An apparatus for label-free analysis of molecules, including interactions and reactions of the molecules, is disclosed. The apparatus is based on detecting molecule movement under the influence of an external electric field. The apparatus is able to achieve sensitive detection of molecular binding to proteins or other molecules, and conformational changes of proteins or other molecules and biochemical reactions of the proteins or other molecules. Applications of the apparatus include screening of drug molecules, kinetic analysis of posttranslational modification of proteins, and small molecule-protein interactions.

An apparatus for label-free analysis of molecules, including interactions and reactions of the molecules, is disclosed. The apparatus is based on detecting molecule movement under the influence of an external electric field. The apparatus is able to achieve sensitive detection of molecular binding to proteins or other molecules, and conformational changes of proteins or other molecules and biochemical reactions of the proteins or other molecules. Applications of the apparatus include screening of drug molecules, kinetic analysis of posttranslational modification of proteins, and small molecule-protein interactions.

In some aspects, the present disclosure relates to methods for reducing the detection of false positive ligation events. In some aspects, the method comprises use of a double split (or “split split”) probe. The methods herein have particular applicability in reducing the detection of false positive ligation events when using ligases that have high ligation efficiency but low specificity (e.g., SplintR® ligase). Also provided are kits comprising probes for use in such methods.

In some aspects, the present disclosure relates to methods for reducing the detection of false positive ligation events. In some aspects, the method comprises use of a double split (or “split split”) probe. The methods herein have particular applicability in reducing the detection of false positive ligation events when using ligases that have high ligation efficiency but low specificity (e.g., SplintR® ligase). Also provided are kits comprising probes for use in such methods.

The present disclosure provides multiplexed methods, and constructs made to be used in said methods, for characterizing microbes from a biological sample to both rapidly identify the microbe and characterize drug susceptibility or resistance and perform microbial taxa identification and nucleic acid target detection at high multiplexity. The methods can also be used to predict future microbe drug susceptibility or resistance.

The present disclosure provides multiplexed methods, and constructs made to be used in said methods, for characterizing microbes from a biological sample to both rapidly identify the microbe and characterize drug susceptibility or resistance and perform microbial taxa identification and nucleic acid target detection at high multiplexity. The methods can also be used to predict future microbe drug susceptibility or resistance.

The present disclosure in some aspects relates to methods and compositions for accurately detecting and quantifying multiple analytes present in a biological sample. In some aspects, the methods and compositions provided herein address one or more issues associated with the stability and/or size of nucleic acid structures such as rolling circle amplification products in the biological sample.

The present disclosure in some aspects relates to methods and compositions for accurately detecting and quantifying multiple analytes present in a biological sample. In some aspects, the methods and compositions provided herein address one or more issues associated with the stability and/or size of nucleic acid structures such as rolling circle amplification products in the biological sample.

Methods for identifying co-occurrence of nucleic acid segments in a nucleic acid sample from a specimen including obtaining a nucleic acid sample from a specimen, determining sequences of first and second nucleic acid segments in nucleic acid fragments of the sample to generate a first and second sets of sequences, generating a first and second sets of probes from the first and second sets of sequences, exposing a detection sample to a member of the first set of probes and a member of the second set of probes, performing a hybridization analysis to determine whether the members of the first and second sets of probes hybridize to the detection sample, and determining whether the first and second nucleic acid segments co-occur in a common cell of the specimen.

Methods for identifying co-occurrence of nucleic acid segments in a nucleic acid sample from a specimen including obtaining a nucleic acid sample from a specimen, determining sequences of first and second nucleic acid segments in nucleic acid fragments of the sample to generate a first and second sets of sequences, generating a first and second sets of probes from the first and second sets of sequences, exposing a detection sample to a member of the first set of probes and a member of the second set of probes, performing a hybridization analysis to determine whether the members of the first and second sets of probes hybridize to the detection sample, and determining whether the first and second nucleic acid segments co-occur in a common cell of the specimen.