Described herein is a method to create dendritic biocompatible polymers from pairs of complementary dendritic nucleic acid monomers in a controlled manner, using polymerization triggers. The dendritic monomers are constituted of nucleic acids and an organic polymer capable of self-assembly. Each polymer contains approximately 200 dendrites that can be used to attach labels and constitute a biologically compatible signal amplification technology. Depending on the context this technology could be used to reveal the presence of a large variety of analytes such as specific nucleic acid molecules, small molecules, proteins, and peptides.

Described herein is a method to create dendritic biocompatible polymers from pairs of complementary dendritic nucleic acid monomers in a controlled manner, using polymerization triggers. The dendritic monomers are constituted of nucleic acids and an organic polymer capable of self-assembly. Each polymer contains approximately 200 dendrites that can be used to attach labels and constitute a biologically compatible signal amplification technology. Depending on the context this technology could be used to reveal the presence of a large variety of analytes such as specific nucleic acid molecules, small molecules, proteins, and peptides.

The present disclosure relates to tagged multi-nucleotide compounds, which comprise a single tag moiety covalently linked to a plurality of nucleoside-5′-oligophosphate moieties. As disclosed herein, these tagged multi-nucleotide compounds have improved characteristics as polymerase substrates and can be used in a range of nucleic acid detection and sequencing methods, including nanopore sequencing-by-synthesis.

The present disclosure relates to tagged multi-nucleotide compounds, which comprise a single tag moiety covalently linked to a plurality of nucleoside-5′-oligophosphate moieties. As disclosed herein, these tagged multi-nucleotide compounds have improved characteristics as polymerase substrates and can be used in a range of nucleic acid detection and sequencing methods, including nanopore sequencing-by-synthesis.

The invention provides novel oligonucleotide probes that have dendrimeric dyes useful for detecting and analyzing biological samples, and compositions and methods thereof. The dendrimeric dye-containing oligonucleotide probes are useful for high sensitivity fluorescence in situ hybridization (FISH) of nucleic acids such as DNA and RNA.

The invention provides novel oligonucleotide probes that have dendrimeric dyes useful for detecting and analyzing biological samples, and compositions and methods thereof. The dendrimeric dye-containing oligonucleotide probes are useful for high sensitivity fluorescence in situ hybridization (FISH) of nucleic acids such as DNA and RNA.

The invention relates to methods of in situ detection of a nucleic acid variation of a target nucleic acid in a sample, including single nucleotide variations, multi-nucleotide variations or splice sites. The method can comprise the steps of contacting the sample with a probe that detects the nucleic acid variation or splice site and a neighbor probe; contacting the sample with pre-amplifiers that bind to the nucleic acid variation probe or splice site probe and neighbor probe, respectively; contacting the sample with a collaboration amplifier that binds to the pre-amplifiers; and contacting the sample with a label probe system, wherein hybridization of the components forms a signal generating complex (SGC) comprising a target nucleic acid with the nucleic acid variation or splice site, the probes and amplifiers; and detecting in situ signal from the SGC on the sample. The invention also provides samples, tissue slides, and kits relating to detection of nucleic acid variations, including single nucleotide variations, multi-nucleotide variations or splice sites, of a target nucleic acid.

The invention relates to methods of in situ detection of a nucleic acid variation of a target nucleic acid in a sample, including single nucleotide variations, multi-nucleotide variations or splice sites. The method can comprise the steps of contacting the sample with a probe that detects the nucleic acid variation or splice site and a neighbor probe; contacting the sample with pre-amplifiers that bind to the nucleic acid variation probe or splice site probe and neighbor probe, respectively; contacting the sample with a collaboration amplifier that binds to the pre-amplifiers; and contacting the sample with a label probe system, wherein hybridization of the components forms a signal generating complex (SGC) comprising a target nucleic acid with the nucleic acid variation or splice site, the probes and amplifiers; and detecting in situ signal from the SGC on the sample. The invention also provides samples, tissue slides, and kits relating to detection of nucleic acid variations, including single nucleotide variations, multi-nucleotide variations or splice sites, of a target nucleic acid.

The present disclosure describes the thermodynamic design and concentrations necessary to design probe compositions with desired optimal specificity that enable enrichment, detection, quantitation, purification, imaging, and amplification of rare-allele-bearing species of nucleic acids (prevalence <1%) in a large stoichiometric excess of a dominant-allele-bearing species (wildtype). Being an enzyme-free and homogeneous nucleic acid enrichment composition, this technology is broadly compatible with nearly all nucleic acid-based biotechnology, including plate reader and fluorimeter readout of nucleic acids, microarrays, PCR and other enzymatic amplification reactions, fluorescence barcoding, nanoparticle-based purification and quantitation, and in situ hybridization imaging technologies.

The present disclosure describes the thermodynamic design and concentrations necessary to design probe compositions with desired optimal specificity that enable enrichment, detection, quantitation, purification, imaging, and amplification of rare-allele-bearing species of nucleic acids (prevalence <1%) in a large stoichiometric excess of a dominant-allele-bearing species (wildtype). Being an enzyme-free and homogeneous nucleic acid enrichment composition, this technology is broadly compatible with nearly all nucleic acid-based biotechnology, including plate reader and fluorimeter readout of nucleic acids, microarrays, PCR and other enzymatic amplification reactions, fluorescence barcoding, nanoparticle-based purification and quantitation, and in situ hybridization imaging technologies.