Element, structure and method for the analysis or transport of liquids

• US 4,258,001 A
• Filed: 12/27/1978
• Issued: 03/24/1981
• Est. Priority Date: 12/27/1978
• Status: Expired due to Term

• Current Assignee: Clinical Diagnostic Systems Inc.
• Original Assignee: Eastman Kodak Company
• Inventors: Pierce, Zona R., Frank, David S.
• Primary Examiner(s): Marcus, Michael
• Application Number:
  US05/973,669
• Time in Patent Office: 818 Days
• Field of Search: 422/55-59, 435/805, 428/327, 428/407, 428/442, 428/339, 23/230 B
• US Class Current: 422/400
• CPC Class Codes: G01N 31/22 using chemical indicators G01N31/02 takes precedence
• CPC Class Codes: G01N 33/525 Multi-layer analytical elements
• CPC Class Codes: G01N 33/54386 Analytical elements
• CPC Class Codes: G01N 33/54391 based on vertical flow
• CPC Class Codes: G01N 33/549 with antigen or antibody entrapped within the carrier
• CPC Class Codes: Y10S 435/805 Test papers
• CPC Class Codes: Y10T 428/254 Polymeric or resinous material
• CPC Class Codes: Y10T 428/269 including synthetic resin or polymer layer or component
• CPC Class Codes: Y10T 428/2998 including synthetic resin or polymer

Abstract

An element for the analysis or transport of liquid, especially aqueous liquids, contains a structure comprising a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to the liquid, and an adhesive concentrated at particle surface areas contiguous to adjacent particles bonding the particles into a coherent, three-dimensional lattice that is non-swellable in the liquid. A substantial portion of the particle surface area in this lattice structure is therefore effectively free from adhesive. The lattice structure has interconnected void spaces among the particles representing a total void volume of about 25 to 80 percent to provide for transport of the liquid. The adhesive comprises an organic polymer different from that of the particles and insoluble in the liquid under analysis. The amount of adhesive in the structure is less than 10 weight percent of the particles.

The particulate structure of these elements can contain interactive compositions useful for the analysis of various substances in liquids, especially high molecular weight proteinaceous substances in aqueous biological liquids. Multi-zone elements containing, in fluid contact, at least two zones having a particulate structure as described above or one such zone together with other functional zones are also disclosed.

Claims

1. A particulate structure for the analysis or transport of a liquid comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent.

2. A particulate structure as defined in claim 1 wherein said organic polymer of said adhesive has a glass transition temperature less than that of said particles.

3. A particulate structure for the analysis of a liquid as defined in claim 1 wherein said particulate structure contains one or more components of an interactive composition for said analysis.

4. A particulate structure for the analysis of a liquid as defined in claim 1 wherein said particulate structure contains an immunoreagent.

5. A particulate structure for the analysis of a liquid as defined in claim 1 wherein the organo-polymeric composition of said particles comprises an organic polymer containing a repeating unit having a chemical group representing an active bonding site for chemical attachment to an interactive composition for said analysis.

6. A particulate structure as defined in claim 1 wherein said particles are solid particles of substantially uniform size.

7. A particulate structure as defined in claim 1 wherein said particles are solid spherical beads having a substantially uniform size within the range of from about 2 to 100 microns.

8. A particulate structure as defined in claim 1 wherein the organic polymer of said particles and said adhesive comprise an addition copolymer of two or more different addition polymerizable monomers, at least one of said addition polymerizable monomers of said particles being common to at least one of said addition polymerizable monomers of said adhesive.

9. A particulate structure as defined in claim 1 wherein said particles contain a colorant.

10. A particulate structure for the analysis or transport of a liquid comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount of from about 1 to less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent;

said particles comprising an addition polymer of an addition polymerizable blend of monomers, the total monomer content of said blend comprising at least one of the following monomers, each of said monomers when present being in the proportions indicated;

(a) up to 100 weight percent of a polymerizable, amino-substituent-free styrene monomer;

(b) up to about 25 weight percent of a polymerizable acrylic ester;

(c) up to 100 weight percent of a polymerizable methacrylic ester;

(d) up to about 30 weight percent of a carboxylic acid containing one or more polymerizable ethylenically unsaturated groups;

(e) up to about 75 weight percent of a nitrile containing one or more polymerizable ethylenically unsaturated groups;

(f) up to about 20 weight percent of a polymerizable amine-substituted styrene monomer;

(g) up to about 20 weight percent of an addition polymerizable monomer containing a crosslinkable group;

(h) up to about 20 weight percent of a polymerizable tertiary aminoalkyl acrylate or methacrylate;

(i) up to 100 weight percent of a polymerizable, N-heterocyclic vinyl monomer;

(j) up to about 20 weight percent of a polymerizable acrylamide or methacrylamide monomer; and

(k) up to about 20 weight percent of a cross-linking monomer containing at least two addition polymerizable groups.

11. An element for the analysis or transport of a liquid, said element comprising a radiation-transmissive support bearing a particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent.

12. A multi-zone element for the analysis or transport of a liquid, said element comprising, in fluid contact, a zone having a particulate structure and at least one other zone permeable to said liquid, said particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent.

13. A multi-zone element for the analysis of a liquid as defined in claim 12 wherein one or more components of an interactive composition for said analysis is located in at least one of said zones.

14. A multi-zone element for the analysis of a liquid as defined in claim 12 wherein at least one of said zones contains an immunoreagent.

15. A multi-zone element as defined in claim 12 wherein the organic polymer of the adhesive in said particulate structure has a glass transition temperature less than that of said particles.

16. A multi-zone element as defined in claim 12 wherein the particles of said particulate structure are solid spherical beads having a substantially uniform size within the range of from about 2 to 100 microns.

17. A multi-zone element for the analysis or transport of a liqud, said element comprising two or more zones in fluid contact, at least two of said zones having a particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent.

18. A multi-zone element for the analysis of a liquid, said element comprising, in fluid contact, a zone having a particulate structure and a reagent zone containing one or more components of an interactive composition for said analysis, said particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent.

19. A particulate structure for the analysis or transport of a liquid comprising:

(a) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to water, said particles having a particle size of from about 1 to 200 microns, and

(b) an adhesive, in an amount less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in water;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in water and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent.

20. A particulate structure for the analysis or transport of a liquid as defined in claim 19 wherein said organic polymer of said adhesive has a glass transition temperature less than that of said particles.

21. A particulate structure for the analysis of a liquid as defined in claim 19 wherein said particulate structure contains one or more components of an interactive composition for said analysis.

22. A particulate structure for the analysis of a liquid as defined in claim 19 wherein said particulate structure contains an immunoreagent.

23. A particulate structure as defined in claim 19 wherein said particles are solid particles of substantially uniform size.

24. A particulate structure as defined in claim 19 wherein the organic polymer of said particles and said adhesive comprise an addition copolymer of two or more different addition polymerizable monomers, at least one of said addition polymerizable monomers of said particles being common to at least one of said addition polymerizable monomers of said adhesive.

25. A particulate structure as defined in claim 19 wherein said particles contain a colorant.

26. An element for the analysis or transport of a liquid, said element comprising a radiation-transmissive support bearing a particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to water, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in water;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in water and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent.

27. A multi-zone element for the analysis or transport of a liquid, said element comprising, in fluid contact, a zone having a particulate structure and at least one other zone permeable to said liquid, said particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to water, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in water;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in water and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent.

28. A multi-zone element for the analysis of a liquid as defined in claim 27 wherein one or more components of an interactive composition for said analysis is located in at least one of said zones.

29. A multi-zone element for the analysis of a liquid as defined in claim 27 wherein at least one of said zones contains an immunoreagent.

30. A multi-zone element as defined in claim 27 wherein the particles of said particulate structure are solid spherical beads having a substantially uniform size within the range of from about 2 to 100 microns.

31. A multi-zone element for the analysis of a liquid, said element comprising, in fluid contact, a zone having a particulate structure and a reagent zone containing one or more components of an interactive composition for said analysis, said particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to water, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in water;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in water and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent;

said particles comprising an addition polymer of an addition polymerizable blend of monomers, the total monomer content of said blend comprising at least one of the following monomers, each of said monomers when present being in the proportions indicated;

(a) up to 100 weight percent of a polymerizable, amino-substituent-free styrene monomer;

(b) up to about 25 weight percent of a polymerizable acrylic ester;

(c) up to 100 weight percent of a polymerizable methacrylic ester;

(d) up to about 30 weight percent of a carboxylic acid containing one or more polymerizable ethylenically unsaturated groups;

(e) up to about 75 weight percent of a nitrile containing one or more polymerizable ethylenically unsaturated groups;

(f) up to about 20 weight percent of a polymerizable amine-substituted styrene monomer;

(g) up to about 20 weight percent of an addition polymerizable monomer containing a crosslinkable group;

(h) up to about 20 weight percent of a polymerizable tertiary aminoalkyl acrylate or methacrylate;

(i) up to 100 weight percent of a polymerizable, N-heterocyclic vinyl monomer;

(j) up to about 20 weight percent of a polymerizable acrylamide or methacrylamide monomer; and

(k) up to about 20 weight percent of a cross-linking monomer containing at least two addition polymerizable groups.

32. An element for the analysis or transport of an aqueous liquid, said element comprising a support bearing a particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount of from about 1 to less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent;

said particles comprising an addition polymer of an addition polymerizable blend of monomers, the total monomer content of said blend comprising at least one of the following monomers, each of said monomers when present being in the proportions indicated;

(a) up to 100 weight percent of a polymerizable, amino-substituent-free styrene monomer;

(b) up to about 25 weight percent of a polymerizable acrylic ester;

(c) up to 100 weight percent of a polymerizable methacrylic ester;

(d) up to about 30 weight percent of a carboxylic acid containing one or more polymerizable ethylenically unsaturated groups;

(e) up to about 75 weight percent of a nitrile containing one or more polymerizable ethylenically unsaturated groups;

(f) up to about 20 weight percent of a polymerizable amine-substituted styrene monomer;

(g) up to about 20 weight percent of an addition polymerizable monomer containing a crosslinkable group;

(h) up to about 20 weight percent of a polymerizable tertiary aminoalkyl acrylate or methacrylate;

(i) up to 100 weight percent of a polymerizable, N-heterocyclic vinyl monomer;

(j) up to about 20 weight percent of a polymerizable acrylamide or methacrylamide monomer; and

(k) up to about 20 weight percent of a cross-linking monomer containing at least two addition polymerizable groups.

33. An element as defined in claim 32 wherein the organo-polymer of the particles in said particulate structure is selected from the group consisting of:

1. Polystyrene

2. Poly(styrene-co-methacrylic acid)

3. Poly(vinyltoluene-co-p-t-butylstyrene-co-methacrylic acid)

34. Poly(vinyltoluene-co-p-t-butylstyrene-co-methacrylic acid-co-divinylbenzene)Poly(methyl methacrylate)Poly(styrene-co-vinylbenzyl chloride-methacrylic acid)Poly(styrene-co-N,N,N-trimethyl-N-vinylbenzylammonium chloride-co-methacrylic acid)Poly(styrene-co-divinylbenzene)Poly(styrene-co-butyl acrylate-co-methacrylic acid)Poly(styrene-co-methacrylic acid-co-divinylbenzene)Poly(vinylbenzyl chloride-co-methacrylic acid-co-divinylbenzene)Poly(styrene-co-2-hydroxyethyl methacrylate-co-methacrylic acid)Poly(methyl methacrylate-co-butyl acrylate)Poly(styrene-co-acrylonitrile)Poly(methyl methacrylate-co-N-(m- and p-vinylbenzyl)-N,N-dimethylamine hydrochloride-co-ethylene dimethacrylate)Poly(methyl methacrylate-co-2-(N,N-diethylaminoethyl methacrylate hydrochloride-co-ethylene dimethacrylate).

37. An element as defined in claim 34, the adhesive contained in said particulate structure of said element comprising an addition copolymer of two or more different addition polymerizable monomers, at least one of the addition polymerizable monomers of the adhesive being common to one of the monomers of the addition copolymer of said particles.

38. An element as defined in claim 34, the adhesive in said particulate structure of said element being present in an amount of from about 1 to 4 percent by weight based on the weight of said particles.

39. An element as defined in claim 34 wherein the adhesive in said particulate structure has a glass transition temperature less than that of said particles.

40. An element for the analysis for an aqueous liquid as defined in claim 34 wherein said element contains one or more components of an interactive composition for said analysis.

41. An element for the analysis of an aqueous liquid as defined in claim 34 wherein said element contains an immunoreagent.

42. An element as defined in claim 34 wherein the particles in said particulate structure are solid spherical beads having a substantially uniform size within the range of from about 2 to 100 microns.

43. An element as defined in claim 34, the adhesive in said particulate structure of said element comprising an addition copolymer of an addition polymerizable blend of monomers selected from the following group:

A. a monomer blend containing from about 1 to 35 weight percent of one or more of said group (a) monomers with the remainder of the blend comprising addition polymerizable alkyl acrylates or methacrylates;

B. a monomer blend containing from about 20 to 95 weight percent of monomers selected from group (a), (b), (c), (g1), (g2), and (k) with the remainder of the monomer blend comprising one or more addition polymerizable monomers having an active hydrogen or salts thereof; and

C. a monomer blend comprising from about 15 to 100 weight percent of one or more monomers selected from the group consisting of 1-vinylimidazole, vinylbenzyl alcohol, ethyl acrylate, or a monomer from group (j) with the remaining monomers of the blend comprising monomers from group (g1).

44. An element as defined in claim 34, the adhesive in said particulate structure of said element comprising an addition copolymer of an addition polymerizable blend of monomers selected from the following group:

A. a monomer blend contaning from about 10 to 30 weight percent of one or more of said group (a) monomers with the remainder of the blend comprising addition polymerizable alkyl acrylates or methacrylates; and

B. a monomer blend containing from about 50 to 95 weight percent of monomers selected from group (a), (b), (c), and (k) with the remainder of the monomer blend comprising one or more addition polymerizable monomers having an active hydrogen or salts thereof.

45. An element as defined in claim 34, the adhesive in said particulate structure of said element comprising an addition copolymer of an addition polymerizable blend of monomers containing from about 50 to 95 weight percent of monomers selected from groups (a), (b), and (c) with the remainder of said blend comprising one or more addition polymerizable monomers having an active hydrogen or salt thereof selected from the group consisting of acrylic acid, methacrylic acid, sulfo- or sulfate-substituted monomers, and the alkali metal and ammonium salts of these monomers.

46. An element as defined in claim 34 wherein the adhesive in said particulate structure is selected from the group consisting of:

1. Poly(n-butyl acrylate-co-styrene-co-2-acrylamido-2-methylpropanesulfonic acid)

2. Poly(butyl acrylate-co-styrene-co-2-acrylamido-2-methylpropanesulfonic acid)

50. A multilayer element as defined in claim 45 wherein the organic polymer of the adhesive in said particulate structure has a glass transition temperature less than that of said particles.

51. A multilayer element as defined in claim 45 wherein the particles of said particulate structure are solid spherical beads having a substantially uniform size within the range of from about 2 to 100 microns.

52. A multilayer element as defined in claim 45 wherein the organo-polymeric composition of the particles in said particulate structure comprises an organic polymer containing a repeating unit having a chemical group representing an active bonding site for chemical attachment to an interactive composition for said analysis.

53. A multilayer element for the analysis of an aqueous liquid as defined in claim 45 wherein at least one of said layers contains an immunoreagent.

54. A multilayer element for the analysis of an aqueous liquid as defined in claim 45 wherein one or more components of an interactive composition for said analysis is located in at least one of said layers.

56. A multilayer element as defined in claim 51 wherein the particles of said particulate structure comprise spherical beads having a uniform particle size within the range of from about 1 to 20 microns and wherein one of said layers having said particulate structure contains an immunoreagent immobilized on said beads.

57. A multilayer element as defined in claim 51 wherein the particles of said particulate structure comprise spherical beads having a uniform particle size within the range of from about 1 to 20 microns and wherein one of said layers having said particulate structure contains an antibody immobilized on said beads.

58. A multilayer element as defined in claim 51 wherein the particles of said particulate structure comprise spherical beads having a uniform particle size within the range of from about 5 to b 20 microns and wherein one of said layers having said particulate structure contains an antibody immobilized on said beads.

35. An element for the analysis or transport of an aqueous liquid, said element comprising a support bearing a particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particle size of from 2 to 200 microns, and

(ii) an adhesive, in an amount of from about 1 to less than 5 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in cosest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent;

said particles comprising an addition copolymer of an addition polymerizable blend of two or more different monomers, the total monomer content of said blend comprising at least one of the following monomers, each of said monomers when present being in the proportions indicated;

(a) up to 99 weight percent of a polymerizable, amino-substituent-free styrene monomer;

(b) up to about 25 weight percent of a polymerizable acrylic ester;

(c) up to 75 weight percent of a polymerizable methacrylic ester;

(d) up to about 30 weight percent of a carboxylic acid containing one or more polymerizable ethylenically unsaturated groups;

(e) up to about 75 weight percent of a nitrile containing one or more polymerizable ethylenically unsaturated groups;

(f) up to about 20 weight percent of a polymerizable amine-substituted styrene monomer;

(g1) up to about 10 weight percent of an addition polymerizable monomer containing a group crosslinkable by a gelatin hardener;

(g2) up to about 10 weight percent of an addition polymerizable monomer containing a group crosslinkable by a diamine;

(h) up to about 20 weight percent of a polymerizable tertiary aminoalkyl acrylate or methacrylate;

(i) up to 75 weight percent of a polymerizable, N-heterocyclic vinyl monomer;

36. (j) up to about 20 weight percent of a polymerizable acrylamide or methacrylamide monomer;

and

(k) up to about 20 weight percent of a cross-linking monomer containing at least two addition polymerizable groups.

47. Poly(ethyl acrylate-co-acrylic acid-co-2-acetoacetoxyethyl methacrylate-co-2-acrylamido-2-methylpropanesulfonic acid)Poly(vinylbenzyl alcohol)Poly(ethyl acrylate)Poly(N-isopropylacrylamide)Poly(2-hydroxyethyl methacrylate-co-2-acetoacetoxyethyl methacrylate)Poly(n-butyl acrylate-co-acrylic acid)Poly(n-butyl acrylate-co-acrylic acid-co-methacrylic acid-co-ethyl acryloylacetate)Poly(n-butyl acrylate-co-acrylic acid-co-ethyl acryloylacetate)Poly(n-butyl acrylate-co-methacrylic acid-co-2-acetoacetoxyethyl methacrylate)Poly(n-butyl acrylate-co-styrene)Poly(n-butyl acrylate-co-2-acrylamido-2-methylpropane-sulfonic acid-co-2-acetoacetoxyethyl methacrylate)Poly(n-butyl acrylate-co-acrylic acid-co-2-acetoacetoxyethyl methacrylate-co-2-acrylamido-2-methylpropane sulfonic acid)Poly(n-butyl methacrylate-co-styrene)Poly(ethyl acrylate-styrene)Poly(n-butyl acrylate-co-2-acrylamido-2-methyl-propanesulfonic acid)Poly(n-butyl acrylate-co-styrene)Poly(2-ethylhexyl acrylate-co-acrylic acid-co-2-acetoacetoxyethyl methacrylate-co-2-acrylamido-2-methylpropanesulfonic acid)Poly(n-butyl acrylate-co-methacrylic acid)Poly(ethyl acrylate-co-acrylic acid)Poly(butyl acrylate-co-styrene-co-2-acetoacetoxyethyl methacrylate-co-2-acrylamido-2-methylpropanesulfonic acid)Poly(butyl acrylate-co-styrene-co-2-acrylamido-2-methylpropanesulfonic acid-co-divinylbenzene)

48. Poly(acrylamide-co-2-acetoacetoxyethyl methacrylate).

49. A multilayer element for the analysis or transport of an aqueous liquid, said element containing two or more superposed layers permeable to said liquid in fluid contact with one another, one of said layers having a particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles nonswellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent.

55. A multilayer element for the analysis or transport of an aqueous liquid, said element containing two or more superposed layers in fluid contact, at least two of said layers having a particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount of from about 1 to less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent;

said particles comprising an addition polymer of an addition polymerizable blend of monomers, the total monomer content of said blend comprising at least one of the following monomers, each of said monomers when present being in the proportions indicated;

(a) up to 100 weight percent of a polymerizable, amino-substituent-free styrene monomer;

(b) up to about 25 weight percent of a polymerizable acrylic ester;

(c) up to 100 weight percent of a polymerizable methacrylic ester;

(d) up to about 30 weight percent of a carboxylic acid containing one or more polymerizable ethylenically unsaturated groups;

(e) up to about 75 weight percent of a nitrile containing one or more polymerizable ethylenically unsaturated groups;

(f) up to about 20 weight percent of a polymerizable amine-substituted styrene monomer;

(g) up to about 20 weight percent of an addition polymerizable monomer containing a crosslinkable group;

(h) up to about 20 weight percent of a polymerizable tertiary aminoalkyl acrylate or methacrylate;

(i) up to 100 weight percent of a polymerizable, N-heterocyclic vinyl monomer;

(j) up to about 20 weight percent of a polymerizable acrylamide or methacrylamide monomer; and

(k) up to about 20 weight percent of a cross-linking monomer containing at least two addition polymerizable groups.

60. A multilayer element as defined in claim 55 wherein the particles in said layer having said particulate structure comprise solid, spherical beads having a uniform particle size within the range of from about 20 to 100 microns.

61. A multilayer element as defined in claim 55 wherein said interactive composition forms or releases a radiometrically detectable species.

62. A multilayer element as defined in claim 55 wherein said interactive composition forms or releases a colorimetrically or fluorometrically detectable species and wherein said element contains a registration layer to receive said detectable species, said registration layer intervening said support and said reagent layer.

63. A multilayer element as defined in claim 55 wherein

(i) said interactive composition forms or releases a colorimetrically or fluorometrically detectable species,

(ii) said element contains a registration layer to receive said detectable species, said registration layer intervening said support and said reagent layer, and

(iii) said element contains a radiation-blocking agent to screen said detectable species in said registration layer from one or more other layers of said element.

65. A multilayer element as defined in claim 60 wherein the particles of said particulate structure comprise spherical beads having a uniform particle size within the range of from about 1 to 20 microns and wherein said immunoreagent is antibody immobilized on said beads.

66. A multiplayer element as defined in claim 60 wherein said immunoreagent is antibody and said layer containing said antibody contains a radiation-blocking agent.

67. A multilayer element as defined in claim 60 wherein said immunoreagent is antibody and said layer containing said antibody contains nonspecific protein.

68. A multilayer element as defined in claim 60 wherein said immunoreagent is antibody and the particles of said layer containing antibody contain a radiation-blocking agent.

69. A multilayer element as defined in claim 60 wherein said immunoreagent is antibody and said element contains an antigen bearing a label comprising a radiometrically detectable species.

70. A multilayer element as defined in claim 60 wherein said immunoreagent is antibody and said element contains an antigen bearing a label comprising a fluorometrically detectable species.

72. A multilayer element as defined in claim 67, the adhesive in said particulate structure comprising an addition copolymer of an addition polymerizable blend of monomers selected from the following group:

A. a monomer blend containing from about 1 to 35 weight percent of one or more of said group (a) monomers with the remainders of the blend comprising addition polymerizable alkyl acrylates or methacrylates;

B. a monomer blend containing from about 20 to 95 weight percent of monomers selected from group (a), (b), (c), (g1), (g2), and (k) with the remainder of the monomer blend comprising one or more addition polymerizable monomers having an active hydrogen or salts thereof; and

C. a monomer blend comprising from about 15 to 100 weight percent of one or more monomers selected from the group consisting of 1-vinylimidazole, vinylbenzyl alcohol, ethyl acrylate, or a monomer from group (j) with the remaining monomers of the blend comprising monomers from group (g1).

73. A multilayer element as defined in claim 67, the adhesive in said particulate structures comprising an addition copolymer of an addition polymerizable blend of monomers selected from the following group:

A. a monomer blend containing from about 10 to 30 weight percent of one or more of said group (a) monomers with the remainder of the blend comprising addition polymerizable alkyl acrylates or methacrylates; and

B. a monomer blend containing from about 50 to 95 weight percent of monomers selected from group (a), (b), (c), and (k) with the remainder of the monomer blend comprising one or more addition polymerizable monomers having an active hydrogen or salts thereof.

74. A multilayer element as defined in claim 67, the adhesive in said particulate structure comprising an addition copolymer of an addition polymerizable blend of monomers containing from about 50 to 95 weight percent of monomers selected from groups (a), (b), and (c) with the remainder of said blend comprising one or more addition polymerizable monomers having an active hydrogen or salt thereof selected from the group consisting of acrylic acid, methacrylic acid, sulfo- or sulfate-substituted monomers, and the alkali metal and ammonium salts of these monomers.

75. A multilayer element as defined in claim 67, the organo-polymer in the particles of said particulate structure being poly(styrene-co-methacrylic acid) or poly(styrene-co-vinylbenzyl chloride-methacrylic acid), and the organic polymer of the adhesive of said particulate structures being poly(n-butyl acrylate-co-styrene-co-2-acrylamido-2-methylpropanesulfonic acid).

76. A multilayer element as defined in claim 67 which contains an antigen bearing a label, said label comprising a polymeric latex bead containing a fluoroescent rare earth chelate.

79. A multilayer element as defined in claim 74 wherein said scintillation layer comprises a particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount less than 10 percent by weight of said particles, comprising a fluor-imbibed latex polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent.

59. A multilayer element for the analysis of an aqueous liquid, said element having a radiation-transmissive support bearing at least one superposed reagent layer permeable to said liquid, said reagent layer containing one or more components of an interactive composition for said analysis, and in fluid contact with and superposed over said reagent layer at least one layer having a particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles nonswellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount of from about 1 to less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent;

said particles comprising an addition polymer of an addition polymerizable blend of monomers, the total monomer content of said blend comprising at least one of the following monomers, each of said monomers when present being in the proportions indicated;

(a) up to 100 weight percent of a polymerizable, amino-substituent-free styrene monomer;

(b) up to about 25 weight percent of a polymerizable acrylic ester;

(c) up to 100 weight percent of a polymerizable methacrylic ester;

(d) up to about 30 weight percent of a carboxylic acid containing one or more polymerizable ethylenically unsaturated groups;

(e) up to about 75 weight percent of a nitrile containing one or more polymerizable ethylenically unsaturated groups;

(f) up to about 20 weight percent of a polymerizable amine-substituted styrene monomer;

(g) up to about 20 weight percent of an addition polymerizable monomer containing a crosslinkable group;

(h) up to about 20 weight percent of a polymerizable tertiary aminoalkyl acrylate or methacrylate;

(i) up to 100 weight percent of a polymerizable, N-heterocyclic vinyl monomer;

(j) up to about 20 weight percent of a polymerizable acrylamide or methacrylamide monomer; and

(k) up to about 20 weight percent of a cross-linking monomer containing at least two addition polymerizable groups.

64. A multilayer element for the analysis of an antigen contained in an aqueous liquid, said element having a radiation-transmissive support bearing two or more superposed layers in fluid contact, at least two of said layers having a particulate structure, the layer with said particulate structure furthest removed from said support containing immobilized immunoreagent, said particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles nonswellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount of from about 1 to less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent;

said particles comprising an addition polymer of an addition polymerizable blend of monomers, the total monomer content of said blend comprising at least one of the following monomers, each of said monomers when present being in the proportions indicated;

(a) up to 100 weight percent of a polymerizable, amino-substituent-free styrene monomer;

(b) up to about 25 weight percent of a polymerizable acrylic ester;

(c) up to 100 weight percent of a polymerizable methacrylic ester;

(d) up to about 30 weight percent of a carboxylic acid containing one or more polymerizable ethylenically unsaturated groups;

(e) up to about 75 weight percent of a nitrile containing one or more polymerizable ethylenically unsaturated groups;

(f) up to about 20 weight percent of a polymerizable amine-substituted styrene monomer;

(g) up to about 20 weight percent of an addition polymerizable monomer containing a crosslinkable group;

(h) up to about 20 weight percent of a polymerizable tertiary aminoalkyl acrylate or methacrylate;

(i) up to 100 weight percent of a polymerizable, N-heterocyclic vinyl monomer;

(j) up to about 20 weight percent of a polymerizable acrylamide or methacrylamide monomer; and

(k) up to about 20 weight percent of a cross-linking monomer containing at least two addition polymerizable groups.

71. A multilayer element for the analysis of an antigen contained in an aqueous liquid, said element having a radiation-transmissive support bearing two or more superposed layers in fluid contact, at least two of said layers having a particulate structure, the layer with said particulate structure furthest removed from said support containing immobilized antibody, said particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in an impermeable to said liquid, said particles having a particle size of from about 2 to 20 microns, and

(ii) an adhesive, in an amount of from about 1 to less than 5 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent;

said particles comprising an addition polymer of an addition polymerizable blend of monomers, the total monomer content said blend comprising at least one of the following monomers, each of said monomers when present being in the proportions indicated;

(a) up to 99 weight percent of a polymerizable, amino-substituent-free styrene monomer;

(b) up to about 25 weight percent of a polymerizable acrylic ester;

(c) up to 75 weight percent of a polymerizable methylacrylic ester;

(d) up to about 30 weight percent of a carboxylic acid containing one or more polymerizable ethylenically unsaturated groups;

(e) up to about 75 weight percent of a nitrile containing one or more polymerizable ethylenically unsaturated groups;

(f) up to about 20 weight percent of a polymerizable amine-substituted styrene monomer;

(g1) up to about 10 weight percent of an addition polymerizable monomer containing a group crosslinkable by a gelatin hardener;

(g2) up to about 10 weight percent of an addition polymerizable monomer containing a group crosslinkable by a diamine;

(h) up to about 20 weight percent of a polymerizable tertiary aminoalkyl acrylate or methacrylate;

(i) up to 75 weight percent of a polymerizable, N-heterocyclic vinyl monomer;

(j) up to about 20 weight percent of a polymerizable acrylamide or methacrylamide monomer; and

(k) up to about 20 weight percent of a cross-linking monomer containing at least two addition polymerizable groups.

77. A multilayer element for the analysis of an antigen contained in an aqueous liquid, said element having a radiation-transmissive support having a monolayer of antibody adsorbed thereto and superposed over said monolayer a particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particule size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount of from about 1 to less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent;

said particles comprising an addition polymer of an addition polymerizable blend of monomers, the total monomer of said blend comprising at least one of the following monomers, each of said monomers when present being in the proportions indicated;

(a) up to 100 weight percent of a polymerizable, amino-substituent-free styrene monomer;

(b) up to about 25 weight percent of a polymerizable acrylic ester;

(c) up to 100 weight percent of a polymerizable methacrylic ester;

(d) up to about 30 weight percent of a carboxylic acid containing one or more polymerizable ethylenically unsaturated groups;

(e) up to about 75 weight percent of a nitrile containing one or more polymerizable ethylenically unsaturated groups;

(f) up to about 20 weight percent of a polymerizable amine-substituted styrene monomer;

(g) up to about 20 weight percent of an addition polymerizable monomer containing a crosslinkable group;

(h) up to about 20 weight percent of a polymerizable tertiary aminoalkyl acrylate or methacrylate;

(i) up to 100 weight percent of a polymerizable, N-heterocyclic vinyl monomer;

(j) up to about 20 weight percent of a polymerizable acrylamide or methacrylamide monomer; and

(k) up to about 20 weight percent of a crosslinking monomer containing at least two addition polymerizable groups.

78. A multilayer element for the analysis of an antigen contained in an aqueous liquid, said element having a radiation-transmissive support bearing a scintillation layer and superposed thereover a particulate structure containing immobilized antibody, said particulate structure comprising:

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount of from about 1 to less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volumn of from about 25 to 80 percent;

said particles comprising an addition polymer of an addition polymerizable blend of monomers, the total monomer content of said blend comprising at least one of the following monomers, each of said monomers when present being in the proportions indicated;

(a) up to 100 weight percent of a polymerizable, amino-substituent-free styrene monomer;

(b) up to about 25 weight percent of a polymerizable acrylic ester;

(c) up to 100 weight percent of a polymerizable methacrylic ester;

(d) up to about 30 weight percent of a carboxylic acid containing one or more polymerizable ethylenically unsaturated groups;

(e) up to about 75 weight percent of a nitrile containing one of more polymerizable ethylenically unsaturated groups;

(f) up to about 20 weight percent of a polymerizable amine-substituted styrene monomer;

(g) up to about 20 weight percent of an addition polymerizable monomer containing a crosslinkable group;

(h) up to about 20 weight percent of a polymerizable tertiary aminoalkyl acrylate or methacrylate;

(i) up to 100 weight percent of a polymerizable, N-heterocyclic vinyl monomer;

(j) up to about 20 weight percent of a polymerizable acrylamide or methacrylamide monomer; and

(k) up to about 20 weight percent of a cross-linking monomer containing at least two addition polymerizable groups.

80. A multilayer element for the analysis of an antigen contained in an aqueous liquid, said element generating an enzyme-induced detectable change corresponding to the presence and/or concentration of said antigen by interaction of said antigen, a separate quantity of the same antigen labelled with said enzyme, and antibody for said antigen;

said element having a radiation-transmissive support bearing two or more superposed layers in fluid contact including a reagent layer comprising at least a portion of an interactive enzyme assay composition which produces said enzyme-induced detectable change and superposed over said reagent layer a layer having a particulate structure containing immobilized antibody, said particulate structure comprising;

(i) a plurality of heat-stable, organo-polymeric particles non-swellable in and impermeable to said liquid, said particles having a particle size of from about 1 to 200 microns, and

(ii) an adhesive, in an amount less than 10 percent by weight of said particles, comprising an organic polymer different from that of said particles and insoluble in said liquid;

substantially all of said adhesive being concentrated on surface areas of adjacent particles where said adjacent particles are in closest proximity, and bonding said particles into a coherent, three-dimensional lattice which is non-swellable in said liquid and which has interconnected void spaces among said particles to provide transport of said liquid, said lattice having a void volume of from about 25 to 80 percent.