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Apparatus and methods for sequencing nucleic acids in microfluidic systems

  • US 5,958,694 A
  • Filed: 10/16/1997
  • Issued: 09/28/1999
  • Est. Priority Date: 10/16/1997
  • Status: Expired due to Term
First Claim
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1. A microfluidic apparatus for determining relative positions in a target nucleic acid sequence that are occupied by a first nucleotide, comprising:

  • a microscale separation channel having first and second ends for separating nucleic acid fragments by size;

    a first source containing a nested set of first nucleotide termination fragments of the target nucleic acid in fluid communication with the separation channel, wherein the fragments terminate at each of the positions in the target occupied by the first nucleotide;

    a second source containing a nested set of second nucleotide termination fragments of the target nucleic acid, in fluid communication with the separation channel, wherein the fragments terminate at each of the positions occupied by the second nucleotide;

    a means for mixing a first concentration of the first nested set with a second concentration of the second nested set in a first mixture, the first concentration being detectably different from the second concentration;

    a means for injecting a portion of the first mixture into the separation channel and transporting the portion through the separation channel; and

    a means for detecting separate fragments of the first and second nested sets in the separation channel.

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