Functionalization of substrate surfaces with silane mixtures

• US 6,660,338 B1
• Filed: 03/08/2001
• Issued: 12/09/2003
• Est. Priority Date: 03/08/2001
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Hargreaves, John S.
• Primary Examiner(s): Dawson, Robert
• Assistant Examiner(s): Feely, Michael J
• Application Number:
  US09/802,653
• Time in Patent Office: 1,006 Days
• Field of Search: 428/428, 428/429, 428/446, 428/447, 428/448, 427/299, 427/337, 427/402, 427/399, 528/10, 528/25, 528/28, 528/33, 528/42, 106/287.13, 106/287.14, 106/287.15, 106/287.16, 435/6, 435/91.1
• US Class Current: 427/399
• CPC Class Codes: B05D 1/18 performed by dipping
• CPC Class Codes: B05D 5/08 to obtain an anti-friction or anti-adhesive surface rendering particulate materials free-flowing in general, e.g. making them hydrophobic B01J2/30
• CPC Class Codes: C03C 17/30 with silicon-containing compounds
• CPC Class Codes: C03C 17/3405 with at least two coatings of organic materials C03C17/36, C03C17/42 take precedence

Abstract

Low surface energy functionalized surfaces on solid supports are provided by contacting a surface of a solid substrate having reactive moieties on the surface with a solution of an organic solvent and water. The surface of the solid substrate is then contacted with a derivatizing composition containing a mixture of silanes. A first silane provides the desired reduction in surface energy, while the second silane enables functionalization with molecular moieties of interest, such as small molecules. Molecular moieties of interest may be attached through cleavable sites. Derivatizing compositions for carrying out the surface functionalization process are provided as well.

Claims

1. A process comprising:

(a) producing a solution of an organic solvent and water;

(b) contacting a surface of a solid substrate, which surface has reactive moieties thereon, with the solution and a derivatizing composition comprising a first silane, R¹—

Si(R^LR^XR^Y) and a second silane, R²—

(L)_n—

Si(R^LR^XR^Y), so that —

Si—

R¹ groups and —

Si—

(L)_n—

R² groups become covalently coupled to the surface, wherein the R^L moieties, which may be identical or different, are leaving groups, R^X and R^Y are independently lower alkyl or leaving groups, R¹ is a chemically inert moiety that lowers the surface energy of the substrate, n is 0 or 1, L is a linking group, and R² is either a functional group enabling covalent binding of a molecular moiety or a modifiable group that may be converted to such a functional group.

2. The process of claim 1, wherein the reactive moieties are selected from the group consisting of hydroxyl, carboxyl, thiol, amino, and combinations thereof.

3. The process of claim 2, wherein the reactive moieties are hydroxyl groups.

4. The process of claim 1, wherein the R^L moieties are selected from the group consisting of halogen and alkoxy.

5. The process of claim 4, wherein the R^L moieties are selected from the group consisting of chloro and lower alkoxy.

6. The process of claim 1, wherein R¹ is an alkyl group.

7. The process of claim 1, wherein n is 1.

8. The process of claim 7, wherein L is a C₁-C₂₄ hydrocarbylene linking group substituted with 0 to 6 substituents selected from the group consisting of lower alkyl, hydroxyl, halogen and amino, optionally containing 1 to 6 —

O—

, —

S—

, —

NR—

, —

CONH—

, —

(CO)—

or —

COO—

linkages, wherein R is hydrogen or lower alkyl.

9. The process of claim 8, wherein L is a C₁-C₂₄ alkylene.

10. The process of claim 9, wherein L is a C₁₀-C₁₈ alkylene.

11. The process of claim 1, wherein R² is —

CH═

CH₂.

12. The process of claim 1, wherein in the first silane, R^X and R^Y are lower alkyl.

13. The process of claim 1, wherein in the second silane, R^X and R^Y are lower alkyl.

14. The process of claim 1, wherein the reactive moieties are selected from the group consisting of carboxyl, thiol, amino, and combinations thereof.

35. The process of claim 1, 15, 26, 32, or 33, wherein the contacting comprises:

(b-1) first contacting the surface with the solution;

(b-2) subsequently adding the silanes to the solution surface combination.

36. The process of claim 1, 15, 26, 32, or 33, wherein the surface of the solid support is contacted, at the same time, with the solution and the silanes.

37. The process of claim 1, 15, 26, 32, or 33, wherein R² is not a thiol.

15. A process for preparing a solid substrate of low surface energy and functionalized with support-bound cleavable ligands, comprising:

(a) producing a solution of an organic solvent and water;

(b) contacting a surface of the substrate, which surface has reactive moieties thereon, with the solution and a derivatizing composition comprising a first silane, R¹—

Si(R^LR^XR^Y) and a second silane, R²—

(L)_n—

Si(R^LR^XR^Y), so that —

Si—

R¹ groups and —

Si—

(L)_n—

R² groups become covalently coupled to the surface, wherein the R^L moieties, which may be identical or different, are leaving groups, R^X and R^Y are independently lower alkyl or leaving groups, R¹ is a chemically inert moiety that lowers the surface energy of the substrate, n is 0 or 1, L is a linking group, and R² is either a functional group or a modifiable group that may be converted to such a functional group;

if R² is a modifiable group, converting it to a functional group; and

(c) coupling a ligand to R² through a linking moiety containing a chemically cleavable site selected from the group consisting of base-cleavable sites, acid-cleavable sites and nucleophile-cleavable sites.

16. The process of claim 15, wherein the cleavable site is base-cleavable.

17. The process of claim 16, wherein the cleavable site is an ester linkage.

18. The process of claim 15, wherein R² is a modifiable group.

19. The process of claim 18, wherein R² is —

CH═

CH₂.

20. The process of claim 19, wherein prior to coupling the ligand, R² is converted to a hydroxyl group by boration and oxidation.

21. The process of claim 15, wherein the ligand is an intact oligomer.

22. The process of claim 21, wherein the oligomer is an oligopeptide or an oligosaccharide.

23. The process of claim 15, wherein the ligand is a first monomer to be used as the starting point for solid phase synthesis of an oligomer.

24. The process of claim 23, wherein the ligand is a nucleotide.

25. The process of claim 15, further including cleaving the ligand from the support at the cleavable site.

26. A process for synthesizing an oligomer array on a solid substrate comprising:

(a) producing a solution of an organic solvent and water;

(b) contacting a surface of the substrate, which surface has reactive moieties thereon, with the solution and a derivatizing composition comprising a first silane, R¹—

Si(R^LR^XR^Y) and a second silane, R²—

(L)_n—

Si(R^LR^XR^Y), so that —

Si—

R¹ groups and —

Si—

(L)_n—

R² groups become covalently coupled to the surface, wherein the R^L moieties, which may be identical or different, are leaving groups, R^X and R^Y are independently lower alkyl or leaving groups, R1 is a chemically inert moiety that lowers the surface energy of the substrate, n is 0 to 1, L is a linking group, and R² is either a functional group enabling covalent binding of a molecular moiety or a modifiable group that may be converted to such a functional group; and

(c) synthesizing a plurality of substrate-bound oligomers at each R² by successively coupling monomers thereto, thereby forming an oligomer array on the functionalized surface provided in step (b).

27. The process of claim 26, wherein the individual monomers are nucleotides and the oligomers are oligonucleotides.

28. The process of claim 26, wherein the individual monomers are protected and a deprotection step is carried out after each successive coupling.

29. The process of claim 26, wherein prior to step (c) a linking group is coupled to each R², and the individual monomers are successively coupled to a free terminus of the linking group.

30. The process of claim 29, wherein the linking group contains a cleavable site.

31. The process of claim 30, wherein the cleavable site is chemically cleavable.

32. A process for preparing an oligomer array, comprising:

(a) producing a solution of an organic solvent and water;

(b) contacting a surface of a substrate, which surface has reactive moieties thereon, with the solution and a derivatizing composition comprising a first silane, R¹—

Si(R^LR^XR^Y) and a second silane, R²—

(L)_n—

Si(R^LR^XR^Y), so that —

Si—

R¹ groups and —

Si—

(L)_n—

R² groups become covalently coupled to the surface, wherein the R^L moieties, which may be identical or different, are leaving groups, R^X and R^Y are independently lower alkyl or leaving groups, R¹ is a chemically inert moiety that lowers the surface energy of the substrate, n is 0 to 1, L is a linking group, and R² is either a functional group enabling covalent binding of a molecular moiety or a modifiable group that may be converted to such a functional group; and

(c) binding a plurality of substrate-bound oligomers to the functionalized substrate by coupling an oligomer to each R².

33. A process for preparing a substrate of low surface energy and functionalized with support-bound cleavable ligands, comprising:

(a) producing a solution of an organic solvent and water;

(b) contacting a surface of the substrate, which surface has reactive moieties thereon, with the solution and a derivatizing composition comprising a first silane, R¹—

Si(R^LR^XR^Y) and a second silane, R²—

(L)_n—

Si(R^LR^XR^Y), so that —

Si—

R¹ groups and —

Si—

(L)_n—

R² groups become covalently coupled to the surface, wherein the R^L moieties, which may be identical or different, are leaving groups, R^X and R^Y are independently lower alkyl or leaving groups, R¹ is a chemically inert moiety that lowers the surface energy of the substrate, n is 0 to 1, L is a linking group, and R² is either a functional group or a modifiable group that may be converted to such as functional group;

if R² is a modifiable group converting it to a functional group; and

(c) coupling a ligand to R² through a linking moiety containing a chemically cleavable site cleavable by an agent selected from the group consisting of lithium aluminum hydride, aluminum trichloride, silver ions, mercuric ions, and fluoride ions.

34. The process of claim 33, further including cleaving the ligand from the support at the cleavable site.

38. A derivatizing composition for functionalizing a surface of a substrate, comprising:

a solution of an organic solvent and water and a first silane, R¹—

Si(R^LR^XR^Y) and second silane R²—

(L)_n—

Si(R^LR^XR^Y), wherein the R^L moieties are independently leaving groups, R^X and R^Y may be identical or different and are either lower alkyl or leaving groups, R¹ is a chemically inert moiety that lowers the surface energy of the substrate, n is 0 or 1, L is a linking group, and R² is —

CH═

CH₂.