Blood Cell Barrier for a Lateral Flow Device

• US 20090142229A1
• Filed: 11/30/2007
• Published: 06/04/2009
• Est. Priority Date: 11/30/2007
• Status: Active Grant

• Current Assignee: Kimberly-Clark Worldwide Incorporated (Kimberly-Clark Corporation)
• Original Assignee: Kimberly-Clark Worldwide Incorporated (Kimberly-Clark Corporation)
• Inventors: Smith, Molly K., MacDonald, J. Gavin
• Granted Patent: US 8,535,617 B2
• Time in Patent Office: Days
• US Class Current: 422/68.100
• CPC Class Codes: G01N 33/491 by separating the blood components G01N15/05 takes precedence

Abstract

A lateral flow device for analyzing a whole blood sample is provided. More specifically, the lateral flow device contains a porous membrane that defines a barrier zone for separating red blood cells from blood plasma (includes plasma in which clotting factors haven been removed), which may then flow to a subsequent detection zone for analysis. The barrier zone is formed from a blood cell barrier composition that includes an unsaturated aliphatic fatty acid or an ester thereof. Without intending to be limited by theory, the present inventors believe such unsaturated aliphatic fatty acid molecules undergo autoxidation in the presence of air and hemoglobin to release peroxides (e.g., hydrogen peroxide) via oxidative saturation of double bonds. In turn, the released peroxides are believed to induce the formation of echinocytes or crenated blood cells. The crenated red blood cells are distorted in shape and less flexible and malleable than normal red blood cells, making them less able to penetrate into the pores of the porous membrane of the lateral flow device. Consequently, the stiffer, less flexible cells cannot move easily into the porous and become trapped at the surface of the membrane, while the liquid components of the sample flow and penetrate through the membrane to the detection zone for analysis.

Claims

1. A lateral flow device for detecting the presence of an analyte in a whole blood sample, the device comprising:

a barrier zone for separating red blood cells from the whole blood sample, wherein the barrier zone is formed from a blood cell barrier composition that comprises an unsaturated aliphatic acid or ester thereof having a carbon chain of at least C₈ and more than one carbon-carbon double bond; and

a detection zone for detecting the analyte, the detection zone being located downstream from the barrier zone and in fluid communication therewith.

2. The lateral flow device of claim 1, wherein the unsaturated aliphatic acid or ester thereof has a carbon chain of at least C₁₅ and at least two carbon-carbon double bonds.

3. The lateral flow device of claim 1, wherein the blood cell barrier composition includes an omega-3 fatty acid, omega-6 fatty acid, an ester of an omega-3 fatty acid, an ester of an omega-6 fatty acid, or a mixture thereof.

4. The lateral flow device of claim 1, wherein the blood cell barrier composition includes linoleic acid, α

-linolenic acid, eicosadienoic acid, eicosatrienoic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, an ester thereof, or a mixture thereof.

5. The lateral flow device of claim 1, wherein the blood cell barrier composition includes linoleic acid or an ester thereof.

6. The lateral flow device of claim 1, further comprising a first porous membrane on which the detection zone is defined.

7. The lateral flow device of claim 6, wherein the barrier zone is also defined on the first porous membrane.

8. The lateral flow device of claim 6, further comprising a second porous membrane on which the barrier zone is defined, the second porous membrane being disposed adjacent to the first porous membrane.

9. The lateral flow device of claim 1, further comprising detection probes that are capable of generating a detection signal within the detection zone.

10. The lateral flow device of claim 9, wherein a receptive material is immobilized within the detection zone that is capable of binding to the detection probes or conjugates thereof.

11. The lateral flow device of claim 10, wherein the detection probes are conjugated with a specific binding member that preferentially binds to the analyte.

12. A method for detecting the presence of an analyte in a whole blood sample, the method comprising:

providing a lateral flow device that comprises a barrier zone and a detection zone in fluid communication therewith, wherein the barrier zone is formed from a blood cell barrier composition that comprises an unsaturated aliphatic acid or ester thereof having a carbon chain of at least C₈ and more than one carbon-carbon double bond;

contacting the barrier zone with the whole blood sample so that blood plasma, is separated from the sample and flows to the detection zone; and

detecting the presence of the analyte within the blood plasma at the detection zone.

13. The method of claim 12, wherein the volume of the whole blood sample is less than about 10 microliters.

14. The method of claim 12, wherein the unsaturated aliphatic acid or ester thereof has a carbon chain of at least C₁₅ and at least two carbon-carbon double bonds.

15. The method of claim 12, wherein the blood cell barrier composition includes an omega-3 fatty acid, omega-6 fatty acid, an ester of an omega-3 fatty acid, an ester of an omega-6 fatty acid, or a mixture thereof.

16. The method of claim 12, wherein the blood cell barrier composition includes linoleic acid, α

-linolenic acid, eicosadienoic acid, eicosatrienoic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, an ester thereof, or a mixture thereof.

17. The method of claim 12, wherein the blood cell barrier composition includes linoleic acid or an ester thereof.

18. The method of claim 12, wherein the lateral flow device comprises a first porous membrane on which the detection zone is defined.

19. The method of claim 18, wherein the barrier zone is also defined on the first porous membrane.

20. The method of claim 18, further comprising a second porous membrane on which the barrier zone is defined, the second porous membrane being disposed adjacent to the first porous membrane.

21. The method of claim 12, wherein the lateral flow device further comprises detection probes that are capable of generating a detection signal within the detection zone.

22. The method of claim 21, wherein a receptive material is immobilized within the detection zone that is capable of binding to the detection probes or conjugates thereof.

23. The method of claim 21, wherein the detection probes are conjugated with a specific binding member that preferentially binds to the analyte.

24. The method of claim 12, further comprising supplying a diluent to the lateral flow device to facilitate flow of the blood plasma to the detection zone.