Abstract: A method for reducing sequencing by synthesis cycle time using a microfluidic device is provided. The microfluidic device comprises a flow cell having an inlet port, an outlet port, and a flow channel extending between the inlet port and the outlet port, wherein the flow channel receives an analyte of interest and one or more reagents for analyzing and detecting molecules. To aid in the acceleration of the reactions, the microfluidic device comprises a mixing device to increase the rates of diffusion of the reagents from the fluid bulk to an active surface of the flow cell. The mixing device comprises at least one of an electrothermal mixing device, an active mechanical mixing device, and a vibrational mixing device.

Abstract: The disclosure provides compositions, methods, and kits that facilitate the characterization of omic variation in tissues while preserving spatial information related to the origin of target analytes in the tissue.

Abstract: Systems, methods and kits are described for culturing one or more biological cells in a microfluidic device, including provision of nutrients and gaseous components configured to enhance cell growth, viability, portability, or any combination thereof. In some embodiments, culturing a single cell may produce a clonal population in the microfluidic device.

Abstract: The invention relates to methods and kits for use in nucleic acid sequencing, in particular methods for use in concurrent sequencing, including concurrent sequencing of tandem insert libraries. Further, the invention relates to methods of detecting mismatched base pairs in nucleic acid sequences. In another embodiment, the disclosed technology relates to using next generation sequencing to determine the nucleotide sequences of two or more polynucleotide sequence portions in a single sequencing run.

Abstract: The invention relates to methods and kits for use in nucleic acid sequencing, in particular methods for use in concurrent sequencing, and in particular concurrent sequencing of tandem insert libraries.

Abstract: Devices, systems, and methods for non-volatile storage include a well activation device operable to modify one or more wells from a plurality of wells of a flow cell to provide a set of readable wells. Readable wells are configured to allow exposure of a well to substances from nucleotide sequencing fluids, and prevent exposure to other substances and fluids, such as nucleotide synthesizing fluids. The well activation device may also modify wells to provide a set of writeable wells. This set of wells is configured to allow exposure to the nucleotide synthesizing fluids and substances; and prevent exposure to the nucleotide sequencing fluids and substances. There may also be provisions made for risk mitigation for data errors such as generating commands to write specified data to a nucleotide sequence associated with a particular location in a storage device, reading the nucleotide sequence and performing a comparison.

Abstract: A method for reducing sequencing by synthesis cycle time using a microfluidic device is provided. The microfluidic device comprises a flow cell having an inlet port, an outlet port, and a flow channel extending between the inlet port and the outlet port, wherein the flow channel receives an analyte of interest and one or more reagents for analyzing and detecting molecules. To aid in the acceleration of the reactions, the microfluidic device comprises a mixing device to increase the rates of diffusion of the reagents from the fluid bulk to an active surface of the flow cell. The mixing device comprises at least one of an electrothermal mixing device, an active mechanical mixing device, and a vibrational mixing device.

Abstract: Systems, methods and kits are described for culturing one or more biological cells in a microfluidic device, including provision of nutrients and gaseous components configured to enhance cell growth, viability, portability, or any combination thereof. In some embodiments, culturing a single cell may produce a clonal population in the microfluidic device.

Abstract: The invention relates to methods for use in nucleic acid sequencing, in particular methods for use in concurrent sequencing.

Abstract: A method of base calling nucleobases of two or more polynucleotide sequence portions, wherein said polynucleotide sequence portions have been selectively processed such that an intensity of the signals obtained based upon the respective first nucleobase is greater than an intensity of the signals obtained based upon the respective second nucleobase.

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: The invention relates to methods of detecting modified cytosines in nucleic acid sequences.

Abstract: The invention relates to methods of detecting modified cytosines in nucleic acid sequences.

Abstract: A system writes input data to a storage device as machine-written polynucleotides; and reads machine written polynucleotides from the storage device as output data. The storage device includes a flow cell including a plurality of storage wells in which machine written polynucleotides may be stored. The storage device may include a set of electrodes corresponding to the storage wells that allow for selective interactions with wells across the surface of a flow cell. Operation of the storage device may include receiving a read request associated with a particular location in the storage device, creating a copy of a nucleotide sequence located at the particular location in the storage device, transferring the copy of the nucleotide sequence to a read location, and reading the copy of the nucleotide sequence at the read location.

Abstract: The technology disclosed is directed to context-dependent base calling. The technology disclosed describes a system including memory storing k-mer-specific centroids for k-mers. The k-mer-specific centroids are learned by training a base calling pipeline to represent base calls of an already base called sequence in k-mer-specific time series, transform the k-mer-specific time series into predicted k-mer-specific centroids, merge the predicted k-mer-specific centroids on a sequencing cycle-by-sequencing cycle basis to generate predicted per-sequencing cycle intensity values, determine a training loss (e.g., a transformation loss) based on comparing the predicted per-sequencing cycle intensity values against known intensity values of the base calls, update the predicted k-mer-specific centroids based on the determined training loss, and store the updated centroids as the k-mer-specific centroids.

Abstract: This application relates to methods of monoclonal clustering. In some examples, the monoclonal clustering utilizes double-stranded DNA.

Abstract: The technology disclosed is directed to cluster segmentation and base calling. The technology disclosed describes a computer-implemented method including segmenting a population of clusters into a plurality of subpopulations of clusters based on one or more prior bases called at one or more prior sequencing cycles of a sequencing run. At a current sequencing cycle of the sequencing run, the method includes applying a mixture of four distributions to current sequenced data of each subpopulation of clusters in the plurality of subpopulations of clusters, the four distributions corresponding to four bases adenine (A), cytosine (C), guanine (G), and thymine (T), and the current sequenced data being generated at the current sequencing cycle. The method further includes base calling clusters in a particular subpopulation of clusters using a corresponding mixture of four distributions.

Abstract: Methods are used for obtaining, cataloguing, and/or storing data derived from a biological source using a flow cell body, electrodes, and an imaging assembly. The data may include DNA and/or RNA obtained from a biological source, such as from the cells of an organism. The methods may be used to obtain, catalog, and/or store data such as DNA or RNA sequence from a pathogen such as a virus and/or a bacteria, human health data over time, and immune system information from an individual. The data obtained using the disclosed methods may be used for a variety of different purposes, including the manufacture of vaccine compositions, and for restoring the immune system of an individual who has undergone an immune system depleting event. The methods may be used for storage of biological cells, which may be used for the screening of compounds, such as small molecules with potential for therapeutic indications.

Abstract: An apparatus includes a flow cell body, a plurality of electrodes, an imaging assembly, and one or more barrier features. The flow cell body defines one or more flow channels and a plurality of wells defined as recesses in the floor of each flow channel. Each well is fluidically coupled with the corresponding flow channel. The flow cell body further defines interstitial surfaces between adjacent wells. Each well defines a corresponding depth. Each electrode is positioned in a corresponding well of the plurality of wells. The electrodes are to effect writing of polynucleotides in the wells. The imaging assembly is to capture images of polynucleotides written in the wells. The one or more barrier features are positioned in the wells, between the wells, or above the wells. The one or more barrier features contain reactions in each well, reduce diffusion between the wells, or reduce optical cross-talk between the wells.

Abstract: Defocus is introduced during sequencing by synthesis by tilt of a flow cell and by variations in flatness of the flow cell. Effects of the defocus are reduced, and base calling quality is improved using techniques relating to dependence of base calling on flow cell tilt. For example, the flow cell surface height is measured throughout the flow cell. A focal height of an imager having a sensor for the sequencing is set, optionally adaptively, one or more times during the sequencing. Each image captured by the sensor is partitioned, e.g., based on differences between focal height and the measured flow cell surface height across areas of the sensor. Filters, e.g., related to defocus correction, are selected based at least in part on the difference between the focal height and the measured flow cell surface height at a particular area of the image being corrected for defocus.