Substrate preparation process

{
  "publication_number": "US5959098A",
  "country": "US",
  "kind": "A",
  "title": "Substrate preparation process",
  "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 an array of polymers on a surface of a substrate, comprising: providing a substrate having first and second surfaces on opposite sides thereof, the first surface coated with functional groups protected with a photolabile protecting group, and the second surface having a coating diposed thereon, said coating including one or more of an index matching compound, a light absorbing compound and an antireflective compound; and sequentially activating and coupling monomers in different selected regions of said substrate to form a plurality of different polymer sequences in different known locations on said surface of said substrate, wherein said activating step comprises directing an activating radiation at said first surface of said substrate.",
    "2. The method according to claim 1, wherein said coating disposed upon said second surface of said substrate comprises an index matching compound.",
    "3. The method according to claim 1, wherein said coating disposed upon said second surface of said substrate is an antireflective compound.",
    "4. The method according to claim 1, wherein said coating disposed upon said second surface of said substrate comprises an index matching compound and a light absorbing compound.",
    "5. The method according to claim 1, wherein said coating disposed upon said second surface of said substrate comprises polyimide.",
    "6. The method according to claim 1, wherein said plurality of different polymer sequences comprises a plurality of different oligonucleotide sequences.",
    "7. A method of coupling monomers to selected regions on a surface of a substrate, comprising: providing functional groups on said surface of said substrate, said functional groups being protected with a photoprotecting group determining a size of transparent regions in a photolithographic mask including transparent regions and opaque regions so that the size of the transparent regions is smaller than that of selected regions of predetermined size on the substrate; exposing said selected regions to an activation radiation to remove said photolabile protecting group in said selected regions, said exposing step comprising directing an activation radiation at said selected regions on said surface of said substrate by shining said activation radiation through said transparent regions in said mask, thereby diffracting said activation radiation to expose regions comprising said selected regions; wherein overlap of regions exposed by the activation radiation is reduced relative to overlap of exposed regions resulting from performing the method using a photolithographic mask having transparent regions the same size as the selected regions of predetermined size; and coupling monomers to said functional groups in said selected regions.",
    "8. The method according to claim 7, wherein said transparent regions in said mask are from about 2% to about 25% smaller in each dimension than said selected regions.",
    "9. The method according to claim 7, wherein said transparent regions in said mask are from about 10% to about 20% smaller in each dimension than said selected regions.",
    "10. A method of deprotecting an array of polymer sequences synthesized on a solid support, comprising contacting said array with a solution containing a substituted alkylamine, wherein said contacting removes protecting groups from nucleobases or phosphate backbones of the polymer sequences, and wherein said polymer sequences remain attached to the solid support following the deprotection.",
    "11. The method according to claim 10, wherein said substituted alkylamine is selected from the group consisting of ethanolamine and ethylenediamine.",
    "12. The method according to claim 10, wherein said solution of substituted alkylamine is a solution of ethylenediamine in ethanol.",
    "13. The method according to claim 10, wherein said solution containing alkylamine is a 1:1 solution of ethylenediamine in ethanol.",
    "14. A method of photoprotecting a functional group coupled to a solid support, the method comprising exposing said functional group to a photoprotecting group transfer agent having the formula: ##STR5## wherein R 1 is a photolabile protecting group and X is a leaving group selected from the group consisting of: ##STR6## wherein: R 4 is selected from the group consisting of NO 2, SO 2 -R 2, and CN, where R 2 is alkyl, substituted alkyl or aryl; and R 5 is selected from the group consisting of adamantyl and t-butyl.",
    "15. The method of claim 1, wherein the said activating radiation is directed at said-first surface of said substrate by directing said radiation at the second surface of the substrate and through the substrate to reach the first surface."
  ],
  "description_excerpt": "Methods for synthesizing a variety of different types of polymers are well known in the art. For example, the \"Merrifield\" method, described in Atherton et al., \"Solid Phase Peptide Synthesis,\" IRL Press, 1989, which is incorporated herein by reference for all purposes, has been used to synthesize peptides on a solid support. In the Merrifield method, an amino acid is covalently bonded to a support made of an insoluble polymer or other material. Another amino acid with an alpha protecting group is reacted with the covalently bonded amino acid to form a dipeptide. After washing, the protecting group is removed and a third amino acid with an alpha protecting group is added to the dipeptide. This process is continued until a peptide of a desired length and sequence is obtained.\n\nMethods have also been developed for producing large arrays of polymer sequences on solid substrates. These large \"arrays\" of polymer sequences have wide ranging applications and are of substantial importance to the pharmaceutical, biotechnology and medical industries. For example, the arrays may be used in screening large numbers of molecules for biological activity, i.e., receptor binding capability. Alternatively, arrays of oligonucleotide probes can be used to identify mutations in known sequences, as well as in methods for de novo sequencing of target nucleic acids.\n\nOf particular note, is the pioneering work described in U.S. Pat. No. 5,143,854 (Pirrung et al.) and PCT Application No. 92/10092 disclose improved methods of molecular synthesis using light directed techniques.",
  "cpc": [
    "C07K 1/047",
    "B01J 19/0046",
    "B01J 2219/00432",
    "B01J 2219/00527",
    "B01J 2219/00529",
    "B01J 2219/00585",
    "B01J 2219/0059",
    "B01J 2219/00596",
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    "B01J 2219/00608",
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    "B01J 2219/00612",
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    "B01J 2219/00626",
    "B01J 2219/00637",
    "B01J 2219/00659",
    "B01J 2219/00689",
    "B01J 2219/00711",
    "B01J 2219/00722",
    "B01J 2219/00725",
    "B82Y 30/00",
    "C07B 2200/11",
    "C07H 21/00",
    "C40B 40/06",
    "C40B 40/10",
    "C40B 60/14",
    "Y02P 20/55",
    "Y10S 436/809"
  ],
  "ipc": [
    "B01J 19/00",
    "C07B 61/00",
    "C07H 21/00",
    "C07K 1/00",
    "C07K 1/04",
    "C12N 15/09",
    "C12Q 1/68",
    "G01N 33/53",
    "G01N 37/00"
  ],
  "assignees": [
    "Affymetrix Inc"
  ],
  "inventors": [
    "Martin Goldberg",
    "Martin Diggelman",
    "Earl Hubbell",
    "Glenn McGall",
    "Nam Quoc Ngo",
    "Macdonald Morris",
    "Mel Yamamoto",
    "Jennifer Tan",
    "Richard P. Rava"
  ],
  "filing_date": "1996-04-17",
  "publication_date": "1999-09-28",
  "grant_date": "1999-09-28",
  "priority_date": "1996-04-17",
  "application_number": "US-63405396-A",
  "family_id": "24542253",
  "cited_by_count": 584,
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}