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Very large scale immobilized polymer synthesis using mechanically directed flow paths

  • US 5,885,837 A
  • Filed: 10/23/1996
  • Issued: 03/23/1999
  • Est. Priority Date: 11/22/1991
  • Status: Expired due to Fees
First Claim
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1. A method of forming an oligonucleotide arrays for hybridization comprising the steps of:

  • a) contacting a substrate with a channel block in a first orientation, said channel block comprising a substantially planar member with a plurality of recessed regions and raised walls on a surface thereof, said recessed regions forming channels, said raised wall effective to produce substantially fluid-tight seals between said raised walls and said substrate upon said contacting to define thereby a first plurality of flow channels between said channel block and said substrate, said first flow channels dividing said substrate surface into at least a first portion and a second portion;

    b) flowing at least a first nucleotide through at least one of said first flow channels; and

    covalently coupling said first nucleotide to said first portion of said substrate surface, said first nucleotide comprising a reactive group protected by a protecting group,c) flowing at least a second nucleotide through at least one of said first channels, and covalently coupling said second nucleotide to said second portion of said substrate surface, said second nucleotide comprising a reactive group protected by a protecting group;

    d) translating said channel block relative to said substrate and contacting said substrate with said channel block in a second orientation to produce substantially fluid-tight seals between said raised walls and said substrate upon said contacting to define thereby a second plurality of flow channels between said channel block and said substrate, said second flow channels dividing said substrate surface into at least a third portion and forth portion, said third and fourth portions each having at least one interaction with each of said first and second portions of said substrate surface;

    e) removing said protective group from at least a portion of said first or second nucleotides to form a first set of deprotected first or second nucleotides and flowing a third nucleotide through at least one of said second flow channels, covalently coupling said third nucleotide to at least a portion of said fist set of deprotected fist or second nucleotides where said first and second portions of said substrate surface intersect with said third portion of said substrate surface to form first and second oligonucleotides; and

    f) removing said protective group from at least a portion of said first and second nucleotides to form a second set of deprotected first or second nucleotides and flowing a fourth nucleotide through at least one of said second flow channels, covalently coupling said fourth nucleotide to at least a portion of said second set of deprotected first or second nucleotides where said fourth portion of said substrate surface intersects with said first and second portions of said substrate surface to form third and fourth oligonucleotides.

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