Abstract: An integrated testing device and fluid module are disclosed, as well as a method of manufacture. Fluid module contains a reservoir containing a test fluid, and a control vessel. The reservoir discharges test fluid into the control vessel, which discharges the test fluid in a controlled way to a test component.

Abstract: Microchip Capillary Electrophoresis (MCE) assays and reagents to assess purity and to identify impurities in protein drug product samples are provided. Methods for analyzing analytes in a protein drug sample are provided.

Abstract: MCE assays and reagents to assess purity and to identify impurities in protein drug product samples are provided. Methods for analyzing analytes in a protein drug sample are provided.

Abstract: Methods of uniquely labeling or barcoding molecules within a nucleus, a plurality of nuclei, a cell, a plurality of cells, and/or a tissue are provided. Kits for uniquely labeling or barcoding molecules within a nucleus, a plurality of nuclei, a cell, a plurality of cells, and/or a tissue are also provided. The molecules to be labeled may include, but are not limited to, RNAs and/or cDNAs.

Abstract: A method for investigating intra- and/or intermolecular interactions involving RNA is provided. The method includes a) synthesizing a RNA/DNA heteroduplex (RDH) comprising a RNA strand of interest paired to a DNA strand; b) binding a first end of the DNA strand and a corresponding first end of the RNA strand to a first element of a nanoscale manipulating device, and a second end of the DNA strand to a second element of the nanoscale manipulating device, leaving a second end of the RNA strand free; c) moving the first and second elements of the manipulating device apart from each other, stretching the DNA strand and causing the RNA strand to peel off the heteroduplex; and d) moving the first and second elements of the nanoscale manipulating device towards each other, allowing the DNA strand to relax and causing the RNA strand to bind again to it. Measurement of a force-displacement relationship during steps c) and d) provides information on intra- and/or intermolecular interactions involving the RNA strand.

Abstract: The identification of mutations that are present in a small fraction of DNA templates is essential for progress in several areas of biomedical research. Though massively parallel sequencing instruments are in principle well-suited to this task, the error rates in such instruments are generally too high to allow confident identification of rare variants. We here describe an approach that can substantially increase the sensitivity of massively parallel sequencing instruments for this purpose. One example of this approach, called “Safe-SeqS” for (Safe-Sequencing System) includes (i) assignment of a unique identifier (UID) to each template molecule; (ii) amplification of each uniquely tagged template molecule to create UID-families; and (iii) redundant sequencing of the amplification products. PCR fragments with the same UID are truly mutant (“super-mutants”) if ?95% of them contain the identical mutation.

Abstract: Methods of uniquely labeling or barcoding molecules within a nucleus, a plurality of nuclei, a cell, a plurality of cells, and/or a tissue are provided. Kits for uniquely labeling or barcoding molecules within a nucleus, a plurality of nuclei, a cell, a plurality of cells, and/or a tissue are also provided. The molecules to be labeled may include, but are not limited to, RNAs and/or cDNAs.

Abstract: Aspects of the disclosure relate to a nucleic acid comprising a heterologous nucleic acid insert flanked by interrupted self-complementary sequences, wherein one self-complementary sequence is interrupted by a cross-arm sequence forming two opposing, lengthwise-symmetric stem-loops, and wherein the other of the self-complementary sequences is interrupted by a truncated cross-arm sequence. Methods of delivering the nucleic acid to a cell are also provided.

Abstract: The invention relates to improved RNA compositions for use in therapeutic applications. The RNA compositions are particularly suited for use in human therapeutic application (e.g., in RNA therapeutics). The RNA compositions are made by improved processes, in particular, improved in vitro-transcription (IVT) processes. The invention also relates to methods for producing and purifying RNA (e.g, therapeutic RNAs), as well as methods for using the RNA compositions and therapeutic applications thereof.

Abstract: The present invention relates to an epigenetic method for identifying IPEX (immunodysregulation polyendocrinopathy enteropathy X-linked) syndrome and/or IPEX-like syndrome in a human subject using the methylation status of F0XP3 and a control gene specific for a CD4 and/or CD3 T cell. The method is used to distinguish IPEX from IPEX-like and from IPEX-unrelated disorders.

Abstract: Next Generation DNA sequencing promises to revolutionize clinical medicine and basic research. However, while this technology has the capacity to generate hundreds of billions of nucleotides of DNA sequence in a single experiment, the error rate of approximately 1% results in hundreds of millions of sequencing mistakes. These scattered errors can be tolerated in some applications but become extremely problematic when “deep sequencing” genetically heterogeneous mixtures, such as tumors or mixed microbial populations. To overcome limitations in sequencing accuracy, a method Duplex Consensus Sequencing (DCS) is provided. This approach greatly reduces errors by independently tagging and sequencing each of the two strands of a DNA duplex. As the two strands are complementary, true mutations are found at the same position in both strands. In contrast, PCR or sequencing errors will result in errors in only one strand.

Abstract: The field of this invention relates to immunohistochemistry (IHC) and in situ hybridization (ISH) for the targeted detection and mapping of biomolecules (e.g., proteins and miRNAs) in tissues or cells for example, for research use and for clinical use such by pathologists (e.g., biomarker analyses of a resected tumor or tumor biopsy). In particular, the use of mass spectrometric imaging (MSI) as a mode to detect and map the biomolecules in tissues or cells for example. More specifically, the field of this invention relates to photocleavable mass-tag reagents which are attached to probes such as antibodies and nucleic acids and used to achieve multiplex immunohistochemistry and in situ hybridization, with MSI as the mode of detection/readout. Probe types other than antibodies and nucleic acids are also covered in the field of invention, including but not limited to carbohydrate-binding proteins (e.g., lectins), receptors and ligands.

Abstract: The invention relates to improved RNA compositions for use in therapeutic applications. The RNA compositions are particularly suited for use in human therapeutic application (e.g., in RNA therapeutics). The RNA compositions are made by inproved processes, in particular, improved in vitro-transcription (IVT) processes. The invention also relates to methods for producing and purifying RNA (e.g, therapeutic RNAs), as well as methods for using the RNA compositions and therapeutic applications thereof.

Abstract: Provided are devices and methods for detecting the presence, absence, and/or characteristics of bacteria. A microfluidic device for characterizing bacteria is provided. The device contains one or more bacteria trapping channels, and one or more pneumatic channels in contact with the bacteria trapping channels, wherein the one or more pneumatic channels are configured to reduce the height of the one or more bacteria trapping channels to thereby trap bacteria in the one or more bacteria trapping channels if said bacteria are present in a liquid biological sample that is introduced into the microfluidic device. Also provided is a method for identifying bacteria that may be used with the microfluidic device.

Abstract: The present invention relates to a mutant reverse transcriptase (RT) with increased thermal stability relative to the wildtype, a nucleic acid encoding the mutant RT, a cell comprising the mutant RT or the nucleic acid, a kit comprising the mutant RT, the use of the mutant RT for cDNA synthesis, method for reverse transcription of RNA comprising synthesizing cDNA with the use of the mutant RT and a method for detecting an RNA marker in a sample with the use of the mutant RT.

Abstract: Methods of uniquely labeling or barcoding molecules within a nucleus, a plurality of nuclei, a cell, a plurality of cells, and/or a tissue are provided. Kits for uniquely labeling or barcoding molecules within a nucleus, a plurality of nuclei, a cell, a plurality of cells, and/or a tissue are also provided. The molecules to be labeled may include, but are not limited to, RNAs and/or cDNAs.

Abstract: The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences. In particular, the present invention provides methods and compositions for improving the efficiency of sequencing reactions by using fewer labels to distinguish between nucleotides and by detecting nucleotides at multiple detection positions in a target sequence.

Abstract: Disclosed is a measurement apparatus that includes: a measurement unit configured to measure a control sample for quality control; a display unit; and a processing unit configured to cause the display unit to display an input screen for setting an evaluation criterion used in the quality control, and, in the measurement apparatus, the processing unit causes the display unit to display a quality control result of a test item, based on the evaluation criterion and a measurement result of the control sample.

Abstract: The present disclosure provides a system comprising a communication interface and computer for assigning a label to the biomolecule fingerprint, wherein the label corresponds to a biological state. The present disclosure also provides a sensor arrays for detecting biomolecules and methods of use. In some embodiments, the sensor arrays are capable of determining a disease state in a subject.

Abstract: The present invention relates to a composition for treating and preventing degenerative brain diseases comprising a complex of vitamin C and an aptamer binding to the vitamin C as an active ingredient, and the composition of the present invention has improved and therapeutic effects in a Parkinson's disease experimental model and so the composition of the present invention can be used as medicines and health functional foods for patients with degenerative brain diseases including Parkinson's disease.

Abstract: Compositions and methods for treating enzyme-deficiency diseases are disclosed. Multidomain therapeutic proteins containing an internalization effector binding domain and a lysosomal replacement enzyme activity are disclosed. The multidomain therapeutic proteins are capable of entering cells, segregating to the lysosome, and delivering the replacement enzyme activity to the lysosome.

Abstract: Biosensor including an array of reaction sites and corresponding light sensors may experience crosstalk in which photons from one reaction site are detected by neighbors of its corresponding light sensor, and such crosstalk may be corrected using sharpening kernels corresponding to the sensors in the array. Such sharpening kernels may be derived from generative matrices, which themselves may be derived from point spread functions representing dispersion of illumination emitted from the reaction sites.

Abstract: Devices and methods are provided for identifying individual monomeric units in sequential order as they are released or cleaved from a polymer strand via an enzyme, which acts on the polymer, and the monomeric units translocate through a transmembrane channel. Methods are also provided for identifying molecules as they translocate through a transmembrane channel.

Abstract: Described herein are nucleic acid molecules and complexes useful for spatiotemporally mapping intra-endosmal thiol disulphide exchange. Aspects of the disclosure relate to a composition comprising a first nucleic acid conjugated to a normalization moiety; and a second nucleic acid conjugated to a catalytic substrate; wherein reaction of the substrate with a catalyst produces a detectable product; and wherein the first and second nucleic acids are complementary or substantially complementary. Further aspects relate to a composition comprising: a first nucleic acid conjugated to a normalization moiety and to a catalytic substrate; and a second nucleic acid; wherein reaction of the substrate with a catalyst produces a detectable product; and wherein the first and second nucleic acids are complementary or substantially complementary.

Abstract: The present disclosure provides for genetically modified organisms that provide numerous health benefits but also have an improved flavor profile and a more palatable aroma for the consumer of the organism.

Abstract: Disclosed herein are therapeutic targets for the correction of the human dystrophin gene by gene editing and methods of use.

Abstract: The present embodiments provide methods, compounds, and compositions useful for inhibiting DGAT2 expression, which may be useful for treating, preventing, or ameliorating a disease associated with DGAT2.

Abstract: A method of using a sequencing cell includes applying voltage across the sequencing cell, acquiring one or more signal values from the sequencing cell, and acquiring one or more correlated signal values that are correlated with respective values of the plurality of acquired signal values thereby forming a plurality of two-dimensional data points. The plurality of two-dimensional data points comprise values in a first dimension that equal the plurality of acquired signal value and values in a second dimension that equal the plurality of correlated signal values. The method can further include computing a plurality of transformed signal values by applying a two-dimensional transformation to the plurality of two-dimensional data points.

Abstract: Apparatus and methods relating to photonic bandgap optical nanostructures are described. Such optical nanostructures may exhibit prohibited photonic bandgaps or allowed photonic bands, and may be used to reject (e.g., block or attenuate) radiation at a first wavelength while allowing transmission of radiation at a second wavelength. Examples of photonic bandgap optical nanostructures includes periodic and quasi-periodic structures, with periodicity or quasi-periodicity in one, two, or three dimensions and structural variations in at least two dimensions. Such photonic bandgap optical nanostructures may be formed in integrated devices that include photodiodes and CMOS circuitry arranged to analyze radiation received by the photodiodes.

Abstract: The invention relates to new in vitro methods for synthesising a polymer, particularly a polynucleotide molecule, having a pre-defined sequence of units such as nucleotides. For synthesising a polynucleotide molecule the methods involve a process of extending a polynucleotide synthesis molecule with a transfer nucleotide. The methods additionally involve repeating the extension process multiple times to iteratively extend the polynucleotide molecule with multiple transfer nucleotides to generate a new polynucleotide molecule having a pre-defined nucleotide sequence. The invention also relates to in vitro methods of joining multiple synthetic polynucleotides following synthesis to form larger synthetic polynucleotides, as well as devices and systems for performing the extension, synthesis and assembly methods of the invention.

Abstract: Presented are methods and compositions for obtaining sequence information from one or more individual cells. The methods are useful for obtaining sequence information for a single nucleotide sequence, and for multiplex generation of sequence information from one or more individual cells.

Abstract: The invention is a novel method of making and using a template for nucleic acid sequencing. The templates include circular and linear templates with symmetric and asymmetric adaptors. The methods include utilizing the templates in an asymmetric fashion.

Abstract: The present disclosure provides RNA polymerase variants for high efficiency transcription.

Abstract: A method of determining a nucleic acid sequence that includes steps of: (a) contacting a primed template nucleic acid with a series of mixtures for forming ternary complexes, wherein each of the mixtures includes a polymerase and nucleotide cognates for at least two different base types suspected of being present at the next template position of the template nucleic acid; (b) monitoring the next template position for ternary complexes formed by the series of mixtures, wherein a signal state indicates presence or absence of ternary complex formed at the next template position by each individual mixture, thereby determining a series of signal states that encodes a base call for the next template position; and (c) decoding the series of signal states to distinguish a correct base call for the next template position from an error in the base call.

Abstract: A method of treating porphyria in a patient is provided comprising knocking down or reducing expression or activity of ?-catenin in the patient. e.g., in the liver of a patient, to an extent effective to treat porphyria in a patient.

Abstract: The present invention relates to chirally controlled oligonucleotides of select designs, chirally controlled oligonucleotide compositions, and methods of making and using the same. In some embodiments, a provided chirally controlled oligonucleotide composition provides different cleavage patterns of a nucleic acid polymer than a reference oligonucleotide composition. In some embodiments, a provided chirally controlled oligonucleotide composition provides single site cleavage within a complementary sequence of a nucleic acid polymer.

Abstract: The present disclosure provides, in some embodiments, methods and compositions for single-molecule detection.

Abstract: Provided herein is technology relating to the amplification-based detection of bisulfite-treated DNAs and particularly, but not exclusively, to methods and compositions for multiplex amplification of low-level sample DNA prior to further characterization of the sample DNA. The technology further provides methods for isolating DNA from blood or blood product samples, e.g., plasma samples.

Abstract: A method of detecting a nucleic acid including mixing a fluid including a target nucleic acid with a detection reagent including a first enzyme for cleaving a first nucleic acid having a first flap and a second enzyme for cleaving a second nucleic acid such that the target nucleic acid, the first nucleic acid and the second nucleic acid form a complex as a first invasive structure, conducting a first reaction which causes the first enzyme to cleave the first flap of the first invasive structure and produces a third nucleic acid that forms a complex, as a second invasive structure, with a fourth nucleic acid having a second flap, and conducting a second reaction which causes the second enzyme to cleave the second flap of the second invasive structure and produces a cleaved product.

Abstract: A method of using a device to detect a target entity in an environment includes introducing the device into the environment. The device includes first and second conductive surfaces, with a first molecular wire electrically coupling the first conductive surface to a capture agent that can interact with the target entity, and a second molecular wire electrically coupling the second conductive surface to a reference compound. The first and the second molecular wires comprise oligonucleotide multiplexes having identical nucleobase sequences and opposite absolute configuration. The method also includes detecting, by the device, an interaction between the capture agent and the target entity, at least in part by amplifying a differential voltage between the first and second conductive surfaces and detecting the interaction based on the differential voltage.

Abstract: A method comprises (a) providing single-stranded DNA; (b) ligating a first adapter to a 3? end of the single-stranded DNA to form a once adapter ligated nucleic acid strand, the first adapter having a first protruding random sequence that is at least 3 bases long and that acts as a splint to join the single-stranded DNA with the first adapter; (c) ligating a second adapter to a 5? end of the once adapter ligated nucleic acid strand to form a twice ligated nucleic acid strand, the second adapter having a second protruding random sequence that is at least 3 bases long and that acts as a splint to join the once adapter ligated nucleic acid strand with the second adapter; and (d) performing an amplification reaction on the twice ligated nucleic acid strand, thereby generating copies of the twice ligated nucleic acid strand.

Abstract: This disclosure relates to an enzymatic method of synthesizing a polynucleotide, comprising a deprotecting step which uses as a deprotecting agent a specific phosphonate compound. It also pertains to a method for deprotecting 3?-O-amino elongated fragments of a polynucleotide in an enzymatic method of synthesizing a polynucleotide, comprising contacting the elongated fragments with this phosphonate compound. This disclosure further relates to a kit for synthesizing a polynucleotide comprising one or more vials of synthesis reagents, at least one of which contains an effective amount of a phosphonate compound and to a specific method for preparing said phosphonate compound.

Abstract: Disclosed herein are methods for performing in situ sequencing of RNA transcripts with non-uniform 5? ends. During reverse transcription (RT) of RNA transcripts, RT enzyme is induced to “template-switch” to a separate oligonucleotide provided as the template for the upstream flanking region. This flanking region is grafted onto the beginning of the cDNA, enabling padlock probe detection, rolling circle amplification, and fluorescent in situ sequencing. Overall, the disclosed method for in situ sequencing can be applicable for analyzing exogenously introduced transcripts (e.g., identifying and determining impact of a perturbation including a CRISPR perturbation or shRNA/siRNA/ASO perturbation), analyzing naturally occurring transcripts (e.g., measuring gene expression, detecting splicing events), and analyzing modified, naturally occurring transcripts (e.g., detecting mutations or gene edits).

Abstract: Translation modulating agents that modulate expression of one or more translation start sites for expanded repeat (e.g., DPR) protein synthesis are provided. Compositions and methods for treating translation start sites for expanded repeat (e.g., DPR) protein synthesis-associated disorders are also provided.

Abstract: The present invention provides methods for testing surgical fluid for biomarkers of disease, including cancer.

Abstract: The invention provides improved methods for synthesizing polynucleotides, such as DNA and RNA, using renewable initiators coupled to a solid support. Using the methods of the invention, specific sequences of polynucleotides can be synthesized de novo, base by base, in an aqueous environment, without the use of a nucleic acid template.

Abstract: Disclosed herein are methods for the detection of the presence of sperm DNA fragmentation in a semen sample. The methods include embedding of sperm cells of the semen sample in a gel, denaturing DNA of the sperm cells, and lysing the nuclear proteins of the sperm cells. The present method includes an ionic surfactant sodium dodycyl sulfate (SDS) and a chaotropic agent urea in the lysis solution for releasing DNA from protamine of chromosome, which significantly reduces the time required for lysis. A kit for detecting sperm DNA fragmentation in a semen sample is also disclosed.

Abstract: The present disclosure relates to compositions of matter and assay methods used to detect one or more target nucleic acids of interest in a sample. The compositions and methods provide signal boost upon detection of target nucleic acids of interest in less than one minute and in some instances instantaneously at ambient temperatures down to 16° C. or less, without amplification of the target nucleic acids yet allowing for massive multiplexing, high accuracy and minimal non-specific signal generation.

Abstract: The present invention comprises Rig I agonists for enhancing the effects of cytotoxic cells and stem Cells. The Rig I agonists can be used in vivo as small molecule therapeutics or in vitro to enhance cells for adoptive cell transfer. Applications include cancer therapy, immune system enhancement, chronic viral infection and treatment of viral induced inflammation and enhancement of virus based therapies.

Abstract: The invention provides methods and apparatus for carrying out multiple amplification reactions in a single reaction chamber by successive cycles of loading reaction mixture, amplifying, and removing spent reaction mixture in a fluidly closed reaction system. In particular, the present invention allows amplification of a plurality of target polynucleotides from a single sample by carrying out under closed-loop control successive amplifications of different target polynucleotides from different portions of the sample.