System and method for plasma separation and measurement

• US 5,589,399 A
• Filed: 10/21/1994
• Issued: 12/31/1996
• Est. Priority Date: 10/21/1994
• Status: Expired due to Fees

• Current Assignee: First Medical, Inc.
• Original Assignee: First Medical, Inc.
• Inventors: Allen, Michael P., Zuk, Robert F., Ensler, Lawrence M.
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): Freed, Rachel
• Application Number:
  US08/326,974
• Time in Patent Office: 802 Days
• Field of Search: 210/645, 210/651, 210/500.36, 210/500.21, 210/506, 210/767, 436/169, 436/170, 436/177, 436/178, 422/63, 422/56-58, 422/66-67, 422/101, 422/100, 435/805, 435/2, 435/11, 435/288, 435/289, 435/291, 435/808, 435/25, 435/28, 435/19, 435/15, 435/14, 435/18.2, 435/287
• US Class Current: 436/169
• CPC Class Codes: G01N 1/2813 Producing thin layers of samples on a substrate, e.g. smearing, spinning-on G01N1/30 takes precedence
• CPC Class Codes: G01N 33/491 by separating the blood components G01N15/05 takes precedence
• CPC Class Codes: G01N 35/1095 for supplying the samples to flow-through analysers for a specific analyser see relevant groups, e.g. under G01N15/00, G01N21/00, G01N27/00, G01N30/00, H01J49/00
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
• CPC Class Codes: Y10T 436/255 including use of a solid sorbent, semipermeable membrane, or liquid extraction

Abstract

The system for transferring plasma to a test substrate comprises an applicator and the test substrate. The applicator includes a blood reservoir and a filter element which separates cellular components from the blood as plasma is passed to the test substrate. The test substrate includes an absorptive element which receives the plasma from the applicator. In one embodiment, measured amounts of plasma are transferred when the absorptive element becomes saturated, thus stopping the flow of plasma. In another embodiment, excess blood and cellular components are removed from the measured plasma by disengaging the applicator from the test substrate. In another embodiment, plasma transferred to the absorptive element is eluted from the absorptive element by subsequent application of an elution medium.

Claims

1. A system for transferring measured amounts of plasma from unmeasured blood samples to a test substrate, said system comprising:

an applicator having a blood-receiving reservoir with a predetermined plasma capacity and a single plasma transfer port having a cross-sectional area and shape in fluid communication with the reservoir and including a filter member extending across the plasma transfer port, wherein the filter member permits the passage of plasma and plasma macromolecules but inhibits the passage of blood cells;

a plasma-receiving test substrate having a surface; and

at least one reaction zone on the substrate surface; and

a single absorptive element on the substrate surface having a contact surface with a shape and area substantially identical to those of the port so that the contact surface is configured to engage the plasma transfer port and a plasma capacity which is less than the plasma capacity of the reservoir, wherein plasma transferred from the reservoir will saturate the absorptive element to provide a measured amount of plasma on the substrate; and

wherein the at least one reaction zone is spaced from said single absorptive element.

2. A system as in claim 1, wherein the applicator further includes a capillary tube for drawing blood into the blood-receiving reservoir.

3. A system as in claim 1, wherein the blood-receiving reservoir has a volume in the range from 50 μ

l to 500 μ

l.

4. A system as in claim 3, wherein the plasma transfer port has an area in the range from 15 mm² to 200 mm² and the filter member has a crowned profile to enhance contact with the contact surface of the absorptive element.

5. A system as in claim 1, wherein the filter member comprises a chromatographic filter element in series with a size-exclusion element, wherein the chromatographic filter element slows the flow of blood cells relative to that of plasma and the size-exclusion element permits plasma flow and blocks the passage of blood cells.

6. A system as in claim 5, wherein the chromatographic filter element has a volume which is sufficiently large to retain blood cells and inhibit blockage of the filter member in order to permit a volume of plasma flow through the filter member which is larger than the plasma capacity of the absorptive element.

7. A system as in claim 6, wherein the chromatographic filter element has a volume in the range from 25 mm³ to 1000 mm³ and is composed of a material selected from the group consisting of glass fiber, polyester fiber, plastic fiber, metal fiber, composite cellulose and synthetic fiber, nylon mesh, polyester mesh, and synthetic fabric.

8. A system as in claim 5, wherein the size-exclusion element comprises a microporous membrane having a pore size below 7 μ

m and composed of a material selected from the group consisting of nitrocellulose, cellulose acetate, regenerated cellulose, polycarbonate, and polyamide.

9. A system as in claim 1, wherein the absorptive element has contact area in the range from 10 mm² to 200 mm² and a plasma capacity below 200 μ

l.

10. A system as in claim 9, wherein the plasma capacity of the absorptive element is in the range from 1 μ

l to 100 μ

l.

11. A system as in claim 1, wherein the absorptive element comprises a fiber capillary matrix or a molded capillary matrix.

12. A system as in claim 11, wherein the fiber capillary matrix is composed of a material selected from the group consisting of cellulose paper, cellulose acetate, nitrocellulose, regenerated cellulose, polyamide, hydrophilic-treated polyethylene, nylon mesh, and hydrophilic-treated polyester mesh.

13. A system as in claim 1 wherein the test substrate is a disk having the absorptive element at the center of a circular fluid-receiving surface and a plurality of reaction zones spaced radially outward from the absorptive element.

16. A system as claimed in claim 1, wherein the absorptive element is free of any reactive components which would interact with target plasma components.

14. A system for transferring measured amounts of plasma from unmeasured blood samples to a test substrate, said system comprising:

an applicator having a blood-receiving reservoir and a plasma transfer port in fluid communication with the reservoir and including a filter member extending across the plasma transfer port, wherein the filter member permits the passage of plasma and plasma macromolecules but inhibits the passage of blood cells, and wherein the plasma transfer port has a plasma port cross-sectional geometry; and

a plasma-receiving test substrate having a surface, said surface having thereon at least one reaction zone, and an absorptive element having a contact surface configured to engage the plasma transfer port and a plasma capacity which is less than a plasma capacity of the reservoir, and at least one reaction zone separated from the absorptive element by a fluid-receiving surface, wherein plasma transferred from the reservoir will saturate the absorptive element to provide a measured amount of plasma on the substrate and wherein the at least one reaction zone is spaced from said single absorptive element.

15. A system as claimed in claim 14, wherein at least one reaction zone comprises a plurality of reaction zones, each reaction zone having a specific binding reagent.

17. A system for transferring measured amounts of plasma from unmeasured blood samples to a test substrate, said system comprising:

an applicator having a blood-receiving reservoir and a plasma transfer port in fluid communication with the reservoir and including a filter member extending across the plasma transfer port, wherein the filter member permits the passage of plasma and plasma macromolecules but inhibits the passage of blood cells, and wherein the plasma transfer port has a plasma port cross-sectional geometry; and

a plasma-receiving test substrate having a surface, said surface having thereon;

an absorptive element having a contact surface configured to engage the plasma transfer port and a plasma capacity which is less than a plasma capacity of the reservoir, and

at least one reaction zone disposed adjacent to the absorptive element, wherein plasma transferred from the reservoir will saturate the absorptive element to provide a measured amount of plasma which can be subsequently transferred to the reaction zone on the substrate.

18. A system as claimed in claim 17, wherein at least one reaction zone is separated from the absorptive element by a fluid-receiving surface, wherein fluid may be eluted from the absorptive element and flow onto the fluid-receiving surface and will be available to react within the reaction zone.

19. A system for transferring measured amounts of plasma from unmeasured blood samples to a test substrate, said system comprising:

an applicator having a blood-receiving reservoir with a predetermined plasma capacity and a single plasma transfer port having a cross-sectional area and shape in fluid communication with the reservoir and including a filter member extending across the plasma transfer port, wherein the filter member permits the passage of plasma and plasma macromolecules but inhibits the passage of blood cells; and

a plasma-receiving test substrate having a surface, said surface having thereon;

a single absorptive element having a contact surface with a shape and area substantially identical to those of the port so that the contact surface is configured to engage the plasma transfer port and a plasma capacity which is less than the plasma capacity of the reservoir, wherein plasma transferred from the reservoir will saturate the absorptive element to provide a measured amount of plasma on the substrate;

a fluid-receiving surface disposed adjacent to the absorptive element, wherein fluid eluted from the absorptive element will flow onto the fluid-receiving surface; and

at least one reaction zone separated from the absorptive element by the fluid-receiving surface, wherein fluid eluted from the absorptive element will be available to react with the reaction zone.