Abstract: Methods for labeling biological samples include (a) contacting a biological sample featuring a target RNA with a probe, where the probe includes a capture moiety that specifically binds to the target RNA, and a plurality of reporter moieties, and (b) for each reporter moiety of the plurality of reporter moieties: contacting the reporter moiety with a catalytic agent that includes an oligonucleotide that specifically binds to the reporter moiety, and a reactive species linked to the oligonucleotide, and contacting the biological sample with a labeling agent that reacts with the reactive species to deposit the labeling agent or a derivative thereof in the sample in proximity to the target RNA.

Abstract: Methods for RNA detection in biological samples include (a) contacting a biological sample with a first composition featuring multiple different types of unlabeled oligonucleotide probes that hybridize to RNA species in the sample; (b) contacting the biological sample with a hybridization agent featuring a chaotropic compound; (c) contacting the biological sample with a second composition that includes multiple different types of labeled oligonucleotide probes, where each of the different types of labeled oligonucleotide probes selectively hybridizes to one of the different types of unlabeled oligonucleotide probes; (d) obtaining at least one image of the biological sample with the multiple different types of labeled oligonucleotide probes bound to the sample; and (e) identifying spatial locations of the RNA species in the sample based on components of the at least one image that correspond to the different types of labeled oligonucleotide probes, where the biological sample is contacted with the second compo

Abstract: Methods include contacting a biological sample with a first probe, where the first probe includes a capture moiety having an oligonucleotide sequence that selectively binds to a RNA in the sample, and a secondary oligonucleotide region that does not bind to the RNA, contacting the sample with a second probe, where the second probe includes a probe binding region that is complementary to, and hybridizes to, a portion of the secondary oligonucleotide region, and includes a reporter moiety, and extending the secondary oligonucleotide region using the second probe as a template to generate an extended secondary oligonucleotide region featuring multiple copies of the reporter moiety, where the reporter moiety includes a plurality of label regions each featuring an oligonucleotide sequence, and one or more of the label regions of the reporter moiety are different from the other label regions of the reporter moiety.

Abstract: Methods for determining locations of analytes include: (a) exposing a biological sample to a plurality of different types of probes, where each different type of probe includes a nucleic acid capture moiety and a detection moiety that includes at least one reporter moiety, where the at least one reporter moiety features multiple label regions, each of the label regions including an oligonucleotide having a sequence; (b) exposing the biological sample to a plurality of optical labels; (c) measuring optical signals generated by optical labels; (d) repeating steps (b) and (c) with different pluralities of optical labels; (e) identifying one or more of the reporter moieties in the sample based on the measured optical signals; and (f) determining a location of one or more of the RNA analytes in the sample based on the identified reporter moieties.

Abstract: Provided herein is a method and system for analyzing a sample. In some embodiments the method makes use of a plurality of capture agents that are each linked to a different oligonucleotide and a corresponding plurality of labeled nucleic acid probes, wherein each of the labeled nucleic acid probes specifically hybridizes with only one of the oligonucleotides. The sample is labeled with the capture agents en masse, and sub-sets of the capture agents are detected using iterative cycles using corresponding subsets of the labeled nucleic acid probes.

Abstract: Methods include (a) contacting a biological sample with a composition featuring a plurality of different types of probes, where each type of probe of the plurality of different types of probes includes a detection moiety that selectively binds to a different type of protein target in the sample, a nanobody bound to the detection moiety, and an oligonucleotide linked to the nanobody and featuring an oligonucleotide sequence, where the oligonucleotide sequence of each type of probe is different from the oligonucleotide sequences of each of the other types of probes of the plurality of probes; and (b) contacting the sample with a set of one or more different types of optical labels, where each different type of optical label of the set of optical labels includes an oligonucleotide that selectively hybridizes to only one type of probe.

Abstract: The disclosure features methods that include: contacting a biological sample having a first target analyte with a first agent, where the first agent includes a first binding species that specifically binds to the first target analyte, and a first oligonucleotide conjugated to the binding species; contacting the biological sample with a second agent, where the second agent includes a first reactive species and a second oligonucleotide conjugated to the first reactive species, to hybridize at least a portion of the second oligonucleotide to at least a portion of the first oligonucleotide; and contacting the biological sample with a first labeling species, where the first labeling species reacts with the first reactive species to deposit the first labeling species or a derivative thereof in the biological sample.

Abstract: The tissue microenvironment is a critical factor to disease mechanism and therapeutic efficiency. Provided here is an imaging platform, methods, and kits which enable measurement of tens of parameters simultaneously within a single tissue, with the potential to reveal unique and important biological associations related to the spatial dimension. The sensitivity of the platform, methods, and kits described herein extends to measure low level markers which can be important for tracking disease progression, diagnosing disease, or both.

Abstract: Provided herein is a method and system for analyzing a sample. In some embodiments the method makes use of a plurality of capture agents that are each linked to a different oligonucleotide and a corresponding plurality of labeled nucleic acid probes, wherein each of the labeled nucleic acid probes specifically hybridizes with only one of the oligonucleotides. The sample is labeled with the capture agents en masse, and sub-sets of the capture agents are detected using iterative cycles using corresponding subsets of the labeled nucleic acid probes.

Abstract: Provided herein are methods, kits, and compositions for the detection of an element of a biological sample using an antibody conjugated to a first oligonucleotide, which connects to a labelled oligonucleotide for detection via an oligonucleotide partially complementary to the first oligonucleotide and partially complementary to the second oligonucleotide.

Abstract: An apparatus attaches to a microscope slide to form an enclosed fluidic chamber with input and output ports, where a tissue or cell sample on the slide can be processed using techniques such as immunohistochemical staining. Flow of reagents within the chamber can be laminar and highly uniform across the sample surface to achieve staining that is free of gradients. The sample can be imaged prior to, during, or after any given processing step. Methods for staining and imaging a sample can be implemented through one or more rounds of labeling, label removal or erasure and imaging. Samples can be imaged many times to achieve very high multiplexing levels. Samples can be placed on an imaging apparatus at various times and removed from the imaging apparatus for certain steps.

Abstract: Provided herein is a method and system for analyzing a sample. In some embodiments the method makes use of a plurality of capture agents that are each linked to a different oligonucleotide and a corresponding plurality of labeled nucleic acid probes, wherein each of the labeled nucleic acid probes specifically hybridizes with only one of the oligonucleotides. The sample is labeled with the capture agents en masse, and sub-sets of the capture agents are detected using iterative cycles using corresponding subsets of the labeled nucleic acid probes.

Abstract: Provided herein is a method and system for analyzing a sample. In some embodiments the method makes use of a plurality of capture agents that are each linked to a different oligonucleotide and a corresponding plurality of labeled nucleic acid probes, wherein each of the labeled nucleic acid probes specifically hybridizes with only one of the oligonucleotides. The sample is labeled with the capture agents en masse, and sub-sets of the capture agents are detected using iterative cycles using corresponding subsets of the labeled nucleic acid probes.

Abstract: Provided herein is a method and system for analyzing a sample. In some embodiments the method makes use of a plurality of capture agents that are each linked to a different oligonucleotide and a corresponding plurality of labeled nucleic acid probes, wherein each of the labeled nucleic acid probes specifically hybridizes with only one of the oligonucleotides. The sample is labeled with the capture agents en masse, and sub-sets of the capture agents are detected using iterative cycles using corresponding subsets of the labeled nucleic acid probes.