Cuvette and Rotor System for Blood Plasma Separation

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority of U.S. Provisional Application No. 62/358,666, filed on July 6, 2016, entitled "Cuvette and Rotor System for Blood Plasma Separation ," the disclosure of which is hereby incorporated by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

N/A

BACKGROUND

The ability to generate clean plasma (i.e., free from red and white blood cells) has many applications in the medical and diagnostics industries.

Centrifugation continues to be the most common method of obtaining plasma from whole blood. This method requires relative centrifugal forces (RCF) of 2000 to 5000 x g for 3 to 10 minutes (where "g" is acceleration due to gravity). The equipment necessary to generate these conditions is generally bulky and operates at high speeds. Re-mixing of blood cells with the plasma after separation can be a problem with this method, requiring either special techniques or special sample tubes to be employed. Therefore, for smaller instruments and so-called "point-of-care" devices that require clean plasma, centrifugation is not an ideal method.

More recently, lateral flow devices have been introduced for various diagnostic tests (e.g., glucose monitoring). These "test strips" separate the plasma from the whole blood as it flows through the capillary structure of a porous medium. The advantage to this approach is that it can be used with small sample volumes and does not require centrifugation. However, because the plasma remains contained in the pores of the strip medium, these strips are generally limited to applications where a colorimetric reflectance measurement is made after components in the plasma react with a reagent. A further disadvantage to these tests is that they tend to be slow, often requiring several minutes for the blood/plasma to travel the required distance through the porous medium.

In cases where an optical transmission or other type of measurement is necessary, there remains a need to quickly separate small volumes of plasma from whole blood that is free of any interfering porous medium. Most attempts to date have incorporated a method or mechanism to apply external pressure or forces to porous separation media in order to extract usable plasma. These devices tend to be cumbersome and unreliable. It is difficult to precisely control the forces applied to the media and the blood sample on such a small scale and nearly impossible to extract all of the plasma from the media. The result is that excessive forces can contaminate the plasma with particulates from the porous medium or by hemolysis of red blood cells. Plasma yield is also poor.

SUMMARY OF THE INVENTION

A cuvette and rotor system for blood plasma separation is provided that addresses the above shortcomings.

The cuvette comprises a housing comprising an upper surface with an access opening therethrough, and a semipermeable membrane within the housing adjacent the access opening. The membrane has an inlet side, accessible via the access opening for receiving a whole blood sample, and an outlet side within the housing. The membrane's pore size is arranged to exclude red blood cells and white blood cells from the outlet side of the membrane and permit passage of plasma to the outlet side. A collection surface is adjacent the outlet side of the membrane within the housing, and a sample chamber is in fluid communication with the collection surface to receive plasma.

The rotor system comprises a rotor assembly mounted for spinning about an axis. The rotor assembly includes a cuvette holder to hold the cuvette at a fixed, non-zero angle with respect to the axis. Upon spinning at low speeds, plasma that has been separated from red and white blood cells in the membrane is subjected to relative centrifugal forces, in some embodiments of about 20 to about 500 x g for about 1 minute, causing it to be drawn into the sample chamber. In some embodiments, the sample chamber can be sized for an anticipated sample volume, such that the centrifugal force simultaneously excludes any air from the chamber, thereby ensuring the chamber is full. The plasma can then be optically tested within the sample chamber in the cuvette or can be withdrawn from the sample chamber for testing outside of the cuvette. The rotor system can include an optical detection assembly for optical testing of the plasma in the cuvette while the cuvette remains in the rotor system after spinning.

The blood plasma separation system can be used with a range of blood sample sizes. A greater volume of plasma can be obtained from a whole blood sample using a semipermeable medium than with prior art blood plasma separation devices that use a semipermeable medium. The system provides fast separation and collection of plasma, and is a relatively gentle process that minimizes hemolysis and contamination. Because of the lower forces and speeds, the system can be much smaller and lighter than that needed for the conventional high speed centrifugation method. A bubble-free plasma sample can be obtained. The sample can be tested in some embodiments directly in the rotor assembly.

DESCRIPTION OF THE DRAWINGS

The invention will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings in which:

Fig. 1 is an isometric view of an embodiment of a cuvette for blood plasma separation;

Fig. 2 is an isometric view of an underside of a top piece of the cuvette of Fig. 1;

Fig. 3 is an exploded isometric view of the cuvette of Fig. 1;

Fig. 4 is a top plan view of the cuvette of Fig. 1;

Fig. 5 is a cross-sectional view along line A- A of Fig. 4;

Fig. 6 is an isometric view of an embodiment of a rotor system for use with the cuvette for blood plasma separation;

Fig. 7 is an isometric view of an interior of the rotor system of Fig. 6;

Fig. 8 is a partially cutaway view of the rotor system of Fig. 7;

Fig. 9 is a cross-sectional view of an optical detector of the rotor system of Fig. 7;

Fig. 10 is an isometric view of an embodiment of a cuvette with a puncturable septa or barrier;

Fig. 11 is a top plan view of the cuvette of Fig. 10;

Fig. 12 is a cross-sectional view along line A-A of Fig. 11;

Fig. 13 is a partially cutaway view of a plasma retrieval system of a rotor system;

Fig. 14 is an isometric view of a bottom piece of a further embodiment of a cuvette with a reaction chamber;

Fig. 15 is an isometric view of the cuvette bottom piece of Fig. 14 with sample in a reaction chamber;

Fig. 16 is an isometric view of the cuvette bottom piece of Fig. 14 with sample in a sample chamber;

Fig. 17 is an isometric view of an embodiment of a cuvette incorporating keying features; Fig. 18 is an isometric view of an embodiment of a cuvette incorporating a sloped collection surface;

Fig. 19 is an isometric top view of a further embodiment of a cuvette incorporating a scoop;

Fig. 20 is an isometric bottom view of the cuvette of Fig. 19;

Fig. 21 is a plan view of the cuvette of Fig. 19;

Fig. 22 is a cross-sectional view along line A- A of Fig. 21;

Fig. 23 is an isometric exploded view of an embodiment of a cuvette with an associated cap;

Fig. 24 is an isometric view of the cuvette of Fig. 23 with the cap in place;

Fig. 25 is an isometric exploded view of a further embodiment of a cuvette; and Fig. 26 is an exploded isometric view of a still further embodiment of a cuvette.

DETAILED DESCRIPTION OF THE INVENTION

A blood plasma separation system is provided having a cuvette 10 to collect and contain a blood sample and an accompanying rotor system 80 to hold and position the cuvette during a plasma separation process.

Referring to Figs. 1-5, one embodiment of a cuvette 10 includes a housing 20 and a semipermeable membrane 40 to initiate blood separation within the housing. One side 42 of the membrane, an inlet or upstream side (A side), is accessible through an opening 22 in an upper surface 24 of the housing. Within the housing, an outlet or downstream side 44 (B side) of the membrane 40 is located adjacent a collection surface 64. A channel 26 extends from the surface 64 to a sample chamber 30. In use, a blood sample is placed on the inlet side 42 of the membrane 40 and begins to permeate through the membrane and onto the collection surface 64. The cuvette 10 is then placed at an appropriate angle in the rotor system 80 (Figs. 6-9, described further below) and spun at a suitable rotational speed for a suitable time. During the rotation, plasma that has collected on the surface 64 is drawn through the channel 26 to the sample chamber 30, where the plasma is accessible for additional testing. In the embodiment of Figs. 1-5, the sample chamber 30 includes aligned optical transmission windows 32, 34 for performing an optical test on a plasma sample in the sample chamber. At least in the area 32, 34 of the sample chamber 30, the top and bottom pieces 52, 62 of the cuvette housing can be formed from a transparent material that permits transmission of a light beam for performing an optical test on a plasma sample within the sample chamber. In some embodiments, plasma can be withdrawn from the sample chamber for further testing outside of the sample chamber, described further below. In some embodiments, an additional reaction chamber can be provided between the surface 64 and the sample chamber, also described further below.

In some embodiments, the semipermeable membrane 40 for blood separation can be formed from a material such as asymmetric polysulfone arranged with pore sizes that decrease from the inlet side to the outlet side, or from a bound glass fiber material. The larger red and white blood cells remain trapped within the larger pores of the membrane, while plasma is able to permeate through the depth of the membrane to the outlet side. In some embodiments, the membrane can include substantially uniform pores sized to exclude red and white blood cells while allowing plasma to permeate through. Suitable semipermeable membranes for blood separation are commercially available as Vivid™ from Pall Corporation or VF2 from GE Healthcare.

In the embodiment illustrated in Figs. 1-5, the cuvette housing 20 includes a top piece 52 and a bottom piece 62 fastened together to hold the membrane in place. The membrane access opening 22 is formed through the top piece. The membrane 40 is attached to an underside 54 of the top piece 52, around the periphery 56 of and fully covering the access opening 22. Although a precise sample volume is not critical to the function of the system, the areal size of the membrane and the access opening can be selected based on an anticipated sample volume for an application. The bottom piece 62 includes the collection surface 64 that aligns with the membrane access opening 22. The collection surface can have an area larger than the membrane access opening. The outlet side 44 of the membrane 40 is in contact with the collection surface 64 of the bottom piece 62.

The collection surface 64 can be optimized to enhance transport of the plasma from the membrane. This optimization can include physical and/or chemical altering of the surface. In some embodiments, the collection surface can be textured to provide capillary channels for the plasma to collect in and travel through. In some embodiments, capillary channels can have dimensions ranging from about 0.001 to about 0.010 inch deep by about 0.001 to about 0.010 inch wide. In some embodiments, capillary channels can have dimensions of about 0.004 inch deep by about 0.004 inch wide. The channels can be in a regular pattern or a random pattern. In some embodiments, a regular pattern can include crossing channels. In some embodiments, a pattern can be similar to a commercially available moldable pattern such as the random pattern Mold-tech MT-11050 (0.0045 inch deep). In some embodiments, the collection surface can be made hydrophilic, for example, with a coating such as polyvinylpyrrolidone (PVP), polyurethane, or polyacrylate. In some embodiments, a hydrophilic surface can be provided by chemical etching or a plasma treatment. In some embodiments, the surface can be a separate component, such as a fine mesh, that is placed between the membrane 40 and the bottom piece 62.

A plasma collection trough 66 surrounds the collection surface 64 in the bottom piece 62. The collection trough is in fluid communication at one end with the channel 26 that extends longitudinally along the bottom piece to the sample chamber 30. The collection trough also includes a vent opening 68 at another end of the housing, to allow gas or air to vent out of the housing during rotation.

Referring to Figs. 6-9, an embodiment of a rotor system 80 includes a rotor assembly 81, motor 97, and an optical detector assembly 110. The rotor assembly is mounted to the motor 97 for spinning about an axis 96. The rotor assembly includes a rotor top piece 83 and a bottom piece 84 nested together to form an angled cuvette holder 86. In the embodiment shown, the cuvette holder is formed in a recess or pocket 92 formed in one or both of the nested top and bottom pieces. Both pieces 83, 84 include an angled member 85 and a flat support plate 87. An opening 94 for inserting the cuvette is provided through the top piece 83. The angled surface 85 is formed to hold the cuvette at a fixed non-zero angle Θ with respect to a spin axis 96 of the rotor assembly. In some embodiments, the angle can range from about 10° to about 80° from the spin axis. In some embodiments, the angle can range from about 30° to about 60°. In some embodiments, light path apertures 98 can be provided in the top and bottom rotor pieces, which align with the sample chamber 30 of an inserted cuvette, for use with an optical detector assembly 110, described further below. The top and bottom pieces can be fastened together in any suitable manner. In some embodiments, the rotor assembly can be formed with multiple cuvette holders to hold multiple cuvettes.

The motor 97 is supported on a base 99 and is connected to the rotor assembly 81 at the flat support plate 87 to cause the rotor assembly to spin. The rotor assembly and motor are enclosed within a housing 102 for safety and to protect the rotor assembly from dirt and other contaminants. The housing includes an upper surface 104 which can have an access opening 106 formed therein for inserting a cuvette. A cuvette containing a sample to be separated and in some embodiments, analyzed can be placed through the opening into the cuvette holder 86 within the rotor assembly. A lid 108 can be provided to close the opening once a cuvette has been inserted into the cuvette holder for the duration of the test. A control panel 109 can be provided on the housing, with controls to adjust test parameters and start a test. Parameters can include, for example, acceleration, speed, and time. In some embodiments, the parameters can be manually adjustable and/or preset parameter values can be provided from which a user can choose. In some embodiments, parameters can be automatically set and non- adjustable by a user.

In use, a whole blood sample is deposited onto the inlet side of the membrane 40 of a cuvette 10. The blood can either be collected onto the membrane directly or one of many available collection devices can be used. The blood sample is absorbed into the pores of the membrane with the red blood cells being excluded toward the inlet side 42 and clean plasma concentrated toward the outlet side 44 as absorption takes place. Once the sample is deposited, the cuvette 10 is placed into the rotor assembly 81 in the position shown in Figs. 7-9 with the sample chamber toward the bottom and the B side of the membrane facing upwardly and outwardly. The rotor assembly 81 is spun about its central axis 96 to create centrifugal forces within the cuvette. The direction of the centrifugal forces and the orientation of the cuvette cause the separated plasma to flow from the collection surface 64 adjacent the membrane into the sample chamber 30.

The rotational speed and duration of the rotor assembly can be minimized to what is necessary to pull the plasma from the collection surface 64 into the sample chamber 30. In some embodiments, the rotation speed can be selected to provide a relative centrifugal force (RCF) that ranges from 20 to 500 x g (where "g" is acceleration due to gravity). As the sample chamber fills, any air or gas present is expelled through the vent 68, so that the final sample is free, or substantially free, of air or gas bubbles. The sample chamber volume can be designed to be slightly smaller than an anticipated plasma volume so that the chamber is completely full at the completion of the spin. Parameters such as the size of the rotor assembly, angle of cuvette, acceleration, speed of spin, and time of spin can be selected based on the specific application.

In some embodiments, the rotor system can include one or more optical detection assemblies 110 to measure one or more components of interest in the plasma. One embodiment of a detection assembly is shown in Figs. 7-9. The optical detection assembly includes a light source 114 on one side of the rotor assembly 81 and a detector 116 on the other side of the rotor assembly. The light source and the detector can be fixed and located in mounting blocks 123 and 124, respectively. An optical axis 118 is defined from the light source to the detector, through the rotor assembly, and is perpendicular to the angle Θ at which the cuvette is held in the rotor assembly at the optical detection assembly. The light source can be any light source suitable for the particular application, such as an LED, halogen, or xenon lamp. One or more filters 122 and/or lenses (not shown) can be included between the light source and the detector anywhere on the optical axis, as determined by the application.

For operation with the optical detector, the top and bottom pieces 83, 84 of the rotor assembly 81 can include apertures 98 aligned with the sample chamber 30 on the cuvette 10. In some embodiments, after spinning for a suitable time, the rotor can come to a stop at the optical detector within the rotor housing 102, with the apertures of the rotor and the sample chamber in the cuvette aligned on the optical axis 118. The light source 114 can be activated to transmit a light beam through the sample chamber, through a filter(s) and/or lens(es) if present, to the detector 1 16. In some embodiments, the rotor assembly can be moved by the motor one way or the other to maximize the detected signal. In some embodiments, a home position for the cuvette holder at the optical detector can be specified, for example by an encoder on the motor or an optical sensor. In some embodiments, the optical measurement can be made while the rotor is spinning, as the cuvette passes the optical detector.

Figs. 10-12 illustrate a further embodiment of a cuvette 210. The housing 220 can be similar to that shown in Figs. 1-5. At the sample chamber 230, a puncturable septum or barrier 231 is provided to allow for retrieval of plasma by a needle or cannula. In some embodiments, the septum can be an elastomer or a foil material that is sealed to the top piece 252 by welding or heat sealing, or could be pinched between the top and bottom pieces 252, 262 during manufacture. In use, the plasma is separated by centrifugation into the sample chamber, and the plasma is removed from the cuvette at a plasma retrieval assembly in the rotor assembly by a needle or cannula penetrating the septum or barrier.

Fig. 13 illustrates an embodiment of a rotor system 80' with a plasma retrieval assembly 130 for a cuvette 210 having a puncturable septum. The rotor system can include a rotor assembly 81 substantially as described above with respect to Figs. 6-9, using like reference numerals for like elements. The plasma retrieval assembly 130 can include a syringe 132 supported by a syringe carriage 134 on a mounting block 136 on the base 99 to align a needle 138 of the syringe with the sample chamber of the cuvette 210. The syringe carriage 134 can translate along the mounting block 136 toward and away from the sample chamber generally perpendicular to the angle Θ of the cuvette in the rotor assembly. The aperture 98 in the bottom piece 84 of the rotor assembly can serve as an access port to allow the needle 138 to access the sample chamber. In this manner, the needle can pierce the septum and extend into the sample chamber. The syringe can be operated to draw plasma through the needle into the syringe, and the needle can then be withdrawn from the sample chamber. Once the plasma sample is in the syringe, it can be dispensed or pumped elsewhere for further testing.

Figs. 14-16 illustrate a further embodiment of a cuvette 310 that includes a reaction chamber 372 located in the fluid path between the collection surface 364 and the sample chamber 330. The top piece of the cuvette and the membrane can be substantially as described above and are not shown. The reaction chamber 372 can be prefilled with one or more reactants or catalysts, or surface(s) of the reaction chamber can be pre-coated with one or more reactants or catalysts, depending on the test to be performed. In use, this cuvette can be subjected to two distinct spin speeds— a lower speed to draw plasma 5 into the reaction chamber, followed by a higher speed to draw the plasma from the reaction chamber into the sample chamber. During the low speed spin, clean plasma 5 flows into the reaction chamber 372 via a first channel 374. A second channel 376 between the reaction chamber and the sample chamber 330 can have a smaller cross-sectional area to form a so-called "capillary valve" to keep plasma in the reaction chamber during the low speed spin. The plasma can remain in the reaction chamber for a sufficient time to allow completion of the reaction, as determined by the particular application. After the reaction is complete, the speed of the rotor assembly is increased to force reacted plasma down the second channel 376 and into the sample chamber 330, where the reacted plasma can be measured optically or retrieved via needle or cannula, as described above.

In some embodiments, keying features can be incorporated into the cuvette and rotor assembly to ensure the cuvette is in the proper orientation with the B side of the membrane facing upwardly and the sample chamber toward the bottom. Fig.17 illustrates an embodiment of a cuvette 410 having keys 415 formed in the top piece 452 of housing 420. The keys can fit within complementary slots (not shown) formed in the cuvette holder of the rotor system. The cuvette 410 can be substantially as described above in other respects.

Fig. 18 illustrates an embodiment of a cuvette 510 in which the housing 520 is generally T-shaped, with a sloped surface 521 to collect a whole blood sample and direct the sample toward the semipermeable membrane in a rectangular collection window 522.

Figs. 19-22 illustrate a further embodiment of a cuvette 610 incorporating a scoop 623 to collect a whole blood sample. The scoop 623 is disposed on an upper end 625 of the housing 620 and includes a funnel-shaped surface 627 to direct a blood sample through an opening 641 in the upper end into a chamber 643 adjacent the input side 642 of a semipermeable membrane 640 within the housing 620. The embodiment shown illustrates a puncturable septum 631 within the sample chamber 630. It will be appreciated that the scoop can be provided on a cuvette having a sample chamber with optical transmission windows for use with an optical test.

In some embodiments, the cuvette can include a cap. Figs. 23 and 24 illustrate an embodiment of a cuvette 710 in which a cap 712 is provided in a configuration that can be slid over an upper end of a cuvette housing. The cuvette 710 can be substantially as described above. The cap can cover the opening 722 to the membrane 740 yet not extend far enough to block access to the sample chamber 732. In use, once a blood sample has been collected onto the inlet side 742 of the membrane 740, the cap can be placed over the end of the cuvette and the cuvette placed in the rotor assembly for a test.

While the cuvette housing of the embodiment shown in Figs. 1-5 is rectangular in profile, other shaped profiles can be envisioned to accommodate different application needs. Fig. 25 illustrates an embodiment of a cuvette 810 in which the housing 820 is rounded on one end 811 and tapered in a region 812 toward the collection chamber 830. The access opening for the semipermeable membrane is circular. Fig. 26 illustrates an embodiment of a cuvette 910 having two sample chambers 930a, 930b to collect two separate plasma samples. Channels 926a, 926b lead from the collection trough 966 to each collection chamber. The chambers are illustrated having the same size in Fig. 26. In some embodiments, the chambers can have different sizes.

In some embodiments, the cuvette can be a single-use, disposable device. In some embodiments, the cuvette can be reusable, and mechanical fasteners, such as screws, can be used for fastening the top and bottom pieces together so that the entire cuvette can be disassembled, cleaned and reused.

The top and bottom pieces of the cuvette housing can be formed of any suitable material. Plastics such as polycarbonate or metals such as aluminum can be used. The cuvette can be transparent, translucent, or opaque. A transparent housing can be useful to determine visually if the sample chamber is sufficiently filled.

The cuvette can be manufactured in any suitable manner. In some embodiments, the top and bottom pieces of the housing can be made by machining, injection molding, casting, or by one of several additive manufacturing processes, such as stereolithography, fused deposition, or selective sintering.

The semipermeable membrane can be attached around its perimeter to the underside of the top piece in order to create a fluid seal. Various attachment methods can be used to attach the membrane, such as mechanical pressure, an adhesive, ultrasonic welding, or thermal welding. The top and bottom pieces can then be bonded together to form the completed cuvette. In some embodiments, the top piece can include a peripheral lip that fits over the periphery of the bottom piece. Any suitable type of bonding can be used, such as an adhesive, ultrasonic welding, or thermal welding, or mechanical fastening. Other housing configurations can be used.

The cuvette and rotor system can be used for a variety of applications. For example and without limitation, in some embodiments, the cuvette and rotor system can be used to test for bilirubin, glucose, potassium, calcium, cholesterol, hemin, homocysteine, protein, uric acid, paracetamol (acetaminophen), creatinine, or triglycerides. As an example for a diagnostic test for bilirubin, a sample of blood of approximately 30 μΙ_, is collected, for example, through a heel stick, onto or into the cuvette. Any excess blood is wiped from the cuvette, and the cuvette is capped (see Fig. 21) and inserted into the rotor. The rotor spins the cuvette at a moderate relative centrifugal force (RCF), such as 50 g, for 30 to 60 sec, to pull plasma from the capillary surface into the sample chamber. An optical detector measures the amount of bilirubin. Once the test is complete, the cuvette is removed and discarded. The estimated time for performing the test is 3 to 5 minutes.

The blood plasma separation system provides a number of advantages. The system can be used with blood sample sizes ranging from several microliters to several milliliters. A greater volume of usable plasma can be obtained from a whole blood sample using the system than with prior art blood plasma separation devices. The system provides fast separation and collection of plasma, and is a relatively gentle process that minimizes hemolysis and contamination. A bubble-free plasma sample can be obtained that is suitable for optical analysis or retrieval for other types of analysis.

Other aspects and embodiments of the invention include the following:

1. A cuvette comprising:

a housing comprising an upper surface, an access opening in the upper surface;

a semipermeable membrane within the housing adjacent the access opening, the membrane having an inlet side and an outlet side, the membrane having a pore size arranged to exclude red blood cells and white blood cells from the outlet side of the membrane and permit passage of plasma to the outlet side;

a collection surface adjacent the outlet side of the membrane within the housing; and a sample chamber within the housing in fluid communication with the collection surface to receive plasma.

2. The cuvette of embodiment 1, further comprising a channel within the housing from the collection surface to the sample chamber. 3. The cuvette of embodiment 2, further comprising a collection trough surrounding the collection surface, the channel in fluid communication with the collection trough.

4. The cuvette of embodiment 3, further comprising a gas vent in communication with the collection trough.

5. The cuvette of any of embodiments 1-4, wherein the housing is formed of an optically transparent material in the sample chamber.

6. The cuvette of any of embodiments 1-5, further comprising a reaction chamber within the housing between the collection surface and the sample chamber.

7. The cuvette of embodiment 6, further comprising a first channel from the collection surface to the reaction chamber and a second channel from the reaction chamber to the sample chamber, wherein the second channel has a smaller cross-sectional area than the first channel.

8. The cuvette of any of embodiments 1-7, wherein one wall of the sample chamber is formed of a puncturable septum.

9. The cuvette of any of embodiments 1-8, further comprising at least a second sample chamber within the housing in fluid communication with the collection surface.

10. The cuvette of any of embodiments 1-9, wherein the membrane pore size is arranged in a gradient decreasing from the inlet side to the outlet side.

11. The cuvette of any of embodiments 1-9, wherein the membrane pore size is substantially uniform from the inlet side to the outlet side.

12. The cuvette of any of embodiments 1-11, further comprising a cap configured to fit over a portion of the housing to cover the access opening and to leave the sample chamber uncovered.

13. The cuvette of any of embodiments 1-12, further comprising a collection scoop disposed to direct a fluid sample to the access opening.

14. The cuvette of any of embodiments 1-13, wherein the housing is rectangular, T- shaped, circular, oval, or irregular in plan view.

15. A blood plasma separation system comprising:

the cuvette of any of embodiments 1-14; and

a rotor system comprising a rotor assembly mounted for spinning about an axis, the rotor assembly comprising a cuvette holder to hold the cuvette at a fixed, non-zero angle with respect to the axis. 16. The system of embodiment 15, wherein the rotor assembly comprises top and bottom truncated conical pieces nested together, and the cuvette holder comprises a cuvette recess between the top and bottom pieces.

17. The system of any of embodiments 15-16, further comprising an optical detector assembly configured to optically test a plasma sample within the cuvette holder, the cuvette holder including apertures aligned with the sample chamber of the cuvette, the optical detector assembly comprising a light source and a light detector arranged on a light path, the light path passing through the apertures in the cuvette holder.

18. The system of any of embodiments 15-17, further comprising an optical detector assembly configured to optically test a plasma sample within the sample chamber of the cuvette.

19. The system of any of embodiments 15-18, further comprising a plasma retrieval assembly including a needle or cannula configured to withdraw plasma from the sample chamber of the cuvette.

20. The system of any of embodiments 15-19, further comprising a plasma retrieval assembly including a syringe translatable toward and away from the sample chamber of the cuvette and operable to draw plasma in the sample chamber into the syringe.

21. The system of any of embodiments 15-20, wherein the angle ranges from about 10° to about 80°.

22. The system of any of embodiments 15-21, wherein the rotor assembly is operable to provide a relative centrifugal force of about 20 to about 500 x g.

23. The system of any of embodiments 15-22, further comprising a housing, the rotor system disposed within the housing, wherein an opening is provided in the housing to access the cuvette holder.

24. The system of any of embodiments 15-23, further comprising a control panel accessible on an outer surface of a or the housing.

25. A rotor system comprising:

a rotor assembly mounted for spinning about an axis, the rotor assembly comprising a cuvette holder to hold a cuvette at a fixed, non-zero angle with respect to the axis; and

an optical detector assembly configured to optically test a plasma sample within a sample chamber of the cuvette, the optical detector assembly comprising a light source and a light detector arranged on a light path, the light path passing through the cuvette holder.

26. A rotor system comprising: a rotor assembly mounted for spinning about an axis, the rotor assembly comprising a cuvette holder to hold a cuvette at a fixed, non-zero angle with respect to the axis; and

a plasma retrieval assembly comprising a needle or cannula configured to withdraw plasma from the sample chamber of the cuvette.

27. A method for separating plasma from whole blood, comprising:

providing a sample of whole blood on an inlet side of the semipermeable membrane of the cuvette of any of embodiments 1-14;

spinning the cuvette to separate plasma from red blood cells and white blood cells and collect the plasma in the sample chamber.

28. The method of embodiment 27, further comprising transmitting a light beam through the plasma in the sample chamber and detecting a transmitted light beam at an optical detector on an opposite side of the sample chamber.

29. The method of any of embodiments 27-28, further comprising withdrawing at least a portion of the plasma from the sample chamber.

30. The method of any of embodiments 27-29, further comprising testing the plasma for bilirubin, glucose, potassium, calcium, cholesterol, hemin, homocysteine, protein, uric acid, paracetamol (acetaminophen), creatinine, or triglycerides, or a combination thereof.

As used herein, "consisting essentially of allows the inclusion of materials or steps that do not materially affect the basic and novel characteristics of the claim. Any recitation herein of the term "comprising," particularly in a description of components of a composition or in a description of elements of a device, can be exchanged with "consisting essentially of or "consisting of."

It will be appreciated that the various features of the embodiments described herein can be combined in a variety of ways. For example, a feature described in conjunction with one embodiment may be included in another embodiment even if not explicitly described in conjunction with that embodiment.

To the extent that the appended claims have been drafted without multiple dependencies, this has been done only to accommodate formal requirements in jurisdictions which do not allow such multiple dependencies. It should be noted that all possible combinations of features which would be implied by rendering the claims multiply dependent are explicitly envisaged and should be considered part of the invention.

The present invention has been described in conjunction with certain preferred embodiments. It is to be understood that the invention is not limited to the exact details of construction, operation, exact materials or embodiments shown and described, and that various modifications, substitutions of equivalents, alterations to the compositions, and other changes to the embodiments disclosed herein will be apparent to one of skill in the art.