Abstract: Biosensor including a device base having a sensor array of light sensors and a guide array of light guides. The light guides have input regions that are configured to receive excitation light and light emissions generated by biological or chemical substances. The light guides extend into the device base toward corresponding light sensors and have a filter material. The device base includes device circuitry electrically coupled to the light sensors and configured to transmit data signals. A passivation layer extends over the device base and forms an array of reaction recesses above the light guides. The biosensor also includes peripheral crosstalk shields that at least partially surround corresponding light guides of the guide array to reduce optical crosstalk between adjacent light sensors.

Abstract: Provided is a computer-implemented method, including inputting to a trained machine learning classifier genomic information of a non-training subject that includes features from a tumor sample, wherein the trained machine learning classifier trained on features of tumor samples obtained from training subjects and their a responsiveness to checkpoint inhibition treatment and the machine-learning classifier is trained to predict responsiveness to the treatment, and generating a checkpoint inhibition responsiveness classification predictive of the subject's responding to the checkpoint inhibition with the trained machine-learning classifier, and reporting the checkpoint inhibition responsiveness classification using a graphical user interface. Also provided are a computer system for performing the method and a machine learning classifier trained by the method.

Abstract: The technology disclosed relates to classification of process cycle images to predict success or failure of process cycles. The technology disclosed includes capturing and processing images of sections arranged on an image generating chip in genotyping process. Image description features of production cycle images are created and given as input to classifiers. A trained classifier separates successful production images from unsuccessful or failed production images. The failed production images are further classified by a trained root cause classifier into various categories of failure.

Abstract: The present disclosure relates to methods, compositions, and kits for treating target nucleic acids, including methods and compositions for fragmenting and tagging nucleic acid (e.g., DNA) using transposome complexes bound to a solid support.

Abstract: A method for measuring thermal resistance between a thermal component of an instrument and a consumable includes contacting a known consumable with a thermal component to be tested; driving the thermal component using a periodic sine wave input based on a predetermined interrogation frequency; measuring temperature outputs from a thermal sensor responsive to the periodic sine wave input; multiplying the temperature outputs by a reference signal in phase with the periodic sine wave input and calculating the resultant DC signal component to determine an in-phase component X; multiplying the plurality of temperature outputs by a 90° phase-shifted reference signal and calculating the resultant DC signal component to determine a quadrature, out-of-phase component Y; calculating a phase offset responsive to the periodic sine wave input based on tan?1 (Y/X) or atan2(X, Y); and determining a resistance value for the thermal interface using a calibrated resistance-phase offset equation and the calculated phase offset.

Abstract: The present disclosure relates to polymer coatings covalently attached to the surface of a substrate and the preparation of the polymer coatings, such as poly(N-(5-azidoacetamidylpentyl)acrylamide-co-acrylamide) (PAZAM), in the formation and manipulation of substrates, such as molecular arrays and flow cells. The present disclosure also relates to methods of preparing a substrate surface by using beads coated with a covalently attached polymer, such as PAZAM, and the method of determining a nucleotide sequence of a polynucleotide attached to a substrate surface described herein.

Abstract: Embodiments provided herewith are directed to self-assembled methods of preparing a patterned surface for sequencing applications including, for example, a patterned flow cell or a patterned surface for digital fluidic devices. The methods utilize photolithography to create a patterned surface with a plurality of microscale or nanoscale contours, separated by hydrophobic interstitial regions, without the need of oxygen plasma treatment during the photolithography process. In addition, the methods avoid the use of any chemical or mechanical polishing steps after the deposition of a gel material to the contours.

Abstract: The technology disclosed directly operates on sequencing data and derives its own feature filters. It processes a plurality of aligned reads that span a target base position. It combines elegant encoding of the reads with a lightweight analysis to produce good recall and precision using lightweight hardware. For instance, one million training examples of target base variant sites with 50 to 100 reads each can be trained on a single GPU card in less than 10 hours with good recall and precision. A single GPU card is desirable because it a computer with a single GPU is inexpensive, almost universally within reach for users looking at genetic data. It is readily available on could-based platforms.

Abstract: Methods and systems for decreasing amplification bias and primer-dimer formation in amplification reactions and for amplifying a plurality of target polynucleotides from a sample in a single reaction and for sequencing the target polynucleotides where samples can include forensic samples and where target polynucleotides can include identity- or ancestry-informative markers, short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs).

Abstract: The technology disclosed relates to inter-model prediction score recalibration. In one implementation, the technology disclosed relates to a system including a first model that generates, based on evolutionary conservation summary statistics of amino acids in a target protein sequence, a first pathogenicity score-to-rank mapping for a set of variants in the target protein sequence; and a second model that generates, based on epistasis expressed by amino acid patterns spanning the target protein sequence and a plurality of non-target protein sequences aligned in multiple sequence alignment, a second pathogenicity score-to-rank mapping for the set of variants. The system also includes a reassignment logic that reassigns pathogenicity scores from the first set of pathogenicity scores to the set of variants based on the first and second score-to-rank mappings, and an output logic to generate a ranking of the set of variants based on the reassigned scores.

Abstract: A detection apparatus that includes (a) an array of responsive pads on a substrate surface; (b) an array of pixels, wherein each pixel in the array has a detection zone on the surface that includes a subset of at least two of the pads; and (c) an activation circuit to apply a force at a first and second pad in the subset, wherein the activation circuit is configured to apply a different force at the first pad compared to the second pad, and wherein the activation circuit has a switch to selectively alter the force at the first pad and the second pad.

Abstract: A fluidic device holder configured to orient a fluidic device. The device holder includes a support structure configured to receive a fluidic device. The support structure includes a base surface that faces in a direction along the Z-axis and is configured to have the fluidic device positioned thereon. The device holder also includes a plurality of reference surfaces facing in respective directions along an XY-plane. The device holder also includes an alignment assembly having an actuator and a movable locator arm that is operatively coupled to the actuator. The locator arm has an engagement end. The actuator moves the locator arm between retracted and biased positions to move the engagement end away from and toward the reference surfaces. The locator arm is configured to hold the fluidic device against the reference surfaces when the locator arm is in the biased position.

Abstract: The technology disclosed present systems and methods to produce an enhanced resolution image from images of a target using structured illumination microscopy (SIM). The method includes transforming at least three images of the target captured by a sensor in a spatial domain into a Fourier domain to produce at least three frequency domain matrices that each include first blocks of complex coefficients and redundant second blocks of complex coefficients that are conjugates to the first blocks. The method includes reducing computing resources required to produce the enhanced resolution image by using first blocks of complex coefficients to produce at least three phase-separated half-matrices in the Fourier domain. The method includes performing one or more intermediate transformation on the phase-separated half-matrices to produce realigned shifted half-matrices. The method includes calculating complex coefficients of second blocks in the Fourier domain to produce full matrices from half-matrices.

Abstract: A device for luminescent imaging includes an array of imaging pixels, a photonic structure over the array of imaging pixels, and an array of features over the photonic structure. A first feature of the array of features is over a first pixel of the array of imaging pixels, and a second feature of the array of features is over the first pixel and spatially displaced from the first feature. A first luminophore is within or over the first feature, and a second luminophore is within or over the second feature. The device includes a radiation source to generate first photons having a first characteristic at a first time, and generate second photons having a second characteristic at a second time. The first pixel selectively receives luminescence emitted by the first and second luminophores responsive to the first photons at the first time and second photons at the second time, respectively.

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: Polynucleotide sequencing methods for sequencing one or more polynucleotide templates use primers bound to a surface as sequencing primers. The surface primers may include at least a portion of a surface oligonucleotide used during cluster formation. The sequencing methods may be used for single stranded sequencing or double stranded sequencing. Double stranded sequencing methods may employ an enzyme that has nick-translation activity. A kit includes all the reagents needed for sequencing does not include sequencing primers. The kit may be used to accomplish the sequencing methods of the present disclosure.

Abstract: The technology disclosed relates to equalizer-based intensity correction for base calling. In particular, the technology disclosed relates to accessing an image whose pixels depict intensity emissions from a target cluster and intensity emissions from additional adjacent clusters, selecting a lookup table that contains pixel coefficients that are configured to increase a signal-to-noise ratio, applying the pixel coefficients to intensity values of the pixels in the image to produce an output, and base calling the target cluster based on the output.

Abstract: An apparatus includes a flow cell body, a plurality of electrodes, an integrated circuit, and an imaging assembly. The flow cell body defines one or more flow channels and a plurality of wells. Each flow channel is configured to receive a flow of fluid. Each well is fluidically coupled with the corresponding flow channel. Each well is configured to contain at least one polynucleotide. Each electrode is positioned in a corresponding well of the plurality of wells. The electrodes are operable to effect writing of polynucleotides in the corresponding wells. The integrated circuit is operable to drive selective deposition or activation of selected nucleotides to attach to polynucleotides in the wells to thereby generate polynucleotides representing machine-written data in the wells. The imaging assembly is operable to capture images indicative of one or more nucleotides in a polynucleotide.

Abstract: A computer-implemented method of predicting phenotypic shift in response to usage of a plurality of drugs on a plurality of phenotypes of a cohort of individuals with a plurality of confounders. The cohort of individuals has associated phenotype measurements, covariate measurements, and drug usage patterns for two separate time points. The phenotype measurements for the first and second time points are covariate-corrected and drug-usage corrected through the use of biostatistics.