Nucleic acid sequencing with nanoscale electrode pairs
AssigneePacific Biosciences of California, Inc.
InventorsStephen Turner, Jeremiah Hanes, Keith Bjornson
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Abstract
Sequencing methods, devices, and systems are described. Arrays of nanoscale electronic elements comprising two electrodes separated by an insulating layer are used to provide sequence information about a template nucleic acid in a polymerase-template complex bound proximate to the insulating region. A sequencing reaction mixture comprising nucleotide analogs having impedance labels is introduced to the array of nanoscale electronic elements under conditions of polymerase mediated nucleic acid synthesis. The time sequence of incorporation of nucleotide analogs is determined by identifying the types of labels of the nucleotide analogs that are incorporated into the growing strand using measured impedance.
Claims18
A chip for sequencing a plurality of single nucleic acid template molecules comprising:
- a substrate comprising;
- a plurality multi-layer capacitive devices,
- each capacitive device comprising a lower electrode layer, above the lower electrode a first insulating layer, above the first insulating layer an upper electrode layer, and above the upper electrode layer a second insulating layer, wherein an edge of the capacitive device is exposed whereby an edge of the lower electrode layer, an edge of the first insulating layer, and an edge of the upper electrode layer are in contact with a sequencing reaction mixture;
- wherein, for each of the of the capacitive devices, a single polymerase enzyme complex comprising a template nucleic acid is bound to the edge of the first insulating layer, which is in contact with the sequencing reaction mixture that comprises;
- a plurality of types of nucleotide analogs each having different capacitive labels;
- and
- a plurality of electrical connection sites for bringing current and voltage to the capacitive devices, and for receiving electrical signals from the devices.
Dependencies are inferred from the claim text.