Diffraction-based diagnostic devices

• US 20030207254A1
• Filed: 05/03/2002
• Published: 11/06/2003
• Est. Priority Date: 05/03/2002
• Status: Active Grant

• Current Assignee: Kimberly-Clark Worldwide Incorporated (Kimberly-Clark Corporation)
• Original Assignee: Kimberly-Clark Worldwide Incorporated (Kimberly-Clark Corporation)
• Inventors: Kaylor, Rosann, Cohen, David
• Granted Patent: US 7,223,368 B2
• Time in Patent Office: Days
• US Class Current: 435/5
• CPC Class Codes: G01N 21/4788 Diffraction for sizing particles G01N15/0205
• CPC Class Codes: G01N 33/543 with an insoluble carrier for immobilising immunochemicals

Abstract

A biosensor includes a substrate with a layer of receptive material disposed thereon. The receptive material is specific for an analyte of interest. A pattern of active and inactive areas of the receptive material are defined in the receptive material layer by a masking process.

Claims

1. A biosensor, comprising:

a substrate member;

a receptive material layer generally uniformly covering a side of said substrate member, said receptive material being specific for an analyte of interest;

a pattern of at least one active area and at least one inactive area of said receptive material defined in said receptive material layer, said receptive material in said inactive area rendered inactive by a crosslinking agent;

wherein said active and inactive areas are defined in a masking process wherein the crosslinking agent is applied generally uniformly over said receptive material layer and a mask is then placed over said substrate member prior to exposing said substrate member to a stimulus for activating said crosslinking agent, areas underlying shielded regions of the mask defining said active areas and areas exposed by the mask having the crosslinking agent activated by the stimulus and defining said inactive areas; and

wherein when said biosensor is exposed to a medium containing said analyte of interest, the analyte binds to said receptive material in said active areas and facilitates subsequent diffraction of transmitted or reflected light in a diffraction pattern corresponding to said active areas.

2. The biosensor as in claim 1, wherein said pattern of active and inactive areas comprises a plurality of said active areas and a plurality of said inactive areas defined by said masking process.

3. The biosensor as in claim 1, wherein said crosslinking agent in said active areas is removed in a washing process.

4. The biosensor as in claim 1, wherein said crosslinking comprises a homobifunctional agent in which both ends of said agent are photosensitive, said stimulus being a light source at a wavelength sufficient to activate said ends of said cross-linking agent.

5. The biosensor as in claim 4, wherein said crosslinking agent comprises (bis-[β

-(4-azidosalicylamido)ethyl]disulfide).

6. The biosensor as in claim 1, wherein said substrate comprises a material from the list of materials consisting of plastics, metal coated plastics and glass, functionalized plastics and glass, silicon wafers, glass, and foils.

7. The biosensor as in claim 1, wherein said substrate member comprises a polymer film coated with a metal.

8. The biosensor as in claim 7, wherein said polymer film comprises polyethylene-terephthalate.

9. The biosensor as in claim 7, wherein said metal is selected from the group consisting of gold, silver, chromium, nickel, platinum, aluminum, iron, copper, gold oxide, titanium, titanium oxide, chromium oxide or zirconium.

10. The biosensor as in claim 7, wherein said metal is gold.

11. The biosensor as in claim 1, wherein said diffraction pattern is visible to the naked eye.

12. The biosensor as in claim 1, wherein said receptive material is at least one of antigens, antibodies, nucleotides, chelators, enzymes, bacteria, yeasts, fungi, viruses, bacterial pili, bacterial flagellar materials, nucleic acids, polysaccharides, lipids, proteins, carbohydrates, metals, hormones, aptamers, peptides, and respective receptors for said materials.

13. The biosensor as in claim 1, wherein said analyte of interest is at least one of a bacteria, yeast, fungus, virus, rheumatoid factor, IgG, IgM, IgA, IgD, and IgE antibodies, carcinoembryonic antigen, streptococcus Group A antigen, viral antigens, antigens associated with autoimmune disease, allergens, tumor antigens, streptococcus group B antigen, HIV I or HIV II antigen, antib ies viruses, antigens specific to RSV, an antibody, antigen, enzyme, hormone, polysaccharide, protein, lipid, carbohydrate, drug, nucleic acid, Neisseria meningitides groups A, B, C, Y and W sub 135, Streptococcus pneumoniae, E. coli K1, Haemophilus influenza type A/B, an antigen derived from microorganisms, PZA and CRP antigens, a hapten, a drug of abuse, a therapeutic drug, an environmental agents, or antigens specific to Hepatitis.

14. A method of making a biosensor, comprising the steps of:

forming a receptive material layer generally uniformly over a surface of a substrate member, the layer containing a receptive material specific for an analyte of interest;

applying an activatable crosslinking agent generally uniformly over the receptive material layer;

placing a mask over the substrate member, the mask having a configuration so as to cover at least one underlying area of the substrate while exposing at least one adjacent area;

exposing the mask and substrate to a stimulus for activating the crosslinking agent such that the crosslinking agent in the exposed areas affixes to and deactivates the receptive material;

removing the mask from the substrate and disassociating the unactivated crosslinking agent from the receptive material in the areas that were covered by the mask to define active areas of the receptive material;

wherein a resulting pattern of active and inactive areas of the receptive material are defined such that when the biosensor is exposed to a medium containing the analyte of interest, the analyte binds to the receptive material in the active areas and facilitates subsequent diffraction of transmitted or reflected light in a diffraction pattern corresponding to the active areas.

15. The method as in claim 14, comprising defining a pattern of the active and inactive areas with the mask, the pattern comprising a plurality of the active areas and a plurality of the inactive areas.

16. The method as in claim 14, wherein the crosslinking agent is a homobifunctional agent in which both ends of said agent are photosensitive.

17. The method as in claim 16, comprising activating the crosslinking agent with a light source.

18. The method as in claim 16, wherein the crosslinking agent comprises (bis-[β

-(4-azidosalicylamido)ethyl]disulfide).

19. The method as in claim 14, comprising disassociating the crosslinking agent in the active areas by washing the substrate member with a solution sufficient to remove the crosslinking agent from the substrate member.

20. The method as in claim 14, comprising selecting the substrate member from the group of materials consisting of plastics, metal coated plastics and glass, functionalized plastics and glass, silicon wafers, glass, and foils.

21. The method as in claim 14, wherein the substrate member comprises a polymer film coated with a metal.

22. The method as in claim 21, wherein the polymer film comprises polyethylene-terephthalate.

23. The method as in claim 21, comprising selecting the metal from the group consisting of gold, silver, chromium, nickel, platinum, aluminum, iron, copper, titanium, titanium oxide, gold oxide, chromium oxide and zirconium.

24. The method as in claim 21, wherein the metal is gold.

25. The method as in claim 14, comprising viewing the diffraction pattern of active areas with the naked eye.

26. The method as in claim 14, comprising selecting the receptive material from at least one of antigens, antibodies, nucleotides, chelators, enzymes, bacteria, yeasts, fungi, viruses, bacterial pili, bacterial flagellar materials, nucleic acids, polysaccharides, lipids, proteins, carbohydrates, metals, hormones, aptamers, peptides, and respective receptors for said materials.

27. The method as in claim 14, wherein the analyte of interest is selected from at least one of a bacteria, yeast, fungus, virus, rheumatoid factor, IgG, IgM, IgA, IgD, and IgE antibodies, carcinoembryonic antigen, streptococcus Group A antigen, viral antigens, antigens associated with autoimmune disease, allergens, tumor antigens, streptococcus group B antigen, HIV I or HIV II antigen, antibodies viruses, antigens specific to RSV, an antibody, antigen, enzyme, hormone, polysaccharide, protein, lipid, carbohydrate, drug, nucleic acid, Neisseria meningitides groups A, B, C, Y and W sub 135, Streptococcus pneumoniae, E. coli K1, Haemophilus influenza type A/B, an antigen derived from microorganisms, PSA and CRP antigens, a hapten, a drug of abuse, a therapeutic drug, an environmental agents, or antigens specific to Hepatitis.