Abstract: A method of automatically sequencing or basecalling one or more DNA (deoxyribonucleic acid) molecules of a biological sample is described. The method comprises using a capillary electrophoresis genetic analyzer to measure the biological sample to obtain at least one input trace comprising digital data corresponding to fluorescence values for a plurality of scans. Scan labelling probabilities for the plurality of scans are generated using a trained artificial neural network comprising a plurality of layers including convolutional layers. A basecall sequence comprising a plurality of basecalls for the one or more DNA molecules based on the scan labelling probabilities for the plurality of scans is determined.

Abstract: Methods, assays, compositions and kits for the ligation of short polynucleotides are presented herein. The short polynucleotides are optionally no more than 7 nucleotides in length, and can be as short as 3 or 4 nucleotides in length. The ligation is optionally performed by CV ligase.

Abstract: A method for sequencing a nucleic acid template includes: (a) performing a first sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a first predetermined ordering of nucleotides and/or reagents to obtain a first sequencing result; (b) after the first sequencing process, performing a second sequencing process including flowing nucleotides and/or reagents to the nucleic acid template according to a second predetermined ordering of nucleotides and/or reagents to obtain a second sequencing result, the second predetermined ordering of nucleotides and/or reagents being different from the first predetermined ordering of nucleotides and/or reagents and at least one of the first and second predetermined orderings of nucleotides and/or reagents being designed for repeat sequencing; and (c) determining a sequence of bases corresponding to at least a portion of the nucleic acid template using both the first sequencing result and the second sequencing result.

Abstract: A method of modeling a background signal when sequencing a polynucleotide strand using sequencing-by-synthesis includes: flowing a series of nucleotide flows onto a reactor array having multiple reaction confinement regions, one or more copies of the polynucleotide strand being located in a loaded reaction confinement region of the reactor array, the loaded reaction confinement region being located in a vicinity of one or more neighboring reaction confinement regions that may or may not be loaded; receiving output signals from the reactor array; and modeling a background signal for the loaded reaction confinement region using the received output signals and a model adapted to account at least for an exchange of ions between the one or more neighboring reaction confinement regions and a headspace adjacent the loaded reaction confinement region and the one or more neighboring reaction confinement regions.

Abstract: A method for operating a bioreactor includes passing a drive shaft into a first tubular connector and a second tubular connector projecting from the first tubular connector, the first tubular connector and the second tubular connector being at least partially disposed within a container, the first tubular connector being more flexible than the second tubular connector, the second tubular connector having a length that comprises at least 20% of a combined length of the first tubular connector and the second tubular connector. Rotating the drive shaft so as to rotate the first tubular connector and the second tubular connector within the container.

Abstract: Provided herein are compositions, methods and uses that relate to an easy, accurate and reliable dual or duplex assay that determines both protein and nucleic acid amounts in a viral preparation in a single container and further determines full versus empty virion content.

Abstract: A thermal cycler system comprises a sample block configured to receive a sample holder configured to receive a plurality of samples; an adaptor configured to surround a periphery of the sample block; and a drip pan configured to surround a periphery of the adaptor. The drip pan comprises one or more ejector mechanisms and one or more openings, the one or more ejector mechanisms configured to respectively extend through the one or more openings into contact with the sample holder in a state of the sample holder received by the sample block and the adaptor surrounding the periphery of the sample block.

Abstract: A system for nucleic acid sequencing includes a machine-readable memory and a processor configured to execute machine-readable instructions. The instructions, when executed by the processor, cause the system to expose template polynucleotide strands in a plurality of defined spaces of a sensor array to a series of flows of nucleotide species, the series comprising a sequence of random flows; and obtain, for each of the series of flows of nucleotide species, a signal indicative of how many nucleotide incorporations occurred for that particular flow to determine a predicted sequence of nucleotides corresponding to the template polynucleotide strands.

Abstract: A fluid manifold system includes a first manifold having portions of opposing flexible sheets welded together to form a fluid flow path therebetween, a fluid inlet communicating with the fluid flow path. The fluid flow path of the first manifold includes: a primary flow path communicating with the fluid inlet of the first manifold; and a plurality of spaced apart secondary flow paths that branch off of the primary flow path. Each secondary flow path has a first end communicating with the primary flow path and an opposing second end, each secondary flow path having a diameter that is smaller than a diameter of the primary flow path. The fluid manifold system also includes a plurality of tubular connectors with each tubular connector being secured to the first manifold at the second end of a corresponding one of the secondary flow paths.

Abstract: In one embodiment, a device is described. The device includes a material defining a reaction region. The device also includes a plurality of chemically-sensitive field effect transistors have a common floating gate in communication with the reaction region. The device also includes a circuit to obtain respective output signals from the chemically-sensitive field effect transistors indicating an analyte within the reaction region.

Abstract: A computer-implemented method for generating a data visualization for operating a digital polymerase chain reaction (dPCR) system comprises, the method comprising receiving fluorescent emission data comprising a plurality of data points corresponding to fluorescence emission from a plurality of reaction sites of a substrate, the fluorescent emission data indicative of presence or absence of amplification product of a dPCR. The method further comprises displaying a data visualization of the plurality of data points in a spatial representation of the substrate such that each data point is displayed at a relative spatial location of its corresponding reaction site of the plurality of reaction sites of the substrate, a first set of data points being displayed with a first indication based on meeting a first quality value threshold and second set of data points being displayed with a second indication, differing from the first indication, based on a second quality value threshold.

Abstract: A method for evaluating variant likelihood includes: providing a plurality of template polynucleotide strands, sequencing primers, and polymerase in a plurality of defined spaces disposed on a sensor array; exposing the plurality of template polynucleotide strands, sequencing primers, and polymerase to a series of flows of nucleotide species according to a predetermined order; obtaining measured values corresponding to an ensemble of sequencing reads for at least some of the template polynucleotide strands in at least one of the defined spaces; and evaluating a likelihood that a variant sequence is present given the measured values corresponding to the ensemble of sequencing reads, the evaluating comprising: determining a measurement confidence value for each read in the ensemble of sequencing reads and modifying at least some model-predicted values using a first bias for forward strands and a second bias for reverse strands.

Abstract: A method for nucleic acid sequencing includes receiving observed or measured nucleic acid sequencing data from a sequencing instrument that receives and processes a sample nucleic acid in a termination sequencing-by-synthesis process. The method also includes generating a set of candidate sequences of bases for the observed or measured nucleic acid sequencing data by determining a predicted signal for candidate sequences using a simulation framework. The simulation framework incorporates an estimated carry forward rate (CFR), an estimated incomplete extension rate (IER), an estimated droop rate (DR), an estimated reactivated molecules rate (RMR), and an estimated termination failure rate (TFR), the RMR being greater than or equal to zero and the TFR being lesser than one. The method also includes identifying, from the set of candidate sequences of bases, one candidate sequence leading to optimization of a solver function as corresponding to the sequence for the sample nucleic acid.

Abstract: Provided herein is a pipette tip for electroporation including an outer surface, a void located within the outer surface, and a conductor located at least partially on or within the outer surface, in electrical communication with at least a portion of the outer surface and the void. Further provided herein is a pipette tip for electroporation including a body, a connector, and an elongated part. The connector is located at the distal end of the body and further includes at least one connecting post, a connecting part in mechanical communication with the connector, and a conductor located at least partially on or within the connector, wherein the conductor surrounds at least a portion of the connecting post. The elongated part also has a void and is located at the distal end of the connector. The void of the body, connector, and elongated part are in fluid communication.

Abstract: Provided are methods and compositions for preparing a library of target nucleic acid sequences that are useful for assessing gene mutations for oncology biomarker profiling of samples. In particular, a target-specific primer panel is provided that allows for selective amplification of oncology biomarker target sequences in a sample. In one aspect, the invention relates to target-specific primers useful for selective amplification of one or more target sequences associated with oncology biomarkers from two or more sample types. In some aspects, amplified target sequences obtained using the disclosed methods, and compositions can be used in various processes including nucleic acid sequencing and used to detect the presence of genetic variants of one or more targeted sequences associated with oncology.

Abstract: An instrument for processing and/or measuring a biological process comprises a sample processing system and an excitation source exhibiting a spectral function of output power or intensity verses wavelength of output power or intensity. The spectral function has a minima wavelength corresponding to a local minima value of the output power or intensity; a first maxima wavelength corresponding to a first local maxima of output power or intensity, the output power or intensity at the first local maxima being greater than the output power or intensity at any wavelength less than the minima wavelength; a second maxima wavelength corresponding to a second local maxima of output power or intensity, the output power or intensity at the second local maxima being greater than the output at any wavelength greater than the minima wavelength; the minima wavelength is between the first maxima wavelength and the second maxima wavelength.

Abstract: The present invention provides methods and compositions that are useful for assessing gene expression for tumor immune response profile of a sample. In particular, a target-specific primer panel is provided that allows for selective amplification of immune response target sequences in a sample. In one aspect, the invention relates to target-specific primers useful for selective amplification of one or more target sequences associated with immune response. In some aspects, amplified target sequences obtained using the disclosed methods, and compositions can be used in various processes including nucleic acid sequencing and used to detect the presence of genetic variants and/or expression levels of one or more targeted sequences associated with immune response.

Abstract: The method includes compressing numbers of reads data for targeted genes of a gene expression assay performed on a test sample. The targeted genes are organized into categories. Each category represents a functional context associated with the targeted genes in that category. The numbers of reads corresponding to targeted genes each category is compressed to form a compressed value for the category. The compressed value is compared to a baseline value for the category to determine an enrichment or a loss of a signature corresponding to the functional context of the category. The method may include analyzing information from multiple assays performed on the test sample, assigning a score value to each assay result and predicting a response to immune-oncology treatment based on the assigned scores.