JP2022113862A - High speed, compact centrifuge for use with small sample volume - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a high speed, compact centrifuge for use with small sample volume.

SOLUTION: In one unlimited embodiment, an automated system is provided for separating one or more components in a biological fluid, wherein the system comprises: (a) a centrifuge comprising one or more bucket configured to receive a container to effect the separation of one or more components in a fluid sample; and (b) the container, wherein the container includes one or more shaped feature that is complementary to a shaped feature of the bucket. In the one unlimited embodiment, the system can has one or more bucket being an oscillation bucket which is in a vertical or nearly vertical position when the centrifuge is in a resting state, and which is in a horizontal or nearly horizontal position when the centrifuge is in a rotating state.

SELECTED DRAWING: None

COPYRIGHT: (C)2022,JPO&INPIT

Description

(Background art of the invention)
Conventional centrifuges are overly large and inefficient to handle centrifugation of small volumes of liquid samples. They also fail to include specific functions desired when processing small sample volumes.

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

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

In one non-limiting example, an automated system is provided for separation of one or more components in bodily fluids. The system includes: (a) a centrifuge including one or more buckets configured to receive a container to effect separation of said one or more components in a bodily fluid sample; and (b) said buckets. and said container having one or more shaped features that are complementary to the shaped features of .

It should be appreciated that embodiments herein may be adapted to have one or more of the following characteristics. In one non-limiting example, the system is in a vertical or near-vertical position when the centrifuge is at rest, and horizontal or near-vertical when the centrifuge is in rotation. It may have one or more buckets that are swinging buckets in a near-horizontal position. Optionally, the system may have a plurality of oscillating buckets spaced radially symmetrically on the centrifuge. Optionally, said bodily fluid sample is a biological fluid. Optionally, said biological fluid is blood. Optionally, the container is configured to contain no more than 100 μL of sample bodily fluid. Optionally, the container is configured to contain no more than 50 μL of sample bodily fluid. Optionally, the volume is configured to contain no more than 25 μL of sample fluid. Optionally, the container is closed at one end and open at the opposite end. Optionally, the container has rounded edges with one or more internal protrusions. Optionally, the system has one or more shaped features that are complementary to shaped features of the centrifuge vessel and is configured to fit within the centrifuge vessel. Includes extraction tip. Optionally, the shaped feature of the bucket includes one or more ledges on which the projecting portion of the container is configured to rest. Optionally, the bucket is configured to have the capacity to receive multiple containers having different shapes, and the shaped feature of the bucket includes a plurality of shelves and has a first shape. A first container is configured to rest on the first shelf and a second container having a second shape is configured to rest on the second shelf.

In yet another embodiment described herein: a centrifuge body; an electric motor for rotating said centrifuge body; and a rotary position integrated with said motor and at least a rotating portion of said electric motor and a detector that uses at least two different types of encoder information to determine said rotational position. is provided.

It should be appreciated that embodiments herein may be adapted to have one or more of the following characteristics. In one non-limiting example, the detector uses at least optical encoders and Hall effect techniques to determine rotational position. Optionally, the detector uses at least optical encoders and Hall effect techniques to determine at least rotational position and rotational velocity. Optionally, the detector has a first surface oriented to detect a type of encoder information and a second surface oriented to detect another type of encoder information. Optionally, said first surface and second surface are oriented in different directions. Optionally, said first surface and second surface are oriented in the same direction. Optionally, said motor includes a plurality of detectors for determining rotational position. Optionally, said motor includes a first encoder disc for providing said first type of encoder information and a second encoder disc for providing said second type of encoder information. Optionally, the motor includes a first encoder disk providing optical encoder information and a second encoder disk providing magnetic encoder information. Optionally, said motor includes an encoder disc providing said first type of encoder information and second type of encoder information. Optionally, the motor includes an encoder disk that provides both optical and magnetic encoder information. Although a motor with integrated encoder components has been described in the context of a centrifuge, others desire that the motor have position and/or speed detector functionality integrated within the motor. It should be understood that it can be adapted for use in scenarios of

In still other embodiments described herein: providing a motor; incorporating a first type of encoder within said motor; incorporating a second type of encoder within said motor; A method comprising determining a rotational position of a rotating portion of an electric motor using the first type of encoder and determining a rotational speed of the rotating portion of the electric motor using a second type of encoder. is provided.

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

In another embodiment described herein, a miniature high speed centrifuge is provided for use with sample containers. The centrifuge may include: a first portion comprising a thermally insulating material; and a second portion comprising a thermally conductive material; the thermally conductive material is configured to conduct heat in a direction away from the container.

In another embodiment described herein, a miniature high speed centrifuge is provided for use with sample containers. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body; and an active cooling unit to minimize heat transfer to the sample; the vessel is arranged to be located in an area with reduced thermal exposure; the active cooling unit is configured to cool the drive mechanism; the stator rotates an electric motor in the drive mechanism; placed coaxially within the child.

In another embodiment described herein, a miniature high speed centrifuge is provided for use with sample containers. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body; and a position detector used to determine the rotational position of the centrifuge body.

In another embodiment described herein, a miniature high speed centrifuge is provided for use with sample containers. The centrifuge comprises a centrifuge body; a drive mechanism for rotating the centrifuge body; and a self-balancing weight coupled to the centrifuge body, wherein such weight • May include a weight in the holder configured to move under centrifugal force into a position to minimize unbalanced rotation of the centrifuge body with uneven loading.

In another embodiment described herein, a miniature high speed centrifuge is provided for use with sample containers. The centrifuge includes a centrifuge body; a drive mechanism for rotating the centrifuge body; and at least one air bearing configured to operatively support the centrifuge.

In another embodiment described herein, a miniature high speed centrifuge is provided for use with sample containers. The centrifuge comprises a centrifuge housing; a centrifuge body; a drive mechanism for rotating the centrifuge body; and at least one air bearing configured to operatively support the centrifuge. At least the air bearing portion is part of the centrifuge housing.

In another embodiment described herein, a miniature high speed centrifuge is provided for use with sample containers. a centrifuge body; a drive mechanism for rotating the centrifuge body; and a force detector configured to detect velocity changes in force outside a predetermined range. of.

It should be appreciated that embodiments herein may be adapted to have one or more of the following characteristics. In one non-limiting example, the centrifuge vessel holder pivots inward toward the central axis of the centrifuge rotor under centrifugal force. Optionally, the centrifugation vessel holder is flush with the rotor body to minimize air resistance. Optionally, the centrifuge vessel holder is configured to alternate downward under centrifugal force. Optionally, if the electrical connections are unobstructed for centrifuging the cooling elements of the centrifuge body, such elements are in motion even during operation of the centrifuge.

In another embodiment described herein, a miniature high speed centrifuge is provided for use with sample containers. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body, the centrifuge body extending downwardly to cover at least a portion of the drive mechanism; The drive mechanism includes a stator and a rotor; said rotor being concentric with the stator.

In another embodiment described herein, a miniature high speed centrifuge is provided for use with sample containers. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body, the centrifuge body extending downwardly to cover at least a portion of the drive mechanism; The drive mechanism includes a stator and a rotor; said stator being concentric with the rotor.

In another embodiment described herein, a miniature high speed centrifuge is provided for use with sample containers. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body; and one or more rocking holders on the centrifuge body for housing the centrifuge containers. the maximum dimension of said rocking holder or sample vessel does not exceed 10 mm;

In another embodiment described herein, a miniature high speed centrifuge is provided for use with sample containers. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body; and one or more rocking holders on the centrifuge body for housing the centrifuge containers. the oscillating holder moves from a first orientation to a second orientation that is more horizontal than the first orientation during operation of the centrifuge;

In another embodiment described herein, a miniature high speed centrifuge is provided for use with sample containers. The centrifuge may include a centrifuge body; a drive mechanism for rotating the centrifuge body; and one or more rocking holders on the centrifuge body for housing the centrifuge containers. the width of the sample vessel is greater than the length of the sample vessel;

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

In yet another embodiment, a miniature high speed centrifuge for use with small volume sample vessels, said centrifuge comprising: a centrifuge rotor; an electric motor for rotating said centrifuge rotor; a plurality of buckets coupled to a separator rotor; and at least one magnet disposed on said buckets for coupling to a stationary portion of said centrifuge when said buckets are at rest. including centrifuge rotors containing mechanical equipment.

It should be appreciated that embodiments herein can be adapted to have one or more of the following features. In a non-limiting example, the rotor includes at least optical encoders and Hall effect sensors to determine rotational position. Optionally, the rotor includes at least one optical encoder and Hall effect sensor for determining rotational position and rotational speed. Optionally, a first encoder disc is included to provide a first type of encoder information and a second encoder disc to provide a second type of encoder information. Optionally, said first encoder disc provides optical encoder information and said second encoder disc provides magnetic encoder information coupled to a motor. Optionally, said bucket is configured to accommodate a container for holding a sample volume of less than 70uL. Optionally, said bucket is configured to accommodate a container for holding a sample volume of less than 80uL. Optionally, said bucket is configured to accommodate a container for holding a sample volume of less than 90uL. Optionally, said bucket is configured to accommodate a container for holding a sample volume of less than 100 uL. Optionally, said bucket is configured to accommodate a container for holding a sample volume of less than 150uL. Optionally, the buckets each have an L-shaped configuration. Optionally, a centrifuge housing is provided and dimensioned to cover at least a portion of a lateral portion of the centrifuge rotor. . Optionally, the housing includes a plurality of notches to allow air to enter when the centrifuge body is rotating.

In another non-limiting embodiment, a method is provided, the method comprising: providing an electric motor coupled to a centrifuge body; rotating a rotating portion of the electric motor using an encoder of the centrifuge body; determining a speed; holding a bucket on the centrifuge body with a magnet in at least one bucket when the centrifuge is at rest. Optionally, said bucket is configured to hold a sample chamber of less than 100uL. Optionally, the method further comprises using a thermally conductive material configured to switch heat away from the container. Optionally, the method includes using an active cooling unit to minimize heat transfer to the sample, wherein the container is placed in an area with reduced thermal exposure; , configured for cooling the drive mechanism. Optionally, the method includes the use of a self-balancing weight coupled to the centrifuge body, such weight dispersing, under centrifugal force, a non-uniform amount of packing material into the sample holder of the centrifuge. to a position to minimize unbalanced rotation of the centrifuge body. Optionally, the method includes using at least one air bearing configured to operatively support the centrifuge. Optionally, the method includes using at least one air bearing configured to operably support a centrifuge, at least a portion of the air bearing being a portion of the centrifuge housing. Optionally, the method includes use of a force detector configured to detect velocity changes in force outside a predetermined force condition. Optionally, the centrifuge vessel holder pivots inward toward the central axis of said centrifuge rotor under centrifugal force. Optionally, the centrifuge vessel holder forms a flush surface with the rotor body to minimize air resistance. Optionally, said centrifuge vessel holder is configured to retract downward under centrifugal force. Optionally, the electrical connection of the centrifuge body to the cooling elements is unobstructed even when the centrifuge is operating and such cooling elements are in motion. Optionally, the centrifuge vessel holder is oriented such that, while the centrifuge is operating, the centrifuge vessel holder moves from the first orientation to a more horizontal orientation than the first orientation. Move to two orientations.

It should be understood that in embodiments in the present disclosure, methods include at least one technical feature of any other embodiment herein. Optionally, the method can include any of at least two technical features of any other embodiment herein.

Optionally, the device may include at least one technical feature of any other embodiment herein. Optionally, the device can include any technical feature of at least two of any other embodiment herein. Optionally, the system can include at least one technical feature of any other embodiment herein. Optionally, the system can include any technical feature of at least two of any other embodiment herein.

This summary is provided to introduce some concepts in a simplified form than those described further below in the Detailed Description of the Invention. This summary is not intended to identify key or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter. .
For example, the present application provides the following items.
(Item 1)
A miniature high speed centrifuge for use with small volume sample vessels, said centrifuge comprising:
centrifuge rotor;
an electric motor for rotating the centrifuge rotor;
a plurality of buckets coupled to the centrifuge rotor; and at least one positioned on the buckets for coupling to a stationary portion of the centrifuge when the buckets are at rest. A centrifuge containing two magnetic devices.
(Item 2)
The centrifuge of item 1, wherein the rotor uses at least an optical encoder and a Hall effect sensor for the detector to determine rotational position.
(Item 3)
The centrifuge of claim 1, wherein the rotor employs at least optical encoder techniques and Hall effect sensors for the detectors to determine at least rotational position and rotational speed.
(Item 4)
The centrifuge of item 1, wherein the detector has a first surface directed to detecting one type of encoder information and a second surface directed to detecting another type of encoder information.
(Item 5)
The centrifuge of item 1, wherein the first encoder disc providing optical encoder information and the second encoder disc providing magnetic encoder information are coupled to the electric motor.
(Item 6)
The centrifuge of item 1, further comprising buckets configured to accommodate volumes for sample volumes of less than 70 μL.
(Item 7)
The centrifuge of item 1, further comprising buckets configured to accommodate volumes for sample volumes of less than 80 μL.
(Item 8)
The centrifuge of item 1, further comprising buckets configured to accommodate volumes for sample volumes of less than 90 μL.
(Item 9)
The centrifuge of item 1, further comprising buckets configured to accommodate volumes for sample volumes of less than 100 μL.
(Item 10)
The centrifuge of item 1, further comprising buckets configured to accommodate volumes for sample volumes of less than 150 μL.
(Item 11)
The centrifuge of item 1, wherein each bucket is L-shaped.
(Item 12)
The centrifuge of item 1, further comprising a centrifuge housing dimensioned to cover at least a portion of a side of the centrifuge rotor.
(Item 13)
The centrifuge of item 1, wherein the housing includes a plurality of notches to allow air to enter when the centrifuge body is rotating.
(Item 14)
A method comprising:
providing an electric motor coupled to the centrifuge body;
determining the rotational speed of the rotating portion of the motor using an encoder on the centrifuge body;
A method comprising: using a magnet in at least one bucket to retain a bucket on the centrifuge body when the centrifuge is at rest.
(Item 15)
15. The method of item 14, wherein the bucket is configured to hold a sample chamber of less than 100 uL.
(Item 16)
15. The method of item 14, further comprising a thermally conductive material configured to switch heat away from the container.
(Item 17)
further comprising an active cooling unit to minimize heat transfer to the sample;
the container is positioned such that the container is positioned in an area with reduced thermal exposure;
15. Method according to item 14, wherein the active cooling unit is arranged for cooling the drive mechanism.
(Item 18)
Further comprising a self-balancing weight coupled to the centrifuge body, such weight balancing the centrifuge body with a non-uniform amount of filling in the sample holder of the centrifuge under centrifugal force. 15. The method of item 14, configured to move to a position to minimize lost rotation.
(Item 19)
15. The method of item 14, further comprising using a centrifuge including at least one air bearing configured to operatively support the centrifuge.
(Item 20)
An item further comprising using a centrifuge comprising at least one air bearing configured to operatively support a centrifuge, at least a portion of the air bearing being a portion of said centrifuge housing. 14. The method according to 14.
(Item 21)
15. The method of item 14, further comprising using a centrifuge including a force detector configured to detect velocity changes in force outside a predetermined force condition.
(Item 22)
The apparatus or method of any one of the preceding items, wherein under centrifugal force, the centrifuge vessel holders or buckets pivot inward toward the central axis of the centrifuge rotor.
(Item 23)
An apparatus according to any one of the preceding items, wherein the centrifugation vessel holder forms a flush surface with the rotor body to minimize air resistance.
(Item 24)
An apparatus according to any one of the preceding items, wherein the centrifuge vessel holder retracts downward under centrifugal force.
(Item 25)
An apparatus according to any one of the preceding items, wherein the electrical connection to the cooling elements of the centrifuge body is unobstructed even when the centrifuge is operating and such cooling elements are in motion.
(Item 26)
of the preceding item, wherein while the centrifuge is operating, the centrifuge vessel holder moves from a first orientation to a second orientation that is more horizontal than the first orientation. A device according to any one of the preceding paragraphs.
(Item 27)
A compact high-speed centrifuge for use with sample vessels, said centrifuge comprising:
Centrifuge body;
including a drive mechanism for rotating said centrifuge body; said centrifuge body extending downwardly to cover at least a portion of said drive mechanism;
the drive mechanism includes a stator and a rotor;
A centrifuge in which the rotor is concentric with the stator.
(Item 28)
A method comprising any at least one technical feature according to any of the above items.
(Item 29)
A method comprising any at least two technical features according to any of the above items.
(Item 30)
A device comprising any at least one technical feature according to any of the above items.
(Item 31)
A device comprising any at least two technical features according to any of the above items.
(Item 32)
A system comprising any at least one technical feature according to any of the above items.
(Item 33)
A system comprising any at least two technical features according to any of the above items.

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

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

6-8 show various views of tube holder embodiments described herein. 6-8 show various views of tube holder embodiments described herein. 6-8 show various views of tube holder embodiments described herein.

9-12 illustrate various embodiments of centrifuges described herein. 9-12 illustrate various embodiments of centrifuges described herein. 9-12 illustrate various embodiments of centrifuges described herein. 9-12 illustrate various embodiments of centrifuges described herein.

Figures 13-16 illustrate various embodiments of centrifuges having thermal control features described herein. Figures 13-16 illustrate various embodiments of centrifuges having thermal control features described herein. Figures 13-16 illustrate various embodiments of centrifuges having thermal control features described herein. Figures 13-16 illustrate various embodiments of centrifuges having thermal control features described herein. Figures 13-16 illustrate various embodiments of centrifuges having thermal control features described herein.

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

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

Figures 19-20 illustrate various embodiments of the devices and methods described herein. Figures 19-20 illustrate various embodiments of the devices and methods described herein.

Figure 21 shows a schematic diagram of one embodiment of an integrated system with sample handling, pretreatment, and analysis components.

FIG. 22 shows yet another embodiment of the device described herein. FIG. 23 shows yet another embodiment of the device described herein.

(Description of specific embodiments)
It is to be understood that the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention as claimed. As used in this patent specification and the appended claims, the singular forms "a,""an," and "the" include plural referents unless the context clearly dictates otherwise. Please note. Thus, for examples, reference to "a material" can include mixtures of materials, "a compound" can include multiple compounds, etc. be. References cited herein are incorporated by reference in their entirety to the extent not inconsistent with the teachings explicitly set forth herein.

In this specification and the claims that follow, reference is made to a series of terms having the following meanings:

“Optional” or “optionally” is used because this description can include situations where the subsequently described situations do and do not occur. It means that it does not have to occur. For example, if the device optionally includes a feature for a sample collection well, this means that this sample collection well may or may not be present, and thus this description The device includes both configurations with sample collection wells and configurations without sample collection wells.

Centrifuge Figures 1, 2 and 3 show scale perspective views of centrifuges (Figure 1 - side view, Figure 2 - front view, Figure 3 - rear view) that may be integrated into the system. This centrifuge may include an electric motor capable of rotating the rotor at 15,000 rpm. One type of centrifuge rotor is shaped somewhat like a fan blade mounted on the motor spindle in a vertical plane. Affixed to the rotor is an element that holds a sample holding element (tip) and the end of the tip distal to the motor shaft provides a ledge or ledge on which to rest. , and provide support to prevent sample escape during centrifugation. The tip is further supported at its proximal end by a mechanical stop in the rotor. This can be provided so that the forces generated during centrifugation do not cause the tip to cut through the soft vinyl cap. The tip can be inserted and removed by standard pick-and-place mechanisms, but is preferably done by pipette. The rotor is a single piece of acrylic (or other material) shaped to minimize vibration and noise during operation of the centrifuge. The rotor is (optionally) shaped such that when oriented at a particular angle to the vertical, other movable components in the instrument can move past the centrifuge. The sample holding element is centrifugally balanced by a counter mass on the opposite side of the rotor so that the center of inertia of rotation is axial with respect to the motor. The centrifuge motor can provide positional data to a computer, which in turn controls the rest position of the rotor (typically vertical before and after centrifugation).

published standards (DIN 58933-1; in the United States, the CLSI (Clinical Laboratory Standards Institute) standard H07-A3 "Procedure for Determining Packed Cell Volume by the Microhematocrit Method" Approved Standard - Third Edition) to minimize centrifugation time (without creating excessive mechanical stress during centrifugation). A convenient size for the child is about 5-10 cm at a rotation of about 10,000-20,000 rpm, giving a red blood cell filling time of about 5 minutes.

In some embodiments, the centrifuge may be a horizontally oriented centrifuge with a swinging bucket design. In some preferred embodiments, the axis of rotation of said centrifuge is vertical. In alternative embodiments, the axis of rotation can be horizontal or at any angle. The centrifuge can spin more than one tube at the same time and can be designed to be fully integrated into an automated system using computer controlled pipettes. In some embodiments, the tube ends may be closed. The oscillating bucket design may allow the centrifugation vessel to be passively oriented in a vertical position when at rest and spin at a fixed angle when rotating. In some embodiments, the rocking bucket may allow the centrifugation vessel to spin in a horizontal orientation. Alternatively, they can spin in vertical and horizontal positions (eg, about 15, 30, 45, 60, or 75 degrees from vertical). Centrifuges with the swinging bucket design meet the positional accuracy and repeatability requirements of robotic systems in which a series of positioning systems are used.

A computer-based control system can use the position information from the optical encoder to rotate the rotor at a controlled speed. For high speed performance, a precise static position using only position feedback may not be maintained so that a suitable motor can be designed. In some embodiments, a cam in combination with a solenoid actuated lever can be used to achieve very precise and stable stops at a fixed number of positions. Using a separate control system and feedback from Hall effect sensors built into the motor, the rotor speed can be very precisely controlled at high speeds.

Because a series of sensitive instruments must work simultaneously in the assay instrument system, the centrifuge design preferably minimizes or reduces vibration. The rotor can be designed aerodynamically with a smooth outer surface - completely enclosing the buckets when they are in a horizontal position. Additionally, vibration damping can be used at multiple locations in the design of the case. It should be understood that any of the embodiments in FIGS. 1-3 can be configured to have any other characteristics described in this disclosure.

Rotor A centrifuge rotor can be a component of the system that holds and spins the centrifuge vessels. The axis of rotation can be vertical and thus the rotor itself can be positioned horizontally. However, in alternate embodiments, different rotation axes and rotor positions may be used. On either side of the rotor that holds the centrifuge vessels are two symmetrically positioned components known as buckets. For the embodiment in which the three buckets are oriented at 120 degrees, alternative configurations are possible in which the buckets are oriented radially symmetrically. Any number of buckets may be provided, including but not limited to 1, 2, 3, 4, 5, 6, 7, 8, or more buckets. The buckets may be evenly spaced from each other. For example, if n buckets are provided, where n is an integer, these buckets are spaced approximately 360/n degrees apart. In other embodiments, the buckets need not be evenly spaced from each other or radially symmetrical.

If the rotor does not move, these buckets can passively fall under the influence of gravity so that the tubes are vertical and they are made accessible by the pipette. FIG. 4 shows an embodiment of the rotor at rest with the buckets vertical. In some embodiments, these buckets can passively drop at a predetermined angle, which can be vertical or non-vertical. When the rotor is spinning, centrifugal forces force these buckets into a generally horizontal position or at an angle. FIG. 5 shows an example of a rotor with speed where the buckets are at a slight angle from horizontal. There may also be physical forced stops for both vertical and horizontal positions that act to enhance their accuracy and positional repeatability.

The rotor can be aerodynamically designed with a disk shape and as few physical properties as possible to minimize vibrations caused by air turbulence. To achieve this, the external geometry of the buckets is precisely rotated so that when the rotor is rotated and the buckets can be forced into a horizontal position, the buckets and rotor can be perfectly aligned. Matches the outer shape of the child.

To facilitate plasma extraction, the rotor may be angled downward toward the ground with respect to the horizontal. This can enforce a fixed spin angle for the buckets, since the bucket angle matches that of the rotor. The sediment resulting from such centrifugation may be angled relative to the tube when placed upright. A narrow extraction tip can be used to aspirate the plasma from the top of the centrifuge container. By placing the extraction tip near the bottom of the gradient created by angled sedimentation, the final volume of plasma can be more efficiently extracted without disturbing the delicate buffy coat.

Various tube designs can be fitted to the equipment bucket. In some embodiments, various tube designs may be closed at their ends. Some are shaped into centrifuge tubes with conventional conical bottoms. Other tube designs may be cylindrical. A tube with a low height-to-cross-sectional area ratio may be suitable for processing cells. Tubes with large ratios (>10:1) are suitable for accurate measurement of hematocrit and other imaging requirements. However, any height to cross-sectional area ratio may be used. The bucket may be formed from any of a number of plastics (polystyrene, polypropylene), or any other material discussed elsewhere herein. Buckets have a capacity of a few microliters to about 1 milliliter. The tubes can be inserted and removed from the centrifuge using a "pick and place" mechanism.

Control System Due to the instrument rotation and positioning requirements of the centrifuge, a dual control system approach may be used. A position-based control system can be implemented that moves the rotor to a particular rotational orientation in precise increments. 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 used. Positional feedback for the position controller can be provided by high resolution optical encoders. For operation of the centrifuge from low speed to high speed, a speed controller can be implemented while using a PID control system directed to speed control. Rotational speed feedback for the speed controller can be provided by a simple Hall effect sensor suite located on the motor shaft. Each sensor may generate one square wave per cycle of motor shaft rotation.

Stop Mechanism In some embodiments herein, a physical stop mechanism may be used to consistently and rigidly position the rotor at a particular position. In one embodiment, this stop mechanism may use a cam along with a lever coupled to the rotor and driven by a solenoid. The cam may be machined into a circular disk having a number of "C" shaped notches on the periphery. To position the centrifuge rotor, its rotational speed is first reduced to at most 30 RPM. In other embodiments, the rotational speed may be reduced to any other amount including, but not limited to, about 5 rpm, 10 rpm, 15 rpm, 20 rpm, 25 rpm, 35 rpm, 40 rpm, or 50 rpm. As soon as the speed is sufficiently reduced, the lever is activated. The end of the lever is a cam follower that slides around the cam with minimal friction. Once the cam follower reaches the center of a particular cut in the cam, the force of the lever actuated by the solenoid overcomes the force of the motor and the rotor is brought to rest. At this point, the motor is electronically braked, and in combination with the stop mechanism, the rotational position can be held precisely and rigidly indefinitely.

Centrifuge Bucket The swing bucket of the centrifuge can be configured to accommodate different types of centrifuge tubes. In preferred embodiments, these various tube types may have a collar or flange at their upper (open) end. This collar or flange feature can rest on the top of the bucket and support the tube during centrifugation. As shown in Figures 6, 7 and 8, various lengths and volumes of conical and cylindrical tubes can be accommodated. Figures 6, 7, and 8 provide examples of buckets, and other bucket designs may be used. For example, FIG. 6 shows an example bucket configuration. The bucket may have side portions that fit into the centrifuge and allow the bucket to swing freely. The bucket may have a closed bottom and an opening at the top. FIG. 7 shows an embodiment of a centrifuge vessel fitted into a bucket. As previously mentioned, the buckets can be shaped to accommodate centrifugation vessels of various configurations. These centrifuge vessels have one or more protruding members that can rest on the buckets. These centrifuge vessels may be shaped with one or more characteristics that allow them to fit into the centrifuge buckets. These features may be shaped features of the tube or may be one or more protrusions. FIG. 8 shows another centrifugation container embodiment that can be mated with the buckets. As previously mentioned, the bucket may have one or more shaped features that allow different shaped centrifuge vessels to fit into the bucket. It should be appreciated that any of the embodiments of the centrifuges in FIGS. 4-8 can be configured to have any other characteristics described in this disclosure.

Centrifuge Tubes and Sample Extraction Techniques The centrifuge tubes and extraction tips can be provided separately and fitted together for extraction of material following centrifugation. The centrifuge tubes and extraction tips can be designed to handle complex processing in automated systems. Any dimensions are provided for illustrative purposes only and other dimensions of the same or different proportions may be utilized.
The system enables one or more of the following:
1. 1. Rapid processing of small blood samples (typically 5-50 μL). 2. Accurate and precise measurement of hematocrit; Efficient removal of plasma 4 . Efficient resuspension of formed elements (red and white blood cells)
5. Leukocyte enrichment (followed by fluorescent antibody labeling and fixation plus red blood cell lysis)
6. Optical determination of erythrocyte lysis and recovery of leukocytes

Specially manufactured tubes and tips may be used in the operation of the centrifuge to meet various constraints placed on the centrifuge vessel and extraction tip overview system. The centrifugation vessel may be a closed-bottom tube designed for spinning in a centrifuge. In some embodiments, the centrifuge vessel can be the tube illustrated in FIG. 7 or have one or more of the features illustrated in FIG. It can possess a unique set of properties that enable a wide range of required functionality, including hematocrit measurement, RBC lysis, pellet resuspension and efficient plasma extraction. The extraction tip can be designed so that it can be inserted into a centrifuge vessel for precise fluid extraction and pellet resuspension. In some embodiments, the extraction tip can be the tip illustrated in FIG. 6 or can be a tip having one or more of the characteristics illustrated in FIG. Exemplary specifications for extraction tips can be found herein and in US patent application Ser. incorporated into the specification.

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

A first usage scenario may entail when 40 μL of heparinized whole blood is sedimented, the maximum volume of plasma is collected, and the hematocrit is measured by computer vision. At 60% hematocrit or less, the required or preferred volume of plasma may be approximately 40 μL*40%=16 μL.

In some embodiments, it is not possible to recover 100% plasma because the buffy coat should not be disturbed, so there is a minimal distance between the bottom of the tip and the top of the sediment. must be preserved. This minimum distance can be determined experimentally, but as a function of the required safety distance (d), the volume (V) sacrificed can be estimated by: V(d)=d*π1.25 mm . For example, for a required safety distance of 0.25 mm, the sacrificed volume is 1.23 μL at 60% hematocrit. This volume can be reduced by reducing the internal radius of the hematocrit portion of the centrifuge vessel. However, in some embodiments, the dimensions of the existing centrifugation vessel can be near minimal, as the narrow portion must completely accommodate the outer radius of the extraction tip, which is greater than 1.5 mm.

Along with plasma extraction, in some embodiments, hematocrit may be required to be measured by computer vision. To facilitate this process, the overall height for a given volume of hematocrit can be maximized by minimizing the internal diameter of the narrow section of the tube. By maximizing the height, the relationship between the change in hematocrit volume and the physical height of the column can be optimized, thus increasing the number of pixels available for measurement. The height of the narrow section of the tube is long enough to accommodate the worst case scenario of 80% hematocrit, yet leaving a small portion of plasma at the top of the column to allow efficient extraction. can. Therefore, 40 μL*80%=32 μL is the volume capacity required for accurate measurement of hematocrit. The volume of the narrow portion of the chip as designed can be about 35.3 μL, which allows some plasma volume to remain even in the worst case.

The second usage scenario is much more complex and requires one, more, or all of the following:
Sedimentation of whole blood Plasma extraction Resuspension and staining of sediment in lysis buffer Sedimentation of remaining leukocytes Removal of supernatant Resuspension of leukocytes Complete extraction of leukocyte suspension

In order to completely resuspend the thick sediment, experiments have shown that the sediment is physically disturbed by a tip capable of reaching all the way to the bottom of the tube containing the sediment. A preferred arrangement for the bottom of the tube used for resuspension would be a hemispherical shape similar to standard commercial PCR tubes. In other embodiments, other tube bottom geometries may be used. The centrifuge vessel, along with the extraction tip, can be designed to observe these geometrical requirements and facilitate the resuspension process while the extraction tip physically contacts the bottom.

During manual resuspension experiments, it was noticed that physical contact between the bottom of the tube and the bottom of the tip could form a seal that prevented migration of bodily fluids. A fine spacing can be used to achieve both complete disruption of the sediment while allowing fluid to flow. In robotic systems, the bottom of the centrifuge vessel may be provided with physical functions to facilitate this process. In some embodiments, this feature may include four small hemispherical protrusions positioned around the bottom of the tube. When the extraction tip is fully inserted into the tube and allowed to provide physical contact, the end of the tip can rest on the protrusions and body fluids flow freely between the protrusions. be able to. This causes a small volume (˜0.25 μL) to be lost across the gap.

During the lysis process, in some implementations the most anticipated fluid volume is 60 μL, which combined with the 25 μL displaced by the extraction tip may require an overall volume capacity of 85 μL. A design with a current maximum volume of 100 μL can exceed this requirement. Other aspects of the second usage scenario require similar or already discussed chip characteristics.

The shape of the top of the centrifugation vessel can be designed to fit with a pipette nozzle. Any pipette nozzle described elsewhere herein or known in the art may be used. The external shape of the top of the tube closely matches that of the reaction chip around which both the flow nozzle and cartridge are designed. In some embodiments, a small ridge circumscribes the inner surface of the top. This protrusion can be a visible marker of maximum fluid height and is designed to facilitate automatic error detection using a computer vision system.

In some embodiments, the distance from the bottom of the fully fitted nozzle to the top of the maximum fluid line is 2.5 mm. This distance is 1.5 mm less than the recommended distance of 4 mm for the extraction tip. This reduced distance may be caused by the need to minimize the length of the extraction tip while adhering to minimum volume requirements. The justification for this reduced distance derives from the specific use of tubes. In some implementations, fluid can be exchanged by the tube only from the top, and the maximum fluid that can be held while engaging the nozzle is the maximum amount of whole blood expected at any given time. This is because it is a large amount (40 μL). This bodily fluid level is well below the bottom of the nozzle. Another concern is that at other times the body fluid volume in the tube is much larger and can wet the tube wall up to the height of the nozzle. In some embodiments, this is done to ensure that the meniscus of any body fluid contained within the tube does not exceed the maximum height of the body fluid, even if the total volume is less than the maximum specification. It is up to the person using the In other embodiments, other features may be provided to keep bodily fluid contained within the tube.

Any dimensions, sizes, volumes or distances provided herein are provided for illustration only. Any other dimension, size, volume or distance that may or may not be proportional to the amounts referred to herein may be used.

The centrifugation vessel is subjected to a series of forces during the process of fluid exchange and rapid insertion and removal of tips. If the tube is constrained, these forces can be strong enough to lift or remove the tube from the centrifuge bucket. To prevent movement, the tube must be secured in some way. To accomplish this, a small ring was added circumscribing the bottom of the outside of the tube. This ring matches the mechanical properties on the bucket and can be easily fitted. As long as the force holding the projection is greater than the force experienced during bodily fluid manipulation, but less than the frictional force when mated with the nozzle, then this problem is solved.

Extraction Tips Extraction tips can be designed to interact with the centrifugation vessel and efficiently extract plasma and resuspend pelleted cells. If desired, the total length (e.g., 34.5 mm) includes that described in U.S. Patent Application No. 12/244,723 (incorporated herein by reference); is not limited, it fits exactly another blood chip, but can be long enough to physically contact the bottom of the centrifuge container. The ability to contact the bottom of the tube may be required in some embodiments for both the resuspension process and complete recovery of the leukocyte suspension.

The required volume of extraction tip is determined by the maximum volume expected to be aspirated from the centrifuge vessel at any given time. In some embodiments, this volume may be approximately 60 μL, less than the chip's maximum capacity of 85 μL. In some embodiments, a tip with a larger volume than required may be provided. Similar to the centrifuge vessel, features of the interior circumscribing the top portion of the chip can be used to mark the height of this maximum volume. The distance between the line of maximum volume and the top of the fitted nozzle may be 4.5 mm, which is considered a safe distance to prevent contamination of the nozzle. Any sufficient distance can be used to prevent nozzle contamination.

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

In one example, plasma can be diluted (eg, 1:10) in a mixture of dextran sulfate (25 mg/dL) and magnesium sulfate (100 mM) and then diluted for 1 minute to precipitate LDL cholesterol. can be incubated. The reaction product is aspirated into a centrifuge tube, then capped and spun at 3000 rpm for 3 minutes. The images are shown in U.S. Patent Application Nos. 13/355,458 and 13/244,947, respectively, and are incorporated herein by reference for all purposes, but were taken prior to centrifugation. Images of the original reaction mixture (showing white precipitate), taken following centrifugation (showing clear supernatant), and taken after LDL cholesterol precipitation (after cap removal).

Examples of other centrifuges that can be used in the present invention are US Pat. 0305392 and 2010/0047790, which are incorporated herein by reference in their entireties.

Example Protocols Many variations of protocols can be used for centrifugation and processing. For example, for blood counts, a typical protocol used in a centrifuge to process and concentrate white blood cells employs one or more of the following steps. The following steps may be provided in a varying order or any of the following steps may be replaced by other steps:
1. Receive 10 μL of anticoagulant anticoagulated blood (pipette injects blood into the bottom of the centrifuge bucket).
2. Erythrocytes and leukocytes are sedimented by centrifugation (<5 min x 10,000 g).
3. Hematocrit is measured by imaging.
4. Plasma is slowly aspirated into the pipette without disturbing the cell pellet (4 μL corresponds to worst case scenario [60% hematocrit]).
5. The pellet is resuspended after adding an appropriate mixture of up to 5 fluorescently labeled antibodies dissolved in 20 μL of buffered saline.
6. Incubate at 37C for 15 minutes.
7. Lysis/fixation reagent is prepared by mixing red blood cell lysis solution (ammonium chloride/potassium bicarbonate) with leukocyte fixation reagent (formaldehyde).
8. Add 30 μL of lysis/fixation reagent (approximately 60 μL total reaction volume).
9. Incubate at 37C for 15 minutes.
10. Leukocytes are sedimented by centrifugation (10,000 g).
11. Remove the supernatant hemolysate.
12. Leukocytes are resuspended by adding buffer (isotonic buffered saline).
13. Accurately measure volume.
14. Deliver the sample to a hemocytometer.

These steps include receiving samples. This 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 volumetric measurement described elsewhere herein. In some examples, the sample can have an anticoagulant.

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

In one embodiment, measurements may also be taken. In some examples, this measurement may be made by imaging or any other detection mechanism described elsewhere herein. For example, the hematocrit of a separated blood sample can be obtained by imaging. Imaging may be done with 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 solid and liquid components, the liquid component can be displaced. Plasma of the blood sample may be removed by pipette. This liquid component can be removed without disturbing the solid component. Said imaging can assist in the removal of liquid constituents, or any other selected constituents of the sample. For example, this imaging can be used to determine where the plasma is located and can assist in positioning the pipette to remove the plasma.

In some embodiments, reagents or other substances may be added to the sample. For example, the solid portion of the sample can be resuspended. Labeled substances can be added. One or more incubations can occur. In some instances, lysing and/or immobilizing reagents may be converted. Additional separation and/or resuspension steps may occur. Dilution and/or concentration can occur as desired.

The volume of the sample can be measured. In some examples, the volume of the sample may be measured in a precise and/or precise manner. The sample volume can be measured by a system with a low coefficient of variation, such as those described elsewhere herein. In some examples, sample volume can be measured using imaging. An image of the sample is captured and the volume of the sample can be calculated from the image.

The sample can be delivered to any desired process. For example, a sample can be delivered for blood count.

In another example, a typical protocol for nucleic acid purification, with or without centrifugation, includes one or more of the following steps. This system can enable DNA/RNA extraction to deliver nucleic acid templates to exponential amplification reactions for detection. This process can be designed to extract nucleic acids from a variety of samples including, but not limited to, whole blood, serum, viral transport media, human and animal tissue samples, food samples, and microbial cultures. This process can be fully automated and extract DNA/RNA consistently and in a quantitative manner. The following steps may be provided in varying order or with other steps replaced by any of the following steps:

1. Sample lysis. Cells in the sample may be lysed using a chaotropic salt buffer. The chaotropic salt buffer contains one or more of the following: but is not limited to 3-6 M guanidine hydrochloride, or guanidinium or guanidinium thiocyanate; ethylenediaminetetraacetic acid (EDTA) at a typical concentration of 1-5 mM; lysozyme at a typical concentration of 1 mg/mL; proteinase-K at a typical concentration of 1 mg/mL; and pH. can be set between 7 and 7.5 using a buffer such as HEPES. In some embodiments, the sample can be incubated at a typical temperature of 20-95° C. for 0-30 minutes. Isopropanol (50%-100% v/v) can be added to the mixture after dissolution.

2. surface filling. Lysed samples include, but are not limited to, resin supports packed in chromatography-style columns, magnetic beads mixed with samples in batch-type fashion, resin suspended in liquefied bed formats. Exposure to a functionalized surface (often in the form of a packed bed of beads) such as samples pumped through and through closed channels over the surface in a tangential flow fashion. be done. The surface can be functionalized to bind nucleic acids (eg, DNA, RNA, DNA/RNA hybrids) in the presence of a lysis buffer. Surface types may include ion exchange functional groups such as silica and functional groups such as diethylaminoethanol (DEAE). Lysed mixtures can be exposed to these surfaces and nucleic acids bind.

3. Washing. The solid surface is washed with a salt solution such as 0-2 M sodium chloride and ethanol (20-80% v/v) solution at pH 7.0-7.5. This washing can be done in the same manner as the filling.

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

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

In some embodiments, it is important to be able to recover packed and enriched cells by centrifugation for cytometry. In some embodiments, this is possible with instruments that have pipetting capabilities. A liquid (typically isotonic buffered saline, a lysing agent, a mixture of lysing agent and fixative in a buffer, or a mixture of labeled antibodies) is dispensed into centrifuge buckets. and can be aspirated and resuspended repeatedly. A pipette tip can be forcefully inserted into a blood cell to expedite the process. Image analysis can assist the process by objectively verifying that all cells have been resuspended.

Use of Pipettes and Centrifuges to Process Samples Prior to Analysis According to embodiments of the invention, the system may have pipette functionality, pick and place and centrifugation capabilities. Such capability allows efficient pretreatment of almost all types of samples and complex assay procedures with very small sample volumes.

In particular, the system makes it possible to separate the formed constituents (erythrocytes and leukocytes) from the plasma. The system may also allow resuspension of formed components. In some embodiments, the system may allow enrichment of leukocytes from immobilized and hemolysed blood. The system may also allow cell lysis to release nucleic acids. In some embodiments, the system may allow purification and concentration of nucleic acids by filtration through a chip filled with (typically beaded) solid phase reagents (eg, silica). The system may also allow elution of purified nucleic acids following solid phase extraction. Precipitate removal and collection (eg LDL cholesterol precipitated with polyethylene glycol) may also be enabled by the system.

In some embodiments, the system may allow purification by affinity. Small molecules such as vitamin-D and serotonin can be adsorbed to beaded (particulate) hydrophobic substrates and then eluted using organic solvents. Antigen can be provided on a substrate coated with antibodies and eluted with acid. The same method can be used to enrich analytes found at low concentrations such as thromboxane-B2 and 6-keto-prostaglandin F1α. Antigens can be presented on a substrate coated with antibodies or aptamers and then eluted.

In some embodiments, the system may allow for chemical modification of specimens prior to assay. For assays of serotonin (5-hydroxytryptamine), for example, it may be required to convert the specimen to a derivative (such as an acetylated form) using a reagent (such as acetic anhydride). This can be done to generate a form of analyte that can be recognized by an antibody.

Liquids can be moved using a pipette (vacuum aspiration and pumping). This pipette can be limited to relatively low positive and negative pressures (approximately 0.1-2.0 atmospheres). Centrifuges can be used to generate much higher pressures when it is necessary to force a liquid through a beaded solid phase medium. For example, if a rotor with a radius of 5 cm is used at a speed of 10,000 rpm, a force of about 5,000 xg (about 7 atmospheres) can be generated to pass through a resistive medium such as a liquid-filled bed. is sufficient for Any centrifuge design and configuration discussed elsewhere herein or known in the art may be used.

It may be the case that hematocrit measurements of very small volumes of blood are performed. For example, inexpensive digital cameras have the ability to take good images of small objects even with poor contrast. Using this capability, the system of the present invention can enable automated measurement of hematocrit in very small volumes of blood.

For example, 1 μL of blood is collected into a microcap glass capillary tube. The capillary is then sealed with curable glue and then centrifuged at 10,000 xg for 5 minutes. Blood cell volume can be easily measured, and the plasma meniscus (indicated by an arrow) is also visible, so hematocrit is accurately measured. This can allow the system not to waste a relatively large volume of blood to make this measurement. In some embodiments, the camera may be used "as is" to capture large images without microscopic manipulation. Other embodiments may use a microscope or other optical technique to magnify the image. In one implementation, the hematocrit is measured using a digital camera without additional optical interfaces, and the measured hematocrit is measured in micrometers that would require many microliter samples in a conventional clinical laboratory. It was the same as that measured by hematocrit. In some embodiments, the length of the sample column and the length of the packed red blood cell column can be measured very accurately (+/-<0.05 mm). Given that the blood sample column is approximately 10-20 mm, the hematocrit standard deviation is much better than 1% and is consistent with that obtained by standard clinical laboratory methods.

The system can allow measurement of erythrocyte sedimentation rate (ESR). The ability of digital cameras to measure very small distances and rate of change of distance can be exploited for measuring ESR. In one example, three blood samples (15 μL) were aspirated into a "reaction chip". Images were captured at 2 minute intervals for 1 hour. Image analysis was used to measure the migration of the interface between red blood cells and plasma.

Measurement accuracy can be estimated by fitting the data to a polynomial function and calculating the standard deviation of the difference between the data and the fitted curve (for all samples). In the previous example, this was determined to be 0.038 mm or <2% CV when related to distance traveled over 1 hour. Therefore, ESR can be accurately measured by this method. Another way to measure ESR is to measure the maximum slope of the distance versus time relationship.

Centrifuges Referring now to Figures 9-11, still further embodiments of centrifuges are described. According to some embodiments of the invention, a system may include one or more centrifuges. Instruments in the system may include one or more centrifuges therein. For example, one or more centrifuges are provided in the instrument housing. A module may have one or more centrifuges. One, two, or more modules of the instrument may have centrifuges therein. The centrifuge may be supported by a modular support structure or housed within a modular housing. This centrifuge can have a compact, flat form factor and occupies only a small footprint. In some embodiments, the centrifuge can be miniaturized for point-of-service applications, yet retains the ability to spin at high speeds of about 10,000 rpm or greater, and up to about 1200 m/m. It has a gravity endurance capacity of s2 or ^more .

In some embodiments, a centrifuge can be configured to accept one or more samples. Centrifuges can be used to separate and/or produce materials of different densities. Examples of such substances include viruses, microorganisms, cells, proteins, environmental compositions, or other compositions. A centrifuge can be used to concentrate cells and/or particles for subsequent measurements.

In some embodiments, a centrifuge can have one or more cavities that can be configured to receive a sample such that the sample can contact the walls of the cavity. Alternatively, the cavity may be configured to receive a sample tube containing a sample therein. Any description herein of cavities may apply to configurations capable of receiving and/or containing a sample or sample vessel. For example, a cavity can include a depression in the material, a bucket format, a protrusion having an interior of the cavity, a member configured to interconnect with a sample vessel. Any description of a cavity may also include shapes that may or may not have concave or inner surfaces. Sample tube examples may include any of the tube or tip designs described elsewhere herein. A sample tube can have an inner surface and an outer surface. The sample tube can have at least one open end configured to receive a sample. This open end may be closed or sealed. The sample tube can have a closed end. The sample tube can be the nozzle of the bodily fluid processing device, which can act as a centrifuge to spin the bodily fluid in the nozzle, with a tip or another tube attached to the nozzle. .

In some embodiments, the centrifuge is 1 or more, 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 8 or more, 10 or more, 12 or more, 15 or more, 20 or more, 30 or more, or 50 or more cavities configured to receive samples or sample tubes.

In some embodiments, the centrifuge is configured to accept small sample volumes. In some embodiments, the cavity and/or sample tube is of 1,000 μL or less, 500 μL or less, 250 μL or less, 200 μL or less, 175 μL or less, 150 μL or less, 100 μL or less, 80 μL or less, 70 μL or less, 60 μL or less, 50 μL or less. , 30 μL or less, 20 μL or less, 15 μL or less, 10 μL or less, 8 μL or less, 5 μL or less, 1 μL or less, 500 nL or less, 300 nL or less, 100 nL or less, 50 nL or less, 10 nL or less, 1 nL or less, 500 pL or less, 100 pL or less, 50 pL or less, 10 pL or less It can be configured to accept sample volumes of 5 pL or less, or 1 pL or less.

In some embodiments, the centrifuge may have a cover that contains the sample within the centrifuge. This cover prevents the sample from aerosolizing and/or evaporating. The centrifuge may optionally have a thin film, oil (eg, mineral oil), wax, or gel that may contain the sample within the centrifuge and/or prevent aerosolization and/or evaporation. This thin film, oil, wax, or gel is provided as a layer overlying the sample, which can be contained within the centrifuge cavity and/or the sample tube.

A centrifuge may be configured to rotate about an axis of rotation. The centrifuge can be spun at any number of revolutions per minute. For example, the centrifuge can run up to 100 rpm, 1,000 rpm, 2,000 rpm, 3,000 rpm, 5,000 rpm, 7,000 rpm, 10,000 rpm, 12,000 rpm, 15,000 rpm, 17,000 rpm, 20,000 rpm, It can be spun at speeds of 25,000 rpm, 30,000 rpm, 40,000 rpm, 50,000 rpm, 70,000 rpm, or 100,000 rpm. At certain times the centrifuge can remain dormant, while at other times the centrifuge can rotate. A centrifuge at rest is not rotating. The centrifuge can be configured to rotate at variable speeds. In some embodiments, the centrifuge can be controlled to rotate at a desired speed. In some embodiments, the rate of change of rotational speed is variable and/or controllable.

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

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

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

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

The centrifuge can have any size. ^{For example , the centrifugal separator can _ _ _ _} Below, it may have a footprint of 10 cm ² or less, 5 cm ² or less, or 1 cm ² or less. The centrifuge is about 5 cm or less, 4 cm or less, 3 cm or less, 2.5 cm or less, 2 cm or less, 1.75 cm or less, 1.5 cm or less, 1 cm or less, 0.75 cm or less, 0.5 cm or less, or 0.5 cm or less. It can have a height of 1 cm or less. In some embodiments, the maximum dimension of the centrifuge is about 15 cm or less, 10 cm or less, 9 cm or less, 8 cm or less, 7 cm or less, 6 cm or less, 5 cm or less, 4 cm or less, 3 cm or less, 2 cm or less, or 1 cm or less. can be

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

The base may be connected to or incorporate the brushless motor rotor, thereby causing the base to rotate about the stator. The base may be fixed to the rotor or integrally rotate with the rotor. The base stator is rotatable and a plane perpendicular to the motor axis of rotation is coplanar with a plane perpendicular to the axis of rotation of the base. For example, the base may have a plane perpendicular to the axis of rotation of the base that passes substantially between upper and lower surfaces of the base. The motor may have a plane perpendicular to the motor axis of rotation that passes substantially through the center of the motor. The base plane and the motor plane are substantially coplanar. The motor plane passes between the upper and lower surfaces of the base.

A brushless motor assembly may include a motor rotor and a stator. The motor assembly may include electronic circuitry. Incorporating a brushless motor into the motor rotor assembly can reduce the overall size of the centrifuge assembly. In some embodiments, the motor assembly does not extend beyond the height of the base. In other embodiments, the height of the motor assembly is about 1.5 times the height of the base, about 2 times the height of the base, about 2.5 times the height of the base, or about 2.5 times the height of the base. about 3 times the height of the base, about 4 times the height of the base, or about 5 times the height of the base. The motor rotor may be surrounded by the base such that the motor rotor is not exposed outside the base.

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

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

The centrifuge receives sample tubes and has a first orientation of the sample tubes when the base is at rest, and a first orientation of the sample tubes when the base is rotating. It can be configured to have two orientations. The first orientation may be a vertical orientation and the second orientation may be a horizontal orientation. The sample tube is angled at about 0 degrees, 5 degrees, 10 degrees, 15 degrees, 20 degrees, 25 degrees, 30 degrees, 35 degrees, 40 degrees, 45 degrees, 50 degrees, 55 degrees, 60 degrees from vertical. degree, 65 degrees, 70 degrees, 75 degrees, 80 degrees, 85 degrees, or any orientation greater than 90 degrees. In some embodiments, the first orientation is closer to vertical than the second orientation. Alternatively, the sample tubes may have the same orientation regardless of whether the base is at rest or rotating. The orientation of the tube may or may not depend on the speed at which the base is rotating.

FIG. 9 shows one non-limiting example of a centrifuge according to embodiments of the invention. The centrifuge may include a base 3600 having a lower surface 3602 and/or an upper surface 3604. FIG. The base may include one, two or more wings 3610a, 3610b.

The wings are configured for folding onto axes extending through the base. In some embodiments, this axis may form a secant line through the base. An axis extending through the base can be a fold axis, which can be formed by one or more pivots 3620 . The wings may include the entire portion of the base on the side of the shaft. The entire portion of the base can be folded, thereby forming said wings. A central portion 3606 of the base may intersect the axis of rotation while the wings do not. A central portion of the base is closer to the axis of rotation than the wings. A central portion of the base can be configured to receive a drive mechanism 3630 . The drive mechanism may be an electric motor or any other mechanism that causes the base to rotate, and may be discussed in further detail elsewhere herein. In some embodiments, the wings have a footprint of about 2%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, or 40% or more of the base footprint. obtain.

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

1, 2, 3, 4, 5, 6 or more cavities may be provided in the wings. For example, wings may be configured to receive one, two or more samples or sample vessels. Each wing may have the capacity to receive the same number of containers or a different number of containers. The wings are configured to receive sample vessels, the sample vessels being oriented in a first orientation when the base is in a rest state and in a second orientation when the base is in a rotating state. can include a cavity that can be configured to be

In some embodiments, the wings may be configured to be at an angle to the central portion of the base. For example, the wings can be between 90 and 180 degrees with respect to the central portion of the base. For example, the wings may be oriented vertically when the base is at rest. The wings may be 90 degrees from the central portion of the base when oriented vertically. The wings may be oriented horizontally when the base is in a rotated state. The wings can be 180 degrees from the central portion of the base when horizontally oriented. The wings can extend from the base to form a substantially uninterrupted surface when the base is in rotation. For example, when the base is in rotation, the wings can be stretched to form a substantially continuous surface of the bottom and/or top of the base. The wings may be configured to fold downward with respect to a central portion of the base.

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

A wing may have a center of gravity 3680 positioned below the fold and/or pivot 3620 . The center of gravity of the wings may be located below the axis extending through the base when the base is at rest. The center of gravity of the wings is located below the axis extending through the base when the base is in a rotated state.

The wings may be formed from two or more different materials with different densities. Alternatively, the wings may be formed from a single material. In one embodiment, the wings may have light weight wing caps 3640 and heavy wing bases 3645 . In some embodiments, the wing caps may be formed from a material with a lower density than the wing bases. For example, the wing caps may be made of plastic, while the wing bases are made of metal such as steel, tungsten, aluminum, copper, brass, iron, gold, silver, titanium, or any combination or alloy thereof. be. A heavier wing base may help provide the wing's center of gravity below the fold-over axis and/or pivot point.

The wing cap and wing base may be connected by any mechanism known in the art. For example, fasteners 3650 can be provided, or adhesives, welds, interlocking features, clamps, hook and loop fasteners, or any other mechanism can be used. The wings may optionally include inserts 3655 . The insert may be formed from a heavier material than the wing cap. The inserts may help provide the wing's center of gravity below the fold-over axis and/or pivot point.

One or more cavities 3670 may be provided in the wing cap, or the wing base, or any combination thereof. In some embodiments, the cavity can be configured to accommodate multiple sample container configurations. The cavity may have an inner surface. At least a portion of the interior surface may contact a sample container. In one embodiment, the cavity is such that a first sample vessel having a first configuration fits within the cavity and a second sample vessel having a second configuration fits within the cavity. It may have one or more shelves or interior surface features that may enable it. The first and second sample vessels having different configurations may contact different portions of the inner surface of the cavity.

The centrifuge may be configured for engagement with fluid handling equipment. For example, the centrifuge may be configured for coupling to a pipette or other fluid handling device. In some embodiments, a watertight seal may be formed between the centrifuge and the fluid handling equipment. The centrifuge can be engaged with the fluid handling device and can be configured to receive a sample from the fluid handling device. The centrifuge is engageable with the fluid handling device and is configured to receive sample vessels from the fluid handling device. The centrifuge may engage the fluid handling device and allow the fluid handling device to pick up or aspirate samples from the centrifuge. The centrifuge is engageable with the fluid handling device and allows the fluid handling device to pick up sample containers.

A sample container may be configured for engagement with the fluid handling device. For example, the sample container may be configured for coupling to a pipette or other fluid handling device. In some embodiments, a liquid tight seal may be formed between the sample container and the fluid handling device. The sample container may be engageable with the fluid handling device and configured to receive a sample dispensed from the fluid handling device. The sample container is engageable with the fluid handling device and allows the fluid handling device to pick up or aspirate sample from the sample container.

A sample container may be configured to extend out from the wings of the centrifuge. In some embodiments, the base of the centrifuge is folded to allow the sample vessels to extend out of the centrifuge wings when the wings are folded and It may be configured to allow the wings to pivot between a state and an extended state.

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

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

In some embodiments, multiple axes of rotation may be provided through the base for the bucket. The axes may be mutually parallel. Alternatively, some axes can be orthogonal or at any other angle with respect to each other. A 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 can be at or closer to the lower surface of the base or the upper surface of the base.

One, two, three, four or more cavities may be provided in the bucket. For example, a bucket can be configured to receive one, two or more samples or sample containers 3740 . Each bucket may have the capacity to receive the same number of containers or a different number of containers. The bucket may include a cavity configured to receive a sample vessel, the sample vessel being oriented in a first orientation when the base is in a rest state, and when the base is in a rotating state. Sometimes it can be configured to be oriented in a second orientation.

In some embodiments, the bucket may be configured to be at an angle to the base. For example, the bucket can be at an angle between 0 and 90 degrees with respect to the base. For example, the bucket may be oriented vertically when the base is at rest. The bucket can be positioned upwardly past the top surface of the centrifuge base when the base is at rest. At least a portion of the sample vessel may extend beyond the top surface of the base when the base is at rest. The wings may be 90 degrees from the central portion of the base when oriented vertically. The bucket may be oriented horizontally when the base is in rotation. The bucket may be 0 degrees from the base when oriented horizontally. The bucket can be retracted into the base to form a substantially uninterrupted top and/or bottom when the base is in a rotating state. For example, the bucket may be retracted to substantially form a continuous surface of the bottom and/or top of the base when the base is in rotation. The bucket may be configured to pivot upwardly relative to the base. The bucket may be configured for at least a portion of the bucket to pivot upwardly past the top surface of the base.

A pivot point for 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 can be positioned between portions of the base to prevent lateral sliding relative to the base.

The bucket may have a center of gravity 3750 positioned below said pivot point 3720 . A center of gravity of the bucket may be located below the point of rotation when the base is at rest. The center of gravity of the bucket may be located below the point of rotation when the base is in rotation.

The buckets may be formed from two or more different materials with different densities. Alternatively, the bucket can be formed from a single piece of material. In one embodiment, the bucket can have a body 3715 and an insert 3717. In some embodiments, the body may be formed from a less dense material than the insert. For example, the body may be formed from plastic while the insert is formed from metal such as tungsten, steel, aluminum, copper, brass, iron, gold, silver, titanium, or any combination or alloy thereof. . A heavier insert may help provide a bucket center of gravity below the pivot point. The bucket material may include a higher density material and a lower density material, with the higher density material positioned below the rotation point. When the centrifuge is at rest, the bucket's center of gravity may be positioned so that the bucket naturally spins with the open end facing up and the heavier end facing down. The center of gravity of the bucket can be positioned such that the bucket naturally retracts when the centrifuge is rotating at a certain speed. The bucket may retract when the speed is at a predetermined speed, which may include a particular speed or any speed mentioned elsewhere herein.

One or more cavities may be provided in the bucket. In some embodiments, the cavity can be configured to accommodate multiple sample container shapes. The cavity may have an inner surface. At least a portion of the interior surface may contact a sample container. In one embodiment, the cavity is such that a first sample vessel having a first shape fits within the cavity and a second sample vessel having a second shape fits within the cavity. may have one or more shelves or interior surface features that may allow for Although the embodiments of Figures 9-11 show centrifugation vessels having a high aspect ratio of height to width, it should be appreciated that embodiments in which the height is less than or equal to the width may also be used in alternative embodiments. be understood.

A sample container may be configured for engagement with the fluid handling device, as previously mentioned. For example, the centrifuge may be configured for connection with pipettes or other fluid handling equipment. The centrifuge may be configured to receive a sample dispensed by the fluid handling device or to provide a sample to be aspirated by the fluid handling device. A centrifuge may be configured to receive or provide sample containers.

A sample container may be configured for engagement with the fluid handling device, as previously mentioned. For example, the sample container may be configured for coupling with a pipette or other fluid handling device.

A sample container may be configured to extend out of the bucket. In some embodiments, the base of the centrifuge is configured such that the sample vessels extend out of the buckets when the buckets are in the retracted state and the buckets are in the retracted state. and protruding states. The sample vessels extending out from the top surface of the centrifuge allow easier transfer of samples or sample vessels to and/or from the centrifuge. In some embodiments, the buckets are configured to be recessed into the rotor, reducing noise and heat generation and reducing power requirements with additional benefits such as reduced power requirements. Create assemblies and mitigate obstacles during operation.

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 channels may also apply to any similar structure. The channel may contain one or more ball bearings. The ball bearing can slide through the channel. The channels can be open, closed, or partially open. The channel may be configured to prevent the ball bearing from dropping out of the channel.

In some embodiments, ball bearings may be placed in sealed/closed raceways within the rotor. This configuration is useful for dynamically balancing the rotor of the centrifuge, especially when simultaneously centrifuging different volumes of sample. In some embodiments, the ball bearings can be external to the motor, making the whole system more robust and compact.

The channel may surround the centrifuge base. In some embodiments, the channel may surround the base of the centrifuge along its circumference. In some embodiments, the channel may be at or near 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 bearing may slide along the circumference of the base of the centrifuge. In some embodiments, the channel surrounds the base some distance away from the axis of rotation. The channel may form a circle with the axis of rotation at the substantial center of the circle.

FIG. 11 shows an additional, non-limiting example of a centrifuge provided by another embodiment described herein. The centrifuge can include a base 3800 having a bottom surface 3802 and/or a top surface 3804 . The base may include one, two or more buckets 3810a, 3810b. A bucket may be coupled to a module frame 3820, which may be connected to the base. Alternatively, the bucket can be directly connected to the base. The bucket may also be attached to weight 3830 .

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

A bucket may be configured to pivot about a bucket pivot that extends through the base and/or module frame. In some embodiments, the axis may form a secant line through the base. The bucket may be configured to pivot about a bucket pivot axis 3840 . The base may be configured to receive a drive mechanism. In one embodiment, the drive mechanism may be an electric motor, such as a brushless electric motor. The drive mechanism may include rotor 3850 and stator 3855 . In some embodiments, the rotor may be a brushless electric motor rotor and the stator may be a brushless electric motor stator. The drive mechanism may be any other mechanism that causes the base to rotate, and may be discussed in greater detail elsewhere herein.

In some embodiments, multiple axes of rotation may be provided through the base for the buckets. These multiple axes can be parallel to each other. Alternatively, some axes can be orthogonal to each other or at any other angle to each other. A 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 or the base closer to the upper surface. In some embodiments, the bucket pivot can be at or near the lower or upper surface of the base. A bucket pivot axis can be at or near 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, a bucket can be configured to receive one, two or more samples or sample containers. Each bucket may have the capacity to receive the same number of containers or a different number of containers. The bucket can include a cavity configured to receive a sample vessel, wherein the sample vessel is oriented in a first orientation when the base is in a rest state, and the sample vessel is oriented in a first orientation when the base is in a rotating state. , can be configured to be oriented in the second orientation.

In some embodiments, the bucket may be configured to be at an angle to the base. For example, the bucket can be at an angle between 0 and 90 degrees with respect to the base. For example, the bucket may be oriented vertically when the base is at rest. The bucket may be positioned upwardly past the top surface of the centrifuge base when the base is at rest. At least a portion of the sample vessel may extend beyond the top surface of the base when the base is at rest. The wings may be 90 degrees from the central portion of the base when oriented vertically. The bucket may be oriented horizontally when the base is in rotation. The bucket may be 0 degrees from the base when oriented horizontally. The bucket can be retracted into the base and/or frame module to form a substantially uninterrupted top and/or bottom when the base is in rotation. For example, the bucket may be retracted to substantially form a continuous surface of the bottom and/or top of the base and/or frame module when the base is in a rotating state. The bucket may be configured to pivot upwardly relative to the base and/or frame module. The bucket may be configured for at least a portion of the bucket to pivot upwardly past the top surface of the base and/or frame module.

The buckets are designed to allow the lowering and picking up of centrifuge tubes, as well as the dispensing of liquids into, and aspiration of liquids from, centrifuge vessels when the centrifuge buckets are present. , can be locked in multiple positions. One technique for accomplishing this is to drive wheels in contact with the centrifuge rotor to precisely position and/or lock the rotor. one or more electric motors. Another approach could be to use a cam profile formed on the rotor without an additional motor or wheel. An accessory of the pipette, such as a centrifuge tip attached to a pipette nozzle, can be pressed against the cam profile on the rotor. This force on the cam surface may induce the rotor to rotate to the desired locked position. Continued application of this force allows the rotor to be rigidly held in the desired position. Multiple such cam shapes may be added to the rotor to allow multiple locking positions. While the rotor is held in one pipette nozzle/tip, another pipette nozzle/tip is used to unload or pick up a centrifuge vessel or to centrifuge in the centrifuge bucket. It may be connected to the centrifuge buckets to perform other functions such as aspirating or dispensing from separator vessels. It should be appreciated that this cam feature may be adapted in any embodiment of the present disclosure.

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

The bucket may be attached to a weight. The weight may be configured to move from a typically fully vertical position to a non-vertical position when the base begins to rotate thereby causing the bucket to pivot. Centrifugal force exerted on the weight may cause the weight to move when the base begins to rotate. The weight may be configured to move away from the axis of rotation when the base begins to rotate at a threshold speed. In some embodiments, the weight may move in a linear direction or in a path. Alternatively, the weight may move along a curved path or any other path. The bucket can be attached to the weight at weight pivot 3860 . One or more pivot pins or protrusions may be used that allow the bucket to move relative to the weight. In some embodiments, the weight can move along a horizontal linear path, thereby causing the bucket to swing upwards or downwards. The weight can move in a linear direction perpendicular to the axis of rotation of the centrifuge. This indicates that the buckets do not extend outward under the bottom surface of the centrifuge rotor. In some embodiments, this allows for centrifuge designs with reduced overall height when the instrument is in operation.

moving the bucket from a rest configuration to generate sufficient centrifugal force such that the sample in the centrifuge vessel is not spilled or repelled outside the vessel when the bucket changes orientation; It should be appreciated that the required force to move into the working configuration is selected. Often the centrifugation vessel is an unsealed, open-topped vessel and therefore cannot accommodate spills from misoriented vessels.

The weights may be arranged between portions of the module frame and/or base. The module frame and/or base may be configured to prevent the weight from sliding out of the base. The module and/or base may restrict the path of the weight. The path of the weight may be restricted to linear directions. One or more guide pins 3870 may be provided that may limit the path of the weight. In some embodiments, the guide pin may pass through the frame module and/or base and the weight.

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

One or more cavities may be provided in the bucket. In some embodiments, the cavity can be configured to accommodate multiple sample container shapes. The cavity may have an interior surface. At least a portion of the interior surface may contact a sample container. In one embodiment, the cavity is such that a first sample vessel having a first configuration fits within the cavity and a second sample vessel having a second configuration fits within the cavity. It may have one or more shelves or interior surface features that may enable it. The first and second sample vessels having different configurations may contact different portions of the inner surface of the cavity.

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

A sample container may be configured for engagement with the fluid handling device, as previously mentioned. For example, the sample container may be configured for coupling with a pipette or other fluid handling device.

A sample container may be configured to extend out of the bucket. In some embodiments, the centrifuge base and/or module frame is configured such that, when the buckets are in the retracted state, the sample vessels extend out of the buckets and the buckets are , can be configured to allow pivoting between retracted and extended states. The sample vessels extending out from the top surface of the centrifuge allow 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 channels may also apply to any similar structure. The channel may contain one or more ball bearings. The ball bearing can slide through the channel. The channels can be open, closed, or partially open. The channel may be configured to prevent the ball bearing from dropping out of the channel.

The channel may surround the base of the centrifuge. In some embodiments, the channel may surround the base of the centrifuge along its circumference. In some embodiments, the channel may be at or near 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 bearing may slide along the circumference of the base of the centrifuge. In some embodiments, the channel surrounds the base at a certain distance from the axis of rotation. The channel may form a circle with the axis of rotation at the substantial center of the circle.

Other examples of centrifuge configurations, including various vibrating bucket configurations, known in the art may be used. See, for example, US Pat. No. 7,422,554, which is hereby incorporated by reference in its entirety. As an example, the bucket swings down rather than up. The bucket can swing to protrude sideways rather than up and down.

The centrifuge may be enclosed in an enclosure or casing. 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 allow fluid handling or other automated equipment to access the centrifuge. The fluid handling and/or other automated equipment may provide samples, access samples, provide sample containers, or access sample containers in a centrifuge. Such access may be allowed to the top, sides and/or bottom of the centrifuge.

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

In some embodiments, sample containers may be provided to or removed from the centrifuge. The sample vessels can be inserted into or removed from the centrifuge using an instrument in an automated process. The sample vessels can extend from the surface of the centrifuge, simplifying automated pick-up and/or retrieval. A sample may be provided in advance in the sample container. Alternatively, sample can be dispensed into and/or picked up from the sample container. Samples can be dispensed into and/or picked up from the sample vessels using the fluid handling system.

In some embodiments, a tip from the fluid handling system may be inserted at least partially into the sample vessel and/or cavity. The tip may be insertable into and removable from the sample vessel and/or cavity. In some embodiments, the sample vessel and tip can be the centrifuge vessel and centrifuge tip, or have any other vessel or tip configuration, as previously described. obtain. In some embodiments, cuvettes may be placed in the centrifuge rotor. This configuration may provide certain advantages over conventional tips and/or containers. In some embodiments, the cuvette is patterned with one or more channels with specialized shapes such that the centrifuged product is automatically separated into separated compartments. obtain. One such embodiment would be a cuvette with tapered channels terminating in compartments separated by narrow openings. Supernatant (eg, plasma from blood) is forced into the compartment by centrifugal force, while red blood cells remain in the channel body. The cuvette can be more complex with several channels and/or compartments. The channels are either separate or connected.

In some embodiments, one or more cameras may be positioned within the centrifuge rotor so as to capture images of the contents of the centrifuge vessel while the rotor rotates. The camera images may be analyzed and/or communicated in real-time, such as by using wireless communication methods. This method can be used to track the rate of cell sedimentation/loading, such as the ESR (erythrocyte sedimentation rate) assay, in which the RBC (red blood cell) sedimentation rate is measured. In some embodiments, one or more cameras may be positioned outside the rotor so as to capture images of the contents of the centrifuge vessel while the rotor rotates. This can be accomplished by using a strobe light source synchronized with the camera and a rotating rotor. Real-time imaging of the centrifuge vessel contents while the rotor is spinning allows rotation of the rotor to be stopped after the centrifugation process is completed, allowing time to It can save and prevent possible overfilling and/or overseparation of the contents.

As seen in FIG. 12, some embodiments may include a window or opening 3825 on the centrifuge vessel holder for viewing the sample contained therein. This may include a camera or other detector that can visualize the sample in the container through a window or opening 3825. Optionally, a window or opening 3825 may be provided for an illumination source to illuminate the sample being processed. Some embodiments may include a detector, such as but not limited to a camera, integrated into the centrifuge rotor to image the sample therein while in the centrifuge. This is beneficial because blood constituents in the sample can be more easily visualized if the camera is in the same coordinate system as the sample. Of course, for embodiments with detectors such as but not limited to cameras, a coordinate system separate from the moving sample is not excluded. Non-visible detectors are not excluded as long as they detect movement of blood constituents in the container.

Some embodiments may also include a corresponding window or opening 3827 of the same or different size as said window or opening 3825 . This window or opening 3827 uses the same opening for both illumination and observation of the sample in the centrifuge container while the container remains in the centrifuge. Some embodiments provide visualization through one window or opening and through another set of windows or openings that may or may not be opposite the first set of windows or openings. have lighting. It should be appreciated that for any of the embodiments herein, the windows or openings may include an optically transparent material covering such windows or openings.

Thermally controlled centrifugation can sometimes result in undesirable changes in sample temperature due, at least in part, to the heat generated by centrifuge operation. One source of heat during centrifuge operation is waste heat from the centrifuge's drive motor and/or drive mechanism. This waste heat is particularly problematic when several samples are being processed sequentially within the same centrifuge, and the heat from each operation accumulates over time causing the sample temperature to rise outside of acceptable limits.

To protect such waste heat or other sources of thermal energy from changing the sample temperature, insulate, actively cool, and/or direct the system to direct thermal energy away from the sample. Make an effort to configure.

In one embodiment, the motor is integrated into the centrifuge such that such integration benefits from efforts to address issues with the motor, centrifuge rotor, buckets, vessels, and/or samples. can receive Methods of addressing such thermal issues include performing one or more of the following simultaneously or sequentially: cooling, thermal isolation, and/or maintaining cooling. Some may involve active techniques to solve thermal problems. Some may include, but are not limited to, passive techniques such as isolating the centrifuge components that connect to heat sources associated with the centrifuge.

Some embodiments may use thermally conductive materials such as, but not limited to, thermal tape to alter the heat transfer profile of the centrifuge. In one non-limiting example, the tape can be configured to divert heat away from thermally sensitive areas on the centrifuge that could thermally shock the sample. . Thermal tapes are designed to provide preferential heat transfer paths between heat-producing components and heat sinks or other cooling equipment (eg, fans, heat spreaders, etc.). Thermal tapes can be tacky pressure sensitive adhesives filled with thermally conductive ceramic fillers that do not require a heat cure cycle to bond to many substrates. This can be used alone or in combination with any other thermal solution described herein.

Some embodiments may employ an active cooler, such as but not limited to a Peltier heater/cooler, to cool the sample and/or one or more of the previously mentioned centrifuge components. . The active cooler may abut the target surface to be cooled. Some embodiments may attach an active heat sink or Peltier heater/cooler to the bucket or holder containing the centrifuge vessel. Optionally, the active cooler may be in the vicinity of the target surface without directly abutting it. For example, an active heat sink or Peltier heater/cooler can be attached to the centrifuge housing in the vicinity of the centrifuge portion that holds the sample.

Some embodiments may attach structure to the outside of the centrifuge housing to aid in convective cooling. Some may also include the addition of fins or ventilation structures to the centrifuge rotor and/or other moving parts of the centrifuge. Some may include the addition of fins or ventilation structures to the fixed portion of the housing near the rotor. Such fins can be used to radiate all waste heat and/or assist convection.

As seen in FIG. 12, some embodiments may use thermally non-conductive materials to alter the heat transfer profile. In an effort to insulate the sample from the heat source, some embodiments may replace some metallic materials with plastics or other strong materials with low thermal conductivity. Some may insulate the sample with foam or other types of insulation to prevent unwanted heat transfer. Some may have the entire centrifuge rotor formed of a material with low thermal conductivity. Some embodiments may have the rotor portion of the centrifuge formed of a material having a low thermal conductivity. As seen in FIG. 12, some embodiments may replace only selected portions, such as but not limited to frame portion 3820, with thermally insulating material.

Referring to FIG. 13A, some embodiments use an external cooling device 400, such as one or more fans or air conditioning sources, such as using cooled or uncooled air or gas convection, during centrifugation. can be used to minimize sample heating. As seen in FIG. 13A, some embodiments place two or more cooling devices 400 around the centrifuge housing 402 to direct convection over the centrifuge. Different arrangements and/or orientations may be used.

As further seen in FIG. 13A, some embodiments include 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. can have an active thermal device 410 such as a FIG. 13A shows that a stationary enclosure 402 can have active thermal devices such as Peltier effect heat sinks 410 located at one or more locations on the enclosure 402 . Some embodiments may use a conventional, passive heatsink instead of or in combination with the Peltier effect heatsink 410 . For purposes of illustration, and without limitation, some of the arrangements shown in FIG. can have

In one embodiment, the Peltier effect heat sink may use electrical power to achieve extremely low temperatures. One embodiment may wire a Peltier effect heat sink to the motor circuit. Of course, other configurations for powering the heatsink are not excluded. Since the opposite side of the heatsink is heated during operation, the heatsink may include ducts, vents, heat spreaders, heatsink fins, heatsink pins, or other elements that remove waste heat from the cold side of the heatsink. It is desirable to be placed in the vicinity of Some may use thermally conductive motor mounts to draw heat away from internal components. One such embodiment may include a fan with aluminum stator blades brazed to an aluminum motor mount. The electric motor is tightly fitted into the housing and glued to a "heat transfer compound" to provide a preferential thermal path for heat to divert away from the electric motor. This may improve heat transfer from the motor to the cooling fins.

Although FIG. 13A shows that thermal regulation elements can be located on the housing or other fixed part of the centrifuge system, similar active or passive thermal devices can be installed on the centrifuge system. It should be understood that it may also be attached to internal and/or movable components of the . As a non-limiting example, FIG. 13B illustrates that the motor, centrifuge rotor 404, buckets, containers, and/or surfaces that contact the sample can be configured to be under the thermal control of instrument 410. show. FIG. 13B shows that active thermal devices 410 can be placed on the peripheral sides of the centrifuge rotor 404 . Optionally, active thermal device 410 may be placed on top of centrifuge rotor 404 . Optionally, an active thermal device 410 may be placed on the underside of centrifuge rotor 404 . Optionally, active thermal equipment 410 can be placed on a side plate, housing, or shield of said electric motor 412 . As a non-limiting example, in some locations shown in FIG. 13B as having active thermal devices 410, those units may be replaced or augmented by passive heat sinks.

Referring to FIGS. 14A-14B, some embodiments may include venting the enclosure around the centrifuge rotor for improved convective airflow. This may include providing holes, cut-outs or shaped openings in the housing and/or the centrifuge rotor to allow air flow. A vent 450 may be formed in a housing 452 around portions of the centrifuge motor. The vents 450 are sized/or positioned to allow greater convective cooling of the centrifuge motor elements. In this non-limiting example, the larger opening 454 is sized to receive the encoder ring leader. It should be appreciated that in addition to vents, the embodiments of Figures 14A-14B may include any of the active or passive thermal elements described in Figures 13A-13B. Based on the location information provided by the various configurations described in this disclosure, some embodiments of the centrifuge can be configured such that the centrifuge can The centrifuge is driven and/or braked so that it can rest at a specific position specified by the instrument.

FIG. 15 shows yet another embodiment in which vents 460 may be formed in a housing 462 near the centrifuge rotor or even in the centrifuge rotor itself. The vent 460 in this embodiment may be positioned to be below the rotating portion of the centrifuge rotor (not shown for ease of illustration). Other embodiments may have more or less vents 460 . Other embodiments include other shapes such as, but not limited to, squares, rectangles, ovals, triangles, trapezoids, parallelograms, pentagons, hexagons, octagons, any other shape, or single or multiple of the foregoing. combinations of vents 460. Some embodiments may have vents 460 that are all the same shape. Some embodiments may have at least one vent 460 with a different shape than at least one other vent 460 .

16A-16D, yet other embodiments position thermal control elements 500 on rotating and/or non-rotating components of the centrifuge to facilitate greater convective heat transfer. obtain. FIG. 16A shows thermal control elements 500 in the form of fins on the outer radiation surface of the centrifuge housing 501 . The fin may have a planar shape. Optionally, some embodiments of thermal control element 500 may be protrusions 502 in the shape of pins. Some embodiments may combine one or more of these structural characteristics. These can be used as passive or active thermal control devices.

In some embodiments, the cross-sectional shape of the fins may be circular, crescent, teardrop, square, square, 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 be pyramidal (including truncated pyramids) or conical (including truncated cones). could be. In still other embodiments, the fins (eg, surface, pin fins) may be curved along the longitudinal length of the fins. Non-limiting examples of curved fin (eg, pin fin) surface profiles include hyperbolic, quadratic, greater than second order polynomial curves, circular arcs, or combinations thereof. In some embodiments the fins are solid structures, while in other embodiments the fins are hollow. In some embodiments, the fins may be partially hollow and partially solid. Hollow fins allow for efficient heat transfer while further reducing the amount of material used to make the heat sink, thereby further reducing manufacturing costs. Alternatively or additionally, the pattern formed by the fins provides additional openings into the interior of the heatsink, and may be ridged around the perimeter of the heatsink to increase airflow within the fins. Can be destroyed by channels along. The channels generated can be any pattern, such as general notch, herringbone, or the like. In some embodiments, the fins are connected together at their bases (or other bond areas) to form a network of connected fins, such as but not limited to multiple rows or columns. be able to. Some may be joined together to form a percolating network of joined fins.

FIG. 16B shows an embodiment having fins 510 on the inner radiating portion of the centrifuge. FIG. 16C shows the lower fins 520 of the centrifuge rotor. FIG. 16D shows that as the centrifuge rotor spins, fins 530 on the circumferential portion of the rotor draw air into the enclosure to help cool the components inside the enclosure. , shows yet a further embodiment, optionally shaped and/or oriented for use with a shaped housing 540 . Of course, some embodiments may combine one, two, three, or all of the above with other cooling elements to maximize the cooling potential of the system. The embodiments of Figures 16B-16D can have various thermal controls coupled with either moving or stationary parts of the centrifuge.

In yet another embodiment, an internal fan-cooled electric motor (colloquially a fan-cooled electric motor) can be used as a self-cooling electric motor. In one embodiment, a fan-cooled motor features a fan mounted axially of the rotor of the motor (usually at the opposite end of the output shaft) that spins with the motor to assist in cooling the motor. Provides increased airflow to internal and external components.

In another embodiment, water cooling may be used to cool the motor housing. In one non-limiting example, a small centrifugal pump can be formed off the shaft with a tank of pre-cooled water circulating around the outside of the motor casing. Other active or passive liquid cooling techniques may also be used. These can be used to cool parts of the motor housing. Some embodiments may be used to cool only the side walls of the motor housing. Some may cool the entire enclosure. Some embodiments may cool only the final portion of the enclosure, such as, but not limited to, the path closest to the sample.

In yet further embodiments, significantly lower winding resistance can be used to reduce the amount of heat generated by the motor. This may include using a motor with fewer windings to improve motor performance and consequently reduce heat production from the motor. Variations in the number of poles and magnets can also be selected to improve motor performance. In this manner, motor components may be selected to provide lower heat production, such as by using motors with lower heat output for normal operating conditions of the centrifuge.

Centrifuge Position Control Referring now to FIGS. 17A-17D, an improvement to the centrifuge rotor position control system will now be described. In one embodiment, various encoder discs or structures, such as but not limited to encoder ring 600, more precisely control and/or detect the position of the centrifuge rotor 604 and are then programmable. A processor can calculate where on the centrifuge rotor 604 the holder is positioned. In such embodiments, accurate information about the position of the centrifuge rotor 604 is used to position the centrifuge rotor 604 in a particular position each time it is stopped. Allows a pipette or sample handling system to accurately engage the centrifuge container when it is time to remove it from the centrifuge without using a "parking" system.

FIG. 17A shows one embodiment of encoder ring 600 for use with detector 602 for reading encoder positions. The encoder ring 600 rotates with the centrifuge rotor 604 so that the encoder ring 600 provides position information of the centrifuge rotor 604 and whether there are any characteristics there. . In one embodiment, encoder ring 600 may have a pattern thereon and may be configured for use with optical detector 602 . In one embodiment, ring 600 is formed of glass or plastic with transparent and opaque regions. Some embodiments may use reflective patterns on ring 600 . Encoder ring 600 may be configured to detect each distinct angle of the encoder ring. Ring 600 may be an absolute encoder or a relative encoder.

FIG. 17B shows another embodiment in which an encoder ring 610 is integrated as part of the centrifuge rotor 604, such as along the circumference of the rotor portion. Detector 612 may be oriented for use with integrated encoder ring 610 . It can be used alone or in combination with other position detection systems. Optionally, some embodiments may use one system for high precision position detection, while another system is used for high speed detection. Movement of the encoder ring 610 from the bottom of the centrifuge rotor 604 reduces the overall vertical space below the centrifuge rotor 604 because the detector 612 and encoder ring no longer occupy the vertical space below the centrifuge rotor 604 . The height of the centrifuge can also be reduced.

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

FIG. 17C shows yet a further embodiment in which the motor 622 may include an encoder ring or device 620 within the motor 622 in making the motor. To determine the motor shaft angular position, the encoder 620 is read by a detector internal to the motor 622 or a detector located external to the motor 622 . Such integrated encoder and motor configurations can be used in centrifuges and other system components such as pipettes in sample handling systems where precise position control from a small motor form factor is desired. As a non-limiting example, relative 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 very thin lines) can be used to enclose the encoder portion of the motor.

FIG. 17D illustrates that other encoder techniques such as but not limited to conductive and/or magnetic encoding may be used instead of or in place of other encoder techniques such as but not limited to optical encoders for rotor position detection. Fig. 3 shows yet another embodiment for use with. Magnetic encoder readers 650 and/or 652 may be positioned at various locations to detect the position of the centrifuge rotor. Other position detection techniques may be used in place of or in combination with the encoder techniques described herein. In some embodiments described herein, these capabilities may be integrated into the device.

Optionally, some embodiments may use separate sensors for velocity and position. The same sensor can be used for both. As a non-limiting example, embodiments can be configured with two or more sensors, one for precision position control and one for velocity control. This modality requires relying on more sophisticated sensors, as each type is optimized for specific purposes, such as high-precision position control at low speeds and velocity control at high speeds. Without, higher centrifuge speeds, such as but not limited to 40000 rpm, can be achieved. A programmable processor may be used to determine when to transition control of the centrifuge rotation based on sensors or otherwise. Optionally, data from both types of sensors can be used in the full time domain to provide precise position and velocity control.

It should be appreciated that in systems where precise control is not possible, a system using stops can be used to ensure that the final rest position of the centrifuge rotor is known. Other embodiments include alignment guides, pins, cams, and cams for moving the centrifuge rotor to known positions so that the sample handling system can accurately engage the centrifuge vessel on the rotor. , and/or other mechanisms may be used. Pipettes can go to the container from a well-known ledge where the centrifuge is stopped. Some embodiments of the centrifuge may be used to move a pipette to a desired position prior to engaging a sample-containing container attached to the centrifuge, or to rotate the centrifuge rotor. To use the pipette to move it to the correct position, it may have a guide.

As can be seen in Figures 17A-17D, the central portion of the centrifuge consists of single bearings, optionally on top of each other, to improve stability when rotating, and in particular to improve bearing life. It has two bearings 660 pressed against it. As seen in FIGS. 17A-17D, multiple bearings can 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.

It should be appreciated that in some embodiments described herein, 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 achieve position and/or velocity detection through the addition of hardware. In one embodiment, rotational position and/or velocity sensing may be configured for one or more rotating portions of said electric motor, or rotating elements attached to the electric motor.

Possibilities for hardware integrated into the motor include, but are not limited to: 1) optical encoders (for position (relative and/or absolute) and/or speed detection), and/or 2) Hall effect sensors (for position (relative) and/or velocity detection) are included. A Hall effect sensor is a semiconductor device in which electron flow is affected by a magnetic field perpendicular to the current flow. In one non-limiting example, Hall effect sensors can be used to detect the position of permanent magnets in a brushless DC electric motor.

Some embodiments may combine multiple types of detector hardware, such as, but not limited to, both Hall effect sensors and optical encoders within the same motor. Optionally, some embodiments may have multiple sensors of the same type within the motor. Of course, other types of position and/or velocity sensing hardware are not excluded from use in combination with embodiments or optical or magnetic encoders herein.

By way of non-limiting example, at least some embodiments of the sensors and/or encoders herein can have 1800 counts per revolution for position sensing and can run speeds up to 12000 RPM. Optionally, at least some embodiments of sensors and/or encoders herein can have 1600 counts per revolution for position sensing and can run speeds up to 10000 RPM. In one embodiment, the encoder has an index in each centrifuge that is co-aligned with the motor assembly for absolute positioning. Some embodiments may use absolute encoders, such as but not limited to multi-bit Gray code encoders and/or single track Gray encoders, for absolute position. Some embodiments may use sinusoidal encoders. Encoder technologies may include, but are not limited to, conductive tracks, optical tracks (including reflective versions), and magnetic encoding tracks detected by Hall effect sensors or magnetoresistive sensors.

For any configuration (sensor or encoder), at least some embodiments herein are such that the total height (not including the output shaft) is less than or equal to 13 mm, while the diameter is less than 35 mm. can be configured to Optionally, some embodiments may have a total height of about 10 mm or less and a diameter of 30 mm or less. In some embodiments, the hardware is designed such that the integration of position and/or speed sensing hardware does not change the external dimensions of the motor housing compared to a motor without sensing hardware. . Optionally, Hall sensors can be mounted in the motor stator slots to minimize size changes.

Optionally, some alternative embodiments may use firmware and/or software to detect rotor position and/or velocity without additional hardware. Examples may include monitoring back EMF, tracking impedance, or using other methods for motor control without sensors. One or more techniques described herein may be combined for use in position and/or velocity detection.

Referring to FIG. 17E, a magnetic sensor, such as a Hall effect sensor assembly 630, which can be integrated directly into the motor assembly, or parts of the centrifuge assembly but outside of the motor, without limitation. Another embodiment of the centrifuge is shown, comprising: FIG. 17E shows an exploded view in which the Hall effect detector 632 and encoder portion 634 are shown. Arrow 636 indicates that assembly 630 can be inserted into centrifuge housing in the orientation shown. As a non-limiting example, this assembly 630 is shown with three detectors 632, but it should be understood that other numbers of detectors can be used. The assembly 630 is shown with all detectors coplanar. It should be appreciated that some embodiments may have detectors on different planes, including, but not limited to, detectors on both sides above and below Hall effect encoder portion 634 . As a non-limiting example, the encoder portion includes multiple magnets and/or other magnetic field generating or interfering components that can be detected by Hall effect detector 632 .

Referring to FIG. 17F, a perspective view of one embodiment of a motor integrated with position and/or velocity detectors is shown. For ease of illustration, some motor components are not shown for this embodiment to provide a clearer view of the encoder components used with the motor. This encoder embodiment can be used to detect shaft position and/or rotor position. In this non-limiting example, detector 670 is used in combination with encoder disc 672 and Hall effect encoder disc 674 . The detector 670 may have a first surface directed to optical encoder information detection and a second surface directed to magnetic encoder information detection. In one non-limiting example, the detector 670 includes a first surface 680 for detecting a first type of encoder information, such as but not limited to optical encoder information, and a magnetic may have a second surface 682 for detecting a second type of encoder information, such as specific type of encoder information. Optionally, some embodiments may allow both the first and second types of encoder information to be both optical, or both magnetic, such as but not limited to. In such a configuration, optionally, at least two encoder types have resolutions, such as one with better low speed resolution for position control and one with better high speed resolution for speed control. can be different. This is true even when using different types of encoder information (such as one optical and one magnetic). Of course, embodiments using even more sensors 670 or more than one encoder information are not excluded.

Still referring to FIG. 17F, magnetic components 676 may be mounted within disk 674 . These elements may all be configured for rotation with the motor shaft 678 . The motor housing H can be extended to cover all, some, or none of the encoder components. Optionally, some embodiments may combine at least two encoder types on a rotating element such as, but not limited to, an encoder disk. In such a configuration, a single disk on the shaft may contain both magnetic and optical encoder components. As a non-limiting example, the outer portion of the ring may have areas for optical encoders, while the inner portion may have magnetic components, or vice versa. Optionally, both are on the same portion of said ring. Optionally, one type of encoder can be on the plane while another component is on the outer surface. Of course, embodiments using more than two types of encoder information on a single rotating component cannot be ruled out. As a non-limiting example, embodiments using a single detector 670 also simplify manufacturing by having a single wire harness for attaching said detector 670, thus simplifying wiring management. can become

FIG. 17G shows yet another type of electric 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. Optionally, stator 644, rotor 640, and stator 642 may be used for increased torque. Any of these embodiments can be configured to have the encoder assemblies shown herein. Encoder elements such as, but not limited to, optical encoder discs or magnetic encoder discs may be directly integrated or attached to the stator or rotor. It should be appreciated that the motor may be adapted for use with other encoder hardware or other encoder techniques. As seen in FIG. 17G, this motor embodiment fits inside the motor housing shown in FIGS. 17A-E to rotate the centrifuge body.

Auto -Balancing Referring to FIG. 18A, some embodiments herein employ an auto-balancing mechanism on the rotor to minimize rotor vibration since not all holders contain samples. can be configured for use. One embodiment can use self-balancing elements 700, such as but not limited to beads, spheres, or weights, to self-balance the centrifuge rotor, and this means that It can be useful to compensate for different sample volumes. Some embodiments can be loaded into several said centrifuge holders without buckets. To allow the auto-balancing element to reach a steady-state position that best minimizes rotational instability of the rotor during operation, said auto-balancing element 700 has channels 710 (covered or , or uncovered). In some embodiments, instead of having continuous channels along the perimeter of the circumference, some embodiments may have channels formed in certain discrete sections, the self-balancing element Stay only in a specific individual section of that channel.

Optionally, as seen in FIG. 18B, some embodiments auto-balance the element only when a speed of minimum rotation is reached and the centrifugal force or other force releases the auto-balance element for movement. A retention feature 720 may be included to release 700 for free movement. This feature 720 can move as indicated by arrow 722 when sufficient speed is reached. This movement releases the auto-balancing element 700 to move to a position for balancing the load on the centrifuge. In this manner, at lower speeds, the self-balancing element 700 does not move freely. This helps minimize noise and rotational instability due to the auto-balancing element 700 being able to easily rotate to non-optimal positions at lower speeds.

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

Referring to FIG. 18C, still further embodiments may have the self-balancing elements 700 in multiple distinct regions 730 on the rotating portion of the centrifuge. In one embodiment, the regions 730 can be coupled together such that the self-balancing element 700 can move from region to region. Optionally, some embodiments may separate each of the regions 730 from each other such that the self-balancing element 700 does not move from one region to another.

Non-Mechanical Bearings In yet other embodiments, some systems may be configured without mechanical bearings and instead using non-mechanical bearings such as, but not limited to, air bearings 720. This air bearing can produce less heat - which can reduce the time required in the centrifuge. Alternatively, it allows longer centrifuge times without the thermal penalty resulting from heat associated with mechanical bearings. Air bearings are available from vendors such as, but not limited to, New Way Air Bearings, Aston, Pennsylvania, USA. Of course, some embodiments may combine the use of both air and mechanical bearings within the same device.

FIG. 19B shows yet another embodiment in which one of the air bearings is ring shaped 722 while the other air bearing 724 is configured to face the sidewall of the centrifuge rotor. As non-limiting examples, air bearing 724 can be shaped in a continuous or non-continuous manner to support the centrifuge rotor.

Obstruction Detection Sensor Referring to FIG. 20, yet another embodiment of a centrifuge apparatus will be described. FIG. 20 is a cross-sectional perspective view showing a centrifuge rotor 800 , such as, but not limited to, a centrifuge disk, rotating as indicated by arrow 802 within a non-rotating housing 804 . The centrifuge may include a detector 810, such as but not limited to an accelerometer, attached to the centrifuge for detecting undesired force changes during centrifuge operation. In one embodiment, the detector 810 is mounted outside the centrifuge housing to detect if an error occurs. The detector 810 is used to detect early signs of abnormal instability in centrifuge operation. If these signs of instability are detected in terms of the rate of abnormal change in force being experienced by the centrifuge, then the centrifuge slows operation prior to catastrophic equipment failure. Alternatively, a programmable processor or the like may be selected as a means to stop. Some embodiments may trigger other actions such as alarms or warnings based on changes in velocity or detection of out-of-threshold forces.

FIG. 20 also illustrates other features discussed herein that are incorporated in embodiments of the present invention. As a non-limiting example, air bearings 722 and/or 724 may be incorporated for use with this embodiment of the device. A vibration damper 816 may also be used to isolate vibrations from the centrifuge from being transmitted to other elements outside the centrifuge housing. FIG. 20 also shows that thermal isolation zones 820, 822, and/or 824 can be used to minimize heat transfer from the electric motor 830 to the centrifuge rotor portion.

It should be understood that the embodiment of FIG. 20 can be configured for use with any of the rotors and/or vessel holders described, including but not limited to those shown in FIGS. 1-12. Some embodiments may have vessel holders that extend mostly above a plane or surface above the centrifuge rotor when the rotor is stationary. Optionally, some embodiments may have vessel holders that extend below the plane or surface below the centrifuge rotor when the rotor is stationary. For those embodiments in which the vessel holders extend below the plane or surface of the centrifuge rotor, clearance for the vessel holders and/or vessels is provided when rotating to the downwardly extended position. To accommodate, housing 804 may be configured to have shaped cutouts. Optionally, some embodiments configure the rotor 800 and/or the entire motor to provide sufficient clearance for the container holder and/or container when rotating to the downwardly extended position. can be mounted higher.

As non-limiting examples, the centrifuge can have dimensions of about 0.1 mm ² , 0.5 mm ² , 1 mm ² , 3 mm ² , 5 mm ² , 7 mm ² , 10 mm ² , 15 mm ² , 20 mm ² , 25 mm ² , 30 mm ² , 40 mm ² , 50 mm ² , 60 mm ² , 70 mm ² , 80 mm ² , 90 mm ² , 100 mm ² , 125 mm ² , 150 mm ² , 200 mm ² , 250 mm ² , 300 mm ² , 500 mm ² , or up to 750 mm ² 0.05 mm, 0.1 mm, 0.5 mm, 0.7 mm, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm , 15 mm, 17 mm, 20 mm, 25 mm, 30 mm, 40 mm, 50 mm, 60 mm, 70 mm, 80 mm, 100 mm, 150 mm, 200 mm, 300 mm, 500 mm, or 750 mm or less (e.g., width, length, height) ).

The embodiment of FIG. 20 is for at least some embodiments herein assuming that the stator is coaxially mounted with the rotor, and that the rotor couples the centrifugal disc to the rotor of the electric motor. A rotor/stator arrangement is also shown, including as integrally formed or integrally formed.

FIG. 20 illustrates, for at least some embodiments herein, a housing 804 shaped to enclose the circumference of at least a centrifugal disk of rotor 800, said centrifugal disk being disposed therein. can provide a controlled area that can be rotated with The rotating elements in this embodiment may include the encoder wheel 600, the centrifugal disc of the rotor 800, and the rotor portion of the electric motor. Enclosure 804 is mounted in enclosure 804 to provide isolation therein for damper 816, so in some embodiments as a shield to keep the vibratory motion of the motor in the enclosure. works. There are bearings 830 and 832 on which the rotating parts are mounted. Optionally, some embodiments can be configured to use only a single bearing. Optionally, some embodiments can be configured to use multiple bearings. Some embodiments may use the electric motor of FIG. 17F or 17G to power the centrifuge of FIG. 20. Optionally centrifuge having one or more of the characteristics described herein. The machine can be attached to the system of FIG. 21 with an overhead sample handling system shown in FIG. 21 or similar. Optionally, such centrifuges are commonly mounted plates, common platforms, or common frames to enable other components 912, 914, or 916 and all to be used by an overhead sample handling system. can be attached to

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

Point of Service System Referring to FIG. 21, it should be understood that the processes described herein may be accomplished using automated techniques. This automated process can be used in an integrated, automated system. In some embodiments, this may be a single device having multiple functional components therein and surrounded by a common housing. This processing technique and method sedimentation means can be preset. Optionally, it may be used as required in the manner described in U.S. Patent Application Serial Nos. 13/355,458 and 13/244,947, both of which are incorporated herein by reference in their entireties for all purposes. It can be based on protocols or procedures that can change dynamically.

As shown in FIG. 21, in one non-limiting example, an integrated device 900 can be provided having a programmable processor 902 that can be used to control multiple components of the device. For example, in one embodiment processor 902 may control single or multiple pipette systems 904 that are movable in the XY and Z directions as indicated by arrows 906 and 908 . The same or different processors may also control other components 912, 914, or 916 in the controller. In one embodiment, one of components 912, 914, or 916 has a centrifuge.

As seen in FIG. 21, control by processor 902 enables pipetting system 904 to obtain a blood sample from cartridge 910 and transfer said sample to one of components 912, 914, or 916. do. Such movement involves dispensing the sample into a removable container in cartridge 910 and then transporting the removable container to one of components 912 , 914 or 916 . Optionally, a blood sample is dispensed directly into a container already attached to one of components 912, 914, or 916. In one non-limiting example, one of these components 912, 914, or 916 is a centrifuge having an imaging configuration to allow both illumination and visualization of samples in vessels. obtain. Other components 912, 914, or 916 perform other analysis, assay, or detection functions.

In one non-limiting example, sample vessels in the centrifuge, such as these components 912, 914, or 916, are placed in one or more compartments for further processing of the sample and/or said sample vessels. may be moved from one of the components 912, 914, or 916 to another component 912, 914, or 916 (or optionally to another location or equipment). A pipette system 904 may be used to engage the sample container in order to move the sample container from a component 912, 914, or 916 to another location within the system. In a non-limiting example, this is to move the sample container to an analysis station (such as but not limited to imaging) and then return the container to the centrifuge for further processing. , is useful. In embodiments, this may be done using a pipetting system 904 or other sample handling system in the instrument. In one non-limiting example, a pipette system 904 or other sample handling system within the instrument is used to pipette, such as containers, tips, etc., from cartridge 910 into one of components 912, 914, or 916 or within the system. to another position (or vice versa). It should also be appreciated that in some embodiments, the pipetting system 904 may also be used to rotate the centrifuge rotor into appropriate positions so that containers can be filled and/or unloaded from known positions. . In such embodiments, the pipette system 904 includes tips, nozzles, nozzles, or other features to engage the centrifuge rotor, or other features that can rotate the rotor until the rotation moves it to a desired orientation. Or other pipetting functions can be used.

22, a further embodiment of centrifuge 1000 will be described. FIG. 22 shows an exploded view of the centrifuge having a cover plate 1010 operably connected to a rotatable frame 1020. FIG. In a non-limiting example, the rotatable frame 1020 can include a self-balancing element 700, which in this embodiment can be a channel having a plurality of weighted spheres 1032 therein. Optionally, some embodiments may have a self-balancing element 700 on the cover plate 1010, shaft 1060, or other rotating portion of the centrifuge 100. Optionally, other self-balancing features now known or that may be developed in the future are incorporated into the rotatable frame 1020, the cover plate 1010, the shaft 1060, or other rotating portion of the centrifuge 100. can be

As seen in this non-limiting example, when the centrifuge disc is rotated by motor shaft 1060, to allow bucket 1040 to oscillate as indicated by arrow 1050. There may be one or more sample vessel holders such as buckets 1040 attached to hinges or other attachments. As seen in this embodiment, the bucket 1040 may have a window or viewing point 1042 that allows the sample containers contained therein to be viewed. Optionally, some embodiments may have no windows. Some embodiments may also have the bucket 1040 have a weighted portion 1044 that biases the bucket toward returning to a vertical or substantially vertical orientation. Some embodiments can bias the bucket 1040 slightly off vertical. Magnets 1062, including but not limited to: There can be coupling devices, such as directly contacting the bucket or spaced from the bucket. In some embodiments, the bucket 1040 can have iron portions and/or magnets thereon to assist in engaging the coupling device, such as magnets 1062 . Optionally, some embodiments may have magnets in the bucket 1040 or in both the bucket 1040 and the shaft 1060 . Some embodiments are not in direct alignment within the bucket 1040 and shaft 1060, one along the long portion of the bucket and the other at the leg of the bucket 1040. An arrangement can have multiple magnets.

Although only two buckets 1040 are shown in FIG. 22, it should be understood that embodiments with more buckets are not excluded. Optionally, when the bucket 1040 is in a rotated position, at least a portion of the bucket is aligned with the cover plate to form a portion that is coplanar with the plane of the cover plate to reduce air resistance. Cavities 1070 in 1010 can be filled. Optionally, less than about 90% of the cavity is filled by the bucket 1040 in the rotated position. Optionally, less than about 80% of the cavity is filled by the bucket 1040 in the rotated position. Optionally, less than about 70% of the cavity is filled by the bucket 1040 in the rotated position.

As seen in the embodiment of FIG. 22, when the centrifuge components are assembled and lowered as indicated by arrow 1102 therein, the cover plate 1010 is positioned at the top of the housing 1100. can be substantially coplanar with the In some embodiments, a position sensor 1110, such as but not limited to a Hall sensor, can be used to detect an indicator 1112 on the rotational position of the centrifuge. This can be useful for determining the rest position of the rotating portion so that the sample handling instrument can accurately engage the bucket 1040 . Optical, electromagnetic and/or other detection techniques may be used for said position detection. Optionally, some embodiments may incorporate position sensing into the motor and/or motor shaft. It should be understood that the parts described in can be incorporated into fewer individual parts. It should be understood that the centrifuge herein can use any of the electric motors (including those with encoders) described herein.

22 and 23 also illustrate that some embodiments may have ventilation features in the sides and/or bottom of the housing 1100, such as but not limited to ventilation ports 1120. FIG. As seen in the side cross-sectional view of FIG. 23, the rotation of the centrifuge discs draws air into the housing 1110 to help cool the centrifuge. The air can be drawn in for rotation of the centrifuge disc, as indicated by arrow 1130 . Some embodiments can have ports 1129 only in the sidewalls of the housing 1110 . Optionally, some may have ports only on the bottom of the housing 1110 . Optionally, some embodiments may have openings in both. FIG. 23 shows that the interior of the housing 1110 can have a shaped bottom portion to help guide air flow into the housing 1110 . Optionally, some embodiments configure the housing 1110 with elastomeric mounts, shock absorbing members, etc. to minimize transmission of vibrations from the centrifuge to some other part of the instrument. can be mounted on As seen in FIG. 23, the centrifuge discs 1150 define a spacing 1160 that is 10% or less of the diameter of the discs 1150 . Optionally, define a spacing 1160 that is 15% or less of the diameter of said disk 1150 . This allows a fit around the centrifuge disc that can minimize unwanted air flows. Optionally, other embodiments include cutouts of larger portions in fewer locations (or smaller cutouts in more locations) in the housing 1100 to provide the desired level of cooling. ).

All of the above can be integrated into a single housing 920 and can be configured for tabletop or floor mounting in a small footprint. In one example, a small footprint floor mounted system may occupy a floor area of about 4 m ² or less. In one example, a small footprint floor mounted system may occupy a floor area of about 3 m ² or less. In one example, a small footprint floor mounted system may occupy a floor area of about 2 m ² or less. In one example, a small footprint floor mounted system may occupy a floor area of about 1 m ² or less. In some embodiments, the footprint of the device is about 4 m ² , 3 m ² , 2.5 m ² , 2 m ² , 1.5 m ² , 1 m ² , 0.75 m ² , 0.5 m ² , 0.3 m ² , 0.2 m ² , 0.1 m ² , 0.08 m ² , 0.05 m ² , 0.03 m ² , 100 cm ² , 80 cm ² , 70 cm ² , 60 cm ² , 50 cm ² , 40 cm ² , 30 cm ² , 20 cm ² , It can be 15 cm ² , or 10 cm ² or less. Some suitable systems in a point-of-service setting are described in US patent application Ser. Nos. 13/355,458 and 13/244,947, both of which are incorporated by reference for all purposes , which is incorporated herein in its entirety. The present embodiments may be configured for use with any module or system described in those patent applications.

As non-limiting examples, the centrifuge can have dimensions of about 0.1 mm ² , 0.5 mm ² , 1 mm ² , 3 mm ² , 5 mm ² , 7 mm ² , 10 mm ² , 15 mm ² , 20 mm ² , 25 mm ² , 30 mm ² , 40 mm ² , 50 mm ² , 60 mm ² , 70 mm ² , 80 mm ² , 90 mm ² , 100 mm ² , 125 mm ² , 150 mm ² , 200 mm ² , 250 mm ² , 300 mm ² , 500 mm ² , or up to 750 mm ² can have The hemocytometer has a having one or more dimensions (e.g., width, length, height) no greater than 17 mm, 20 mm, 25 mm, 30 mm, 40 mm, 50 mm, 60 mm, 70 mm, 80 mm, 100 mm, 150 mm, 200 mm, 300 mm, 500 mm, or 750 mm; can.

Although the present invention has been described and illustrated with reference to specific embodiments thereof, various adaptations and variations of procedures and protocols will occur to those skilled in the art without departing from the spirit and scope of the invention. , modifications, substitutions, deletions, or additions may be made. For example, with any of the embodiments described above, it should be understood that other techniques for plasma separation may also be used with or instead of centrifugation. For example, one embodiment may centrifuge the sample for the first cycle, and then the sample is placed in a filter to then remove the formed blood constituents to complete the separation. can be Although the present embodiments are described in the context of centrifugation, other accelerated separation techniques can also be adapted for use with the systems herein. It should also be understood that although the present embodiments are described in the context of blood samples, the techniques herein can be configured for application to other samples (biological or otherwise). Any of the embodiments herein can be configured to have the encoders and/or sensors described in this disclosure. Any of the embodiments herein can be configured to have the location detection device described in this disclosure. Any of the embodiments herein can be configured to have the auto-shutdown feature described in this disclosure. Any of the embodiments herein can be configured to have the thermal control functionality described in this disclosure.

Optionally, at least one embodiment may use a variable speed centrifuge. With feedback such as but not limited to imaging the position of the interface in the sample, the speed of the centrifuge is varied over time to maintain a linear compression curve (until complete compression). and the ESR data are derived from the centrifuge speed profile rather than from the sedimentation curve. In such a system, one or more processors may be used for feedback control of the centrifuge to have a linear compression curve while also recording the speed profile of the centrifuge. Sedimentation velocity data is calculated based on the centrifuge speed, depending on which interface is tracked. In one non-limiting example, higher centrifuge speeds are used to maintain a linear curve as compression nears completion.

Additionally, those skilled in the art will recognize that any embodiment of the present invention may be applied to the collection of sample bodily fluids from humans, animals, or other subjects. Optionally, the volume of blood used for the sedimentation test is 1 mL or less, 500 μL or less, 300 μL or less, 250 μL or less, 200 μL or less, 170 μL or less, 150 μL or less, 125 μL or less, 100 μL or less, 75 μL or less, 50 μL or less, 25 μL or less, It may be 20 μL or less, 15 μL or less, 10 μL or less, 5 μL or less, 3 μL or less, 1 μL or less, 500 nL or less, 250 nL or less, 100 nL or less, 50 nL or less, 20 nL or less, 10 nL or less, 5 nL or less, or 1 nL or less.

Additionally, concentrations, amounts, and other numerical data may be presented herein in a range format. Such range formats are used merely for convenience and brevity, and are used not only for the numerical values explicitly recited as the limits of the ranges, but also for the ranges as if each were explicitly presented. It should be understood that all individual numerical values and subranges subsumed within should be interpreted flexibly as inclusive. For example, a particle size range of about 1 nm to about 200 nm includes not only the explicitly stated ranges of about 1 nm and about 200 nm, but also individual sizes such as 2 nm, 3 nm, 4 nm, and 10 nm to 50 nm, 20 nm to It should also be construed to include sub-ranges such as 100 nm.

Publications discussed or cited in the specification 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 such publication is not entitled to antedate it 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 in this specification are herein incorporated by reference to disclose and describe whether the publications are cited in structure and/or method. The following applications are fully incorporated herein by reference for all purposes: U.S. Patent Application Nos. 13/355,458, 13/244,947, 13/769,820, 61/852, 489, 61/930432, U.S. Provisional Patent Application No. 61/673,037, entitled "Rapid Measurement of Formed Blood Component Sedimentation Rate from Small Sample Volumes," filed Jul. 18, 2012; U.S. Provisional Patent Application No. 61/930,462; U.S. Patent Nos. 8,380,541, 8,088,593; U.S. Patent Application No. 2012/0309636; U.S. Patent Application No. 61/676,178, filed July 26; PCT/US2012/57155, filed September 25, 2012; U.S. Patent Application No. 13/244,949, filed September 26, 2011; and U.S. Provisional Patent Application No. 61, filed September 26, 2011 U.S. Provisional Patent Application No. 13/244,947; U.S. Provisional Patent Application entitled "High Speed, Compact Centrifuge for Use with Small Sample Volumes," filed Jul. 18, 2012; 61/673,245, U.S. Provisional Patent Application No. 61/675,758, entitled "High Speed, Compact Centrifuge for Use with Small Sample Volumes," filed Jul. 25, 2012; U.S. Provisional Patent Application No. 61/706,753, entitled "High Speed, Compact Centrifuge for Use with Small Sample Volumes," filed Sep. 27; U.S. Patent Publication No. 2012/0309636; U.S. Patent Application No. 61/676,178, filed July 26, 2012; PCT/US2012/57155, filed September 25, 2012 issue, U.S. Patent Application No. 13/244,946 filed September 26, 2011; U.S. Patent Application No. 13/244,949 filed September 26, 2011; and September 26, 2011 US patent application Ser. No. 61/673,245, filed on Jan.

While the above is a complete description of the preferred embodiments of the invention, various alternatives, modifications and equivalents may be used. The scope of the present 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. Unless a given claim is clearly articulated using the phrase "means for," the appended claims are not to be interpreted as containing means-plus-function limitations. As used throughout this description and the claims below, the terms “a,” “an,” “the,” unless the context clearly indicates otherwise, It should be understood to include multiple meanings. Furthermore, as used throughout the description of this specification and the claims below, the meaning of the term "in", unless the context clearly indicates otherwise, is to use the term "in". , and "on". Finally, furthermore, as used throughout this description and the following claims, the meaning of "and", "or", unless the context clearly dictates otherwise, is includes and disjunctive conjunctions and may be used interchangeably. Thus, unless the context clearly dictates otherwise, when the terms "and" or "or" are used in context, the usage of such connections is defined as "and/or (and /or)” is not excluded.

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

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