SURFACE MODIFICATIONS AND METHODS FOR THEIR SYNTHESIS AND USE

• US 20110143967A1
• Filed: 12/14/2010
• Published: 06/16/2011
• Est. Priority Date: 12/15/2009
• Status: Abandoned Application

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: TRUE, Randall J., BARONE, Anthony D., McGALL, Glenn H.
• Application Number:
  US12/967,963
• Publication Number:
  US 20110143967A1
• Time in Patent Office: Days
• US Class Current: 506/32
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07F 7/188 by reactions involving the formation of Si-O linkages

Abstract

Novel processes are disclosed for forming an array of polymers by functionalizing the surface of particles by methods that include covalently attaching a functionalized silicon compound. Substrates such as microparticles having functionalized silicon compounds attached thereto are produced by introducing at least one carboxyl group directly by silanating a carboxylated silane compound to the surface of a microparticle. In a further aspect of the invention, the silane compound is a dipodal carboxylated silane.

Claims

1. A method of forming an array of nucleic acids comprising:

silanating a surface of a substrate by steps comprising;

covalently attaching a plurality of functionalized silicon compounds the surface of the substrate, wherein during the silanation step at least one carboxyl group is directly introduced by silanating the surface of the substrate with a carboxylated silane compound; and

conjugating two or more oligonucleotides to the carboxylated silane compounds to form an array of nucleic acids covalently attached to the carboxylated silane compound on the surface of the substrate.

2. A method according to claim 1, wherein the substrate is a microparticle.

3. A method of functionalizing a surface comprising:

covalently attaching a functionalized silicon compound of Formula 1 to a surface of a substrate, to form a modified surface of Formula 2, wherein Formula 1 is a silicon compound having the structure;

4. The method of claim 3, wherein x is 1 or 2 and Q is N.

5. The method of claim 4, wherein each R¹ group is methoxy.

6. The method of claim 5, wherein x is 2 and L is a C₃-C₁₀ straight chain alkyl group.

7. The method of claim 6, wherein L is a C₃ alkyl group.

8. The method of claim 7, wherein A¹ is a C₃-C₁₀ straight chain alkyl group.

9. The method of claim 8, wherein A¹ is a C₃ straight chain alkyl group further comprising a carbonyl.

10. The method of claim 9, wherein Q-A¹-Y is Q-C(═

O)CH₂CH₂CH₂—

Y.

11. The method of claim 10, wherein Y is a carboxyl group.

12. The method of claim 3, wherein L is a straight chain C₃-C₆ alkyl group.

13. The method of claim 3, wherein the compound of Formula 1 is selected from the

14. The method of claim 12, wherein L is a straight chain C₃ alkyl group.

15. The method of claim 3, wherein the compound of Formula 1 is represented by a compound of Formula 1(A) or 1(B):

16. The method of claim 3, wherein the method further comprises:

covalently attaching a plurality of functionalized silicon compounds to the surface; and

forming an array of nucleic acids covalently attached to the functionalized silicon compounds on the surface.

17. The method of claim 3, wherein the derivatizable functional group Y is an aldehyde.

18. The method of claim 3, wherein the derivatizable functional group Y is a hydrazine or protected hydrazine.

19. The method of claim 3, wherein the derivatizable functional group Y is a carboxylate.

20. The method of claim 3, wherein the derivatizable functional group Y is an azide.

21. The method of claim 3, wherein the derivatizable functional group Y is an alkene.

22. The method of claim 3, wherein the derivatizable functional group Y is an alkyne.

23. The method of claim 3, wherein the derivatizable functional group Y is a thiol.

24. The method of claim 15, wherein the plurality of functionalized silicon compounds are covalently attached to encoded microparticles.

49. The method of claim 15, wherein the compound is a compound of Formula 1(A), and each R¹ group is methoxy, each L group is propyl, Q is N, A¹ is C₃-C₁₀ straight chain alkyl and Y is COOH.

50. The method of claim 15, wherein A¹ is a C₃-C₁₀ straight chain alkyl and comprises one or more organofunctional moieties selected from the group consisting of ether, amine, sulfide, sulfonyl, sulfate, carbonyl, thione, ester, thioester, carbonate, thiocarbonate, carbamate, thiocarbamate, amide, thioamide, urea and thiourea group.

51. The method of claim 49, wherein A¹ is a C₃ straight chain alkyl group further comprising a carbonyl.

52. The method of claim 50, wherein Q-A¹-Y is Q-C(═

O)CH₂CH₂CH₂—

Y.

53. The method of claim 51, wherein Y is a carboxyl group.

25. A method of functionalizing a surface comprising:

covalently attaching a plurality of functionalized silicon compounds of Formula 3 to the surface of a substrate, to form an aldehyde modified surface of Formula 4; and

reacting the surface of Formula 4 with a hydrazine-modified oligonucleotide structure of Formula 5 to produce a hydrazine-modified oligonucleotide modified surface structure of Formula 6, wherein the compound of Formula 3 has the following formula;

26. The method of claim 25, wherein each occurrence of R¹ is methoxy.

27. The method of claim 25, further comprising:

forming an array of nucleic acids by covalently attaching a plurality of compounds of Formula 5 to the plurality of functionalized silicon compounds on the surface.

28. The method of claim 25, wherein the derivatizable functional group Y is a hydroxyl group, activated hydroxyl group or protected hydroxyl group.

29. The method of claim 27, wherein the functionalized silicon compounds are covalently attached to encoded microparticles.

30. A method of functionalizing a surface comprising:

covalently attaching a plurality of functionalized silicon compounds of Formula 7 to the surface of a substrate to form an hydrazine modified surface of Formula 8;

reacting the surface of Formula 8 with an aldehyde-modified oligonucleotide structure of Formula 9 to produce a surface structure of Formula 10;

wherein the compound of Formula 7 has the following formula;

31. The method of claim 30, wherein the method further comprises

forming an array of nucleic acids by covalently attaching a plurality of compounds of Formula 9 to the plurality of functionalized silicon compounds on the surface.

32. The method of claim 30, wherein the derivatizable functional group is a hydroxyl group, activated hydroxyl group or protected hydroxyl group.

33. The method of claim 31, wherein the functionalized silicon compounds are covalently attached to encoded microparticles.

34. A method of functionalizing a surface comprising:

covalently attaching a plurality of functionalized silicon compounds of Formula 11 to the surface of a substrate, to form an hydrazine modified surface of Formula 8 or 8(A);

reacting the surface of Formula 8 with an aldehyde-modified oligonucleotide structure of formula 9 to produce the surface structure of Formula 10;

wherein, the silicon compound of Formula 11 has the following Formula;

35. The method of claim 34, further comprising:

forming an array of nucleic acids covalently attached to the functionalized silicon compounds on the surface.

36. The method of claim 35, wherein the functionalized silicon compounds are covalently attached to encoded microparticles.

37. The method of claim 34, wherein the functionalized silicon compound is a compound of Formula 11 is:

38. The method of claim 37, wherein the method comprises:

covalently attaching a plurality of functionalized silicon compounds to the surface; and

forming an array of nucleic acids covalently attached to the functionalized silicon compounds on the surface.

39. The method of claim 38, wherein the functionalized silicon compounds are covalently attached to encoded microparticles.

40. A compound having the Formula:

41. The compound of claim 40, wherein A¹ comprises one or more organofunctional moieties selected from the group consisting of ether, amine, sulfide, sulfonyl, sulfate, carbonyl, thione, ester, thioester, carbonate, thiocarbonate, carbamate, thiocarbamate, amide, thioamide, urea and thiourea group.

42. The compound of claim 40, wherein A¹ comprises a carbonyl moiety.

43. The compound of claim 40, wherein each R¹ group is methoxy, each L group is propyl, Q is N, A¹ is a C₃-C₁₀ straight chain alkyl and Y is COOH.

44. The compound of claim 40, wherein each R¹ group is methoxy, each L group is propyl, Q is N, A¹ is —

C(═

O)CH₂CH₂—

, and Y is COOH.

45. The compound of claim 41, wherein A¹ comprises a carbonyl moiety.

46. The compound of claim 42, wherein A¹ is a C₃ straight chain alkyl group comprising a carbonyl moiety.

47. The compound of claim 45, wherein A¹ is a C₃-C₁₀ alkyl group.

48. The compound of claim 47, wherein A¹ comprises a carbonyl moiety.