Functionalized silicon compounds and methods for their synthesis and use

• US 6,262,216 B1
• Filed: 10/13/1998
• Issued: 07/17/2001
• Est. Priority Date: 10/13/1998
• Status: Expired due to Term

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: McGall, Glenn
• Primary Examiner(s): Riley, Jezia
• Application Number:
  US09/172,190
• Time in Patent Office: 1,008 Days
• Field of Search: 528/10, 528/25, 528/28, 528/33, 422/50, 422/68.1
• US Class Current: 528/10
• CPC Class Codes: C03C 17/30 with silicon-containing compounds
• CPC Class Codes: C03C 2218/113 by sol-gel processes
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: C08G 73/0206 Polyalkylene(poly)amines
• CPC Class Codes: C09D 179/02 Polyamines
• CPC Class Codes: C09D 183/08 containing silicon bound to organic groups containing atoms other than carbon, hydrogen, and oxygen
• CPC Class Codes: C09D 183/14 in which at least two but not all the silicon atoms are connected by linkages other than oxygen atoms C09D183/10 takes precedence
• CPC Class Codes: Y10T 428/31663 As siloxane, silicone or silane

Abstract

Provided are functionalized silicon compounds and methods for their synthesis and use. The functionalized silicon compounds include at least one activated silicon group and at least one derivatizable functional group. Exemplary derivatizable functional groups include hydroxyl, amino, carboxyl and thiol, as well as modified forms thereof, such as activated or protected forms. The functionalized silicon compounds may be covalently attached to surfaces to form functionalized surfaces which may be used in a wide range of different applications. In one embodiment, the silicon compounds are attached to the surface of a substrate comprising silica, such as a glass substrate, to provide a functionalized surface on the substrate, to which molecules, including polypeptides and nucleic acids, may be attached. In one embodiment, after covalent attachment of a functionalized silicon compound to the surface of a solid silica substrate to form a functionalized coating on the substrate, an array of nucleic acids may be covalently attached to the substrate. Thus, the method permits the formation of high density arrays of nucleic acids immobilized on a substrate, which may be used, for example, in conducting high volume nucleic acid hybridization assays.

Claims

1. A functionalized silicon compound having a structure of Formula 2:

wherein R₁ and R₂ are independently selected from the group consisting of alkoxy and halide, and R₃ is selected from the group consisting of alkoxy, halide and alkyl;

wherein L₁ and L₂ are both —

(CH₂)_n—

, wherein n=2 to 10; and

wherein A₁ is a moiety comprising one or more derivatizable functional groups selected from the group consisting of hydroxyl, amino, carboxyl, thio, halo and sulfonate.

2. The functionalized silicon compound of claim 1, wherein A₁ comprises a plurality of the derivatizable functional groups.

4. The functionalized silicon compound of claim 1, wherein the silicon compound is compound II:

3. A functionalized silicon compound having a structure of Formula 2:

wherein R₁ and R₂ are independently selected from the group consisting of alkoxy and halide, and R₃ is selected from the group consisting of alkoxy, halide and alkyl;

wherein L₁ and L₂ are both —

(CH₂)_n—

, wherein n=2 to 10; and

wherein A₁ is a moiety comprising a hydroxyl group.

15. The compound of claim 3, wherein the hydroxyl group is activated or protected.

5. A method of fimctionalizing a surface, the method comprising covalently attaching to the surface a functionalized silicon compound, wherein the functionalized silicon compound comprises at least one derivatizable functional group and a plurality of activated silicon groups, wherein the silicon compound is a compound having a structure of Formula 2:

wherein R₁ and R₂ are independently selected from the group consisting of alkoxy and halide, and R₃ is selected from the group consisting of alkoxy, halide and alkyl;

wherein L₁ and L₂ are both —

(CH₂)_n—

, wherein n=2 to 10; and

wherein A₁ is a moiety comprising one or more derivatizable functional groups selected from the group consisting of hydroxyl, amino, carboxyl, thio, halo and sulfonate.

6. The method of claim 5, wherein the derivatizable functional group is a hydroxyl group.

7. The method of claim 5, wherein A₁ comprises a plurality of the derivatizable functional groups.

8. The method of claim 5, wherein the silicon compound is compound II:

9. The method of claim 5, wherein the surface is the surface of a substrate comprising silica.

10. The method of claim 5, wherein the substrate is in a form selected from the group consisting of particles, films and chips.

11. The method of claim 5, wherein the method comprises covalently attaching a plurality of functionalized silicon compounds surface;

and

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

12. The method of claim 11, wherein the derivatizable functional group is hydroxyl.

13. The method of claim 6, wherein the hydroxyl group is activated or protected.

14. The method of claim 12, wherein the hydroxyl group is activated or protected.

16. The method of claim 12, wherein the density of the covalently attached nucleic acids on the surface is greater than about 60 different nucleic acids per 1 cm².