Abstract: The present disclosure provides method and systems for improving nanopore-based analyses of polymers. The disclosure provides methods for selectively modifying one or more monomeric subunit(s) of a kind a pre-analyte polymer that results polymer analyte with a modified subunit. The polymer analyte produces a detectable signal in a nanopore-based system. The detectable signal, and/or its deviation from a reference signal, indicates the location of the modified subunit in the polymer analyte and, thus, permits the identification of the subunit at that location in the original pre-analyte polymer.

Abstract: In some examples, a structure is contacted with polynucleotides having a variety of lengths and each including first and second adapters. The structure includes a substrate including first and second regions spaced apart from one another by a gap of at least 100 nm, a first set of capture primers coupled to the first region of the substrate, and a second set of capture primers coupled to the second region of the substrate. The first adapter of the polynucleotide is hybridized to a capture primer of the first set of capture primers. Based on that polynucleotide being sufficiently long to bridge the gap, it is amplified using the first and second sets of capture primers. Based upon that polynucleotide being insufficiently long to bridge the gap, it is not amplified. Optionally, a wall may be disposed in the gap.

Abstract: Presented herein are methods and compositions for concatenating template strands during the bridge amplification process. The methods are useful for surface amplification at improved densities. The methods and compositions provided herein enable creation of clusters that are brighter, but at the same densities as currently achieved using standard cluster amplification.

Abstract: There is set forth herein a device comprising structure defining a detector surface configured for supporting biological or chemical substances, and a sensor array comprising light sensors and circuitry to transmit data signals using photons detected by the light sensors. The device can include one or more features for reducing fluorescence range noise in a detection band of the sensor array.

Abstract: In some examples, a method includes disposing a first hydrogel within a first recess of a substrate and over a pillar. The substrate may include a second recess in which the pillar is disposed, and a wall separating the first recess from the second recess. While the first hydrogel is disposed within the first recess, the pillar may be removed. After removing the pillar, a second hydrogel may be disposed within the second recess. Also provided herein are nonlimiting examples of manners in which recesses, walls, and patterned hydrogels may be formed.

Abstract: A system, a method and a non-transitory computer readable storage medium for base calling are described. The base calling method includes processing through a neural network first image data comprising images of clusters and their surrounding background captured by a sequencing system for one or more sequencing cycles of a sequencing run. The base calling method further includes producing a base call for one or more of the clusters of the one or more sequencing cycles of the sequencing run.

Abstract: Provided herein include various examples of an apparatus, flow cells that include these examples of the apparatus, and methods of making these examples of the apparatus. The apparatus can include a molding layer over a substrate and covering sides of a light detection device. The molding layer comprises a first region and a second region, which, with the active surface of the light detection device, form a contiguous surface. A waveguide integration layer is between the contiguous surface and a waveguide. The waveguide integration layer comprises optical coupling structures over the first and second regions, to optically couple light waves from a light source to the waveguide. The waveguide utilizes the light waves to excite light sensitive materials in nanowells. A nanostructure layer over the waveguide comprises the nanowells. Each nanowell shares a vertical axis with a location on the active surface of the light detection device.

Abstract: Substrates comprising dual functional polymer layered surfaces and the preparation thereof by using UV nano-imprinting processes are disclosed. The substrates can be used as flow cells, nanofluidic or microfluidic devices for biological molecules analysis.

Abstract: Disclosed herein include recombinant terminal deoxynucleotidyl transferases (TdTs). In some embodiments, the recombinant TdT comprises an amino acid sequence that is at least 80% identical to a bovine TdT, wherein the recombinant TdT comprises one or more amino acid substitution mutations at one or more positions functionally equivalent to Glu191, Lys193, Glu194, Asp242, Lys287, Phe296, Met299, Thr342, and His421 in the bovine TdT.

Abstract: The present application relates to tertiary amine substituted coumarin derivatives and their uses as fluorescent labels. These compounds may be used as fluorescent labels for nucleotides in nucleic acid sequencing applications.

Abstract: Presented herein are polymerase enzymes for improved incorporation of nucleotide analogues, in particular nucleotides which are modified at the 3? sugar hydroxyl, as well as methods and kits using the same.

Abstract: A test cartridge for insertion into an analysis instrument having an actuation mechanism, the test cartridge having one or more sensors for measuring an aspect of the actuation mechanism.

Abstract: A system includes a fluidic device, a flow control valve, a first reagent fluid reservoir fluidly connectable to the fluidic device by the flow control valve, a first fluid buffer reservoir fluidly connectable to the fluidic device by the flow control valve, and a common fluid buffer source fluidly connectable to the fluidic device by the flow control valve. The flow control valve permits flow comprising: (i) flow from the first reagent fluid reservoir to the fluidic device, (ii) flow from the common fluid buffer source to the fluidic device, (iii) flow from the fluidic device to the first fluid buffer reservoir, (iv) flow from the first reagent fluid reservoir to the fluidic device, and (v) flow from the first fluid buffer reservoir to the fluidic device.

Abstract: Presented herein are altered polymerase enzymes for improved incorporation of nucleotides and nucleotide analogues, in particular altered polymerases that maintain high fidelity under reduced incorporation times, as well as methods and kits using the same.

Abstract: Embodiments of systems, methods, and compositions provided herein relate to methods of simultaneously analyzing multiple analytes in a single sample using a single assay. Some embodiments relate to simultaneous analysis of DNA and RNA in a single sample, for example, to the simultaneous generation of DNA and RNA libraries.

Abstract: The technology disclosed relates to artificial intelligence-based base calling. The technology disclosed relates to accessing a progression of per-cycle analyte channel sets generated for sequencing cycles of a sequencing run, processing, through a neural network-based base caller (NNBC), windows of per-cycle analyte channel sets in the progression for the windows of sequencing cycles of the sequencing run such that the NNBC processes a subject window of per-cycle analyte channel sets in the progression for the subject window of sequencing cycles of the sequencing run and generates provisional base call predictions for three or more sequencing cycles in the subject window of sequencing cycles, from multiple windows in which a particular sequencing cycle appeared at different positions, using the NNBC to generate provisional base call predictions for the particular sequencing cycle, and determining a base call for the particular sequencing cycle based on the plurality of base call predictions.

Abstract: The technology disclosed relates to determining tag signals from measured intensities for purposes of base calling in next-generation sequencing. In particular, the measured intensities are collected by light sensors in a sensor array directed to a sample surface including pixel areas and holding a plurality of clusters during a sequence of sampling events. Each light sensor is directed to and measuring intensity from one of the pixel areas during each sampling event. The method includes adjusting the measured intensities from a pixel in the pixel areas for background intensity based on variations in background levels of the light sensors in the sensor array and determining an intensity of a tag signal originating from the pixel based on the adjusted measured intensities of the pixel.

Abstract: In some examples, a nucleoside triphosphate analogue may include a sugar, a nucleobase coupled to the sugar, a triphosphate group coupled to the sugar, a heteroatom coupled to an alpha phosphate of the triphosphate group, and a first substituent coupled to the heteroatom. The heteroatom may be selected from the group consisting of oxygen, nitrogen, and carbon. The first substituent may include at least one of an alkyl chain or a polymer.