Patent ID: 9353412
Filing Date: 2016-05-31
CPC Classification: C12Q

Claim Text:
1. A method of determining a sequence of nucleotides for a nucleic acid sample, comprising providing an array of nucleic acid templates, wherein the nucleic acid templates comprise nucleotide sequence fragments of the nucleic acid sample; contacting the array of nucleic acid templates with conformationally labeled polymerases and at least four different nucleotide species under conditions wherein the conformationally labeled polymerases catalyze sequential addition of the nucleotide species to form nucleic acid complements of the nucleic acid templates, wherein the different nucleotide species comprise at least one non-natural nucleotide analog, wherein the sequential addition of each different nucleotide species produces a conformational signal change from the conformationally labeled polymerase and wherein the rate or time duration for the conformational signal change is distinguishable for each different nucleotide species; detecting a series of the conformational signal changes from the conformationally labeled polymerase under the conditions and at individual locations of the array; and determining the sequence of nucleotides for the nucleic acid sample by determining the rates or time durations for the conformational signal changes at the individual locations of the array, wherein the determining comprises distinguishing at least 10 fold difference between the rate or time duration for the conformational signal changes of the at least one non-natural nucleotide analog and the other different nucleotide species that are added to form the nucleic acid complements of the nucleic acid templates, and wherein the at least one non-natural nucleotide analog lacks probes that are detected in the method to determine the sequence of nucleotides for the nucleic acid sample.