Increased signal to noise in nucleic acid sequencing
AssigneePacific Biosciences of California, Inc.
InventorsChad Fleischer, Denis Malyshev
Life of this patent
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Abstract
A method for identifying a nucleotide in a template nucleic acid by (a) providing a plurality of primer-template nucleic acid hybrids, wherein the primers have an extendable 3′ end; (b) contacting the plurality with: (i) blocked nucleotides to produce a first subset of the primer-template nucleic acid hybrids that include a blocked nucleotide at the 3′ end, and (ii) a ternary complex inhibitor to produce a second subset of the primer-template nucleic acid hybrids that include a ternary complex inhibitor; (c) forming ternary complexes that each include a polymerase, a primer-template nucleic acid hybrid of the first subset, and a cognate nucleotide; and (d) detecting the ternary complexes, thereby identifying a nucleotide in the template nucleic acid.
Claims18
A method for identifying a nucleotide in a template nucleic acid, comprising
- (a) providing a plurality of primer-template nucleic acid hybrids, wherein the primers comprise an extendable 3′ end;
- (b) after step (a) contacting the plurality with:
- (i) blocked nucleotides to produce a first subset of the primer-template nucleic acid hybrids that each comprise a blocked nucleotide at the 3′ end, and
- (ii) a ternary complex inhibitor to produce a second subset of the primer-template nucleic acid hybrids that each comprise a ternary complex inhibitor;
- (c) after steps (a) and (b) forming ternary complexes that each comprise a polymerase, a primer-template nucleic acid hybrid of the first subset, and a cognate nucleotide, wherein the cognate nucleotide is a cognate of a next base of the template nucleic acid;
- and
- (d) after steps (a), (b) and (c) detecting the ternary complexes, thereby identifying a nucleotide in the template nucleic acid.
Dependencies are inferred from the claim text.