CN110538725A - High speed centrifuge and method for small volume samples - Google Patents

Abstract

The invention relates to a high speed centrifuge and method for small volume samples. In one non-limiting example, an automated system for separating one or more components in a biological fluid is provided, wherein the system comprises: (a) a centrifuge comprising one or more buckets configured for receiving a container to effect the separation of one or more components in a fluid sample; and (b) the container, wherein the container comprises one or more shaped features that are complementary to the shaped features of the bucket.

Description

High speed centrifuge and method for small volume samples

This application is a divisional application of the invention patent application having international application date of 22/1/2015, international application number of PCT/US2015/012541, application number of 201580015162.5 at the national stage of entry, entitled "method for high-speed centrifugation of small volume samples".

Background

Conventional centrifuges are too large and inefficient at centrifuging for processing small volumes of liquid samples. They have not included certain features that are desirable when dealing with small sample volumes.

Is incorporated by reference

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

Disclosure of Invention

It should be understood that embodiments in the present disclosure may be adapted to have one or more of the features described herein.

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

It should be understood that embodiments herein may be adapted to have one or more of the following features. In one non-limiting example, the system may have one or more buckets that are swing buckets that are in or near a vertical position when the centrifuge is stationary and in or near a horizontal position when the centrifuge is rotating. Alternatively, the system may have a plurality of 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 100uL or less of sample fluid. Optionally, the container is configured to contain 50uL 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 comprises an extraction tip having one or more shaping features complementary to the shaping features of the centrifuge vessel and configured to fit within the centrifuge vessel. Optionally, the shaped feature of the bucket comprises one or more shelves on which the protruding portion of the container is configured to rest. Optionally, the bucket is configured to be able to receive a plurality of containers having different configurations, and wherein the shaping feature of the bucket comprises a plurality of shelves, wherein a first container having a first configuration is configured to rest on a first shelf and a second container having a second configuration is configured to rest on a second shelf.

In yet another embodiment described herein, there is provided a compact high speed centrifuge, the centrifuge comprising a centrifuge body; a motor for rotating the centrifuge body; and a detector integrated with the motor and configured to determine at least a rotational position of a rotating portion of the motor, wherein the detector uses at least two different types of encoder information to determine the rotational position.

It should be understood that embodiments herein may be adapted to have one or more of the following features. In one non-limiting example, the detector determines the rotational position using at least an optical encoder and hall effect technology. Optionally, the detector determines at least the rotational position and the rotational speed using at least an optical encoder and hall effect technology. 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 in the same direction. Optionally, the motor comprises a plurality of detectors for determining the rotational position. Optionally, the motor further comprises a first encoder disk providing a first type of encoder information and a second encoder disk providing a second type of encoder information. Optionally, the motor further comprises a first encoder disk providing optical encoder information and a second encoder disk providing magnetic encoder information. Optionally, the motor comprises an encoder disc providing a first type of encoder information and a second type of encoder information. Optionally, the motor includes an encoder disk that provides both optical encoder information and magnetic encoder information. It should be understood that while the motor with integrated encoder 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 speed detector features into the motor.

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

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

In another embodiment described herein, a compact high speed centrifuge for use with a sample container is provided. The centrifuge may include: a first portion comprising a thermally insulating material; a second portion comprising a thermally conductive material; wherein the container is arranged such that the container is located in an area having a thermally insulating material; wherein the thermally conductive material is configured to direct heat in a direction 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 include a centrifuge body; a drive mechanism for rotating the centrifuge body; an active cooling unit for minimizing heat transfer to the sample; wherein the container is arranged such that the container is located in an area having reduced thermal exposure; the active cooling unit is configured to cool the drive mechanism; wherein the stator is positioned coaxially 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 an automatic 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 load amounts in a sample holder of the centrifuge.

In another embodiment described herein, a compact high speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body; and at least one air bearing configured to support the centrifuge 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 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; a force detector for detecting a change in the rate of force outside a predetermined range of force-receiving conditions.

It should be understood that embodiments herein may be adapted to have one or more of the following features. In one non-limiting example, the centrifuge vessel holder pivots inwardly toward a central axis of the centrifuge rotor under centrifugal force. Optionally, the centrifuge vessel holder forms a flush surface with the rotor body to minimize aerodynamic drag. Optionally, the centrifuge vessel holder is configured for retracting downward under centrifugal force. Optionally, electrical connections to centrifuge body cooling elements therein are uninterrupted, even if such elements are in operation 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, wherein the centrifuge body extends downward to cover at least a portion of the drive mechanism; wherein the drive mechanism comprises 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 downward to cover at least a portion of the drive mechanism; wherein the drive mechanism comprises 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 swing-out holders on the centrifuge body for containing centrifuge vessels; wherein the swing type holder or the sample container has a maximum dimension of no more than 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 swing-out holders on the centrifuge body for containing centrifuge vessels; wherein the pendulum-type holder moves from a first orientation to a second orientation that is more horizontal than the first orientation during centrifugation.

In another embodiment described herein, a compact high speed centrifuge for use with a sample container is provided. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body; one or more swing-out holders on the centrifuge body for containing centrifuge vessels; wherein 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 low volume sample containers is provided, the centrifuge comprising a centrifuge rotor; a motor for rotating the centrifuge rotor; a plurality of buckets coupled to the centrifuge rotor; and at least one magnetic device located on the bucket, the magnetic device being positioned to couple the bucket to a stationary portion of the centrifuge when the bucket is in a stationary position.

It should be understood that embodiments herein may be adapted to have one or more of the following features. In one non-limiting example, the rotor includes at least an optical encoder and a hall effect sensor to determine rotational position. Optionally, the rotor comprises at least an optical encoder and a hall effect sensor to determine at least rotational position and rotational speed. Optionally, a first encoder disk is included and provides the first type of encoder information and a second encoder disk 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 receive a vessel for holding a sample volume of no more than 70 uL. Optionally, the bucket is configured to receive a vessel for holding a sample volume of no more than 80 uL. Optionally, the bucket is configured to receive a vessel for holding a sample volume of no more than 90 uL. Optionally, the bucket is configured to receive a vessel for holding a sample volume of no more than 100 uL. Optionally, the bucket is configured to receive 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 a side 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, a method is provided that includes 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 using at least one magnet in a bucket 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 more than 100 uL. Optionally, the method comprises 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 container is arranged such that it is located in an area where heat exposure is reduced; the active cooling unit is configured to cool the drive mechanism. Optionally, the method comprises using an automatic balancing weight coupled to the centrifuge body, wherein such weight is configured to move under centrifugal force to a position that minimizes unbalanced rotation of the centrifuge body with uneven load amounts in a sample holder of the centrifuge. Optionally, the method comprises using at least one air bearing configured to support the centrifuge in operation. Optionally, the method comprises 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 comprises using a force detector configured to detect a change in rate of force outside a predetermined range of force-receiving conditions. Optionally, the centrifuge vessel holder is pivoted inwardly towards the central axis of the centrifuge rotor under centrifugal force. Optionally, the centrifuge vessel holder forms a flush surface with the rotor body to minimize aerodynamic drag. Optionally, the centrifuge vessel holder is configured for retracting downward under centrifugal force. Optionally, the electrical connections to the centrifuge body cooling elements are not interrupted, even if such elements are in operation during centrifugation. Optionally, the centrifuge vessel holder moves from a first orientation to a second orientation that is more horizontal than the first orientation during centrifugation.

It is to be understood that embodiments in the present disclosure provide a method including 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, an apparatus may include at least any one technical feature from any of the other embodiments herein. Optionally, a device may include at least any two technical features from any of the other embodiments herein. Optionally, a system may include at least any one technical feature from any of the other embodiments herein. Optionally, a system may include at least any two technical features from any of the other embodiments herein.

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

Drawings

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

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

Fig. 6-8 show various views of embodiments of a vessel holder as described herein.

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

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

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

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

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

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

Fig. 22-23 illustrate yet another embodiment of an apparatus as described herein.

Detailed Description

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" can include mixtures of materials, reference to "a compound" can include compounds, and the like. The references cited herein are hereby incorporated by reference in their entirety unless they conflict in a certain extent with the teachings set forth explicitly in this specification.

In this specification and in the claims which follow, reference will be made to a number of terms which shall be defined to have the following meanings:

"optional" or "optionally" means that the subsequently described circumstance may or may not occur, such that the description includes instances where the circumstance occurs and instances where it does not. For example, if the device optionally contains features for a sample collection well, this means that the sample collection well may or may not be present, and thus the description includes both structures in which the device possesses a sample collection well and structures in which a sample collection well is not present.

centrifugal machine

Fig. 1, 2 and 3 show perspective views of a centrifuge (fig. 1-side view, fig. 2-front view, fig. 3-rear view) that can be integrated into a system. The centrifuge may contain an electric motor capable of rotating the rotor at 15000 rpm. One type of centrifuge rotor is shaped somewhat like fan blades mounted on a motor shaft in a vertical plane. The element holding the sample fixation element (tip) and providing a ledge or shelf on which the end of the tip distal to the motor shaft rests and which provides support during centrifugation so that the sample cannot escape is affixed to the rotor. The tip may be further supported at its proximal end by a mechanical stop in the rotor. 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 may be inserted and removed by a standard pick and place mechanism, but is preferably a pipette. The rotor is a block of monoacrylic acid (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 particular angle to the vertical. The sample holding element is centrifugally balanced by a counter-mass on the opposite side of the rotor so that the centre of moment of inertia is axial with respect to the motor. The centrifuge motor may provide position data to a computer, which may in turn control the resting position of the rotor (generally vertical before and after centrifugation).

In order to minimize centrifugation time (without generating too much mechanical stress during centrifugation), a convenient size of the rotor is in the range of about 5-10cm, rotated at about 10000- "20000 rpm, providing a time of about 5min for packing red blood cells, according to published standards (DIN 58933-1; for the US CLSI Standard H07-A3" Procedure for dividing Packed Cell Volume by the Microhematocrit Method "; approved Standard-third edition).

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. The centrifuge may be capable of rotating two or more vessels simultaneously, and may be designed to be fully integrated into an automated system employing computer-controlled pipettes. In some embodiments, the bottom of the vessel may be closed. The swing bucket design can allow the centrifuge vessel to be passively oriented in a vertical position when stopped, and to rotate outward to a fixed angle when rotated. In some embodiments, the oscillating bucket may allow the centrifuge vessel to rotate outward to a horizontal orientation. Or they may be rotated outward to any angle between the vertical and horizontal positions (e.g., about 15, 30, 45, 60, or 75 degrees from vertical). A centrifuge with a swing bucket design can meet the positional accuracy and repeatability requirements of a robotic system that employs several positioning systems.

The computer-based control system may use position information from the optical encoder to rotate the rotor at a controlled slow speed. Since an appropriate motor can be designed for high speed performance, position feedback need not be used separately to maintain an accurate static position. In some embodiments, a cam in combination with a solenoid actuated lever may be employed to achieve a very accurate and stable stop at a fixed number of positions. The speed of the high speed rotor can be controlled very accurately using a separate control system and feedback from hall effect sensors built into the motor.

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

Rotor

The centrifuge rotor may be an assembly of the system that can hold and rotate one or more centrifuge vessels. The axis of rotation may be vertical and thus the rotor itself may be positioned horizontally. However, in alternative embodiments, different rotational axis and rotor positions may be employed. There are two assemblies, called buckets, positioned symmetrically on either side of the rotor holding the centrifuge vessel. Alternative configurations are possible in which the buckets are oriented radially symmetrically, e.g., 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 one another. For example, if n buckets are provided, where n is an integer, the buckets may be spaced about 360/n degrees from each other. In other embodiments, the buckets need not be evenly spaced about each other or radially symmetric.

When the rotor is stationary, these buckets may be passively lowered under the influence of gravity to position the vessels vertically and make them accessible to the pipette. Fig. 4 shows an example of a stationary rotor, where the bucket is vertical. In some embodiments, the bucket may be passively lowered to a predetermined angle, which may or may not be vertical. As the rotor rotates, the bucket is forced by centrifugal force into a nearly horizontal position or a predetermined angle. Fig. 5 shows an example of a rotor at a speed where the bucket is at a small angle to the horizontal. There may be a physical hard stop for both the vertical and horizontal positions for implementing its accuracy and positional repeatability.

The rotor may 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 external geometry of the bucket may be precisely matched to the external geometry of the rotor so that the bucket and rotor can be perfectly aligned when the rotor is rotating and the bucket may be forced to be horizontal.

To facilitate plasma extraction, the rotor may be angled relative to horizontal downward toward the ground. Since the angle of the bucket can be matched to the angle of the rotor, a fixed angle of rotation of the bucket can be implemented in this way. The sediment resulting from such a configuration may be angled with respect to the vessel when the vessel is placed vertically. A narrow extraction tip can be used to aspirate plasma from the top of the centrifuge vessel. By placing the extraction tip near the bottom of the slope created by the angular sediment, the final volume of plasma can be extracted more efficiently without disturbing the sensitive buffy coat.

A variety of tube designs can be accommodated in the bucket of the device. In some embodiments, various tube designs may be closed-ended. Some tube designs are shaped like conventional centrifuge tubes with a tapered bottom. Other tube designs may be cylindrical. Tubes with a lower height to cross-sectional area ratio may facilitate cell processing. Tubes with large ratios (>10:1) may be suitable for accurate measurement of hematocrit and other imaging requirements. However, any height to cross-sectional area ratio may be employed. The bucket may be made of any of several plastics (polystyrene, polypropylene) or any other material discussed elsewhere herein. The bucket may have a capacity ranging from a few microliters to about 1 milliliter. The tubes may 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 device, a dual control system approach may be used. To index the rotor to a particular rotational orientation, a position-based control system may 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 may be provided by a high resolution optical encoder. In order to run the centrifuge at low to high speeds, a speed controller may be implemented while employing a PID control system tuned for speed control. The rotation rate feedback for the speed controller may be provided by a simple set of hall effect sensors placed on the motor shaft. Each sensor may generate a square wave upon one cycle of each motor shaft rotation.

Stop mechanism

in order to consistently and securely position the rotor in a particular position, 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 may be shaped like a disk having a number of "C" shaped notches machined around the perimeter. To position the centrifuge rotor, its rotational speed may first be reduced 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 5rpm, 10rpm, 15rpm, 20rpm, 25rpm, 35rpm, 40rpm, or 50 rpm. Once the speed is sufficiently slow, the lever can be actuated. Located at the end of the lever is a cam follower that can slide along the circumference of the cam with minimal friction. Once the cam follower reaches the center of a particular slot in the cam, the force of the solenoid actuated lever may overcome the force of the motor and may stop the rotor. At that time, the motor may be electronically braked, and in combination with the stop mechanism, the rotational position can be held very accurately and securely indefinitely.

Centrifuge bucket(s)

The centrifuge pendulum bucket may be configured to house different types of centrifuge tubes. In a preferred embodiment, the various tube types may have a collar or flange at their upper (open) end. Such a collar or flange feature may rest on the upper end of the bucket and support the tube during centrifugation. As shown in fig. 6,7 and 8, tapered and cylindrical tubes of various lengths and volumes may be accommodated. Fig. 6,7, and 8 provide examples of buckets, and other bucket designs may be employed. For example, fig. 6 shows an example of a bucket configuration. The bucket may have a side portion that engages the centrifuge and allows the bucket to swing freely. The bucket may have a closed bottom and an opening at its top end. Fig. 7 shows an example of a centrifuge vessel fitted with a bucket. As previously mentioned, the bucket may be shaped for receiving centrifuge vessels of various configurations. The centrifuge vessel may have one or more protruding members that can rest on the bucket. The centrifuge vessel may be shaped with one or more features that may cooperate with the centrifuge bucket. The feature may be a shaped feature or one or more protrusions of the vessel. Fig. 8 shows an example of another centrifuge vessel that can be fitted with a bucket. As previously described, the bucket may have one or more shaping features that may allow differently configured centrifuge vessels to fit with the bucket. It should be understood that any of the embodiments of the centrifuge in fig. 4-8 may be configured with any of the other features described in this disclosure.

Centrifuge tube and sample extraction technique

The centrifuge tube and extraction tip may be provided separately and may be fitted 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.

The system may implement one or more of the following:

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

2. Accurate and precise measurement of hematocrit

3. High efficiency plasma removal

4. Highly effective resuspending of formed components (red and white blood cells)

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

6. Optical confirmation of erythrocyte lysis and recovery of leukocytes

Overview of centrifuge vessel and extraction tip

The centrifuge can be operated using custom vessels and tips to meet a variety of constraints placed on the system. The centrifuge vessel may be a closed-bottom tube designed to rotate in a centrifuge. In some embodiments, the centrifugation vessel may be the vessel shown in fig. 7, or may have one or more of the features shown in fig. 7. It can have several unique features that support a wide range of desired functions, including hematocrit measurement, RBC lysis, pellet resuspension, and efficient plasma extraction. The extraction tip may be designed for insertion into a centrifuge vessel 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 descriptions of extraction tips are discussed herein and may be found in U.S. application serial numbers 13/355,458 and 13/244,947, which are incorporated herein by reference in their entirety for all purposes.

Centrifugal vessel

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

A first use scenario may require 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 required or preferred plasma volume may be about 40uL by 40% ═ 16 uL.

In some embodiments, it will not be possible to recover 100% of the plasma because the buffy coat must not be disturbed and therefore a minimum distance must be maintained between the bottom of the tip and the top of the sediment. This minimum distance can be determined experimentally, but the volume (V) sacrificed as a function of the required safety distance (d) can be estimated using the following equation: v (d) ═ d pi 1.25mm 2. For example, for the case of a 60% hematocrit, the sacrificial volume may be 1.23uL for a required safety distance of 0.25 mm. This volume can be reduced by reducing the internal diameter of the hematocrit portion of the centrifuge vessel. However, since in some embodiments this narrow portion must fully house the outer diameter of the extraction tip (which may not be less than 1.5mm), 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 a given volume of hematocrit can be maximized by minimizing the inner diameter of the narrow portion of the vessel. By maximizing the height, the relationship between the change in hematocrit volume and the physical change in column height can be optimized, thereby increasing the number of pixels available for measurement. The height of the narrow portion of the vessel can also be long enough to accommodate the worst case scenario, 80% hematocrit, while still leaving a small portion of plasma at the top of the column to allow for efficient extraction. Thus, 40uL by 80% — 32uL may be the volume capacity required for accurate hematocrit measurement. The volume of the narrow portion of the tip designed may be about 35.3uL, which may allow some volume of plasma to remain, even in the worst case.

The second usage scenario involves more and may require one, more or all of the following:

Precipitating the whole blood

Extraction of plasma

resuspending the pellet in lysis buffer and stain

Precipitating the remaining White Blood Cells (WBC)

Removing the supernatant

Resuspending WBCs

Complete extraction of WBC suspension

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

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

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

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

In some embodiments, the distance from the bottom of the fully mated mouth to the top of the maximum fluid line is 2.5 mm. This distance is 1.5mm less than the recommended distance 4mm followed by the extraction tip. This reduced distance may be affected by the need to: the length of the extraction tip is minimized while complying with minimum volume requirements. The reason for this reduced distance stems from the particular use of the vessel. Since in some implementations fluid may only be exchanged with the vessel from the top, the maximum fluid it will have when mated with the mouth is the maximum total blood volume (40uL) expected at any given time. The height of the 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 and wet the walls up to the height of the mouth. In some embodiments, the fluid will be up to 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 amount. 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 size, dimension, 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 quickly inserting and removing tips, the centrifuge vessel may be subjected to some forces. If the vessel is unconstrained, these forces may be strong enough to lift or otherwise move the vessel away from the centrifuge bucket. To prevent movement, the vessel should be fixed in some way. To achieve this, a small ring circumscribing the bottom exterior of the vessel was added. The ring can easily mate with compliant mechanical features on the bucket. This problem is solved as long as the retention force of the nubs is greater than the force experienced during fluid manipulation but less than the friction force when engaging with the mouth.

extraction tip

The extraction tip can be designed to interface with a centrifuge vessel to efficiently extract plasma and resuspend sedimented cells. If desired, its overall length (e.g., 34.5mm) may exactly match the overall length of another blood tip, including but not limited to those described in U.S. serial No. 12/244,723 (incorporated herein by reference), but may be long enough to physically contact the bottom of the centrifuge vessel. In some embodiments, the ability to contact the bottom of the vessel may be required for both the resuspension process and for complete recovery of the leukocyte suspension.

The volume of extraction tip required may 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 60uL, which may be less than the maximum capacity of the tip of 85 uL. In some embodiments, a tip having a volume greater than the desired volume may be provided. As with centrifuge vessels, internal features that circumscribe the interior of the upper portion of the tip can be used to mark the height of this maximum volume. The distance between the line of maximum volume and the top of the mating spout may be 4.5mm, which may be considered a safe distance to prevent contamination of the spout. Any sufficient distance sufficient to prevent mouth contamination may be used.

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

In one example, plasma may be diluted into a mixture of dextran sulfate (25mg/dL) and magnesium sulfate (100mM) and incubation may then be performed for 1 minute to precipitate LDL-cholesterol. The reaction product may be aspirated into the tube of the centrifuge, followed by capping and spinning at 3000rpm for three minutes. Images of the initial reaction mixture taken before centrifugation (showing white precipitates), after centrifugation (showing clear supernatant), and LDL-cholesterol precipitate taken (after removal of the lid) were as shown in U.S. application serial nos. 13/355,458 and 13/244,947, respectively, and are incorporated herein by reference in their entireties for all purposes.

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

Example scheme

Many variations of the protocol can be used for centrifugation and processing. For example, a typical protocol for processing and concentrating leukocytes for cell counting using a centrifuge may include one or more of the following steps. The steps below may be provided in a different order, or any of the steps below may be replaced with other steps:

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

2. Erythrocytes and leukocytes were sedimented by centrifugation (<5min x 10000 g).

3. Measurement of hematocrit by imaging

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

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

6. Incubate at 37 ℃ for 15 minutes.

7. The lysis/fixation reagent was prepared by mixing a red blood cell lysis solution (ammonium chloride/potassium bicarbonate) with a leukocyte fixation reagent (formaldehyde).

8. 30uL of lysis/immobilization reagent was added (total reaction volume approximately 60 uL).

9. Incubate at 37 ℃ for 15 minutes.

10. Leukocytes were sedimented by centrifugation (10000 g).

11. The supernatant hemolysis product was removed.

12. The leukocytes were resuspended by adding buffer (isotonic buffered saline).

13. The volume is accurately measured.

14. The sample is delivered to a cytometer.

The step may include receiving a sample. The sample may be a bodily fluid, such as blood, or any other sample described elsewhere herein. The sample may 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 may occur via centrifugation, magnetic separation, lysis, or any other separation technique known in the art. In some embodiments, the sample may be blood, and red blood cells and white blood cells may be separated.

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

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

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

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

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

In another example, a typical protocol for nucleic acid purification, which 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 an exponential amplification reaction for detection. The process can be designed for extracting nucleic acids from a variety of samples including, but not limited to, whole blood, serum, virus transport media, human and animal tissue samples, food samples, and bacterial cultures. The process can be fully automated and can extract DNA/RNA in a consistent and quantitative manner. The steps below may be provided in a different order, or any of the steps below may be replaced with other steps:

1. The sample is lysed. A chaotropic salt buffer may be used to lyse cells in a sample. The chaotropic salt buffer may comprise one or more of the following: chaotropic salts such as, but not limited to, 3-6M guanidine hydrochloride or guanidine thiocyanate; sodium Dodecyl Sulfate (SDS) at typical concentrations of 0.1-5% v/v; ethylenediaminetetraacetic acid (EDTA) at typical concentrations of 1-5 mM; lysozyme at a typical concentration of 1 mg/mL; proteinase-K at a typical concentration of 1 mg/mL; and a buffer such as HEPES can be used to set the pH at 7-7.5. In some embodiments, the sample can be in a typical temperature of 20-95 ℃ buffer temperature in 0-30 minutes. Isopropanol (50% -100% v/v) may be added to the mixture after lysis.

2. And (4) surface loading. The lysed sample may be exposed to a functionalized surface (typically in the form of a packed bed of microbeads), such as, but not limited to, a resin support packed in a chromatography column, magnetic beads mixed with the sample in a batch-wise fashion, a sample pumped through a suspension resin in a fluidized bed mode, and a sample pumped through a closed channel in a tangential flow fashion over the surface. The surface can be functionalized to bind nucleic acids (e.g., DNA, RNA, DNA/RNA hybrids) in the presence of a lysis buffer. Surface types may include silica and ion exchange functional groups such as Diethylaminoethanol (DEAE). The lysed mixture may be exposed to the surface and the nucleic acid conjugate.

3. And (6) washing. The solid surface is washed with a salt solution, such as a 0-2M sodium chloride and ethanol (20-80% v/v) salt solution at a pH of 7.0-7.5. The washing can be achieved in the same way as loading.

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

The system may employ many variations of these or other schemes. Such protocols may 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 that have been packed and concentrated by centrifugation for cell counting. In some embodiments, this may be achieved by using a pipetting device. A liquid (typically isotonic buffered saline, a lysing agent, a mixture of lysing agent and fixing agent, or a mixture of labeled antibodies in a buffer) can be dispensed into the centrifuge bucket and repeatedly aspirated and resuspended. The tip of the pipette may be forced into the accumulated cells to facilitate this process. Image analysis aided this process by objectively verifying that all cells had been resuspended.

Processing samples using pipettes and centrifuges prior to analysis

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

In particular, the system may support the separation of the forming components (red and white blood cells) from the plasma. The system may also support resuspension of the forming components. In some embodiments, the system may support concentration of leukocytes from fixed and hemolyzed blood. The system may also support lysis of the cells to release the nucleic acids. In some embodiments, the system can support nucleic acid purification and concentration by filtration through a tip packed with (typically beaded) solid phase reagents (e.g., silica). The system may also allow elution of purified nucleic acid after solid phase extraction. The system may also support removal and collection of the precipitate (e.g., LDL-cholesterol precipitated using polyethylene glycol).

In some embodiments, the system can support affinity purification. Small molecules such as vitamin-D and serotonin can be absorbed onto beaded (particulate) hydrophobic substrates and subsequently eluted using organic solvents. The antigen may be provided on a substrate coated with the antibody and eluted with an acid. The same method can be used to concentrate analytes found at low concentrations, such as thromboxane-B2 and 6-keto-prostaglandin F1 alpha. The antigen may be provided onto a substrate coated with the antibody or aptamer and then eluted.

In some embodiments, the system may support chemical modification of the analyte prior to the assay. For example, to determine serotonin (5-hydroxytryptamine), 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 in order to produce a form of analyte that is recognized by the antibody.

A pipette may be used to move the liquid (vacuum suction and pumping). Pipettes may be limited to relatively low positive and negative pressures (about 0.1-2.0 atmospheres). When desired, a centrifuge can be used to generate a much higher pressure to force the liquid through the beaded solid phase medium. For example, using a rotor with a radius of 5cm at a speed of 10000rpm, a force of about 5000x 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 are capable of capturing good images of small objects even when the contrast is poor. With this capability, the system of the present invention can support automated measurement of hematocrit with very small volumes of blood.

For example, 1uL of blood can be drawn into a microliter glass capillary. The capillary may then be sealed with a curable adhesive and then subjected to centrifugation at 10000x g for 5 minutes. The packed cell volume can be easily measured and the plasma meniscus (indicated by the arrow) may also be visible, so that the 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 may be used "as is" without operating the microscope to obtain a larger image. In other embodiments, the image may be magnified using a microscope or other optical technique. In one implementation, a digital camera is used to determine hematocrit without additional light interference, and the measured hematocrit is the same as that determined by conventional microperfolit lab methods, which require many microliters of sample. In some embodiments, the length of the sample column and the length of the column of packed red blood cells (+/- <0.05mm) can be measured very accurately. Assuming that the blood sample column can be about 10-20mm, the standard deviation of hematocrit can be much better than the 1% match obtained by standard laboratory methods.

The system can support measurement of Erythrocyte Sedimentation Rate (ESR). The ESR can be measured using the ability of a digital camera to measure very small distances and rates of change of distance. In one example, three blood samples (15uL) were aspirated into the "reaction tip". Images were captured within one hour at two minute intervals. Image analysis is used to measure the movement of the interface between the red blood cells and the plasma.

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

Centrifugal machine

Referring now to fig. 9-11, 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 apparatus in the system. For example, one or more centrifuges may be provided within the device housing. The module may have one or more centrifuges. There may be a centrifuge 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. The centrifuge may have a form factor that is compact, flat, and occupies only a small footprint. In some embodiments, the centrifuge may be miniaturized for point-of-service applications, yet still be capable of rotating at high rates equal to or exceeding about 10000rpm and capable of withstanding gravitational accelerations of up to about 1200m/s2 or greater.

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

In some embodiments, the centrifuge may have one or more chambers configurable to receive a sample. The chamber may be configured to receive a sample directly within the chamber such that the sample may contact the chamber walls. Alternatively, the cavity may be configured to receive a sample vessel in which a sample may be contained. Any description herein of a chamber is applicable to any configuration that can receive and/or contain a sample or sample container. For example, the cavity may include an indentation in the material, a bucket-shaped, a projection with a hollow interior, a member configured to interconnect with the sample container. Any description of a cavity may also include configurations that may or may not have a concave or inner surface. Examples of sample vessels may include any of the vessel or tip designs described elsewhere herein. The sample vessel may 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 may have a closed end. The sample vessel may be a mouth of a fluid processing device that may act as a centrifuge to spin fluid among the mouth, a tip, or another vessel attached to such a mouth.

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

In some embodiments, the centrifuge may be configured to receive a small volume of sample. In some embodiments, the cavity and/or sample vessel can be configured to receive a sample volume of 1000 μ L or less, 500 μ L or less, 250 μ L or less, 200 μ L or less, 175 μ L or less, 150 μ L or less, 100 μ L or less, 80 μ L or less, 70 μ L or less, 60 μ L or less, 50 μ L or less, 30 μ L or less, 20 μ L or less, 15 μ L or less, 10 μ L or less, 8 μ L or less, 5 μ L or less, 1 μ L or less, 500nL or less, 300nL or less, 100nL or less, 50nL or less, 10nL or less, 1nL or less, 500pL or less, 100pL or less, 50pL or less, 10pL or less, 5pL or less, or 1pL or less.

In some embodiments, the centrifuge may have a lid that may contain the sample within the centrifuge. The cover may prevent sample fogging and/or evaporation. The centrifuge may optionally have a membrane, oil (e.g., mineral oil), wax, or gel that may contain and/or prevent the sample from being atomized and/or evaporated within the centrifuge. A membrane, oil, wax or gel may be provided as a layer over the sample that may be contained within the chamber and/or sample vessel of the centrifuge.

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

in some embodiments, the axis of rotation may be vertical. Alternatively, the axis of rotation may be horizontal, or may have any angle between vertical and horizontal (e.g., about 15, 30, 45, 60, or 75 degrees). In some embodiments, the axis of rotation may be in a fixed direction. Alternatively, the axis of rotation may be varied during use of the device. The rotation axis angle may or may not vary when the centrifuge is rotating.

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

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

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

The centrifuge may be of any size. For example, the centrifuge may have a footprint of about 200cm2 or less, 150cm2 or less, 100cm2 or less, 90cm2 or less, 80cm2 or less, 70cm2 or less, 60cm2 or less, 50cm2 or less, 40cm2 or less, 30cm2 or less, 20cm2 or less, 10cm2 or less, 5cm2 or less, or 1cm2 or less. The centrifuge can have a height of about 5cm or less, 4cm or less, 3cm or less, 2.5cm or less, 2cm or less, 1.75cm or less, 1.5cm or less, 1cm or less, 0.75cm or less, 0.5cm or less, or 0.1cm or less. In some embodiments, the maximum dimension of the centrifuge can be about 15cm or less, 10cm or less, 9cm or less, 8cm or less, 7cm or less, 6cm or less, 5cm or less, 4cm or less, 3cm or less, 2cm or less, or 1cm or less.

The centrifuge base may be configured to receive a drive mechanism. The drive mechanism may be a motor, or any other mechanism that enables the centrifuge to rotate about a rotational axis. The drive mechanism may be a brushless motor, which may include a brushless motor rotor and a brushless motor stator. The brushless motor may be an induction motor. The brushless motor rotor may surround the brushless motor stator. The rotor may be configured to rotate about the stator about an axis of rotation.

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

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

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

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

The centrifuge may be configured to receive the sample vessel and may be configured to place the sample vessel in a first orientation when the base is stationary and to place the sample vessel in a second orientation when the base is rotated. The first orientation may be a vertical orientation and the second orientation may be a horizontal orientation. The sample vessel may have any orientation, wherein the sample vessel may be at greater than and/or equal to about 0,5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, or 90 degrees from vertical. 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.

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

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

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

1, 2, 3, 4, 5,6 or more cavities may be provided in the wings. For example, the wings may be configured to receive one, two or more samples or sample vessels. Each wing may be capable of receiving 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 is oriented toward the first orientation when the base is stationary and configured to be oriented toward the second orientation when the base is rotated.

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

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

The wings may have a center of gravity 3680 that is positioned below the fold axis and/or pivot point 3620. When the base is stationary, the center of gravity of the wing may be positioned lower than the shaft extending through the base. The center of gravity of the wing may be positioned lower than the shaft extending through the base as the base rotates.

The wing portions may be formed of two or more different materials having different densities. Alternatively, the wing portion may be formed of a single material. In one example, the wing sections may have a lightweight wing cover 3640 and a heavy wing base 3645. In some embodiments, the wing cover may be formed of a material having a lower density than the wing base. For example, the wing cover may be formed of plastic, while the wing base is formed of metal, e.g., steel, tungsten, aluminum, copper, brass, iron, gold, silver, titanium, or any combination or alloy thereof. The heavier wing base may help provide a wing centroid below the fold axis and/or pivot point.

The wing cover and wing base may be connected by any 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 flap cover. The insert may help provide the wing centroid below the fold axis and/or pivot point.

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

The centrifuge may be configured to engage a fluid processing device. For example, the centrifuge may be configured for connection to a pipette or other fluid handling device. In some embodiments, a water-tight seal may be formed between the centrifuge and the fluid handling device. The centrifuge may be engaged with a fluid processing device and configured to receive a sample dispensed from the fluid processing device. The centrifuge may be engaged with a fluid handling device and configured to receive a sample vessel from the fluid handling device. The centrifuge may be engaged with a fluid handling device and allow the fluid handling device to pick up or aspirate a sample from the centrifuge. The centrifuge may be engaged with a fluid handling device and allow the fluid handling device to pick up the sample vessel.

The sample vessel may 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. In some embodiments, a water-tight seal may be formed between the sample vessel and the fluid handling device. The sample vessel is engageable with a fluid handling device and is configured to receive a sample dispensed from the fluid handling device. The sample vessel may engage with the fluid handling device and allow the fluid handling device to pick up or aspirate a sample from the sample vessel.

The sample vessel may be configured to extend out of the centrifuge wing. In some embodiments, the centrifuge base may be configured to allow the sample vessel to extend out of the centrifuge wing when the wing is folded and to allow the wing to pivot between the folded state and the extended state.

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

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

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

1, 2, 3, 4, or more cavities may be provided in the bucket. For example, the bucket may be configured to receive one, two, or more samples or sample vessels 3740. Each bucket may be capable of receiving the same number of vessels or a different number of vessels. The bucket may include a cavity configured to receive a sample vessel, wherein the sample vessel is oriented in a first orientation when the base is stationary and configured to be oriented in a second orientation when the base is rotated.

In some embodiments, the bucket may be configured to be angled with respect to the base. For example, the bucket may be between 0 and 90 degrees of the base. For example, the bucket may be vertically oriented when the base is stationary. The bucket may be positioned upwardly over 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 stationary. The wings may be oriented 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 may be at 0 degrees to the base when oriented horizontally. As the base is rotated, the bucket may retract into the base, thereby forming a substantially uninterrupted top and/or bottom surface. For example, as the base rotates, the bucket may retract, thereby forming a substantially continuous surface of the bottom and/or top surfaces of the base. The bucket may be configured to pivot upward relative to the base. The bucket may be configured such that at least a portion of the bucket may pivot upward past the top surface of the base.

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

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

The bucket may be formed of two or more different materials having different densities. Alternatively, the bucket may be formed from a single material. In one example, the bucket may have a body 3715 and an internal insert 3717. In some embodiments, the body may be formed of a material having a lower density than the insert. For example, the body may be formed of plastic and the insert formed of metal, such as tungsten, steel, aluminum, copper, brass, iron, gold, silver, titanium, or any combination or alloy thereof. A heavier insert may help provide the bucket center of mass below the point of rotation. The bucket material may include a denser material and a less dense material, where the denser material is positioned below the point of rotation. The center of mass of the bucket may be positioned: so that when the centrifuge is at rest the bucket naturally swings with the open end up and the heavier end down. The center of mass of the bucket may be positioned: so that the bucket naturally retracts when the centrifuge is rotated at a certain speed. The bucket may be retracted when the speed is at a predetermined speed, which may include any speed or any of the speeds mentioned elsewhere.

One or more cavities may be provided within the bucket. In some embodiments, the cavity may be configured to receive a plurality of sample vessel configurations. The cavity may have an inner surface. At least a portion of the inner surface may contact the sample vessel. In one example, the cavity may have one or more such shelves or interior surface features: it may allow a first sample vessel having a first configuration to fit within the cavity and a second sample vessel having a second configuration to fit within the cavity. A first sample vessel and a second sample vessel having different configurations may contact different portions of the inner surface of the cavity. While the embodiments in fig. 9-11 show centrifuge vessels having a high aspect ratio in height over width, it should be understood that embodiments having a height equal to or less than width may also be used in alternative embodiments.

As previously described, the centrifuge may be configured to interface with a fluid processing device. For example, the centrifuge may be configured for connection to a pipette or other fluid handling device. The centrifuge may be configured to receive a sample dispensed by the fluid processing device or to provide a sample to be aspirated by the fluid processing device. The centrifuge may be configured to receive or provide a sample vessel.

As mentioned previously, the sample vessel may 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 extended state. Sample vessels 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 reduced drag during operation, with additional benefits such as reduced noise and heat generation and lower power requirements.

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

In some embodiments, ball bearings may be placed in a sealed/closed track within the rotor. Such an arrangement is useful for dynamically balancing the centrifuge rotor, particularly when simultaneously centrifuging different volumes of sample. In some embodiments, the ball bearings may be external to the motor, making the overall system more robust and compact.

The channel may surround the centrifuge base. In some embodiments, the channel may surround the base along the perimeter of the centrifuge base. In some embodiments, the channel may be at or closer to 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. The ball bearings are slidable along the perimeter of the centrifuge base. In some embodiments, the channel may surround the base at a distance from the axis of rotation. The channel may form a circle with the axis of rotation at substantially the center of the circle.

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

The module frame may be connected to the base. The module frame may be connected to the base at a boundary, which 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 axis that extends through the base and/or the module frame. In some embodiments, the shaft may form a cut through the base. The bucket may be configured to pivot about a bucket pivot 3840. The base may be configured to receive a drive 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 may be any other mechanism that can cause the base to rotate, and may be discussed in further detail elsewhere herein.

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

1, 2, 3, 4, or more cavities may be provided in the bucket. For example, the bucket may be configured to receive one, two, or more samples or sample vessels. Each bucket may be capable of receiving the same number of vessels or a different number of vessels. The bucket may include a cavity configured to receive a sample vessel, wherein the sample vessel is oriented in a first orientation when the base is stationary and configured to be oriented in a second orientation when the base is rotated.

In some embodiments, the bucket may be configured to be angled with respect to the base. For example, the bucket may be between 0 and 90 degrees of the base. For example, the bucket may be vertically oriented when the base is stationary. The bucket may be positioned upwardly over 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 stationary. The wings may be oriented 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 may be at 0 degrees to the base when oriented horizontally. As the base rotates, the bucket may retract into the base and/or frame module, thereby forming a substantially uninterrupted top and/or bottom surface. For example, as the base rotates, the bucket may retract, forming a substantially continuous surface with the bottom and/or top surfaces of the base and/or frame module. The bucket may be configured to pivot upward relative to the base and/or frame module. The bucket may be configured such that: such that at least a portion of the bucket can pivot upward past the top surface of the base and/or frame module.

The bucket may be locked in multiple positions to support the discharge and pick up of centrifuge tubes, as well as to draw and dispense liquids into and out of the centrifuge vessel while the centrifuge vessel is in the centrifuge bucket. One technique to accomplish this is one or more motors that drive a wheel in contact with the centrifuge rotor to finely position and/or lock the rotor. Another approach may be to use a CAM (CAM) shape formed on the rotor without the need for an additional motor or wheel. An accessory from the pipette, such as a centrifuge tip attached to a pipette tip, may be pressed down onto a cam shape on the rotor. This force on the cam surface may cause the rotor to rotate to a desired locked position. The continued application of this force may enable the rotor to be held securely in the desired position. A plurality of such cam shapes may be added to the rotor to support a plurality of locking positions. While the rotor is held by one pipette nozzle/tip, the other pipette nozzle/tip may interface with the centrifuge bucket to discharge or pick up centrifuge vessels or perform other functions, such as aspirating or dispensing from centrifuge vessels in the centrifuge bucket. It should be understood that this cam feature may be adapted for use with any of the embodiments mentioned in this disclosure.

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

The bucket may be attached to a counterweight. The counterweight may be configured to move as the base begins to rotate, 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 weight may be caused to move by centrifugal force exerted on the weight. The counterweight may be configured to move away from the axis of rotation when the base begins to rotate at the threshold speed. In some embodiments, the counterweight may move in a linear direction or path. Alternatively, the counterweight may move along a curved path or any other path. The bucket may be attached to the weight at weight 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 linear path, causing the bucket to pivot up or down. The weight may be moved in a linear direction orthogonal to the rotation axis of the centrifuge. This means that the bucket does not extend outwardly 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 outwardly from the vessel as the bucket changes orientation. Typically, the centrifuge vessel may be an open-topped vessel that is 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 off the base. The module and/or the base may limit the path of the counterweight. The path of the counterweight may be restricted to a straight direction. One or more guide pins 3870 may be provided that may limit the weight path. In some embodiments, the guide pins may pass through the frame module and/or the base and the counterweight.

A biasing force may be provided to the counterweight. The biasing force may be provided by a spring 3880, a resilient mechanism, a pneumatic mechanism, a hydraulic mechanism, or any other mechanism. The biasing force may maintain the weight in the first position when the base is stationary, while centrifugal force from rotation of the centrifuge may cause the weight to move to the second position when the centrifuge rotates at a threshold speed. The counterweight may return to the first position when the centrifuge is back at rest or the speed drops below a predetermined rotational speed. When the counterweight is in the first position, the bucket may have a first orientation; and when the counterweight is in the second position, the bucket may have a second orientation. For example, when the counterweight is in the first position, the bucket may have a vertical orientation; and when the counterweight is in the second position, the bucket 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 a plurality of sample vessel configurations. The cavity may have an inner surface. At least a portion of the inner surface may contact the sample vessel. In one example, the cavity may have one or more such shelves or interior surface features: it may allow a first sample vessel having a first configuration to fit within the cavity and a second sample vessel having a second configuration to fit within the cavity. A first sample vessel and a 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 to interface with a fluid processing device. For example, the centrifuge may be configured for connection to a pipette or other fluid handling device. The centrifuge may be configured to receive a sample dispensed by the fluid processing device or to provide a sample to be aspirated by the fluid processing device. The centrifuge may be configured to receive or provide a sample vessel.

as mentioned previously, the sample vessel may 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 module frame may be configured to allow a 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 extended state. Sample vessels 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 passageways. Any description of the channels may also be applicable to any similar structure. The channel may contain one or more ball bearings. The ball bearing is slidable through the channel. The channels may be open, closed or partially open. The channel may be configured to prevent the ball bearing from falling out of the channel.

The channel may surround the centrifuge base. In some embodiments, the channel may surround the base along the perimeter of the centrifuge base. In some embodiments, the channel may be at or closer to 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. The ball bearings are slidable along the perimeter of the centrifuge base. In some embodiments, the channel may surround the base at a distance from the axis of rotation. The channel may form a circle with the axis of rotation at substantially the center of the circle.

Other examples of centrifuge configurations known in the art may be used, including various oscillating bucket configurations. See, for example, U.S. patent No. 7,422,554, which is hereby incorporated by reference in its entirety for all purposes. For example, the bucket may swing downward instead of upward. The bucket can swing to project sideways rather than up or down.

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

The sample may be dispensed and/or picked up from the chamber. The sample may 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. The sample may be dispensed and/or picked up using a tip having any of the configurations described elsewhere herein. The dispensing and/or aspiration of the sample may be automated.

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

In some embodiments, a tip from a fluid handling system may be at least partially inserted into a sample vessel and/or cavity. The tip may be insertable and removable from the sample vessel and/or the cavity. In some embodiments, the sample vessel and tip may be a centrifuge vessel and centrifuge tip as previously described, or have any other vessel or tip configuration. In some embodiments, the pocket may be placed in a centrifuge rotor. Such a configuration may provide certain advantages over conventional tips and/or vessels. In some embodiments, the vessel can be patterned with one or more channels having a specialized geometry to allow for automatic separation of the products of the centrifugation process into individual compartments. One such embodiment may be a vessel having tapered channels terminating in a compartment separated by narrow openings. Supernatant (e.g., plasma from blood) may be forced into the compartment by centrifugal force while red blood cells remain in the main channel. The vessel may be more complex, with several channels and/or compartments. The channels may be isolated or connected.

In some embodiments, one or more cameras may be placed in the centrifuge rotor such that they can image the contents of the centrifuge vessel as the rotor rotates. The camera images may be analyzed and/or transmitted in real time, for example, by using wireless communication methods. This method can be used to track sedimentation rate/cell packing-for example for ESR (erythrocyte sedimentation rate) measurements, where the RBC (red blood cell) sedimentation rate is measured. In some embodiments, one or more cameras may be positioned outside the rotor that can image the contents of the centrifuge vessel as the rotor rotates. This can be achieved by using a stroboscopic illumination source that is synchronously timed with the camera and the rotating rotor. Real-time imaging of centrifuge vessel contents as the rotor is spinning may allow for stopping the spinning of the rotor after the centrifugation process is complete, saving time and possibly preventing excessive build-up and/or excessive separation of the contents.

As seen in fig. 12, some embodiments may include a window or opening 3825 on the centrifuge vessel holder to allow viewing of the sample contained therein. This may involve a camera or other detector that may visualize the sample in the vessel through a 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 a detector, such as a camera, in the centrifuge, such as, but not limited to, a detector integrated into the centrifuge rotor, to image the sample therein. This may be beneficial because the movement of any blood components in the sample may be more easily visualized if the camera is in the same frame of reference as the sample. Of course, embodiments are not excluded in which the detector, such as but not limited to a camera, is in a different reference frame than the sample being moved. Nor are non-visual detectors excluded as long as they detect movement of blood components in the vessel.

Some embodiments may also include a corresponding window or opening 3827, the window or opening 3827 being 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 vessel is held in the centrifuge. Alternatively, 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. For 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 undesirable changes in the temperature of the sample due, at least in part, to the heat generated by the centrifugation operation. One source of heat during centrifugation is waste heat from the drive motor and/or drive mechanism of the centrifuge. This waste heat can be particularly problematic if several samples are processed sequentially in the same centrifuge, and during that time period heat from each operation accumulates, which can undesirably raise the sample temperature outside of an 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 undesirable 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 related to the motor, centrifuge rotor, bucket, vessel, and/or sample. Methods for addressing such heat dissipation issues may include simultaneously or sequentially performing one or more of: cooling, thermal isolation and/or maintenance cooling. Some embodiments may involve active techniques to address heat dissipation issues. Some embodiments may involve passive techniques such as, but not limited to, thermally isolating centrifuge components connected to a heat source associated with the centrifuge.

Some embodiments may use thermally conductive materials such as, but not limited to, thermal tape, to change the heat transfer profile of the centrifuge. In one non-limiting example, the band may be configured to direct heat away from a heat sensitive region on the centrifuge that would have a thermal effect on the sample. The thermal tape is designed to provide a preferential heat transfer path between the heat generating components and a heat sink or other cooling device (e.g., fan, heat spreader, etc.). The thermal tape may be a tacky pressure sensitive adhesive loaded with a thermally conductive ceramic filter that does not require a thermal cure cycle to form a bond to many substrates. This may 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. The active cooler may 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 houses the centrifuge vessel. Alternatively, the active cooler may be proximate to the target surface but not in direct contact therewith. For example, an active heat sink or peltier heater/cooler may be attached to the centrifuge housing in proximity to the portion of the centrifuge holding the sample.

Some embodiments may mount a structure external to 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 the vanes or air moving structure to a stationary portion of the housing near the rotor. Such fins may be used to radiate any excess heat and/or to assist convection.

as seen in fig. 12, some embodiments may use non-conductive materials to alter the heat transfer profile. Some embodiments may modify some metallic materials to plastic materials or other robust materials with low thermal conductivity in an effort to insulate the sample from the heat source(s). Some embodiments may isolate the sample from foam or other types of insulating materials to prevent unwanted heat transfer. Some embodiments may have a centrifuge rotor that is made entirely of a low thermal conductivity material. Some embodiments may have only portions of the centrifuge rotor made of a low thermal conductivity material. As seen in fig. 12, some embodiments may replace only selected portions with thermally insulating material, such as, but not limited to, replacing frame portion 3820.

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

As further seen in fig. 13A, some embodiments may have an active thermal device 410, such as but not limited to a peltier effect heat sink, attached to one or more components of the centrifuge system (such as but not limited to the centrifuge housing 402). 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 a conventional passive heat sink in place of or in conjunction with the 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 units replaced or enhanced by passive heat sinks.

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

Although fig. 13A illustrates that the thermal conditioning elements may be placed on a housing or other non-moving part of the centrifuge system, it should be understood that similar active or passive thermal device(s) may also be mounted on the internal and/or moving components of the centrifuge system. By way of non-limiting example, fig. 13B illustrates that the motor, centrifuge rotor 404, bucket, vessel, and/or surface in contact with the sample can also be configured to be under the thermal control of the device(s) 410. Fig. 13B illustrates that the active thermal devices 410 may be located on the perimeter side surface of the centrifuge rotor 404. Alternatively, the active thermal device 410 may be located on the top surface of the centrifuge rotor 404. Alternatively, the active thermal device 410 may be located on the underside surface of the centrifuge rotor 404. Alternatively, the active thermal devices 410 may be located on a shroud, casing, 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 units replaced or enhanced by passive heat sinks.

Referring now to fig. 14A-14B, some embodiments may involve venting a housing around a centrifuge rotor to improve convective airflow. This may involve placing holes, cutouts, or shaped openings in the housing and/or centrifuge rotor to allow air flow. The vent 450 may be formed in a housing 452 that surrounds a portion of the centrifuge motor. The meter vent 450 may be sized and/or positioned to allow for greater convective cooling of the motor components of the centrifuge. In this non-limiting example, the larger opening 454 is sized to receive an encoder ring reader. It should be understood that the embodiments in fig. 14A-14B may include any of the active thermal elements or passive thermal elements described in fig. 13A-13B in addition to the vent(s). Based on the position information provided as described by the various configurations described in this disclosure, some embodiments of the centrifuge may be configured to drive and/or brake the centrifuge such that the centrifuge is stopped at a particular position specified by a user and/or device (such as, but not limited to, a programmable processor).

Fig. 15 shows yet another embodiment in which the vent holes 460 may be formed in a housing 462 near 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 greater or lesser number of vents 460. Other embodiments may have other shapes for the vent holes 460 such as, but not limited to, square, rectangular, oval, triangular, trapezoidal, parallelogram, pentagonal, hexagonal, octagonal, any other shape, or a single combination or multiple combinations of the foregoing. Some embodiments may have a plurality of vent holes 460 that all have the same shape. Some embodiments have vent holes 460 that may have at least one vent hole that has a shape that is different from the shape of at least one other vent hole 460.

Referring now to fig. 16A-16D, still other embodiments may position the thermal control element 500 on a rotating and/or non-rotating component of a 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 a centrifuge housing 501. The fins may have a planar configuration. Alternatively, some embodiments of the thermal control element 500 may be a protrusion in the shape of the sheath 502. Some embodiments may incorporate one or more of these structural features. These structural features may be used as passive or active thermal control devices.

In some embodiments, the cross-sectional shape of the airfoil can be circular, crescent, teardrop, square, rectangular, triangular, polygonal, or any other shape. The cross-sectional shape of the fins may or may not be the same along the longitudinal length of the fins. For example, in some embodiments, the fins may have a generally cylindrical shape; in other embodiments, the fins may have a pyramidal (including truncated pyramidal) or pyramidal (including truncated pyramidal) shape. In still other embodiments, the surface of the tab (e.g., sheath-tab) may be curved along the longitudinal length of the tab. Non-limiting examples of surface profiles of curved fins (e.g., sheath-fins) include hyperbolic curves, quadratic curves, polynomial curves having an order 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. The hollow fins may allow for efficient heat transfer while further reducing the amount of material to be used to make the heat sink, thereby further reducing manufacturing 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 may have any pattern, such as a generally crossed file, fish-ridge or wave pattern. In some embodiments, the tabs may be coupled together at their bases (or other connection regions) to form a connected network of tabs, such as, but not limited to, a plurality of columns or rows. Some of the tabs may be joined to form a percolating network of joined tabs.

FIG. 16B shows an embodiment with fins 510 on the inner radial portion of the centrifuge. Fig. 16C shows a fin 520 located on the underside of the centrifuge rotor. Fig. 16D illustrates a still further embodiment in which fins 530 on a circumferential portion of the rotor may be optionally shaped and/or oriented for use with a shaped housing 540 to draw air into the housing to help cool components therein as the centrifuge rotor rotates. Of course, some embodiments may combine one, two, three, or all of the above components with other cooling elements to maximize the cooling potential of the system. The embodiments in fig. 16B-16D may have various thermal control means coupled to the moving or stationary portions of the centrifuge.

In yet another embodiment, an internal fan-cooled electric motor (in colloquial terms, a fan-cooled motor) may be used as a self-cooling electric motor. In one embodiment, the fan-cooled motor features an axial fan (typically on the opposite end as the output shaft) attached to the motor rotor that rotates with the motor, providing increased, auxiliary-cooling airflow to 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 may be built out of 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 may 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 having the closest access to the sample.

In still further embodiments, significantly reducing the winding resistance may be used to reduce the amount of 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. The number of poles and magnets can also be selectively varied to improve motor performance. In this manner, the motor assembly may 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 fig. 17A-17D, improvements to the position control system for 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 where a fixture on centrifuge rotor 6604 is positioned. In such embodiments, accurate information regarding the position of the centrifuge rotor 604 would allow a pipette or sample processing system to accurately engage centrifuge vessels as such vessels are removed from the centrifuge without the use of a "parking" system to consistently position the centrifuge rotor 604 at a particular location when it is stopped.

FIG. 17A illustrates one embodiment of an encoder ring 600 for use with a detector 602 for reading the position of an encoder. The encoder ring 600 will rotate with the centrifuge rotor 604 such that the encoder ring 600 will provide position information of the centrifuge rotor 604 and any features thereon. In one embodiment, the encoder ring 600 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 a reflective pattern on the ring 600. The encoder ring 600 may be configured to detect each different angle of the encoder ring. The loop 600 may be an absolute encoder or an incremental encoder.

FIG. 17B shows another embodiment in which an encoder ring 610 is integrated as part of the centrifuge rotor 604, such as along a circumferential perimeter portion of the rotor. The detector 612 is oriented for use with the integrated encoder ring 610. The detector may 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 rate sensing. 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, the centrifuge rotor 604 is hollow to allow components to be positioned within the rotor 604 during centrifuge operation. In one embodiment, the entire centrifuge vessel is contained within the profile of the centrifuge rotor when the centrifuge is in operation.

Fig. 17C shows a still further embodiment, wherein the motor 622 may incorporate the encoder ring or device 620 into the motor 622 during the manufacturing 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 may be used in centrifuges as well as in other system components such as pipettes in sample processing systems where accurate position control is desired due to the small form factor of the motor. By way of example and not limitation, incremental encoders may be used on 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.

FIG. 17D illustrates yet another embodiment in which other encoder techniques, such as, but not limited to, conductive encoding and/or magnetic encoding, are used to detect rotor position in lieu of or in conjunction with other encoder techniques, such as, but not limited to, optical encoders. 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 a 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 having more than one sensor may be configured to have one sensor for fine position control and one sensor for speed control. In this way, higher centrifuge speeds, such as but not limited to 40000rpm, can be achieved without resorting to more complex sensors, as each type can be optimized for its specific purpose, such as high accuracy position control at low speeds and speed control at higher speeds. A programmable processor may be used to determine when to transition control of centrifuge rotation based on one sensor or another. Alternatively, data from both types of sensors may 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, systems using stops may 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 may be transferred to the vessel. Some embodiments of the centrifuge may also have a guide rail to guide the pipette to a desired location or to use the pipette to move it to the correct location before the centrifuge rotor engages any sample-containing vessels mounted on the centrifuge.

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

In some embodiments described herein, it is to be understood that the motor may be enhanced with position and/or speed 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 portions of the motor or rotating elements attached to the motor.

possibilities for hardware integration with the motor include, but are not limited to, 1) (one or more optical encoders (for position (relative and/or absolute) and/or velocity sensing) and/or 2) (one or more hall effect sensors (for position (relative) and/or velocity sensing). A hall effect sensor is a semiconductor device in which the flow of electrons is influenced by a magnetic field perpendicular to the direction of current flow. In one non-limiting example, hall effect sensor(s) can 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. Alternatively, 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 embodiments herein or from use in conjunction with optical or magnetic encoders.

By way of non-limiting example, at least some embodiments of sensors and/or encoders herein can be implemented at speeds up to 12000RPM (at least 1800 counts per revolution) for position sensing. Optionally, at least some embodiments of the sensors and/or encoders herein can be implemented at speeds up to 10000RPM (at least 1600 counts per revolution) for position sensing. In one embodiment, the encoder has an index that is constantly aligned with the motor assembly in each centrifuge for absolute positioning. Some embodiments may use an absolute encoder, such as, but not limited to, a multi-bit Gray (Gray) code encoder and/or a single-rail Gray encoder, to obtain the absolute position. Some embodiments may use a sinusoidal coder. Encoder technology may include, but is not limited to, conductive tracks, optical tracks (including reflective versions), and magnetically encoded tracks sensed by hall effect sensors or magnetoresistive sensors.

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

Alternatively, some alternative embodiments may use firmware and/or software that detects the position and/or speed of the rotor without additional hardware. Examples may include monitoring back emf, tracking impedance, or using other techniques for sensorless motor control. One or more of the techniques described herein may be used in combination for position and/or velocity sensing.

Referring now to fig. 17E, another embodiment of a centrifuge having a magnetic sensor, such as, but not limited to, a hall effect sensor assembly 630, which may be integrated directly into the motor assembly or located external to the motor but as part of the centrifuge assembly, is shown. Fig. 17E shows an exploded view in which the hall effect detector 632 and encoder portion 634 are shown. Arrow 636 shows that assembly 630 can be inserted into the centrifuge housing in the direction as shown. By way of non-limiting example, the assembly 630 is shown with three detectors 632, but it should be understood that other numbers of detectors may be used. Assembly 630 is also shown with all detectors on the same plane. It should be understood 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 interfering components that can be detected by the hall effect detector 632.

Referring now to fig. 17F, a perspective view of one embodiment of a motor with integrated position and/or speed sensing is shown. For ease of illustration, some motor assemblies are not shown for this embodiment in order to provide a clear view of the encoder assemblies used with the motors. The encoder embodiments may be used to detect shaft position and/or rotor position. In this non-limiting example, the detector 670 is used in conjunction with the encoder disk 672 and the 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 second surface 682 for detecting a second type of encoder information, such as, but not limited to, magnetic encoder information. Alternatively, some embodiments may have both the first type of encoder information and the second type of encoder information be of the same type, such as, but not limited to, being both optical or both magnetic. In such a configuration, the resolution may optionally be different between the at least two encoder types, where one encoder type provides 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 different types of encoder information are used, such as one being optical and one being magnetic. Of course, embodiments using even more sensors 670 or more than two types of encoder information are not excluded.

Still referring to fig. 17F, a magnetic assembly 676 may be mounted in the disc 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. Alternatively, some embodiments may incorporate at least two encoder types onto one rotating element such as, but not limited to, an encoder disk. In one such configuration, a single disc on the shaft may include both the magnetic encoder assembly and the optical encoder assembly. By way of non-limiting example, the outer portion of the ring may have a region for an optical encoder while the inner portion has a magnetic component, or vice versa. Optionally, both are located on the same portion of the ring. Alternatively, one type of encoder type may be located on a planar surface, while another component is located on a side of the disk. ). Of course, embodiments using more than two types of encoder information on a single rotating assembly are not excluded. By way of example and not limitation, embodiments using a single detector 670 may also simplify manufacturing by having a single wire harness attached to the detector 670, thus simplifying wire management.

Fig. 17G illustrates yet another type of motor that can be configured to include one or more encoder assemblies disclosed herein. Some embodiments may use one rotor 640 and one stator 642 in the motor design. Alternatively, 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 assemblies shown herein. Some embodiments may attach or integrate an encoder element such as, but not limited to, an optical encoder disk or a magnetic encoder disk 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 fig. 17G, this embodiment of the motor may be configured to fit inside the motor housing shown in fig. 17A-17E to rotate the centrifuge body.

Automatic balancing

Referring now to fig. 18A, some embodiments herein may be configured to minimize rotor vibration using an automatic balancing mechanism on the rotor, not all holders containing samples. One embodiment may use an automatic balancing element 700 such as, but not limited to, beads, spheres, or weights to automatically balance the centrifuge rotor, and this may be useful to compensate for different sample volumes in different buckets. Some embodiments may be loaded into 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 circumference, some embodiments may have channels formed in certain discrete segments that have self-balancing elements that will stay only in certain of their discrete channel segments.

As optionally seen in fig. 18B, some embodiments may include a securing feature 720 that only releases the auto-balancing element 700 to move freely once a minimum rotational speed is reached and centrifugal or other force releases the auto-balancing element for movement. When sufficient speed is reached, the feature 720 may move as indicated by arrow 722. This movement releases the automatic balancing element 700 to move to a position that balances the load on the centrifuge. In this manner, the auto-balancing element 700 is not able to move freely at slower speeds. This may help minimize noise and rotational instability that may be caused by the ability of the auto-balancing element 700 to easily roll to a non-optimal balancing position at slower speeds.

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

Referring now to fig. 18C, a further embodiment may have the automatic balancing elements 700 located in multiple separate areas 730 on the rotating portion of the centrifuge. In one embodiment, the regions 730 may be connected to each other such that the auto-balancing element 700 may move between the regions. Optionally, some embodiments may isolate each of the regions 730 from each other such that the auto-balancing element 730 does not move from one region 730 to another.

Non-mechanical bearing(s)

In still further embodiments, some systems may be configured without mechanical bearings and instead use non-mechanical bearings, such as, but not limited to, air bearings 720. The air bearings may generate less heat-which may reduce the time required for the centrifuge. Or it may support longer centrifuge times without heat loss that may be caused by heat associated with the mechanical bearings. Air Bearings are available from suppliers such as, but not limited to, the Aston Neewey Air bearing (New Way Air Bearings of Aston) of Pennsylvania, U.S.A. Of course, some embodiments may combine the use of both air and mechanical bearings in the same device.

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

Fault detection sensor

Referring now to fig. 20, yet another embodiment of a centrifuge apparatus will now be described. FIG. 20 is a cutaway perspective view illustrating a centrifuge rotor 800, such as but not limited to a centrifuge disk, which centrifuge rotor 800 rotates within a non-rotating housing 804 as indicated by arrow 802. The centrifuge may include a detector 810, such as, but not limited to, an accelerometer or the like mounted on the centrifuge, to detect undesirable force changes during operation of the centrifuge. In one embodiment, 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 an early indication of abnormal instability in centrifuge operation. If these signs of instability are detected in terms of abnormal rates of change in the forces experienced by the centrifuge, the centrifuge may choose to slow or stop operation, such as by way of a programmable processor, prior to catastrophic device failure. Some embodiments may trigger other actions, such as alarms or alerts, based on detection of a rate of change or force outside of a threshold range.

Fig. 20 also illustrates other features discussed herein that are incorporated into the present embodiments. 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 of the centrifuge housing. FIG. 20 also illustrates that thermal insulation zones 820, 822, and/or 824 may be used to minimize heat transfer from motor 830 to other portions of the centrifuge rotor.

It should be understood that the embodiment in fig. 20 may be configured for any of the rotor and/or vessel holder configurations described, including but not limited to those shown in fig. 1-12. Some embodiments have vessel holders that may extend mostly above the upper plane or surface of the centrifuge rotor when the rotor is stationary. Optionally, some embodiments may have a vessel holder that extends 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 clearance when the vessel holder and/or vessel are rotated in the downwardly extending position. Optionally, some embodiments may mount the rotor 800 higher and/or 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, the centrifuge may have a footprint area of about less than or equal to 0.1mm2, 0.5mm2, 1mm2, 3mm2, 5mm2, 7mm2, 10mm2, 15mm2, 20mm2, 25mm2, 30mm2, 40mm2, 50mm2, 60mm2, 70mm2, 80mm2, 90mm2, 100mm2, 125mm2, 150mm2, 200mm2, 250mm2, 300mm2, 500mm2, or up to 750mm 2. The cell counter may have one or more dimensions (e.g., width, length, height) less than or equal to 0.05mm, 0.1mm, 0.5mm, 0.7mm, 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 15mm, 17mm, 20mm, 25mm, 30mm, 40mm, 50mm, 60mm, 70mm, 80mm, 100mm, 150mm, 200mm, 300mm, 500mm, or 750 mm.

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

Fig. 20 also illustrates that, for at least some embodiments herein, a housing 804 shaped to enclose at least a circumferential perimeter of a centrifuge disk of the rotor 800 may provide a controlled area within which the centrifuge disk may 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 shield to retain the vibratory motion of the motor within the housing, as the damper 816 may be mounted to the housing 804 to provide isolation therein. There may be bearings 830 and 832 to which the rotating portion can be mounted. Alternatively, some embodiments may be configured to use only a single bearing. Optionally, some embodiments may be configured to use multiple bearings. Some embodiments may use the motors in fig. 17F-17G to power the centrifuge in fig. 20. Alternatively, a centrifuge having one or more of the features described herein may 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. Alternatively, such centrifuges may be mounted on a common mounting plate, common platform, or common frame with other components 912, 914, or 916, as well as all components available for use with an overhead sample processing system.

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

Service point system

Referring now to FIG. 21, it should be understood that the processes described herein may be performed using automated techniques. Automated processes may be used in integrated automation systems. In some embodiments, such automated processing may be in a single instrument having multiple functional components therein and surrounded by a common housing. The processing techniques and methods for sedimentation measurement may be pre-set. Alternatively, the treatment techniques and methods may be based on protocols or protocols that may be dynamically changed as needed in the manner described in U.S. patent application serial nos. 13/355,458 and 13/244,947, both of which are incorporated by reference herein for all purposes.

In one non-limiting example as shown in fig. 21, the integrated instrument 900 may be equipped with a programmable processor 902 that may be used to control various components of the instrument. For example, in one embodiment, the processor 902 may control a single or multiple pipette system 904, the pipette system 904 being movable in the X-Y direction as well as the Z direction as indicated by arrows 906 and 908. The same or a different processor 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 take a blood sample from cartridge 910 and move the sample to one of components 912, 914 or 916. Such movement may involve dispensing a sample into a removable vessel in the cartridge 910 and then transporting the removable vessel to one of the 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 having an imaging configuration to allow illumination and visualization of the sample in the container. Other components 912, 914 or 916 perform other analysis, determination or detection functions.

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

Referring now to FIG. 22, a still further embodiment of a centrifuge 1000 will now be described. Fig. 22 shows an exploded perspective view of a centrifuge 1000 having a cover plate 1010 operatively coupled to a rotatable frame 1020. In this non-limiting example, the rotatable frame 1020 may have an auto-balancing element 700, and in this embodiment, the auto-balancing element 700 may be a channel 1030 having a plurality of weight balls 1032 therein. Optionally, some embodiments may have an automatic balancing element 700 in the cover plate 1010, shaft 1060, or other rotating portion of the centrifuge. Optionally, other automatic balancing features currently known or later developed may be incorporated into the rotatable frame 1020, cover plate 1010, shaft 1060 or other rotating portions of the centrifuge 100.

As seen in this non-limiting example, there may be one or more sample vessel holders such as bucket 1040 attached in a hinge or other attachment that allows bucket 1040 to swing as indicated by arrow 1050 when motor shaft 1060 rotates the centrifuge disk. As seen in this embodiment, bucket 1040 can have window(s) or viewing portion(s) 1042 that allow viewing of the sample vessels contained therein. Alternatively, some embodiments may lack a window. Some embodiments may also have 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 bucket 1040 slightly off vertical. There may be a coupling device such as, but not limited to, a magnet 1062 (in direct contact with or spaced from the bucket at rest position) to assist in having a consistent rest position so that any vessel in the bucket 1040 can be easily loaded or unloaded. In some embodiments, bucket 1040 can have a ferrous portion and/or a magnet thereon to assist in engagement with a coupling device such as magnet 1062. Optionally, some embodiments may have magnets in bucket 1040 or in both bucket 1040 and shaft 1060. Some embodiments may have magnets in the bucket 1040 and shaft 1060 that are not directly aligned, such as one magnet along a longer portion of the bucket, while the other magnet is located in the "foot" portion of the bucket 1040.

Although only two buckets are shown in fig. 22, it should be understood that embodiments having multiple buckets are not excluded. Optionally, at least a portion of the bucket 1040 can fill the cavity 1070 in the cover plate 1010 to create a portion flush with the plane of the cover plate when the bucket 1040 is in a rotated position, thereby reducing drag. Optionally, only about 90% or less of the area in the cavity is filled by bucket 1040 in the rotated position. Optionally, only about 80% or less of the area in the cavity is filled by bucket 1040 in the rotated position. Optionally, only about 70% or less of the area in the cavity is filled by 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 arrow 1102, the cover 1010 may be substantially flush with the top of the housing 1100. In some embodiments, a position sensor 1110, such as but not limited to a hall sensor, may be used to sense an indicator 1112 on the rotating portion of the centrifuge. This may be useful for determining the resting position of the rotating portion so that the sample processing device can accurately engage the bucket 1040. The position 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 features described herein into fewer individual features for ease of assembly or other reasons. It should be understood that the centrifuge herein may use any motor as described herein (including those having an encoder).

Fig. 22 and 23 also illustrate that some embodiments may have venting features, such as, but not limited to, a vent port 1120 in the side and/or bottom of the housing 1100. As seen in the side cross-sectional view of fig. 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 the housing 1110. Alternatively, some embodiments may have ports only in the bottom of the housing 1110. Optionally, some embodiments may have openings in both. Fig. 23 shows that the interior of the housing can have a shaped bottom portion to assist in directing the airflow into the housing 1110. Optionally, some embodiments may mount the housing 1110 over a resilient mount, shock absorbing member, or the like, to minimize any transmission of vibrations from the centrifuge to any other portion of the apparatus. As seen in fig. 23, centrifuge disk 1150 defines a gap 1160 that is 10% or less of the diameter of disk 1150. Optionally, centrifuge disk 1150 defines a gap 1160, which gap 1160 is 5% or less of the diameter of disk 1150. This allows a fit that minimizes the desired air flow around the centrifuge disk. Alternatively, other embodiments may have cutouts over a larger portion of the casing 1100, with cutouts at fewer locations (or smaller cutouts at 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 desktop or small footprint floor mounting. In one example, a small footprint floor mounting system may occupy a floor area of about 4m2 or less. In one example, a small footprint floor mounting system may occupy a floor area of about 3m2 or less. In one example, a small footprint floor mounting system may occupy a floor area of about 2m2 or less. In one example, a small footprint floor mounting system may occupy a floor area of about 1m2 or less. In some embodiments, the instrument footprint may be less than or equal to about 4m2, 3m2, 2.5m2, 2m2, 1.5m2, 1m2, 0.75m2, 0.5m2, 0.3m2, 0.2m2, 0.1m2, 0.08m2, 0.05m2, 0.03m2, 100cm2, 80cm2, 70cm2, 60cm2, 50cm2, 40cm2, 30cm2, 20cm2, 15cm2, or 10cm 2. Some suitable systems in the service point setting are described in U.S. patent application serial nos. 13/355,458 and 13/244,947, which are incorporated herein by reference in their entirety 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, the centrifuge may have a footprint area of about less than or equal to 0.1mm2, 0.5mm2, 1mm2, 3mm2, 5mm2, 7mm2, 10mm2, 15mm2, 20mm2, 25mm2, 30mm2, 40mm2, 50mm2, 60mm2, 70mm2, 80mm2, 90mm2, 100mm2, 125mm2, 150mm2, 200mm2, 250mm2, 300mm2, 500mm2, or up to 750mm 2. The cell counter may have one or more dimensions (e.g., width, length, height) less than or equal to 0.05mm, 0.1mm, 0.5mm, 0.7mm, 1mm, 2mm, 3mm, 4mm, 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 15mm, 17mm, 20mm, 25mm, 30mm, 40mm, 50mm, 60mm, 70mm, 80mm, 100mm, 150mm, 200mm, 300mm, 500mm, or 750 mm.

While the invention has been described and illustrated with reference to certain specific embodiments thereof, those skilled in the art will appreciate that various adaptations, changes, modifications, substitutions, deletions, or additions of procedures and protocols may be made without departing from the spirit and scope of the invention. For example, with respect to any of the above embodiments, it will be appreciated that other techniques for plasma separation may be used in conjunction with or in place of centrifugation. For example, one embodiment may centrifuge a sample at an initial stage, which may then be positioned into a filter, which in turn removes the formed blood components to complete the separation. Although the present invention is described in the context of centrifugal separation, other accelerated separation techniques may also be suitable for use in the systems herein. It should also be understood that although the present invention is described in the context of a blood sample, the techniques herein may also be configured to be applicable to other samples (biological or additional samples). Any of the embodiments herein may be configured with the encoders and/or sensors described in the present disclosure. Any of the embodiments herein may be configured with the position detection device 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 the present disclosure.

Alternatively, at least one embodiment may use a variable speed centrifuge. With feedback, such as but not limited to imaging of the location 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 ESR data extracted from the speed curve of the centrifuge 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, sedimentation rate data is calculated based on centrifuge speed. In one non-limiting example, a higher centrifuge speed is used to maintain a linear curve as compaction nears completion.

Furthermore, one skilled in the art will recognize that any embodiment of the present invention may be adapted for collecting sample fluid from a human, animal, or other subject. Alternatively, the volume of blood used for sedimentation testing may be 1mL or less, 500 μ L or less, 300 μ L or less, 250 μ L or less, 200 μ L or less, 170 μ L or less, 150 μ L or less, 125 μ L or less, 100 μ L or less, 75 μ L or less, 50 μ L or less, 25 μ L or less, 20 μ L or less, 15 μ L or less, 10 μ L or less, 5 μ L or less, 3 μ L or less, 1 μ L or less, 500nL or less, 250nL or less, 100nL or less, 50nL or less, 20nL or less, 10nL or less, 5nL or less, or 1nL or less.

In addition, concentrations, amounts, and other numerical data may be presented herein in a range format. It is to be understood that such a range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a size range of about 1nm to about 200nm should be interpreted to include not only the explicitly recited limits of about 1nm and about 200nm, but also include individual sizes such as 2nm, 3nm, 4nm, and sub-ranges such as 10nm to 50nm, 20nm to 100nm, and the like.

The publications discussed or cited herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed. All publications mentioned herein are incorporated herein by reference to disclose and describe the structures and/or methods in connection with which the publications are cited. The following applications are also incorporated herein by reference for all purposes: U.S. patent application Ser. Nos. 13/355,458, 13/244,947, 13/769,820, 61/852,489, 61/930432, U.S. provisional application Ser. No. 61/673,037 entitled "Rapid Measurement of Formed Blood Component separation Rate from Small Sample Volumes" filed on 7, 18, 2012; U.S. provisional application serial No. 61/930,462, filed on month 1, 22, 2014; U.S. Pat. nos. 8,380,541, 8,088,593; U.S. patent publication numbers 2012/0309636; U.S. patent application serial No. 61/676,178 filed on 26/7/2012; PCT/US2012/57155 filed on 9, 25, 2012; U.S. application serial No. 13/244,946 filed on 26/9/2011; united states patent application 13/244,949 filed on 26/9/2011; and U.S. application serial No. 61/673,245 filed on 26/9/2011; U.S. provisional application Ser. No. 61/673,245 entitled "High Speed, Compact Centrifuge for Use with Small Sample Volumes" filed on day 18, 2012, U.S. provisional application Ser. No. 61/675,758 entitled "High Speed, Compact Centrifuge for Use with Small Sample Volumes" filed on day 25, 2012, and U.S. provisional application Ser. No. 61/706,753 entitled "High Speed, Compact Centrifuge for Use with Small Sample Volumes" filed on day 27, 2012, 9, 27; U.S. Pat. nos. 8,380,541, 8,088,593; U.S. patent publication numbers 2012/0309636; U.S. patent application serial No. 61/676,178 filed on 26/7/2012; PCT/US2012/57155 filed on 9, 25, 2012; U.S. application serial No. 13/244,946 filed on 26/9/2011; united states patent application 13/244,949 filed on 26/9/2011; and U.S. application serial No. 61/673,245 filed on 26/9/2011.

While the above is a complete description of the preferred embodiments of the invention, it is also possible to use various alternatives, modifications, and equivalents. The scope of the invention should, therefore, be determined not with reference to the above description, but instead should be determined with reference to the appended claims along with their full scope of equivalents. Any feature (whether preferred or not) may be combined with any other feature (whether preferred or not). The following claims should not be construed to include device-plus-function limitations unless such limitations are expressly set forth in a given claim using the phrase "device for …". It should be understood that the meaning of "a", "an", and "the" as used in the description herein and throughout the claims that follow includes plural references unless the context clearly dictates otherwise. In addition, the meaning of "in …" as used in the description herein and throughout the claims that follow includes "in …" and "on …" unless the context clearly dictates otherwise. Finally, the meaning of "and" or "as used in the description herein and throughout the claims that follow includes both connectivity and reverse connectivity and may be used interchangeably unless the context clearly dictates otherwise. Thus, use of such conjunctions in the context of use of the terms "and" or "does not exclude the meaning of" and/or "unless the context clearly dictates otherwise.

This document contains material which is subject to copyright protection. For example, all figures shown herein are of copyrighted material. The copyright owner (applicant herein) has no objection to the facsimile reproduction by anyone of the patent document or the disclosure, as it appears in the patent and trademark office patent file or records, but otherwise reserves all copyright rights whatsoever. The following notice should apply: copyright 2012 and 2014 selanorsis limited.

Claims (26)

1. A high speed centrifuge for small volume samples, the centrifuge comprising:

A centrifuge rotor;

A motor for rotating the centrifuge rotor;

A plurality of buckets coupled to the centrifuge rotor; and

At least one magnetic device on the bucket positioned to couple the bucket to a stationary portion of the centrifuge when the bucket is in a stationary position.

2. The centrifuge of claim 1 wherein said rotor comprises at least an optical encoder and a hall effect sensor for determining rotational position.

3. The centrifuge of claim 1 wherein said rotor comprises at least an optical encoder and a hall effect sensor for determining at least rotational position and rotational speed.

4. The centrifuge of claim 1 further comprising a first encoder disk providing a first type of encoder information and a second encoder disk providing a second type of encoder information.

5. The centrifuge of claim 1, wherein the first encoder disk providing optical encoder information and the second encoder disk providing magnetic encoder information are coupled to the motor.

6. A centrifuge as in claim 1 further comprising wherein the bucket is configured to receive a vessel for holding a sample volume of no more than 70 uL.

7. The centrifuge of claim 1, further comprising wherein the bucket is configured to receive a vessel for holding a sample volume of no more than 80 uL.

8. The centrifuge of claim 1, further comprising wherein the bucket is configured to receive a vessel for holding a sample volume of no more than 90 uL.

9. A centrifuge as in claim 1 further comprising wherein the bucket is configured to receive a vessel for holding a sample volume of no more than 100 uL.

10. A centrifuge as in claim 1 further comprising wherein the bucket is configured to receive a vessel for holding a sample volume of no more than 150 uL.

11. A centrifuge as in claim 1 wherein the buckets each have an L-shaped configuration.

12. The centrifuge of claim 1 further comprising a centrifuge housing sized to cover at least a portion of a side of the centrifuge rotor.

13. The centrifuge of claim 1, wherein the housing comprises a plurality of cutouts to allow air to enter as the centrifuge body rotates.

14. A method for high speed centrifugation of a small volume of sample, comprising:

Providing a motor coupled to a centrifuge body;

Determining a rotational speed of a rotating portion of the motor using an encoder on the centrifuge body;

When the centrifuge is in a stopped condition, at least one magnet in a bucket is used to hold the bucket on the centrifuge body.

15. A method as in claim 14, wherein the bucket is configured to hold a vessel having a sample chamber of no more than 100 uL.

16. The method of claim 14, further comprising using a thermally conductive material configured to direct heat in a direction away from the container.

17. The method of claim 14, further comprising using an active cooling unit for minimizing heat transfer to the sample, wherein the container is arranged such that the container is located in an area of reduced thermal exposure; the active cooling unit is configured to cool the drive mechanism.

18. The method of claim 14, further comprising using an automatic 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 if the amount of load in a sample holder of the centrifuge is not uniform.

19. The method of claim 14, further comprising using at least one air bearing configured to support the centrifuge in operation.

20. The method of claim 14, 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.

21. The method of claim 14, further comprising using a force detector configured to detect changes in force rate outside of a range of predetermined force conditions.

22. The apparatus or method of any of the preceding claims, wherein the centrifuge vessel holder or bucket pivots inwardly toward a central axis of the centrifuge rotor under centrifugal force.

23. The apparatus of any preceding claim, wherein the centrifuge vessel holder forms a flush surface with the rotor body to minimize aerodynamic drag.

24. The apparatus of any one of the preceding claims, wherein the centrifuge vessel holder is configured to retract downwardly under centrifugal force.

25. Apparatus according to any one of the preceding claims, wherein the electrical connection to the centrifuge body cooling element is uninterrupted, even if such element is in operation during centrifugation operation.

26. The apparatus of any preceding claim, wherein the centrifuge vessel holder moves from a first orientation to a second orientation that is more horizontal than the first orientation during centrifugation operation.