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US 11,111,521 B2Granted
Compositions and methods for analyte detection
AssigneePresident and Fellows of Harvard College
InventorsGeorge M. Church, Je-hyuk Lee, Richard C. Terry, Evan R. Daugharthy
Life of this patent
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Abstract
Methods of making a three-dimensional matrix of nucleic acids within a cell is provided.
Claims72
A method for biological analysis, comprising:
- (a) providing a cell or tissue sample, wherein said cell or tissue sample comprises an analyte at a spatial location in said cell or tissue sample;
- (b) binding a detection reagent to said analyte at said spatial location, wherein said detection reagent comprises (i) a probe that binds to said analyte and (ii) one or more pre-determined subsequences;
- (c) performing a plurality of detection steps at said spatial location to obtain a time series of signal signatures corresponding to said analyte, wherein said plurality of detection steps comprises (i) detecting a first detectable label associated with said one or more pre-determined subsequences to obtain a first signal signature at said spatial location at a first time point of said time series;
- (ii) removing said first detectable label from said one or more pre-determined subsequences;
- and (iii) detecting a second detectable label associated with said one or more pre-determined subsequences to obtain a second signal signature at said spatial location at a second time point of said time series, wherein said second time point of said time series is subsequent to said first time point of said time series;
- and
- (d) using said time series of signal signatures to identify said analyte at said spatial location in said cell or tissue sample.
4 more elements
A method for biological analysis, comprising:
- (a) binding a detection reagent to a target nucleic acid molecule at a spatial location in a cell or tissue sample, wherein said detection reagent comprises a nucleic acid molecule comprising (i) a probe sequence that binds to said target nucleic acid molecule and (ii) a label that identifies said probe, wherein said label comprises a first predetermined subsequence and a second predetermined subsequence;
- (b) performing a plurality of detection steps at said spatial location to obtain a time series of signal signatures corresponding to said label, wherein said plurality of detection steps comprises (i) using a first decoder probe complementary to said first predetermined subsequence to associate a first detectable label with said first pre-determined subsequence;
- (ii) detecting said first detectable label in said cell or tissue sample to obtain a first signal signature at said spatial location at a first time point of said time series of signal signatures;
- (iii) removing said first detectable label from said cell or tissue sample;
- and (iv) using a second decoder probe complementary to said second predetermined subsequence to associate a second detectable label with said second pre-determined subsequence;
- and (v) detecting said second detectable label in said cell or tissue sample to obtain a second signal signature at said spatial location at a second time point of said time series of signal signatures, wherein said second time point of said time series is subsequent to said first time point of said time series;
- and
- (c) using said time series of signal signatures to identify said analyte at said spatial location in said cell or tissue sample.
5 more elements
Dependencies are inferred from the claim text.