 . Alternatively, the blood sample is dispensed directly into a container already mounted on one of the assemblies 912 , 914 or 916 . In one non-limiting example, one of these components 912, 914 or 916 may be a centrifuge with an imaging configuration to allow illumination and visualization of the sample in the container. Other components 912, 914 or 916 perform other analytical, assay or detection functions.

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

Referring now to Figure 22, a still further embodiment of a centrifuge 1000 will now be described. FIG. 22 shows an exploded perspective view of centrifuge 1000 with cover plate 1010 coupled to rotatable frame 1020 in operation. In this non-limiting example, the rotatable frame 1020 may have a self-balancing element 700, which in this embodiment may be a channel 1030 having a plurality of weighted spheres 1032 therein. Optionally, some embodiments may have a self-balancing element 700 in the cover plate 1010, the shaft 1060, or other rotating parts of the centrifuge. Alternatively, other self-balancing features currently known or developed in the future may 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 buckets 1040 that are attached to allow the buckets 1040 to e.g. into a hinge or other attachment that swings as indicated by arrow 1050 . As seen in this embodiment, the bucket 1040 may have window(s) or viewing portion(s) 1042 that allow viewing of the sample vessel contained therein. Optionally, some embodiments may have no windows. Some embodiments may also have the 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 off vertical. Coupling means such as, but not limited to, magnets 1062 (in direct contact with or spaced from the bucket in the rest position) may be present to assist in having a consistent rest position so that any utensils in the bucket 1040 can be easily loaded or unloaded. In some embodiments, the bucket 1040 may have a ferrous portion and/or magnets thereon to aid in engagement with a coupling device such as a magnet 1062. Optionally, 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 located at the "foot" of the bucket 1040 .

Although only two buckets are shown in Figure 22, it should be understood that embodiments with multiple buckets are not excluded. Optionally, when the bucket 1040 is in the rotated position, at least a portion of the bucket can fill the cavity 1070 in the 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 area of the cavity is filled with the bucket 1040 in the rotated position. Optionally, only about 80% or less of the area in the cavity is filled with the bucket 1040 in the rotated position. Optionally, only about 70% or less of the area in the cavity is filled with the bucket 1040 in the rotated position.

As seen in this embodiment of FIG. 22 , when the centrifuge assembly is assembled and lowered into the housing 1100 as indicated by arrows 1102 , the cover plate 1010 may be substantially flush with the top of the housing 1100 . In some embodiments, position sensors 1110 such as, but not limited to, Hall sensors may be used to sense indicators 1112 on rotating portions of the centrifuge. This may be useful for determining the rest position of the rotating part so that the sample processing device can accurately engage the bucket 1040. Location detection may be performed using optical detection techniques, electromagnetic detection techniques, and/or other detection techniques. Optionally, some embodiments may incorporate position sensing into the motor and/or motor shaft. It should be appreciated that some embodiments may integrate the parts described herein into fewer individual parts for ease of assembly or other reasons. It should be understood that the centrifuges herein may use any motor as described herein (including those with encoders).

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

All of the foregoing embodiments may be integrated within a single housing 920 and configured for benchtop or small footprint floor mounting. In one example, a small footprint floor mounted system may occupy a floor area of about 4 m ² or less. In one example, a small footprint floor mounted system may occupy a floor area of about 3 m ² or less. In one example, a small footprint floor mounted system may occupy a floor area of about 2 m ² or less. In one example, a small footprint floor mounted system may occupy a floor area of about 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 , 0.1m ² , 0.08m ² , 0.05m ² , 0.03m ² , 100cm ² , 80cm ² , 70cm ² , 60cm ² , 50cm ² , 40cm ² , 30cm ² , 20cm ² , 15cm ² or 10cm ² . Some suitable systems in point-of-service settings are described in US Patent Application Serial Nos. 13/355,458 and 13/244,947, the entire contents of which are incorporated herein by reference for all purposes. The present embodiments may be configured for use with any of the modules or systems described in those patent applications.

By way of non-limiting example, a centrifuge may have a diameter of approximately less than or equal to 0.1 mm ² , 0.5 mm ² , 1 mm ² , 3 mm ² , 5 mm ² , 7 mm ² , 10 mm ² , 15 mm ² , 20 mm ² , 25 mm ² , 30 mm ² , 40mm ² , 50mm ² , 60mm ² , 70mm ² , 80mm ² , 90mm ² , 100mm ² , 125mm ² , 150mm ² , 200mm ² , 250mm ² , 300mm ² , 500mm ² or up to 750mm ² footprint. Cell counters can have less than or equal to 0.05mm, 0.1mm, 0.5mm, 0.7mm, 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 15mm, 17mm, 20mm , 25mm, 30mm, 40mm, 50mm, 60mm, 70mm, 80mm, 100mm, 150mm, 200mm, 300mm, 500mm, or 750mm in one or more dimensions (eg, width, length, height).

While the present invention has been described and illustrated with reference to certain specific embodiments thereof, those skilled in the art will appreciate that various modifications can be made to procedures and protocols without departing from the spirit and scope of the invention , change, modify, replace, delete or add. 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 instead of centrifugation. For example, one embodiment may initially centrifuge the sample, which may then be positioned into a filter, which in turn removes the blood components formed 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 invention is described in the context of blood samples, the techniques herein may also be configured to apply to other samples (biological or otherwise). Any of the embodiments herein may be configured with the encoders and/or sensors described in this disclosure. Any of the embodiments herein may be configured with a location detection device as described in this disclosure. Any of the embodiments herein may be configured with the auto-stop feature described in this disclosure. Any of the embodiments herein may be configured with the thermal control feature(s) described in this disclosure.

Alternatively, at least one embodiment may use a variable speed centrifuge. Using feedback, such as, but not limited to, imaging of the position of the interface(s) in the sample, the speed of the centrifuge can be varied to make the compaction curve linear with time (until full compaction), and from the speed of the centrifuge ESR data were extracted from the curve rather than the sedimentation rate curve. In such a system, one or more processors may be used to feedback control the centrifuge to have a linear compaction profile, while also recording the speed profile of the centrifuge. Depending on which interface is tracked, the sedimentation rate data is calculated based on the centrifuge speed. In one non-limiting example, a higher centrifuge speed is used to maintain a linear curve as compaction nears completion.

Furthermore, those skilled in the art will recognize that any of the embodiments of the present invention may be adapted to collect sample fluids from humans, animals or other subjects. Alternatively, the volume of blood used for the sedimentation test 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 volume.

Additionally, concentrations, amounts, and other numerical data may be presented herein in a range format. It should be understood that such range formats are used only for convenience and brevity, and should be flexibly construed to include not only the values expressly listed as the limits of the range, but also all individual values or subranges subsumed within that range, As if each value and subrange were explicitly listed. For example, the size range of about 1 nm to about 200 nm should be construed to include not only the expressly listed limits of about 1 nm and about 200 nm, but also individual sizes such as 2 nm, 3 nm, 4 nm and sub-units such as 10 nm to 50 nm, 20 nm to 100 nm, etc. scope.

Publications discussed or cited herein are provided solely for their disclosure prior to the filing date of this application. Nothing herein should be construed as an admission that the present invention is not entitled to antedate these publications by virtue of prior invention. Furthermore, the dates of publication provided may differ from the actual dates of publication, 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 in connection with which the publications are cited. The following applications are also incorporated herein by reference for all purposes: US Patent Application Serial Nos. 13/355,458, 13/244,947, 13/769,820, 61/852,489, 61/930432, filed July 18, 2012, entitled US Provisional Application Serial No. 61/673,037 for "RapidMeasurement of Formed Blood Component Sedimentation Rate from Small SampleVolumes"; US Provisional Application Serial No. 61/930,462, filed January 22, 2014; US Patents 8,380,541, 8,088,593; US Patent Publication No. 2012/0309636; US Patent Application Serial No. 61/676,178, filed July 26, 2012; PCT/US2012/57155, filed September 25, 2012; US Application Serial No., September 26, 2011 13/244,946; US Patent Application 13/244,949, filed September 26, 2011; and US Application Serial No. 61/673,245, filed September 26, 2011; U.S. Provisional Application Serial No. 61/673,245, "High Speed, Compact Centrifuge for Use with Small Sample Volumes", U.S. Provisional Application Serial No. 61/673,245, filed July 25, 2012, U.S. Provisional Application Serial, entitled "High Speed, Compact Centrifuge for Use with Small Sample Volumes" Serial No. 61/675,758 and US Provisional Application Serial No. 61/706,753, "High Speed, Compact Centrifuge for Use with Small Sample Volumes," filed September 27, 2012; US Patents 8,380,541, 8,088,593; US Patent Publication No. 2012/ 0309636; US Patent Application Serial No. 61/676,178, filed July 26, 2012; PCT/US2012/57155, filed September 25, 2012; US Application Serial No. 13/, filed September 26, 2011 244,946; US Patent Application 13/244,949, filed September 26, 2011; and US Application Serial No. 61/673,245, filed September 26, 2011.

While the above is a complete description of the preferred embodiments of the present invention, it is possible to employ various alternatives, modifications and equivalents. The scope of the invention should, therefore, be determined not with reference to the above description, but should instead be determined with reference to the appended claims, along with their full scope of equivalents. Any feature (whether preferred or not) can be combined with any other feature (whether preferred or not). The following claims should not be construed to include means-plus-function limitations, unless such limitations are 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, as used in the description herein and throughout the claims that follow, the meaning of "in" includes "in" and "on" unless the context clearly dictates otherwise. Finally, as used in the description herein and throughout the claims that follow, "and" and "or" are meant to include both conjunctive and disjunctive conjunctivities and are used interchangeably unless the context clearly dictates otherwise. Thus, in contexts where the terms "and" or "or" are used, the use of such conjunctions does not exclude the meaning of "and/or" unless the context clearly dictates otherwise.

This document contains copyrighted material. For example, all drawings shown herein are copyrighted material. The copyright owner (the applicant here) has no objection to the facsimile reproduction of the patent document and disclosure as they appear in the US Patent and Trademark Office patent file or records, but otherwise reserves all copyright rights whatsoever. The following notice shall apply: Copyright 2012-2014 Theranos Incorporated.

Claims (6)

1. A method for high-speed centrifugation of a small volume sample, comprising: providing a motor coupled to the centrifuge rotor, the motor for rotating the centrifuge rotor; using an encoder on the centrifuge rotor to determine the rotational speed of the rotating portion of the motor; When the centrifuge is in a stopped condition, the bucket is held on the stationary portion of the centrifuge using at least one magnet in the bucket, wherein the bucket is coupled to the centrifuge rotor, the bucket is configured to use For holding containers with no more than 100 μL of sample chamber. 2. The method of claim 1, further comprising using a thermally conductive material configured to direct 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 vessel is arranged such that the vessel is located in an area where thermal exposure is reduced; the An active cooling unit is configured to cool the drive mechanism. 4. The method of claim 1, further comprising using a self-balancing weight coupled to the centrifuge rotor, wherein the self-balancing weight is configured such that the amount of load in the sample holder of the centrifuge is different. Homogeneous, move under centrifugal force to a position that minimizes unbalanced rotation of the centrifuge rotor. 5. The method of claim 1, further comprising using at least one air bearing configured to support the centrifuge in 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.