Patterned binding of functionalized microspheres for optical diffraction-based biosensors

• US 6,573,040 B2
• Filed: 12/08/2000
• Issued: 06/03/2003
• Est. Priority Date: 12/11/1998
• Status: Expired due to Term

• Current Assignee: Kimberly-Clark Worldwide Incorporated (Kimberly-Clark Corporation)
• Original Assignee: Kimberly-Clark Worldwide Incorporated (Kimberly-Clark Corporation)
• Inventors: Everhart, Dennis S., Kaylor, Rosann M., McGrath, Kevin
• Primary Examiner(s): BORIN, MICHAEL L
• Application Number:
  US09/733,204
• Publication Number:
  US 20010004526A1
• Time in Patent Office: 907 Days
• Field of Search: 435/5, 435/7.21, 435/291
• US Class Current: 435/5
• CPC Class Codes: B01J 2219/00382 Stamping
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 21/4788 Diffraction for sizing particles G01N15/0205
• CPC Class Codes: G01N 21/7743 the reagent-coated grating coupling light in or out of the waveguide
• CPC Class Codes: G01N 33/54346 Nanoparticles
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/553 Metal or metal coated

Abstract

The present invention provides an inexpensive and sensitive system and method for detecting analytes present in a medium. The system comprises a diffraction enhancing element, such as functionalized microspheres, which are modified such that they are capable of binding with a target analyte. Additionally, the system comprises a polymer film, which may include a metal coating, upon which is printed a specific, predetermined pattern of a analyte-specific receptors. Upon attachment of a target analyte to select areas of the polymer film, either directly or with the diffraction enhancing element, diffraction of transmitted and/or reflected light occurs via the physical dimensions and defined, precise placement of the analyte. A diffraction image is produced which can be easily seen with the eye or, optionally, with a sensing device.

Claims

1. A system for detecting an analyte in a medium comprising:

a diffraction enhancing element having a receptor material thereon that is specific for the analyte; and

a sensing device comprising;

a polymer film; and

an analyte-specific receptor layer printed in a pattern onto the polymer film wherein the analyte-specific receptor layer has a receptor material thereon that is specific for the analyte;

wherein the analyte-specific receptor layer is printed in a pattern such that when the sensing device binds an analyte, the sensing device diffracts transmitted light to form a diffraction pattern;

wherein the diffraction pattern is visible to an unaided eye.

2. The system of claim 1, further comprising a metal coating on the polymer film and wherein the analyte-specific receptor layer is printed onto the metal coating.

3. The system of claim 2, wherein the metal coating is selected from gold, silver, chromium, nickel, platinum, aluminum, iron, copper, gold oxide, chromium oxide or zirconium.

4. The system of claim 3, wherein the metal coating is gold.

5. The system of claim 4, wherein the gold coating is between approximately 1 nanometer and 1000 nanometers in thickness.

6. The system of claim 1, wherein the polymer film is selected from polyethylene-terephthalate, acrylonitrile-butadiene-styrene, acrylonitrile-methyl acrylate copolymer, cellophane, cellulosic polymers such as ethyl cellulose, cellulose acetate, cellulose acetate butyrate, cellulose propionate, cellulose triacetate, polyethylene, polyethylene-vinyl acetate copolymers, ionomers (ethylene polymers) polyethylene-nylon copolymers, polypropylene, methyl pentene polymers, polyvinyl fluoride, or aromatic polysulfones.

7. All The system of claim 6, wherein the polymer film is polyethylene-terephthalate.

8. The system of claim 1, wherein the polymer film is optically transparent.

9. The system of claim 8, wherein the polymer film has an optical transparency between 5% and 95%.

10. The system of claim 8, wherein the polymer film has an optical transparency between approximately 20% and 80%.

11. The system of claim 1, wherein there are two or more analyte-specific receptor layers with each layer having different chemical properties.

12. The system of claim 1, wherein the analyte is selected from bacteria, yeast, fungus, virus, rheumatoid factor, IgG, IgM, IgA 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 or nucleic acid, Neisseria meningitides groups A, B, C, Y and W sub 135, Streptococcus pneumoniae, E. coli K1, Haemophilus influenza type B, an antigen derived from microorganisms, a hapten, a drug of abuse, a therapeutic drug, an environmental agent, or antigens specific to Hepatitis.

13. The system of claim 12, wherein the analyte is bacteria, yeast, fungus or virus.

14. The system of claim 1, wherein the receptor material is selected from antigens, antibodies, oligonucleotides, chelators, enzymes, bacteria, yeasts, fungi, viruses, bacterial pili, bacterial flagellar materials, nucleic acids, polysaccharides, lipids, proteins, carbohydrates, metals, hormones or receptors for said materials.

15. The system of claim 1, wherein the diffraction enhancing element is selected from glass, cellulose, synthetic polymers or plastics, latex, polystyrene, polycarbonate, bacterial or fungal cells.

16. The system of claim 1, wherein the diffraction enhancing element is polystyrene latex microspheres.

17. The system of claim 1, further comprising a blocking material applied to the non-printed areas of the polymer film.

18. The system of claim 17, wherein the blocking material is selected from β

-casein, an albumin, a surfactant, polyethylene glycol, polyvinyl alcohol, or sulfur derivatives thereof.

19. The system of claim 1, wherein the sensing device further comprises a layer of blocking material on the polymer film through which the analyte-specific receptor material is printed.

20. The system of claim 19, wherein the blocking material is selected from β

-casein, an albumin, a surfactant, polyethylene glycol, polyvinyl alcohol, or sulfur derivatives thereof.

21. A system for detecting an analyte in a medium comprising:

a diffraction enhancing element having a receptor material thereon that is specific for the analyte; and

a sensing device comprising;

a polymer film coated with metal; and

an analyte-specific receptor layer printed in a pattern onto the polymer film wherein the analyte-specific receptor layer has a receptor material thereon that is specific for the analyte;

wherein the analyte-specific receptor layer is printed in a pattern such that when the sensing device binds an analyte, the sensing device diffracts reflected light to form a diffraction pattern;

wherein the diffraction pattern is visible to an unaided eye.

22. The system of claim 21, wherein the metal coating is selected from gold, silver, chromium, nickel, platinum, aluminum, iron, copper, gold oxide, chromium oxide or zirconium.

23. The system of claim 22, wherein the metal coating is gold.

24. The system of claim 23, wherein the gold coating is between approximately 1 nanometer and 1000 nanometers in thickness.

25. The system of claim 21, wherein the polymer film is selected from polyethylene-terephthalate, acrylonitrile-butadiene-styrene, acrylonitrile-methyl acrylate copolymer, cellophane, cellulosic polymers such as ethyl cellulose, cellulose acetate, cellulose acetate butyrate, cellulose propionate, cellulose triacetate, polyethylene, polyethylene-vinyl acetate copolymers, ionomers (ethylene polymers) polyethylene-nylon copolymers, polypropylene, methyl pentene polymers, polyvinyl fluoride, or aromatic polysulfones.

26. The system of claim 25, wherein the polymer film is polyethylene-terephthalate.

27. The system of claim 21, wherein there are two or more analyte-specific receptor layers with each layer having different chemical properties.

28. The system of claim 21, wherein the analyte is selected from bacteria, yeast, fungus, virus, rheumatoid factor, IgG, IgM, IgA 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 or nucleic acid, Neisseria meningitides groups A, B, C, Y and W sub 135, Streptococcus pneumoniae, E. coli K1, Haemophilus influenza type B, an antigen derived from microorganisms, a hapten, a drug of abuse, a therapeutic drug, an environmental agent, or antigens specific to Hepatitis.

29. The system of claim 28, wherein the analyte is bacteria, yeast, fungus or virus.

30. The system of claim 21, wherein the receptor material is selected from antigens, antibodies, oligonucleotides, chelators, enzymes, bacteria, yeasts, fungi, viruses, bacterial pili, bacterial flagellar materials, nucleic acids, polysaccharides, lipids, proteins, carbohydrates, metals, hormones or receptors for said materials.

31. The system of claim 21, wherein the diffraction enhancing element is selected from glass, cellulose, synthetic polymers or plastics, latex, polystyrene, polycarbonate, bacterial or fungal cells.

32. The system of claim 21, wherein the diffraction enhancing element is polystyrene latex microspheres.

33. The system of claim 21, further comprising a blocking material applied to the non-printed areas of the polymer film.

34. The system of claim 33, wherein the blocking material is selected from β

-casein, an albumin, a surfactant, polyethylene glycol, polyvinyl alcohol, or sulfur derivatives thereof.

35. The system of claim 21, wherein the sensing device further comprises a layer of blocking material on the metal-coated polymer film through which the analyte-specific receptor material is printed.

36. The system of claim 35, wherein the blocking material is selected from β

-casein, an albumin, a surfactant, polyethylene glycol, polyvinyl alcohol, or sulfur derivatives thereof.

37. A system for detecting an analyte in a medium comprising:

a diffraction enhancing element having a receptor material thereon that is specific for the analyte; and

a sensing device comprising;

a polymer film coated with metal; and

an analyte-specific receptor layer printed in a pattern onto the metal-coated polymer film wherein the analyte-specific receptor layer has a receptor material thereon that is specific for the analyte;

wherein the analyte-specific receptor layer is printed in a pattern such that when the sensing device binds an analyte, the sensing device diffracts transmitted light to form a diffraction pattern;

wherein the diffraction pattern is visible to an unaided eye.