Abstract: Methods of forming an integrated device, and in particular forming one or more sample wells in an integrated device, are described. The methods may involve forming a metal stack over a cladding layer, forming an aperture in the metal stack, forming first spacer material within the aperture, and forming a sample well by removing some of the cladding layer to extend a depth of the aperture into the cladding layer. In the resulting sample well, at least one portion of the first spacer material is in contact with at least one layer of the metal stack.

Abstract: The present invention relates to antisense oligonucleotides that are capable of modulating expression of Tau in a target cell. The oligonucleotides hybridize to MAPT mRNA. The present invention further relates to conjugates of the oligonucleotide and pharmaceutical compositions and methods for treatment of Tauopathies, Alzheimzer's disease, fronto-temporal dementia (FTD), FTDP-17, progressive supranuclear palsy (PSP), chronic traumatic encephalopathy (CTE), corticobasal ganglionic degeneration (CBD), epilepsy, Dravet syndrome, depression, seizure disorders and movement disorders.

Abstract: A sensing device can use electromagnetic resonance to detect properties of a sample. For example, the sensing device can be immersed into a sample, placed in proximity to a sample, or otherwise located within sensing range of a sample. The sensing device can transmit a signal onto the sample and receive a reflected signal using a resonating structure. The sensing device can analyze the reflected signal to detect a constituent in the sample, such as a concentration of the constituent in the sample.

Abstract: Methods of preparing a plurality of sample-barcoded anchor-domain-flanked gene specific deoxyribonucleic acid (DNA) fragments from a template nucleic acid, e.g., ribonucleic acid (RNA), sample are provided. Aspects of the methods include employing a set of gene specific primer pairs, wherein each pair of gene specific primers is made up of a forward primer and a reverse primer, at least one of which includes a sample barcode domain. The methods find use in a variety of different applications, including high-throughput sequencing, e.g., expression profiling, applications, including of small biological samples, e.g., single-cells.

Abstract: The present disclosure provides compositions, methods, systems, and devices for polynucleotide processing and analyte characterization. Such polynucleotide processing may be useful for a variety of applications, including analyte characterization by polynucleotide sequencing. The compositions, methods, systems, and devices disclosed herein generally describe barcoded oligonucleotides, which can be bound to a bead, such as a gel bead, useful for characterizing one or more analytes including, for example, protein (e.g., cell surface or intracellular proteins), genomic DNA, and RNA (e.g., mRNA or CRISPR guide RNAs). Also described herein, are barcoded labelling agents and oligonucleotide molecules useful for “tagging” analytes for characterization.

Abstract: Provided herein are methods and compositions for improved sequencing techniques using, for example, polymeric particles and/or three-dimensional structures.

Abstract: A method includes exciting, at a first time period, a first set of pixels in an excitation array, wherein the first set of pixels comprises more than one pixel, and no pixel in the first set of pixels is adjacent to another pixel in the first set of pixels. The method also includes exciting, at a second time period, a second set of pixels in the excitation array wherein the second set of pixels comprises more than one pixel, and no pixel in the second set of pixels is adjacent to another pixel in the second set of pixels. The method retrieves excitation data, wherein the excitation data is comprised of data from the first set of pixels and data from the second set of pixels, and the excitation data is capable of being combined to reconstruct an image of a target object for rendering on a display.

Abstract: The invention provides methods, compositions, kits and devices for the detection of target molecules. In some embodiments, the invention allows for multiplexed target molecule detection.

Abstract: A medical detection substrate and a manufacturing method thereof, a medical detection chip and a medical detection system are provided. The medical detection substrate includes: a substrate, and a detection unit on the substrate; the detection unit includes two groups of test electrodes, the substrate includes a plurality of recessed portions, and the at least two groups of test electrodes are located in the plurality of recessed portions and spaced apart by insulation bank portions. The two groups of test electrodes are insulated and spaced apart by the insulation bank portions, so as to effectively avoid a transverse interference electric field to be generated between the two groups of test electrodes, thereby effectively improving the detection accuracy and sensitivity of the medical detection substrate, and providing a reliable basis for disease diagnosis.

Abstract: Material in a supply chain is tracked by a method of applying a DNA taggant set to a first batch of the material produced by a first supplier of the material. The DNA taggant set corresponds to a tag string corresponding to the first supplier. The first batch is aggregated with a second batch to create an aggregated lot. A sample is selected from the aggregated lot and tested to determine a DNA taggant set of the sample. After selecting a sample from the aggregated lot, the sample may be labeled with a grade and then placed in a receptacle corresponding to the grade.

Abstract: In various aspects, the present disclosure provides methods, compositions, reactions mixtures, kits, and systems for sequencing both RNA and DNA from a single source sample. In some embodiments, RNA is treated so as to differentiate RNA sequences from DNA sequences derived from the same sample. In some embodiments, the RNA and DNA are cell-free polynucleotides.

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: Provided herein are methods of making, amplifying, and sequencing tagged nucleic acid complements, compositions including interposing oligonucleotide barcodes, and kits useful in obtaining long-range sequence data.

Abstract: The invention relates to methods for conducting solid-phase binding assays. One example is an assay method having improved analyte specificity where specificity is limited by the presence of non-specific binding interactions.

Abstract: The present disclosure encompasses methods of error corrected sequencing (ECS) that enable detection of very rare mutations well below the error rate of convention next generation sequencing (NGS). Further, the methods disclosed herein enable multiplex targeting of genomic DNA.

Abstract: The present invention relates to methods for haplotype determination and, in particular, haplotype determination at the whole genome level as well as targeted haplotype determination.

Abstract: Method of performing a droplet-based assay. The method may include obtaining droplets encapsulated by an immiscible liquid and packed closely together in a monolayer, performing a reaction in the droplets while packed closely together in the monolayer; and collecting data related to an analyte from a plurality of the droplets while the droplets remain closely packed together in the monolayer.

Abstract: Provided herein are methods of identifying the origin of a nucleic acid sample. The methods include forming a reaction mixture comprising a nucleic acid sample comprising nucleic acid molecules from a single cell and a set of barcodes, incorporating the set of barcodes into the nucleic acid molecules of the sample, and identifying the set of barcodes incorporated into the nucleic acid molecules of the single cell thereby identifying the origin of the nucleic acid sample.

Abstract: The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

Abstract: The invention provides methods, systems, and computer readable medium for detecting ploidy of chromosome segments or entire chromosomes, for detecting single nucleotide variants and for detecting both ploidy of chromosome segments and single nucleotide variants. In some aspects, the invention provides methods, systems, and computer readable medium for detecting cancer or a chromosomal abnormality in a gestating fetus.

Abstract: The application relates to proteome analysis in single cells. Specifically, disclosed are high throughput methods of detecting proteins in single cells using barcoding, aptamers and single cell sequencing. Solid supports used in recording the cell-of-origin of target proteins and target proteins expressed in the cell-of-origin are disclosed. Additionally, methods of detecting proteins and mRNA in single cells are disclosed. Additionally, methods of detecting protein interactions are disclosed. Additionally, methods of detecting post translationally modified proteins in single cells are disclosed. The application also relates to solid supports or beads and methods of producing said solid supports or beads for use in the described methods.

Abstract: Methods and systems for sequencing a nucleic acid molecule are described that comprise imaging a first surface and an axially-displaced second surface using a compensation-free optical system, the system comprising an objective lens and at least one image sensor, wherein said optical system has a numerical aperture (NA) of less than 0.6 and a field-of-view (FOV) of greater than 1.0 mm2; and) processing the images of the first surface and the axially-displaced second surface to correct for optical aberration such that the images of the first surface and the axially-displaced second surface have substantially the same optical resolution.

Abstract: Systems, kits, and methods for detecting and quantifying proteomic activity using DNA-encoded probes are provided, where the proteomic activity may be enzymatic activity or ligand binding affinity. Such systems and methods encode quantitative proteomic activity information into DNA sequence populations and utilize DNA-linked substrates or ligands as activity probes. The systems, kits, and methods that are directed to detecting ligand affinity further include crosslinking steps to ensure the integrity of the DNA-linked ligands during purification and washing. Signal detection involves the chemical manipulation of a probe population downstream of sample exposure and application of purifying, selective pressure for desired products. Selection-induced changes in DNA abundance between the initial pool and the purified pool indicate sample activity.

Abstract: Systems and method for validation of sequencing results can amplify a target region of a nucleic acid sample in the presence of a primer pool including target specific and variant specific primers. The variant specific primers can include variant specific barcodes and variant specific sequences. An amplicon can be sequenced to determine the sequence of the variant specific barcode. The variant can be identified based on the sequence of the variant specific barcode, and the location of the variant can be determined by mapping the amplicon to a reference sequence.

Abstract: Methods are provided herein for identifying rare and/or unknown DNA sequences by next-generation sequencing approaches. Isolated double-stranded (ds), single-stranded (ss), or ds/ss DNA is fragmented and the fragments are polished, phosphorylated, and tailed, as necessary. Fragmentation can be enzymatic or mechanical. A universal adapter sequence is ligated to each fragment, wherein the adapter can have a top strand without a 5? phosphate, a 3? with an —H in place of the —OH, and/or a 3? extra base complementary to any base added to the polished fragments. The ligatamers may then serve as templates for amplification using a forward primer complementary to the adapter sequence and a reverse primer targeted to the fragment sequence. Compositions produced by these methods and kits adapted for performing these methods are also described herein.

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: Methods for preparing a sequencing library from a DNA-containing test sample are provided, including methods for rescuing one or more partially ligated DNA fragments to enhance library preparation conversion efficiencies. The subject methods can further be used to improve recovery of duplex sequence information from double-stranded DNA.

Abstract: The invention provides monoferrocenyl compounds of general formula I. The invention also provides substrates labelled with the compounds, functionalised derivatives of the compounds and methods of using the compounds, functionalised derivatives and labelled substrates in electrochemical assays.

Abstract: The present invention includes a method, kits, and assays for identifying a human subject as having an increased risk of developing an autoimmune disease, or a human subject with multiple sclerosis caused by elevated soluble Interleukin 7 receptor (sIL7R), by obtaining a biological sample and detecting or measuring in the biological sample an amount of a soluble Interleukin-7 receptor (sIL7R) and an amount of an RNA Helicase DDX39B, whereby a lower expression of DDX39B and a higher secretion of sIL7R identifies the subject from which the biological sample was obtained as having an increased risk of developing an autoimmune disease, when compared to a human subject not having an autoimmune disease. The present invention also includes a method of modifying a treating of subjects based on the lower expression of RNA Helicase DDX39B alone or in combination with an increase in sIL7R.

Abstract: The present invention is concerned with compositions and methods for improving the rate of correct sample identification in indexed nucleic acid library preparations for multiplex next generation sequencing by modifying or blocking 5? and 3? ends of pooled indexed polynucleotides from multiple samples, with an optional exonuclease treatment, prior to amplification and sequencing.

Abstract: Aspects of the present invention include analyzing nucleic acids from single cells using methods that include using tagged polynucleotides containing multiplex identifier sequences.

Abstract: Methods of uniquely labeling or barcoding molecules within a cell, a plurality of cells, and/or a tissue are provided. Kits for uniquely labeling or barcoding molecules within 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, cDNAs, DNAs, proteins, peptides, and/or antigens.

Abstract: This invention provides methods and systems of DNA synthesis including providing an encoding unit comprising an enzyme, a single-stranded DNA (ssDNA) and a nanopore, providing a lipid bilayer having on opposite sides a cis and a trans reservoir each having a different buffer composition, wherein the nanopore is within the lipid bilayer and the enzyme and the ssDNA are in the cis reservoir, providing an electrode over the lipid bilayer wherein the electrode can modulate voltage across the lipid bilayer, wherein the enzyme catalyzes DNA synthesis in response to the voltage.

Abstract: A method of mass or mobility spectrometry comprising obtaining one or more sample spectra for a sample. The one or more sample spectra are subjected to pre-processing and then multivariate and/or library based analysis so as to classify the sample. Before the sample spectra are acquired, a library of background spectra, each background spectrum relating to a certain class of sample material, is constructed. The background spectra in this library are used to subtract the background from a sample spectrum during the pre-processing of this sample spectrum.

Abstract: The invention relates to a method for selecting a sequence set from a library of expressed nucleic acid sequences, wherein cells are provided, each cell comprises an expressed nucleic acid sequence expressed as a target protein. The cells are encapsulated by treating them with a cationic polysaccharide and subsequently treating them with an anionic polysaccharide, yielding encapsulated cells, perforating the membrane of the encapsulated cells, yielding solubilized compartments, contacting them with a ligand to said target protein, the ligand bearing a detectable label, and selecting a subset of solubilized compartments as a function of detectable label and isolating the expressed nucleic acid sequences from the selection as a selected sequence set.

Abstract: A fluorescence image analyzer, analyzing method, and pretreatment evaluation method capable of determining with high accuracy whether a sample is positive or negative are provided. A pretreatment part performs pretreatment including a step of labeling a target site with a fluorescent dye to prepare a sample. A fluorescence image analyzer measures and analyzes the sample. The fluorescent image analyzer includes light sources to irradiate light on the sample, imaging part to capture the fluorescent light given off from the sample irradiated by light, and processing part for processing the fluorescence image captured by the imaging part. The processing part extracts the bright spot of fluorescence generated from the fluorescent dye that labels the target site from the fluorescence image for each of a plurality of cells included in the sample, and generates information used for determining whether the sample is positive or negative based on the bright spots extracted for each of the plurality of cells.

Abstract: An integrated circuit includes a photodetection region configured to receive incident photons. The photodetection region is configured to produce a plurality of charge carriers in response to the incident photons. The integrated circuit includes at least one charge carrier storage region. The integrated circuit also includes a charge carrier segregation structure configured to selectively direct charge carriers of the plurality of charge carriers directly into the at least one charge carrier storage region based upon times at which the charge carriers are produced.

Abstract: A method and apparatus for simultaneously determining multiple different biological molecule types in a sample include labeling each different biological molecule type in a biological sample with a unique combination of a plurality of labels. Each different biological molecule type is selected from a population of M different biological molecules types. The plurality of labels is selected from a population of L different labels; and, M is greater than L. Measurements are obtained of relative abundances of the L different labels in the sample. Relative abundance of up to M different biological molecule types in the sample are determined based on the measurements and a method of compressed sensing.

Abstract: Disclosed herein are compositions and methods for treating cancer. Further provided herein are compositions and methods for reducing, inhibiting, or preventing resistance of cancer to tyrosine kinase inhibitors. The methods may include administering an anti-resistance agent such as a CYP51A1 inhibitor or an agonist of miRNA-764 (SEQ ID NO: 4) to a subject. A tyrosine kinase inhibitor may also be administered to the subject in addition to the anti-resistance agent.

Abstract: The invention pertains to an assay that is capable of detecting a mutant polynucleotide in a plurality of polynucleotides. In one embodiment, the assay of the invention is capable of detecting one copy of a mutant polynucleotide in about 50,000 to about 100,000 copies of polynucleotides. The assay of the invention can be used to identify a mutant viral quasispecies or a mutant mRNA encoding an oncogenic protein from a tumor sample. The assay of the invention involves producing the single stranded complements of each of a plurality of polynucleotides containing the target sequence, wherein each of the single stranded complements contain a unique tag sequence and amplifying the single stranded complements by PCR using several sets of primers designed to introduce the sequences appropriate for a paired-end sequencing analysis of the amplified polynucleotides. The invention also pertains to kits for carrying out the assays of the invention.

Abstract: Presented are methods and compositions for preparing samples for amplification and sequencing. Particular embodiments relate to methods of preparing nucleic acid-containing cellular samples for library amplification, wherein the methods include providing nucleic acid containing-cellular samples from blood or FFPE samples, lysing cells of the sample to liberate nucleic acids, and performing tagmentation without purifying the liberated nucleic acids.

Abstract: Aspects of the present invention include analyzing nucleic acids from single cells using methods that include using tagged polynucleotides containing multiplex identifier sequences.

Abstract: Disclosed herein are methods of high-throughput mapping of viral neutralizing antibody epitopes. Also disclosed are in vitro immunoprecipitation-based adenoassociated virus Barcode-Seq-based methods of mapping viral neutralizing antibody epitopes. In some embodiments, a method of high-throughput mapping of viral NtAb conformational epitopes can be utilized, which may comprise HP scanning of mutant viral libraries, immunoprecipitation (IP), and/or next-generation sequencing (NGS) technology. In some embodiments, a method of identifying one or more dominant epitopes in a viral vector may comprise contacting a mutant capsid of a virus with serum from a subject previously exposed to the virus and immunopredpitating serum immunoglobulins from the serum. In various embodiments, the viral vector may be an AAV vector.

Abstract: The present invention relates to a method of analyzing a composition of nucleic acids derived from a single cell using a microplate including a plurality of reaction wells, the microplate having one bead arranged in one reaction well, the one bead having bound thereto a plurality of molecules of single-stranded oligonucleotides, the single-stranded oligonucleotides each having a nucleic acid capture sequence exposed at the 3? end and a barcode sequence on the 5? side of the nucleic acid capture sequence, the barcode sequence including a base sequence that differs from bead to bead.

Abstract: This invention provides methods of using labeled primers or probes for nucleic acid target detection and to detect the identity or presence of a nucleotide at certain positions in nucleic acid sequences with single molecule sensitivity using nanopore detection, and sets of oligonucleotide primers for use in such methods, as well as methods of quantitative PCR coupled with nanopore detection.

Abstract: A method for making an asymmetrically-tagged sequencing library is provided. In some embodiments, the method may comprise: obtaining a symmetrically-tagged library of cDNA or genomic DNA fragments, hybridizing a tailed first primer to the 3? sequence tag of the library and extending the same to produce primer extension products, and amplifying the primer extension products using a pair of tailed primers to produce asymmetrically-tagged library.

Abstract: Aspects of the present invention include analyzing nucleic acids from single cells using methods that include using tagged polynucleotides containing multiplex identifier sequences.

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: Improved resolution and detection of nanoparticles are achieved when a nanopore connecting liquid compartments in a device running on the Coulter principle is provided with fluid coatings such as lipid walls. Fluid lipid walls are made of a lipid bilayer, and preferably include lipid anchored mobile ligands as part of the lipid bilayer. By varying the nature and concentration of the mobile ligand in the lipid bilayer, multifunctional coatings of lipids are provided.

Abstract: The present disclosure relates to systems and methods for cellular imaging and identification through the use of a light sheet flow cytometer. In one implementation, a light sheet flow cytometer may include a light source configured to emit light having one or more wavelengths, at least one optical element configured to form a light sheet from the emitted light, a microfluidic channel configured to hold a sample, and an imaging device. The imaging device may be adapted to forming 3-D images of the sample such that identification tags attached to the sample are visible.