Abstract: The present invention relates to systems and methods for manipulating droplets within a high through put microfluidic system.

Abstract: Provided herein are methods and systems for structure-assisted evolution of multivalent aptamers using a single stranded DNA or single-stranded RNA nanostructure as a structural support. Also provided herein are methods for constructing ssDNA or ssRNA nanostructures as structural supports suitable for structure-assisted evolution of multivalent aptamers.

Abstract: Methods, compositions, and kits are provided for nucleic acid analysis, including single cell analysis.

Abstract: This invention generally relates to systems and methods for the formation and/or control of fluidic species, and articles produced by such systems and methods. In some cases, the invention involves unique fluid channels, systems, controls, and/or restrictions, and combinations thereof. In certain embodiments, the invention allows fluidic streams (which can be continuous or discontinuous, i.e., droplets) to be formed and/or combined, at a variety of scales, including microfluidic scales. In one set of embodiments, a fluidic stream may be produced from a channel, where a cross-sectional dimension of the fluidic stream is smaller than that of the channel, for example, through the use of structural elements, other fluids, and/or applied external fields, etc. In some cases, a Taylor cone may be produced.

Abstract: In one aspect, the present invention relates to a method for obtaining structural information about an encoded molecule. The encoded molecule may be produced by a reaction of a plurality of chemical entities and may be capable of being connected to an identifier oligonucleotide containing codons informative of the identity of the chemical entities which have participated in the formation of the encoded molecule. In a certain embodiment, primers are designed complementary to the codons appearing on the identifier oligonucleotide, and the presence, absence or relative abundance of a codon is evaluated by mixing a primer with the identifier oligonucleotide in the presence of a polymerase and substrate (deoxy)ribonucleotide triphosphates and measuring the extension reaction. In another aspect, the invention provides a method for selecting compounds which binds to a target.

Abstract: This disclosure provides methods and compositions that are useful for enriching a particular population of nucleic acids (a “population of interest”) within a complex mixture of nucleic acids. The population of interest may make up a minor portion of a complex mixture of nucleic acids. The methods and compositions provided herein are useful for detecting, predicting, diagnosing, or monitoring a disease or disorder, particularly a disease or disorder caused by a foreign microbe or pathogen.

Abstract: Microfluidic methods for barcoding nucleic acid target molecules to be analyzed, e.g., via nucleic acid sequencing techniques, are provided. Also provided are microfluidic, droplet-based methods of preparing nucleic acid barcodes for use in various barcoding applications. The methods described herein facilitate high-throughput sequencing of nucleic acid target molecules as well as single cell and single virus genomic, transcriptomic, and/or proteomic analysis/profiling. Systems and devices for practicing the subject methods are also provided.

Abstract: System, including methods and apparatus, for spacing droplets from each other and for detection of spaced droplets.

Abstract: A system, methods, and apparatus are described to collect and prepare single cells and groups of cells from microsamples of specimens and encode spatial information of the physical position of the cells in the specimen. In some embodiment, beads or surfaces with oligonucleotides containing spatial barcodes are used to analyze DNA or RNA. The spatial barcodes allow the position of the cell to be defined and the nucleic acid sequencing information, such as target sequencing, whole genome, gene expression, used to analyze the cells in a microsample for cell type, expression pattern, DNA sequence, and other information, in the context of the cell's physical position in the specimen. In other embodiment, markers such as isotopes are added to a microsample to encode spatial position with mass spectoscopy or other analysis. The spatial encoded information is then readout by analysis such as DNA sequencing, mass spectrometry, fluorescence, or other methods.

Abstract: Methods of generating a nucleic acid signature for identifying particles associated in a partition are provided. In one aspect, the method comprises: partitioning a sample into a plurality of partitions comprising a particle comprising a solid support surface, the solid support surface having a plurality of oligonucleotide primers conjugated thereon, wherein the oligonucleotide primers comprise a barcode sequence, and wherein the partitions have 0, 1, or more than 1 particles per partition; providing in a partition a substrate comprising a barcode sequence or repeating clonal barcode sequences; and in the partition, associating a first particle conjugated to oligonucleotide primers comprising a first barcode sequence and a second particle conjugated to oligonucleotide primers comprising a second barcode sequence to a barcode sequence from the substrate, thereby generating a nucleic acid signature for the particles in the partition.

Abstract: Disclosed herein are compositions and methods for sequencing, analyzing, and utilizing samples such as single samples. Also disclosed herein are compositions and methods for matching together two or more sequences from a sample. Also disclosed herein are compositions and methods for expressing and screening molecules of interest.

Abstract: Provided herein are compositions and methods for detecting the binding of a peptide to an MHC molecule, and the binding of a peptide:MHC complex to a TCR. In preferred embodiments, the compositions and methods are in a highly-multiplexed way. The compositions and methods disclosed herein can be used to provide direct information on which peptides are bound to an MHC molecule. Also provided is a method for simultaneously detecting a large number of peptides for binding to an MHC molecule and/or a T cell. A method for detecting competitive binding of a large number of peptides to an MHC molecule and/or a T cell is also disclosed. Also provided herein is a method for simultaneously detecting a large number of specific TCRs. The compositions and methods of the present invention are useful for vaccine design, research and monitoring of autoimmune and infectious disease, immunogenicity testing of therapeutics, and tissue typing.

Abstract: The invention provides a method of preparing a nucleic acid population suitable for RNA sequencing. The method involves amplifying a double-stranded DNA and a poly T sequence by using the DNA constituted of any additional nucleic acid sequence X, poly T sequence, mRNA sequence isolated from a biological sample, poly A sequence and any additional nucleic acid sequence Y in this order as a template, a first primer containing any additional nucleic acid sequence X having amine added to the 5?-terminal (and a poly T sequence), and a second primer containing any additional nucleic acid sequence Y (and a poly T sequence), followed by fractionalizing the DNA, phosphorylating the DNA, preparing cDNA by using the DNA as a template and a third primer, adding adenine (A) to the cDNA, linking a DNA, and amplifying the DNA by using the DNA as a template, a fourth primer, and a fifth primer.

Abstract: Provided herein are methods, compositions and kits for the generation of bisulfite-converted next generation sequencing (NGS) libraries. The methods, compositions and kits provided herein can be useful, for example, for the production of libraries from genomic DNA that allow for determination of the methylation status across the genome, i.e. the methylome. The methods, compositions and kits provided herein can also be utilized to query methylation status at a particular genomic locus or loci. Moreover, the methods provided herein can be employed for high-throughput sequencing of bisulfite-converted DNA while maintaining the directional (strandedness) information of the original nucleic acid sample.

Abstract: The present invention provides synthetic canine antibody libraries, as well as polypeptides, nucleic acids, vectors, host cells and methods used in conjunction with these libraries. The present invention also provides antibodies isolated from such libraries.

Abstract: The present invention relates to systems, devices and methods for diagnosing cancer. In various embodiments, the present invention provides a method for quantifying a 5?-htRNA; a method for quantifying a 3?-htRNA; a method for obtaining a DNA library of 5?-htRNAs and a DNA library of 5?-htRNAs obtained therefrom; and a method for obtaining a DNA library of 3?-htRNAs and a DNA library of 3?-htRNAs obtained therefrom. The invention also teaches a method for determining the presence or absence of a cancer cell in a biological sample; a method of diagnosing cancer in a subject; and a method of prognosing cancer in a subject.

Abstract: Embodiments provided herein relate to methods and compositions for preparing nucleic acid libraries. Some embodiments include preparing libraries from nucleic acids obtained from degraded samples, such as ancient samples and fixed samples.

Abstract: The present disclosure generally relates to methods and compositions of linking, amplifying, and sequencing nucleic acid molecules. Also disclosed is the use of 5?-5?linked oligonucleotides for linking nucleic acid molecules for sequencing of the ends of long nucleic acid template molecules, or for sequencing polymorphism or different target genes or different RNAs simultaneously.

Abstract: Provided herein is a method for capturing DNA molecules in solution. The method may comprise: extracting DNA from a sample that comprises endogenous DNA and environmental DNA to produce extracted DNA; ligating universal adaptors to the extracted DNA; hybridizing the extracted DNA, in solution, with affinity-tagged RNA probes generated by: in vitro transcribing a library of fragmented reference genomic DNA that has been ligated to an RNA promoter adaptor, in the presence of an affinity-tagged ribonucleotide; binding the product with a capture agent that is tethered to a substrate in the presence of RNA oligonucleotides that are complementary to the adaptors, thereby capturing the hybridized DNA molecules on the substrate; washing the substrate to remove any unbound DNA molecules; and releasing the captured DNA molecules. A kit for performing the method is also provided.

Abstract: Method for studying constituents of individual molecular complexes by labelling the molecules belonging to the same complex with at least one set of molecular constructs, wherein each set member includes a Unique Identifying Sequence (UIS), which is a nucleic acid sequence unique for each set member, and at least one Common Tag Sequence (CTS), which is a nucleic acid sequence common to all set members, by: attaching the molecular construct to the complex by ligating or hybridizing the molecular construct to a nucleic acid molecule of the complex, or ligating or hybridizing the tag to a nucleic acid linked to an affinity binder that binds specifically to a constituent of the complex; labelling the molecules belonging to the same complex using the molecular construct tags as primers or templates in a nucleic acid polymerization reaction; and analyzing the composition of the complex by analyzing combinations of UISs and CTSs.