Substrate preparation process

• US 6,307,042 B1
• Filed: 02/04/1999
• Issued: 10/23/2001
• Est. Priority Date: 04/17/1996
• Status: Expired due to Term

• Current Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Original Assignee: Affymetrix, Inc. (Thermo Fisher Scientific Incorporated)
• Inventors: Morris, MacDonald, Rava, Richard P., McGall, Glenn, Goldberg, Martin, Tan, Jennifer, Diggelman, Martin, Ngo, Nam Quoc, Hubbell, Earl, Yamamoto, Mel
• Primary Examiner(s): Riley, Jezia
• Application Number:
  US09/244,568
• Time in Patent Office: 992 Days
• Field of Search: 435/6, 536/22.1, 536/23.1, 536/24.3, 536/24.32, 536/25.3
• US Class Current: 506/16
• 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 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• 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 2219/00621 by physical means, e.g. trenches, raised areas
• 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 2219/00689 using computers
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• 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: 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: C07K 1/047 : Simultaneous synthesis of different peptide species; Peptide libraries
• 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 60/14 : for creating libraries
• CPC Class Codes: Y02P 20/55 : Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
• CPC Class Codes: Y10S 436/809 : Multifield plates or multicontainer arrays

Abstract

The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

Claims

1. A method of forming a plurality of individual polymer arrays, comprising:

providing a plurality of substrate wafers, each of said substrate wafers having a first surface, said first surface having functional groups disposed thereon, said functional groups being protected with a removable protecting group;

exposing a plurality of first known locations on said first surface of each of said substrate wafers to an activator at an activation station to remove said removable protecting groups from said functional groups in said first known locations;

moving said substrate wafers batch-wise to a coupling station;

contacting said plurality of wafers with a monomer containing solution at said coupling station, to couple the monomers to said functional groups in said known locations on said surface of said plurality of substrate wafers;

returning said substrate wafers batch-wise to said activation station;

repeating said exposing, moving and contacting steps at further known locations on said plurality of substrate wafers to form a plurality of individual polymer arrays on said first surface of each of said substrate wafers.

2. The method according to claim 1, wherein said contacting step comprises simultaneously contacting said plurality of substrate wafers with said monomer containing solution.

3. The method according to claim 1, wherein said removable protecting group is a photolabile protecting group and said activator is light.

4. The method according to claim 1, wherein said exposing step comprises simultaneously contacting at least a first of said plurality of substrate wafers with a first monomer containing solution and contacting a second of said plurality of substrate wafers with a second monomer containing solution.

5. The method according to claim 1, wherein said activator comprises an activation radiation and said exposing step comprises directing said activation radiation at said first surface of said plurality of substrate wafers, and wherein a second surface of said plurality of substrate wafers includes a layer of one or more of an index matching compound, a light absorbing compound and an antireflective compound disposed thereon.

6. The method according to claim 5, wherein said layer disposed upon said second surface of said substrate comprises an index matching compound.

7. The method according to claim 5, wherein said layer disposed upon said second surface of said substrate is an antireflective compound.

8. The method according to claim 5, wherein said layer disposed absorbing compound.

9. The method according to claim 5, wherein said layer disposed upon said second surface of said substrate comprises polyimide.

10. The method according to claim 1, wherein said plurality of different polymer sequences comprises a plurality of different nucleic acid sequences.