Linking to chemical array assemblies with metal layers

• US 20040076963A1
• Filed: 10/21/2002
• Published: 04/22/2004
• Est. Priority Date: 10/21/2002
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Hargreaves, John S.
• Granted Patent: US 7,129,046 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00518 in the shape of tapes
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• 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 2219/0061 The surface being organic
• 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 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00691 using robots
• 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: 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 50/14 : Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: G01N 33/553 : Metal or metal coated

Abstract

A method of producing a front surface modified substrate, which substrate includes a metal layer, and which is useful in the fabrication of an array of multiple probes bonded to a front surface of a substrate at different features of the array. The method includes providing the substrate wherein the front surface displays functional groups. The front surface is contacted with linker molecules each having a group which binds the linker molecule to the front surface following a reaction with a surface displayed functional group, which reaction does not produce a reagent which attacks the metal layer. To fabricate an array the front surface may be contacted with the probes or probe precursors to bind the probes or probe precursors to the front surface bound linker molecules.

Claims

1. A method of fabricating an array of multiple probes bonded to a front surface of a substrate at different features of the array, which substrate includes a metal layer, the method comprising:

(a) providing the substrate wherein the front surface displays functional groups;

(b) contacting the front surface with linker molecules each having a group which binds the linker molecule to the front surface following a reaction with a surface displayed functional group, which reaction does not produce a reagent which attacks the metal layer; and

(c) contacting the front surface with the probes or probe precursors to bind the probes or probe precursors to the front surface bound linker molecules and produce the array.

2. A method according to claim 1 wherein the reaction does not produce an acid.

16. A method of using an array, comprising exposing an array produced by the method of claim 1 to a sample.

17. A method according to claim 16 additionally comprising reading the array.

18. A method comprising forwarding a result of a reading obtained by the method of claim 17, to a remote location.

19. A method comprising transmitting data representing a result of a reading obtained by the method of claim 17.

20. A method comprising receiving a result of a reading obtained by the method of claim 17.

21. An array produced according to the method of claim 1.

3. A method of fabricating an array of multiple probes bonded to a front surface of a substrate at different features of the array, which substrate includes a metal layer, the method comprising:

(a) providing the substrate wherein the front surface displays hydroxyl groups;

(b) contacting the front surface with linker molecules each having a silyloxy group which binds the linker molecule to the front surface through an ether linkage following reaction with a surface displayed hydroxyl group; and

(c) contacting the front surface with the probes or probe precursors to bind the probes or probe precursors to the front surface bound linker molecules and produce the array.

4. A method according to claim 3 wherein the probes are produced on the front surface by in situ synthesis comprising repeatedly contacting each of multiple different feature locations with probe precursors.

5. A method according to claim 3 wherein the substrate comprises a back layer, a front layer on which the front surface is located, and a metal layer positioned between the back layer and front layers.

7. A method according to claim 5 wherein (b) comprises subjecting the front surface to alkaline conditions.

8. The method according to claim 3, wherein the probes are polymers.

9. The method according to claim 8, wherein the polymers are nucleic acids.

10. The method according to claim 8, wherein the polymers are peptides.

11. The method according to claim 3 wherein the metal layer comprises chromium.

12. The method according to claim 3, wherein the silyloxy group is a silyl alkoxide.

13. The method according to claim 3 wherein the silyl alkoxide is an ethoxide.

14. A method according to claim 3, additionally comprising converting a linker functional group to a probe or probe precursor reactive functional groups where the probe or probe precursor in (c) does not bind to the surface bound linker molecules following contact.

15. A method according to claim 3 wherein the substrate comprises a back layer, a transparent front layer on which the front surface is located, and a metal layer positioned between the back layer and front layers

6. A method according to claim 53 wherein the front layer comprises glass.

22. A method of producing a front surface modified substrate, which substrate includes a metal layer, the method comprising:

(a) providing the substrate wherein the front surface displays functional groups; and

(b) contacting the front surface with linker molecules each having a group which binds the linker molecule to the front surface following a reaction with a surface displayed functional group, which reaction does not produce a reagent which attacks the metal layer.

23. A method according to claim 22 wherein the reaction does not produce an acid.

24. A method of producing a front surface modified substrate, which substrate includes a metal layer, the method comprising:

(a) providing the substrate, wherein the front surface displays hydroxyl groups;

(b) contacting the front surface with linker molecules each having a silyloxy group which binds the linker molecule to the front surface through an ether linkage following reaction with a surface displayed hydroxyl group.

25. A method according to claim 24 wherein the substrate comprises a back layer, a front layer on which the front surface is located, and a metal layer positioned between the back layer and front layers.

26. A method according to claim 25 wherein the front layer comprises glass.

27. The method according to claim 24 wherein the metal layer comprises chromium.