Described is a method for screening an encoded chemical library, which library comprises a plurality of different chemical structures each releasably linked to an encoding tag, the method comprising the steps of: (a) providing said library of tagged chemical structures; (b) releasing each chemical structure from its tag to produce a plurality of free, tagless chemical structures (TCSs); (c) screening the TCSs by contacting them with a assay system under conditions whereby a spatial association between each TCS and its tag is maintained, to produce a plurality of different screened TCSs each spatially associated with its tag; and (d) identifying a screened TCS by decoding a tag that is spatially associated therewith.

Described is a method for screening an encoded chemical library, which library comprises a plurality of different chemical structures each releasably linked to an encoding tag, the method comprising the steps of: (a) providing said library of tagged chemical structures; (b) releasing each chemical structure from its tag to produce a plurality of free, tagless chemical structures (TCSs); (c) screening the TCSs by contacting them with a assay system under conditions whereby a spatial association between each TCS and its tag is maintained, to produce a plurality of different screened TCSs each spatially associated with its tag; and (d) identifying a screened TCS by decoding a tag that is spatially associated therewith.

This invention relates to compositions of matter, methods, modules and instruments for automated mammalian cell growth and mammalian cell transduction followed by nucleic acid-guided nuclease editing in live mammalian cells. The present compositions and methods entail viral delivery of an editing cassette to live mammalian cells such that the editing cassettes edit the cells and the edited cells continue to grow, preferably using a fully-automated end-to-end instrument to process the cells without human intervention to enhance cell processing uniformity and to maintain the integrity of the cell culture.

The invention provides methods for controlling the density of different molecular species on the surface of a solid support. A first mixture of different molecular species is attached to a solid support under conditions to attach each species at a desired density, thereby producing a derivatized support having attached capture molecules. The derivatized support is treated with a second mixture of different molecular species, wherein different molecular species in the second mixture bind specifically to the different capture molecules attached to the solid support. One or more of the capture molecules can be reversibly modified such that the capture molecules have a different activity before and after the second mixture of molecular species are attached. In particular embodiments, the different molecular species are nucleic acids that are reversibly modified to have different activity in an amplification reaction.

Methods for generating a sequencing library from a sample comprising a plurality of single-stranded DNA molecules are provided, along with methods of using the generated sequencing library for detecting cancer, determining cancer stage, monitoring cancer progression, and/or determining a cancer classification from a test sample obtained from a subject.

The invention is directed to methods for massively parallel template-free enzymatic synthesis of a plurality of different polynucleotides of predetermined sequences. In one aspect, methods of the invention employ large scale arrays of reaction sites each associated with at least one working electrode for controlling deprotection and deblocking steps at predetermined user selected sites. In another aspect, the invention provides template-free enzymatic synthesis with proofreading, wherein completed polynucleotides at predetermined reaction sites are sequenced using a sequencing by synthesis technique, particularly employing electrochemically labile blocking groups.

This invention relates to compositions of matter, methods, modules and instruments for automated mammalian cell growth and mammalian cell transduction followed by nucleic acid-guided nuclease editing in live mammalian cells.

This invention relates to compositions of matter, methods, modules and instruments for automated mammalian cell growth, reagent bundle creation and mammalian cell transfection followed by nucleic acid-guided nuclease editing in live mammalian cells.

This invention relates to compositions of matter, methods, modules and automated, end-to-end closed instruments for automated mammalian cell growth, reagent bundle creation and mammalian cell transfection followed by nucleic acid-guided nuclease editing in live mammalian cells.

It has been established that one or more large double stranded DNA fragments (each 2,000 to 40,000 base pairs in size) can be captured and isolated from genomic DNA fragments using sequence specific PNA hybridization probes. Compositions and methods for enrichment of a multiplicity of long DNA sequences selected from the genome of any eukaryote are provided. Capture is performed using multiple PNA molecules with gamma-modified chiral backbones, comprising a mixture of neutral and positive chemical groups. Two or more PNA probes with covalently bound haptens, preferably biotin, target each DNA domain of interest for capture, isolation, and subsequent sequencing analysis of the multiplicity of enriched targets, including DNA methylation sequencing. The methods include enhancement of probe-DNA binding specificity through single strand binding proteins (SSB).