Liquid permeable composition in dry reagent devices

• US 7,713,474 B2
• Filed: 10/14/2004
• Issued: 05/11/2010
• Est. Priority Date: 01/15/2002
• Status: Active Grant

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Inventors: Hildenbrand, Karlheinz, Lin, Spencer, Pugia, Michael J., Schulman, Lloyd S.
• Primary Examiner(s): Griffin; Walter D
• Assistant Examiner(s): Mui; Christine T
• Application Number:
  US10/966,858
• Publication Number:
  US 20050129572A1
• Time in Patent Office: 2,035 Days
• Field of Search: 422/58, 422/56, 422/57, 422/55, 422/50, 600/347, 427/2.13, 427/2.11, 427/2.1
• US Class Current: 422/421
• CPC Class Codes: G01N 33/525 Multi-layer analytical elements
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding

Abstract

A device for detecting an analyte in a fluid sample includes a liquid permeable composition for making a physical separation between compositions of the sample or for reacting with components. The liquid permeable composition has adhesive properties and can be used to make a multi-layered test strip or the composition can be used in the sample wells of microfluidic devices.

Claims

1. A device for detection of an analyte in a liquid sample comprising:

a liquid permeable layer for transferring portions of said liquid sample,

two adjacent layers in contact with and adhering to said liquid permeable layer, at least one of said adjacent layers containing reagents for detecting said analyte,

said liquid permeable layer comprising a blend of an aqueous polymer dispersion and a water soluble polymer applied as a coating on one of said two adjacent layers and dried at a temperature of about 40°

C. to 90°

C. to form a dried liquid permeable layer having a dried thickness of about 3 to 100 mils (75 to 2540 μ

m),

said dried liquid permeable layer on one of said two adjacent layers having been pressed together with the second of said two adjacent layers with a pressure of about 3 to 100 psi sufficient to cause said two adjacent layers to adhere to said liquid permeable layer, and

the pressed liquid permeable layer and two adjacent layers having been further cured such that the pressed liquid permeable layer adheres to said two adjacent layers while retaining liquid permeability.

2. A device of claim 1 further comprising additives in said liquid permeable layer or said two adjacent layers which chemically react with components in said liquid sample.

3. A device of claim 2 wherein said additives include indicator dyes or particles to provide a detectable response with said analyte.

4. A device of claim 2 wherein said additives include exchange resins to remove buffering components and ascorbate scavengers to remove ascorbate interference.

5. A device of claim 2 wherein said additives include particles and polymers to provide a detectable response or remove interfering components.

6. A device of claim 2 wherein said additives include metals and chelates to provide a detectable response or remove interfering components.

7. A device of claim 2 wherein said additives include enzymes to provide a detectable response or remove interfering components.

8. A device of claim 2 wherein said additives include antibodies or other affinity molecules to provide a detectable response or separate interfering components.

9. A device of claim 2 wherein said additives include fillers to adjust opacity or reflectance.

10. A device of claim 2 wherein said additives include surface active substance to increase fluid flow.

11. A device of claim 1 wherein the liquid permeability of said liquid permeable layer is adjusted by changing the ratio of said aqueous polymer dispersion to said water soluble polymer.

12. A device of claim 11 wherein said aqueous polymer dispersion is a polyurethane dispersion and said water soluble polymer is at least one member of the group consisting of a polyethylene oxide, a polyvinyl pyrrolidone and a polyvinyl alcohol.

13. A device of claim 12 wherein the ratio of said aqueous polymer dispersion to said water soluble polymer is 50:

1 to 1;

1 on a weight basis.

14. A method of analyzing a liquid sample wherein said sample is contacted with dry reagents in at least one layer containing said reagents which react with analytes in said sample to provide a detectable response, said method characterized by including a liquid permeable layer in contact with and adhering to two adjacent layers, said liquid permeable layer comprising a blend of an aqueous polymer dispersion and a water soluble polymer for transferring portions of said liquid sample between said layers, said liquid permeable layer being applied as a liquid coating on one of said two adjacent layers and dried at a temperature of about 40°

C. to 90°

C. to form said liquid permeable layer having a dry thickness of about 3 to 100 mils (75 to 2,540 μ

m), and then pressed together with the other of said two adjacent layers with a pressure of about 3 to 100 psi sufficient to cause said liquid permeable layer to adhere to said adjacent layers and then further dried in place between said two adjacent layers such that the liquid permeable layer adheres to both of said two adjacent layers while retaining liquid permeability.

15. A method of claim 14 wherein said liquid permeable layer concentrates said liquid sample by passing said sample through said liquid permeable layer.

16. A method of claim 14 wherein said liquid permeable layer or said two adjacent layers include additives which chemically react with components in said liquid sample.

17. A method of claim 16 wherein said additives include indicator dyes or particles to provide a detectable response with said analyte.

18. A method of claim 16 wherein said additives include exchange resins to remove buffering components and ascorbate scavengers to remove ascorbate interference.

19. A method of claim 16 wherein said additives include particles and polymers to provide a detectable response or remove interfering components.

20. A method of claim 16 wherein said additives include metals and chelates to provide a detectable response or remove interfering components.

21. A method of claim 16 wherein said additives include enzymes to provide a detectable response or remove interfering components.

22. A method of claim 16 wherein said additives include antibodies or other affinity molecules to provide a detectable response or separate interfering components.

23. A method of claim 16 wherein said additives include fillers to adjust opacity or reflectance.

24. A method of claim 16 wherein said additives include surface active substance to increase fluid flow.

25. A method of claim 14 wherein the liquid permeability of said liquid permeable layer is adjusted by changing the ratio of said aqueous polymer dispersion to said water soluble polymer.

26. A method of claim 25 wherein said aqueous polymer dispersion is a polyurethane dispersion and said water soluble polymer is at least one member of the group consisting of a polyethylene oxide, a polyvinyl pyrrolidone and a polyvinyl alcohol.

27. A method of claim 26 wherein the ratio of said aqueous polymer dispersion to said water soluble polymer is 50:

1 to 1;

1 on a weight basis.

28. A multi-layer device for detection of an analyte in a fluid sample comprising:

(a) a first layer for receiving said fluid sample;

(b) a second layer for receiving at least a portion of said sample from said first layer; and

(c) a liquid permeable adhesive layer disposed in contact with and adhering to said first and second layers, said liquid permeable adhesive layer being diffusible to fluids and comprising a blend of an aqueous polymer dispersion and a water soluble polymer which has been cast as a liquid coating on one of said first and second layers and dried at a temperature of about 40°

C. to 90°

C. to form said liquid permeable layer having a dry thickness of about 3 to 100 mils (75 to 2,540 μ

m), then pressed together with the other of said two adjacent layers and dried in place between said first and second layers with a pressure of about 3 to 100 psi sufficient to cause said first and second layers to adhere to said liquid permeable layer and at temperatures such that said adhesive layer adheres to said first and second layers while retaining liquid permeability, at least one of said combined layers of (a), (b), (c) containing reagents and being capable of detecting said analyte.

29. A device of claim 28 wherein said first layer is an absorbent layer which absorbs and spreads said fluid sample over said device.

30. A device of claim 28 wherein said first layer is an absorbent layer which comprises a reagent for reaction with an analyte in said sample.

31. A device of claim 28 wherein said first layer is an absorbent layer which comprises a reagent for reaction with interfering components of said sample.

32. A device of claim 28 wherein said second layer is an absorbent layer which absorbs and retains a component from said sample.

33. A device of claim 28 wherein said second layer is an absorbent layer which comprises a reagent for reacting with an analyte in said sample.

34. A device of claim 31 wherein said component from said sample is the product of a reaction of an analyte in said first absorbent layer.

35. A device of claim 28 wherein said liquid permeable adhesive layer is capable of making a physical separation of said fluid sample.

36. A device of claim 28 wherein said liquid permeable adhesive layer is capable of reacting with components of said sample and thereby trapping them in said liquid permeable adhesive layer.

37. A device of claim 28 wherein said liquid permeable adhesive layer contains additives capable of reacting with components of said sample and thereby preventing their passage through said liquid permeable adhesive layer.

38. A device of claim 28 wherein said liquid permeable adhesive layer is an anionic polyurethane dispersion in combination with a water soluble polymer.

39. A device of claim 28 wherein said liquid permeable adhesive layer is an anionic polyurethane dispersion in combination with a cationic acrylic dispersion as the water soluble polymer.

40. A device of claim 28 wherein said liquid permeable adhesive layer is a cationic polyurethane dispersion in combination with a water soluble polymer.

41. A device of claims 38 or 40 wherein said water soluble polymer is at least one member of the group consisting of a polyethylene oxide, a polyvinylpyrrolidone and a polyvinylalcohol.

42. A device of claim 29 wherein said first absorbent layer is a filter paper.

43. A device of claim 30 wherein said reagent for reaction with an analyte in said first absorbent layer is a member of the group consisting of oxidases, reductases, and proteases used in clinical assays, and antibodies, nucleic acids, antigens, and proteins used in binding assays.

44. A device of claim 31 wherein said reagent for reaction with an interfering component of said sample is a member of the group consisting of enzymes to metabolize the interferent, reactants to convert the interferent to non-reactive form, and binding agents to trap the interferent.

45. A device of claim 32 wherein said second absorbent layer is a filter paper.

46. A device of claim 33 wherein said reagent for reacting with an analyte in said second absorbent layer is a member of the group consisting of indicators producing signals in response to the analyte and enzymes or reactants for signal amplification.

47. A device of claim 34 wherein said product of the reaction of an analyte in said first absorbent layer is detected by a member of the group consisting of enzymes used in clinical assays and affinity binders used in binding assays and reactions in which a moiety of the analyte is detached.

48. A device of claim 37 wherein additives to said liquid permeable adhesive layer capable of reacting with components of said sample are members of the group consisting of affinity binders or enzymes for removing interferents or generating signals.

49. The device of claim 28 further comprising additional absorbent layers disposed between said first and second layers, each of said additional absorbent layers being separated from the closest neighbor layer by an additional liquid permeable adhesive layer, said liquid permeable adhesive layer being diffusible to said fluid sample and comprising a blend of an aqueous polymer dispersion and a water soluble polymer which has been cast, pressed, and dried to form said adhesive layer while retaining permeability.

50. A method of detecting an analyte in a fluid sample comprising applying said fluid sample to a multi-layer device of claim 28 and measuring the amount of analyte present in said sample.