Macromolecular arrays on polymeric brushes & methods for preparing the same

• US 20060134672A1
• Filed: 11/30/2005
• Published: 06/22/2006
• Est. Priority Date: 09/01/1999
• Status: Abandoned Application

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Frank, Curtis W., McGall, Glenn, Chang, Ying Chih
• Application Number:
  US11/289,897
• Publication Number:
  US 20060134672A1
• Time in Patent Office: Days
• US Class Current: 435/6
• 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: C08F 289/00 Macromolecular compounds obtained by polymerising monomers on to macromolecular compounds not provided for in groups C08F251/00 - C08F287/00
• CPC Class Codes: C08F 290/06 Polymers provided for in subclass C08G
• CPC Class Codes: C08F 4/02 Carriers therefor
• CPC Class Codes: C08L 51/08 grafted on to macromolecular compounds obtained otherwise than by reactions only involving unsaturated carbon-to-carbon bonds
• CPC Class Codes: C08L 51/10 grafted on to inorganic materials
• CPC Class Codes: C40B 40/00 Libraries per se, e.g. arrays, mixtures
• CPC Class Codes: G01N 33/544 the carrier being organic

Abstract

Polymeric brush substrates and methods for their preparation are provided. Methods are also provided for preparing macromolecular arrays on such polymeric brush substrates. Using polymeric brush substrates allows control over functional site density as well as wettability and porosity of the substrate. These polymeric brushes are useful in solid-phase synthesis of arrays of peptides, polynucleotides or small organic molecules.

Claims

1-8. -8. (canceled)

9. A method for affixing functional sites to a surface of a solid substrate, the method comprising:

(a) providing a substrate to which one or more free radical initiators are covalently attached, wherein each free radical initiator has a radical generation site distal to the substrate; and

(b) contacting the substrate with a mixture of linking monomers and diluent monomers under conditions that promote free radical polymerization from the radical generation sites of the initiators to produce a brush polymer comprising functional sites, wherein the density of the functional sites is determined by the ratio of functional monomers to diluent monomers.

10. The method of claim 9, wherein the linking monomers comprise a vinyl group.

11. The method of claim 9, wherein the linking monomers comprise at least two different linking monomers.

12. The method of claim 9, wherein the initiator is an azo type initiator.

13. The method of claim 9, wherein the functional sites are selected from the group consisting of amino, hydroxyl, carboxyl or sulfydryl.

14. The method of claim 9, wherein the ratio of linking monomers to diluent monomers is from about 1:

2 to about 1;

200.

15. The method of claim 9, wherein the ratio of linking monomers to diluent monomers is from about 1:

2 to about 1;

2000.

16. The method of claim 9, wherein the monomers independently have the structure:

17. The method of claim 9, wherein the substrate comprises glass or silica.

18. A substrate capable of supporting macromolecular array synthesis, the substrate comprising polymer brushes formed by free radical polymerization, wherein said polymer brushes comprise hydroxyl, amino, or carboxyl, groups or a combination thereof.

19. The substrate of claim 18, wherein the density of the polymer brushes is 0.1 to 1000 pmoles of individual polymer chains per cm2 of substrate surface area.

20. The substrate of claim 18, further comprising an array of macromolecules attached to polymeric brushes on the substrate.

21. The substrate of claim 20, wherein the macromolecules comprise polynucleotides.