Spatially encoded biological assays
DCFirst Claim
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1. A method of associating presence or abundance of a target biological molecule with a location of interest of a tissue sample, comprising:
- delivering a plurality of probes to a tissue sample, wherein at least one probe of the plurality of probes comprises a protein that specifically binds a target biological molecule of the tissue sample, wherein the protein is conjugated to an oligonucleotide having a sequence, andwherein (i) each of the at least one probe comprises a protein that specifically binds a different target biological molecule of the tissue sample, and (ii) the protein of each of the at least one probe is conjugated to a different oligonucleotide having a sequence;
imaging the tissue sample to identify a location of interest of the tissue sample; and
sequencing all or a portion of the sequence(s) of the oligonucleotide(s) or a complement thereof, from the at least one probe specifically bound to the target biological molecule(s) in the location of interest of the tissue sample, and using the determined sequence(s) to associate presence or abundance of the target biological molecule(s) with the location of interest of the tissue sample.
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Abstract
The present invention provides assays and assay systems for use in spatially encoded biological assays. The invention provides an assay system comprising an assay capable of high levels of multiplexing where reagents are provided to a biological sample in defined spatial patterns; instrumentation capable of controlled delivery of reagents according to the spatial patterns; and a decoding scheme providing a readout that is digital in nature.
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30 Claims
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1. A method of associating presence or abundance of a target biological molecule with a location of interest of a tissue sample, comprising:
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delivering a plurality of probes to a tissue sample, wherein at least one probe of the plurality of probes comprises a protein that specifically binds a target biological molecule of the tissue sample, wherein the protein is conjugated to an oligonucleotide having a sequence, and wherein (i) each of the at least one probe comprises a protein that specifically binds a different target biological molecule of the tissue sample, and (ii) the protein of each of the at least one probe is conjugated to a different oligonucleotide having a sequence; imaging the tissue sample to identify a location of interest of the tissue sample; and sequencing all or a portion of the sequence(s) of the oligonucleotide(s) or a complement thereof, from the at least one probe specifically bound to the target biological molecule(s) in the location of interest of the tissue sample, and using the determined sequence(s) to associate presence or abundance of the target biological molecule(s) with the location of interest of the tissue sample. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30)
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Specification