A dry reagent delivery system with membrane having porosity gradient

• US 4,774,192 A
• Filed: 01/28/1987
• Issued: 09/27/1988
• Est. Priority Date: 01/28/1987
• Status: Expired due to Term

• Current Assignee: Home Diagnostics Incorporated, Jack L. Aronowitz
• Original Assignee: Technimed Corporation
• Inventors: Aronowitz, Jack L., Terminiello, Louis
• Primary Examiner(s): NOT, DEFINED
• Application Number:
  US07/007,983
• Time in Patent Office: 608 Days
• Field of Search: 422/56, 435/4, 435/7, 435/11, 435/12, 435/14, 435/805, 435/810, 435/22, 435/25, 436/810, 436/518, 436/531, 436/530, 436/808, 436/817, 436/901
• US Class Current: 436/530
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2300/0887 Laminated structure
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 3/5023 with a sample being transported to, and subsequently stored in an absorbent for analysis
• CPC Class Codes: G01N 33/526 the element being adapted for a specific analyte
• CPC Class Codes: Y10S 435/805 Test papers
• CPC Class Codes: Y10S 435/81 Packaged device or kit
• CPC Class Codes: Y10S 436/808 Automated or kit
• CPC Class Codes: Y10S 436/81 Tube, bottle, or dipstick
• CPC Class Codes: Y10S 436/817 Steroids or hormones
• CPC Class Codes: Y10S 436/901 Drugs of abuse, e.g. narcotics, amphetamine

Abstract

Dry chemistry reagent system, kit and method for detection of an analyte such as glucose, cholesterol, urea, antigen or antibody. The reagent system is a porous membrane or bibulous film having a porosity gradient from one planar surface to the other. In the membrane are uniformly distributed an indicator, a flow control agent and a reagent cocktail. The membrane is also modified by a conditioning agent.

Claims

1. A method for the preparation of a dry chemistry reagent system for analysis of heterogenous fluid samples, said method comprising:

(a) providing a porous membrane having an essentially uniform composition, said porous membrane being characterized as having two planar surfaces and a porosity gradient from one planar surface to the other, the inherent porosity on at least one of said planar surfaces being essentially exclusive of particulate matter on the order of magnitude of cells present in biological fluid samples;

(b) sequentially imbibing into said porous membrane (i) an indicator and (ii) a reagent cocktail specific for reaction with an analyte believed to be present in the fluid sample; and

(c) contacting said porous membrane with an absorption effective amount of conditioning agent, said conditioning agent enhancing the absorption characteristics of the porous membrane to fluid samples, said contact of said porous membrane with a conditioning agent occurring either independent of and prior to time to contact of said porous membrane with an indicator or subsequent to contact of said porous membrane with said indicator.

2. The method of claim 1, wherein the porous membrane is conditioned with an absorption effective amount of a conditioning agent selected from the group consisting of albumin, polyvinyl pyrolidone, polyethylene glycol, carbohydrates, carboxymethyl cellulose (water soluble), methyl cellulose, glycerine and polyoxyethylene ethers.

3. The method of claim 1, wherein the porous membrane is cast from a material selected from the group consisting of a cellulose acetate-cellulose nitrate ester, nylon and polysulfone.

4. The method of claim 1, wherein the reagent cocktail is specific for glucose.

5. The method of claim 1, wherein the reagent cocktail is specific for cholesterol.

6. The method of claim 1, wherein the reagent cocktail is specific for urea.

7. The method of claim 1, wherein the reagent cocktail is specific for detection of an antigen or an antibody.

8. The method of claim 7, wherein the reagent cocktail contains an angiten or antibody which is conjugated to a mimic of an analyte.

9. The method of claim 7, wherein the reagent cocktail is specific for detection of hormones, pharmaceutical compounds, drugs of abuse or proteinaceous materials which are capable of evoking an immune response.

10. The method of claim 7, wherein a portion of the reagent cocktail is deposited upon one of the planar surfaces of the porous membrane so as to be retained thereon without substantial penetration into the matrix of the porous membrane.

11. A dry chemistry reagent system for detection of an analyte in a heterogenous fluid sample, said system comprising:

a porous membrane of essentially uniform composition and a porosity gradient from one planar surface thereof to the other, wherein said porous membrane'"'"'s inherent fluid absorption and distribution characteristics have been modified by imbibing a conditioning agent, an indicator, flow control agent and reagent cocktail into its matrix, the effect of such absorption being to effect an essentially uniform distribution of indicator, flow control agent and reagent cocktail within the porous membrane thereby enhancing the uniformity of internal structure of said film so as to enhance the uniformity of absorption and modulate the rate of absorption of the fluid sample and its interaction with the reagent cocktail.

12. The system of claim 11, wherein the porous membrane is conditioned with an absorption effective amount of a conditioning agent selected from the group consisting of albumin, polyvinyl pyrolidone, polyethylene glycol, carbohydrates, carboxymethyl cellulose, methyl cellulose, glycerine and polyoxyethylene ethers.

13. The system of claim 11, wherein the porous membrane is cast from a material selected from the group consisting of a cellulose acetatecellulose nitrate ester, nylon and polysulfone.

14. The system of claim 11, wherein the reagent cocktail is specific for detection of glucose.

15. The system of claim 11, wherein the reagent cocktail is specific for detection of cholesterol.

16. The system of claim 11, wherein the reagent cocktail is specific for detection of urea.

17. The system of claim 11, wherein the reagent cocktail is specific for detection of an antigen or an antibody.

18. The system of claim 17, wherein the reagent cocktail contains an antigen or antibody which is conjugated to a mimic of an analyte.

19. The system of claim 17, wherein the reagent cocktail is specific for detection of hormones, pharmaceutical compounds, drugs of abuse or proteinaceous materials which are capable of evoking an immune response.

20. The system of claim 17, wherein a portion of the reagent cocktail is deposited upon one of the planar surfaces of the porous membrane so as to be retained thereon without substantial penetration into the matrix of the porous membrane.

21. A rapid analytical method for screening a heterogenous fluid sample for an analyte of interest, comprising:

(a) providing a dry chemistry reagent system comprising a porous membrane of essentially uniform composition and a porosity gradient from one planar surface thereof to the other, wherein said porouse membrane'"'"'s inherent fluid absorption characteristics have been modified by sequentially imbibing a conditioning agent, an indicator, flow control agent and reagent cocktail into its matrix, the effect of such absorption being to effect an essentially uniform distribution of indicator, flow control agent and reagent cocktail within the porous membrane thereby enhancing the uniformity of internal structure of said porous membrane so as to modulate both the rate and the uniformity of absorption of the fluid sample and its interaction with the reagent cocktail;

(b) applying a heterogenous fluid sample to the sample receptive surface of the bibulous medium of the reagent system; and

(c) monitoring the surface of the bibulous medium opposite to the sample receptive surface for a change of color or fluorescence or for the development of color or fluorescence.

22. The analytical method of claim 21, wherein the porous membrane is conditioned with an absorption effective amount of a conditioning agent selected from the group consisting of albumin, polyvinyl pyrolidone, polyethylene glycol, carbohydrates, carboxymethyl cellulose, methyl cellulose, glycerine and polyoxyethylene ethers.

23. The analytical method of claim 21, wherein the porous membrane is cast from a material selected from the group consisting of a cellulose acetate-cellulose nitrate ester, nylon and polysulfone.

24. The analytical method of claim 21, wherein the reagent cocktail is specific for detection of glucose.

25. The analytical method of claim 21, wherein the reagent cocktail is specific for detection of cholesterol.

26. The analytical method of claim 21, wherein the reagent cocktail is specific for detection of urea.

27. The analytical method of claim 21, wherein the reagent cocktail is specific for detection of an antigen or an antibody.

28. The analytical method of claim 27, wherein the reagent cocktail contains an antigen or antibody which is conjugated to a mimic of an analyte.

29. The analytical method of claim 27, wherein the reagent cocktail is specific for detection of hormones, pharmaceutical compounds, drugs of abuse or proteinaceous materials which are capable of evoking an immune response.

30. The analytical method of claim 27, wherein a portion of the reagent cocktail is deposited upon one of the planar surfaces of the porous membrane so as to be retained thereon without substantial penetration into the matrix of the porous membrane.

31. A test kit for analysis of a heterogenous fluid sample, said kit comprising:

(a) dry chemistry reagent system comprising a porous membrane of essentially uniform composition and a porosity gradient from one planar surface thereof to the other, wherein said porous membrane inherent fluid absorption and distribution characteristics have been modified by sequentially imbibing a conditioning agent, an indicator and reagent cocktail into its matrix, the effect of such absorption being to effect an essentially uniform distribution of indicator, flow control agent and reagent cocktail within the porous membrane thereby enhancing the uniformity of internal structure of said film so as to modulate both the rate and uniformity of absorption of the fluid sample and its interaction with the reagent cocktail; and

(b) a standard for comparison with the indicator of the dry chemistry reagent system.

32. The test kit of claim 31, wherein the porous membrane is conditioned with an absorption effective amount of a conditioning agent selected from the group consisting of albumin, polyvinyl pyrolidone, polyethylene glycol, carbohydrates, carboxymethyl cellulose, methyl cellulose, glycerine and polyoxyethylene ethers.

33. The test kit of claim 31, wherein the porous membrane is cast from a material selected form the group consisting of a cellulose acetatecellulose nitrate ester, nylon and polysulfone.

34. The test kit of claim 31, wherein the reagent cocktail is specific for detection of glucose.

35. The test kit of claim 31, wherein the reagent cocktail is specific for detection of cholesterol.

36. The test kit of claim 31, wherein the reagent cocktail is specific for detection of urea.

37. The test kit of claim 31, wherein the reagent cocktail is specific for detection of an antigen or an antibody.

38. The test kit of claim 37, wherein the reagent cocktail contains an antigen or antibody which is conjugated to a mimic of an analyte.

39. The test kit of claim 37, wherein the reagent cocktail is specific for detection of hormones, pharmaceutical compounds, drugs of abuse or proteinaceous materials which are capable of evoking an immune response.

40. The test kit of claim 37, wherein a portion of the reagent cocktail is deposited upon one of the planar surfaces of the porous membrane so as to be retained thereon without substantial penetration into the matrix of the bibulous film.