Surface treatment method for bio-arrays

• US 20030082294A1
• Filed: 10/31/2001
• Published: 05/01/2003
• Est. Priority Date: 10/31/2001
• Status: Abandoned Application

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Dellinger, Geraldine F., Dellinger, Douglas J., Bruhn, Laurakay
• Application Number:
  US10/001,056
• Publication Number:
  US 20030082294A1
• Time in Patent Office: Days
• US Class Current: 427/2.1
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding

Abstract

The invention provides novel methods for surface treatment of bioarrays to provide desirable substrate surface characteristics, and novel methods for fabrication of bioarrays. The present invention encompasses a process of contacting the surface of a substrate having biomolecules deposited thereupon with a basic, aqueous solution, followed by contacting the surface with a blocking agent that bonds preferentially to surface reactive moieties on the surface and reduces background signal and/or reduces the number of sites available for non-specific binding to occur. The invention also encompasses bioarrays fabricated using such process.

Claims

1. A method of treating a surface of a bioarray having biomolecules deposited thereupon, the method comprising contacting the surface of the bioarray with a basic solution, and then contacting the surface of the bioarray with a blocking agent.

2. The method of claim 1, wherein the basic solution comprises at least 20% water and has a pH greater than 9.

3. The method of claim 1, wherein the basic solution is applied for less than about five minutes.

4. The method of claim 1, wherein the surface is positively charged due to positively charged reactive moieties bound to the surface.

5. The method of claim 1, wherein the blocking agent is an anhydride.

6. The method of claim 5, wherein the blocking agent is a cyclic anhydride.

7. The method of claim 6, wherein the cyclic anhydride is selected from the group consisting of succinic anhydride, maleic anhydride, and glutaric anhydride.

8. The method of claim 1, wherein the biomolecules are bound on the surface via a reactive moiety that is bound to the surface, wherein the reactive moiety can react to covalently bind the biomolecule to the surface.

9. The method of claim 8, wherein the reactive moiety comprises an amine group.

10. The method of claim 1, wherein the biomolecules are selected from the group consisting of polypeptides, polynucleotides, and polysaccharides.

11. A method of fabricating an array of biomolecules bound on a substrate surface, the method comprising obtaining a substrate having reactive moieties present thereupon, depositing biomolecules onto the substrate surface, wherein at least some biomolecules are bound to at least some of the reactive moieties present on the substrate, contacting the substrate surface with a basic solution, and contacting the substrate surface with a blocking agent to block at least some of the reactive moieties to yield the array.

12. The method of claim 11, wherein the biomolecules are synthesized in situ on the substrate surface.

13. The method of claim 11, wherein the basic solution comprises at least 20% water and has a pH greater than 9.

14. The method of claim 11, wherein the basic solution is applied for less than about five minutes.

15. The method of claim 11, wherein the surface is positively charged due to positively charged reactive moieties bound to the surface.

16. The method of claim 11, wherein the blocking agent is an anhydride.

17. The method of claim 16, wherein the blocking agent is a cyclic anhydride.

18. The method of claim 17, wherein the cyclic anhydride is selected from the group consisting of succinic anhydride, maleic anhydride, and glutaric anhydride.

19. The method of claim 11, wherein the reactive moieties comprises amine groups.

20. The method of claim 11 wherein the biomolecules are selected from the group consisting of polypeptides, polynucleotides, and polysaccharides.

26. The improved method of claim 17, wherein the biomolecules are selected from the group consisting of polypeptides, polynucleotides, and polysaccharides.

21. In a method of fabricating a bioarray upon a substrate having a surface, the method comprising:

depositing biomolecules on the surface; and

contacting the surface with a blocking agent;

the inprovement comprising;

after depositing the molecules on the surface and before contacting the surface with the blocking agent, contacting the surface with a basic solution.

22. The improved method of claim 21, wherein the basic solution comprises at least 20% water and has a pH greater than 9.

23. The improved method of claim 21, wherein the basic solution is applied for less than about five minutes.

24. The improved method of claim 21, wherein the surface is positively charged due to positively charged reactive moieties bound to the surface.

25. The improved method of claim 21, wherein the blocking agent is an acylating agent selected from succinic anhydride, maleic anhydride, and glutaric anhydride.