Real-time redox sequencing
AssigneePacific Biosciences of California, Inc.
InventorsJonas Korlach, Stephen Turner, Lei Sun
Life of this patent
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Abstract
Real time redox sequencing methods, devices, and systems are described. Arrays of redox devices comprising one or two electrodes are used to provide sequence information about a template nucleic acid in a polymerase-template complex bound proximate to the electrode(s). A sequencing reaction mixture comprising nucleotide analogs comprising redox labels is introduced to the array of redox devices under conditions of polymerase mediated nucleic acid synthesis. The time sequence of incorporation of nucleotide analogs is determined by electrochemically identifying the redox labels of the nucleotide analogs that are incorporated into the growing strand.
Claims10
A system for sequencing a template nucleic acid comprising:
- a housing having housing electrical connection sites;
- a chip that reversibly mates with the housing comprising a substrate comprising:
- chip electrical connection sites that reversibly connect to the housing electrical connection sites;
- a plurality of redox devices, each redox device comprising at least one nanoscale redox electrode and a single polymerase enzyme complex bound to the at least one nanoscale redox electrode or to the substrate proximate to the at least one nanoscale redox electrode, wherein the polymerase enzyme complex comprises a polymerase enzyme and a template nucleic acid;
- a fluid reservoir comprising a sequencing reaction mixture in contact with the redox devices, the sequencing reaction mixture comprising a plurality of types of nucleotide analogs, each having a different redox label, wherein each redox label is connected to the nucleotide portion of the analog through a linker of a length whereby the redox labels are oxidized and reduced while an analog is associated with the polymerase enzyme complex;
- an electronic control system electrically connected to the nanoscale electrodes through the electrical connections to apply desired voltages to the nanoscale redox electrodes and for determining the current to and from the nanoscale redox electrodes;
- and
- a computer that receives information on the current to and from the nanoscale redox electrodes over time and uses such information to identify a sequence of the template nucleic acid.
Dependencies are inferred from the claim text.