Integral analytical element

• US 3,992,158 A
• Filed: 01/02/1975
• Issued: 11/16/1976
• Est. Priority Date: 08/16/1973
• Status: Expired due to Term

• Current Assignee: Eastman Kodak Company
• Original Assignee: Eastman Kodak Company
• Inventors: Przybylowicz, Edwin P., Millikan, Allan G.
• Primary Examiner(s): Reese, Robert M.
• Application Number:
  US05/538,072
• Time in Patent Office: 684 Days
• Field of Search: 23/253 TP, 195/103.5, 426/87, 426/88, 116/114 AM, 116/114 P
• US Class Current: 422/428
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: C12Q 1/60 involving cholesterol
• CPC Class Codes: G01N 2035/00099 Characterised by type of test elements
• CPC Class Codes: G01N 33/525 Multi-layer analytical elements
• CPC Class Codes: G01N 35/00029 provided with flat sample substrates, e.g. slides G01N35/028 takes precedence
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus

Abstract

An integral analytical element capable of use in the analysis of liquids, the element having at least two superposed layers including a spreading layer and a reagent layer, in fluid contact. Optionally, the element can be carried on a support material. The spreading layer, which can be an isotropically porous layer, spreads within itself at least a component of a liquid sample applied to the element, or a reaction product of such component, to obtain a uniform concentration of at least one such spread substance at the surface of the spreading layer which faces the reagent layer. The reagent layer, which is desirably uniformly permeable to at least one dissolved or dispersed component of the liquid sample or a reaction product of such a component, can include a matrix in which is distributed a material that can interact with, for example, an analyte or analyte reaction product to produce a detectable change in the element, such as one detectable by measurement of electromagnetic radiation. In a preferred embodiment, the interactive material can chemically react with an analyte or analyte reaction product to produce a color change in the element. In another preferred embodiment, the sample spreading layer can filter out chemically interfering or other undesirable materials and obtain selective spreading of sample components and/or it can provide a reflective background, often useful in obtaining analytical results.

Claims

1. An integral element for analysis of liquids, said element comprising, in fluid contact, an isotropically porous spreading layer comprising a non-fibrous material, and a reagent layer permeable to a substance spreadable within the spreading layer or a reaction product of such a substance.

2. An integral element as described in claim 1 and further comprising a plurality of isotropically porous spreading layers.

3. An integral element as described in claim 1, wherein the isotropically porous layer is an outer layer of said element.

4. An integral element as described in claim 1 and further comprising a plurality of reagent layers.

5. An integral element as described in claim 1, wherein the isotropically porous layer is resistant to liquid under analysis.

6. An integral element as described in claim 5 wherein the reagent layer is of lower permeability to the spreadable substance than is the spreading layer.

7. An integral element for analysis of liquids, said element comprising a support having thereon, in fluid contact, an isotropically porous spreading layer comprising a non-fibrous material, and a reagent layer permeable to a substance spreadable within the spreading layer or a reaction product of such a substance, the reagent layer being interposed in the element between the support and the isotropically porous layer.

8. An integral element as described in claim 7 wherein the support transmits electromagnetic radiation of a wavelength within the region between about 200 nm and about 900 nm.

9. An integral element as described in claim 8 and further comprising a reflective layer in fluid contact with and interposed between the spreading layer and the reagent layer.

10. An integral element as described in claim 8 wherein the support is substantially transparent to electromagnetic radiation of a wavelength within the region between about 200 nm and about 900 nm.

11. An integral element as described in claim 10 wherein the reagent layer is of lower permeability to the spreadable substance than is the spreading layer.

12. An integral element for analysis of liquids, said element comprising a support having thereon, in fluid contact, a water-resistant, isotropically porous spreading layer comprising a non-fibrous material, and a reagent layer permeable to substance that is dissolved or dispersed in an aqueous liquid and is spreadable within the spreading layer, said substance comprising a component of the liquid or a reaction product of such a component, the reagent layer being interposed in the element between the support and the isotropically porous layer.

13. An integral element as described in claim 12 wherein the isotropically porous layer is the outermost layer.

14. An integral element as described in claim 12 wherein the support transmits electromagnetic radiation of a wavelength within the region between about 200 nm and about 900 nm.

15. An integral element as described in claim 12 wherein the support is substantially transparent to electromagnetic radiation of a wavelength within the region between about 200 nm and about 900 nm.

16. An integral element as described in claim 12 wherein the reagent layer is of substantially uniform permeability to the dissolved or dispersed substance.

17. An integral element as described in claim 12 wherein the reagent layer comprises a matrix having distributed therein a material interactive with an analyte or a precursor of an analyte or a reaction product thereof to effect a detectable change in the element.

18. An integral element as described in claim 17 wherein the isotropically porous layer contains a surfactant.

19. An integral element as described in claim 17 wherein the isotropically porous layer contains a pigment.

20. An integral element as described in claim 17 wherein the material interactive with an analyte or precursor of an analyte or reaction product thereof is one that, upon such interaction, effects a detectable color change in the element.

21. An integral element as described in claim 17 wherein the support, the isotropically porous layer and the reagent layer transmit electromagnetic radiation of a wavelength within the region between about 200 nm and 900 nm.

22. An integral element as described in claim 17 wherein the reagent layer matrix comprises a hydrophilic colloid.

23. An integral element as described in claim 22 wherein the hydrophilic colloid comprises gelatin, poly(vinylalcohol), agarose, poly(vinyl pyrrollidone or polyacrylamide.

24. An integral element for the analysis of liquids, said element comprising a support that transmits electromagnetic radiation of a wavelength in the region between about 200 nm and 900 nm, said support having thereon, in fluid contact, a water-resistant, isotropically porous spreading layer comprising a blush polymer, and a reagent layer interposed between the isotropically porous layer and the support and comprising a hydrophilic colloid having distributed therein a material interactive with an analyte or a precursor of an analyte or a reaction product of an analyte to effect a detectable change in the element.

25. An integral element as described in claim 24 wherein the blush polymer comprises a cellulose ester, a polycarbonate, a polyurethane, or a polyamide.

26. An integral element as described in claim 24 wherein the isotropically porous layer also comprises a pigment.

27. An integral element as described in claim 24 wherein the reagent layer is of lower permeability to the spreadable substance than is the spreading layer.

28. An integral element as described in claim 24 wherein the isotropically porous layer also comprises a surfactant.

29. An integral element as described in claim 28 wherein the isotropically porous layer also comprises a pigment.

30. An integral element for the analysis of liquids, said element comprising a support that transmits electromagnetic radiation of a wavelength within the region between about 200 nm and 900 nm, said support having thereon, in fluid contact, an isotropically porous spreading layer comprising a pigment, and a reagent layer of lower permeability than said spreading layer, the reagent layer being interposed between the isotropically porous layer and the support and comprising a hydrophilic colloid having distributed therein a material interactiv with an analyte or a precursor of an analyte or a reaction product of an analyte to effect a detectable change in the element.

31. An integral element as described in claim 30 wherein the pigment comprises titanium dioxide or barium sulfate.

32. An integral element as described in claim 30 wherein the isotropically porous layer also comprises a surfactant.

33. An integral element for the analysis of liquids, said element comprising a support that is transparent to electromagnetic radiation of a wavelength within the region between about 200 nm and 900 nm, the support having thereon, in fluid contact, (a) a water-resistant, isotropically porous layer comprising a member selected from the group consisting of a blush polymer, a pigment, a microcrystalline colloid, resinous beads, glass beads and diatomaceous earth, and (b) a reagent layer of lower permeability than said spreading layer, the reagent layer interposed between the support and the isotropically porous layer and comprising a hydrophilic colloid selected from the group consisting of gelatin, polyvinyl alcohol, poly(vinylpyrrolidone) and polyacrylamide and having distributed therein a material interactive with an analyte or a precursor of an analyte or a product of an analyte to effect a detectable change in the element.

34. An integral element as described in claim 33 wherein the blush polymer comprises a cellulose ester, a polycarbonate, a polyurethane, or a polyamide.

35. An integral element as described in claim 33 wherein the support comprises a polymer selected from the group consisting of a cellulose ester, a polycarbonate and poly(ethyleneterephthalate).

36. An integral element as described in claim 33 wherein the interactive material is interactive with glucose and comprises glucose oxidase, peroxidase and either O-dianisidine hydrochloride or 1,7-dihydroxynaphthalene together with 4-aminoantipyrene.

37. An integral element as described in claim 33 wherein the interactive material is interactive with uric acid and comprises copper sulfate and neocuproine.

38. An integral element as described in claim 33 comprising a plurality of reagent layers containing material interactive in the presence of serum glutamic-oxalacetic transiminase or a product thereof, wherein a first reagent layer contains interactive material comprising α

-ketoglutarate and aspartate ions and a second reagent layer contains NADH.

39. A method for analysis of liquids comprising

a. applying a liquid sample to an integral element comprising, in fluid contact, an isotropically porous spreading layer comprising a non-fibrous material, and a reagent layer permeable to a substance spreadable within the spreading layer or a reaction product of such a substance, to effect a detectable change in the element in the presence of an analyte and

b. detecting any such change produced in the element.

40. A method as described in claim 39 wherein the sample is applied as a free drop or contact spot.

41. A method as described in claim 39 wherein said change is detected in a region of the element totally within the region of the element in which said change is produced.

42. An integral element for analysis of liquids, said element comprising, in fluid contact, an isotropically porous spreading layer comprising a non-fibrous, isotropically porous material, and a reagent layer permeable to a substance spreadable within the spreading layer or a reaction product of such a substance.

43. An integral element for analysis of liquids, said element comprising a support having thereon, in fluid contact, an isotropically porous spreading layer comprising a non-fibrous, isotropically porous material and a reagent layer permeable to a substance spreadable within the spreading layer or a reaction product of such a substance, the reagent layer being interposed in the element between the support and the isotropically porous layer.

44. An integral element for analysis of liquids, said element comprising a support having thereon, in fluid contact, an isotropically porous spreading layer comprising a non-fibrous material, and a reagent layer of substantially uniform permeability to a substance spreadable within the spreading layer or a reaction product of such a substance, the reagent layer being interposed in the element between the support and the isotropically porous layer.

45. An integral element for analysis of liquids, said element comprising a support having thereon, in fluid contact, a water-resistant, isotropically porous spreading layer comprising a non-fibrous, isotropically porous material, and a reagent layer that is permeable to substance dissolved or dispersed in an aqueous liquid and spreadable within the spreading layer, said substance comprising a component of the liquid or a reaction product of such a component, the reagent layer being interposed in the element between the support and the isotropically porous layer.

46. An integral element for analysis of liquids, said element comprising a support that transmits electromagnetic radiation of a wavelength within the region between about 200 nm and about 900 nm, said support having thereon, in fluid contact, non-fibrous layers comprising an isotropically porous spreading layer, and a reagent layer that is permeable to substance spreadable within the spreading layer or a reaction product of such a substance, the reagent layer being interposed in the element between the support and the isotropically porous layer.

47. An integral element as described in claim 46 wherein the isotropically porous spreading layer is water-resistant and the reagent layer comprises a matrix having distributed therein a material interactive with an analyte or a precursor of an analyte or a reaction product of an analyte to effect a detectable change in the element.

48. An integral element for the analysis of liquids, said element comprising a support that transmits electromagnetic radiation of a wavelength within the region between about 200 nm and about 900 nm, said support having thereon, in fluid contact, an isotropically porous spreading layer comprising a member selected from the group consisting of a blush polymer and particulate matter, and a reagent layer interposed between the isotropically porous layer and the support and comprising a matrix having distributed therein a material interactive with an analyte or a precursor of an analyte or a reaction product of an analyte to effect a detectable change in the element.

49. An integral element as described in claim 48 wherein the particulate matter comprises a member selected from the group consisting of a pigment, a microcrystalline colloid, resinous beads, glass beads and diatomaceous earth.

50. An integral element as described in claim 48 wherein the particulate matter comprises a microcrystalline colloid.

51. An integral element as described in claim 48 wherein the matrix comprises a hydrophilic colloid,

52. An integral element for analysis of liquids, said element comprising a support having thereon, in fluid contact, an isotropically porous spreading layer comprising a non-fibrous material, a reflective layer and a reagent layer, the reflective layer and the reagent layer being permeable to substance spreadable within the spreading layer or a reaction product of such a substance, the reagent layer being interposed between the support and the spreading layer and the reflective layer being interposed between the reagent layer and the spreading layer.

53. A method for analysis of liquids comprising

a. applying a liquid sample to an integral element comprising (i) a support that transmits electromagnetic radiation of a wavelength within the region between about 200 nm and about 900 nm, and in fluid contact on said support, (ii) an isotropically porous spreading layer comprising a member selected from the group consisting of a blush polymer and particulate matter, and (iii) a reagent layer interposed between the isotropically porous layer and the support, to effect a detectable change in the element in the presence of an analyte and

b. detecting any such change produced in the element.

54. A method as described in claim 53 wherein said change is detected in the region of the element totally within the region of the element in which such change is produced.

55. A method as described in claim 53 wherein the sample is applied as a free drop or contact spot.