This disclosure provides a powerful screening platform that combines pre-templated instant partitions with DNA-encoded library (DEL) technologies to identify target small molecule interactions and analyze their intracellular effects in single cell resolution using methods that require minimal sample preparation and affordable sequencing costs.

This disclosure provides a powerful screening platform that combines pre-templated instant partitions with DNA-encoded library (DEL) technologies to identify target small molecule interactions and analyze their intracellular effects in single cell resolution using methods that require minimal sample preparation and affordable sequencing costs.

The present disclose provides methods and systems for amplifying and quantifying nucleic acids and for detecting the presence or absence of a target in a sample. The methods and systems provided herein may utilize a device comprising a plurality of partitions separated from an external environment by a gas-permeable barrier. Certain methods disclosed herein involve subjecting nucleic acid molecules in the plurality of partitions to conditions sufficient to conduct nucleic acid amplification reactions. The nucleic acid molecules may be subjected to controlled heating in the plurality of partitions to generate data indicative of a melting point(s) of the nucleic acid molecules.

The present disclose provides methods and systems for amplifying and quantifying nucleic acids and for detecting the presence or absence of a target in a sample. The methods and systems provided herein may utilize a device comprising a plurality of partitions separated from an external environment by a gas-permeable barrier. Certain methods disclosed herein involve subjecting nucleic acid molecules in the plurality of partitions to conditions sufficient to conduct nucleic acid amplification reactions. The nucleic acid molecules may be subjected to controlled heating in the plurality of partitions to generate data indicative of a melting point(s) of the nucleic acid molecules.

Provided herein are compositions and methods for simultaneously measuring target oligonucleotides and protein in single cells. Compositions comprise an antibody-tagged oligonucleotide, including an origin specific barcode handle sequence, a first primer handle sequence, a second primer handle sequence, and a target binding region. The composition may also include an adapter sequence, a unique molecular identifier (UMI), and a poly-A sequence. Methods for simultaneously measuring target oligonucleotides and protein in single cells generally involve delivering a mixture of the composition to a population of cells and encapsulating individual cells in an individual discrete volume comprising PCR primers on a bead. The individual discrete volume may be suspended in a reverse transcription mixture and the nucleotide sequence of the origin specific barcode handle sequence may be detected, thereby assigning the target oligonucleotide and protein of interest to a specific individual discrete volume, while maintaining information about sample origin of the target oligonucleotide.

Provided herein are compositions and methods for simultaneously measuring target oligonucleotides and protein in single cells. Compositions comprise an antibody-tagged oligonucleotide, including an origin specific barcode handle sequence, a first primer handle sequence, a second primer handle sequence, and a target binding region. The composition may also include an adapter sequence, a unique molecular identifier (UMI), and a poly-A sequence. Methods for simultaneously measuring target oligonucleotides and protein in single cells generally involve delivering a mixture of the composition to a population of cells and encapsulating individual cells in an individual discrete volume comprising PCR primers on a bead. The individual discrete volume may be suspended in a reverse transcription mixture and the nucleotide sequence of the origin specific barcode handle sequence may be detected, thereby assigning the target oligonucleotide and protein of interest to a specific individual discrete volume, while maintaining information about sample origin of the target oligonucleotide.

Devices and methods for de novo synthesis of large and highly accurate libraries of oligonucleic acids are provided herein. Devices include structures having a main channel and microchannels, where the microchannels have a high surface area to volume ratio. Devices disclosed herein provide for de novo synthesis of oligonucleic acids having a low error rate.

Devices and methods for de novo synthesis of large and highly accurate libraries of oligonucleic acids are provided herein. Devices include structures having a main channel and microchannels, where the microchannels have a high surface area to volume ratio. Devices disclosed herein provide for de novo synthesis of oligonucleic acids having a low error rate.

This invention provides ultra-sensitive methods and compositions for detecting patient-specific mutations from cell free nucleic acids (cfDNA) without sequencing. Methods of the invention make use of fluidic partitions for multiplex amplification of cfDNA and thereby create a library of uniformly amplified amplicons. The uniformly amplified amplicons can be split into any number of different detection reactions (while maintaining detection sensitivity) for single-plex detection of mutations present in cfDNA. These methods provide substantially improved signal to noise ratio and easier discrimination of low-abundance mutations.

This invention provides ultra-sensitive methods and compositions for detecting patient-specific mutations from cell free nucleic acids (cfDNA) without sequencing. Methods of the invention make use of fluidic partitions for multiplex amplification of cfDNA and thereby create a library of uniformly amplified amplicons. The uniformly amplified amplicons can be split into any number of different detection reactions (while maintaining detection sensitivity) for single-plex detection of mutations present in cfDNA. These methods provide substantially improved signal to noise ratio and easier discrimination of low-abundance mutations.