Abstract: Light detection devices and related methods are provided. The devices may comprise a reaction structure for containing a reaction solution with a relatively high or low pH and a plurality of reaction sites that generate light emissions. The devices may comprise a device base comprising a plurality of light sensors, device circuitry coupled to the light sensors, and a plurality of light guides that block excitation light but permit the light emissions to pass to a light sensor. The device base may also include a shield layer extending about each light guide between each light guide and the device circuitry, and a protection layer that is chemically inert with respect to the reaction solution extending about each light guide between each light guide and the shield layer. The protection layer prevents reaction solution that passes through the reaction structure and the light guide from interacting with the device circuitry.

Abstract: An example resin composition includes an epoxy resin matrix, a first photoacid generator, and a second photoacid generator. The first photoacid generator includes an anion having a molecular weight less than about 250 g/mol. The second photoacid generator includes an anion having a molecular weight greater than about 300 g/mol. In an example, i) a cation of the first photoacid generator has, or ii) a cation of the second photoacid generator has, or iii) the cations of the first and second photoacid generators have a mass attenuation coefficient of at least 0.1 L/(g*cm) at a wavelength of incident light to cure the resin composition.

Abstract: Apparatus and methods for controlling heating of an objective in a linescanning sequencing system to improve resolution are disclosed. In accordance with a first implementation, an apparatus includes or comprises a beam source for providing input radiation and a beam shaping group including or comprising one or more optical elements positioned to receive the input radiation from the beam source, and to perform beam shaping on the input radiation to form a shaped beam. The apparatus further including or comprising an objective positioned to receive the shaped beam and to transform the shaped beam into a probe beam and configured to provide the probe beam to a focal plane of the objective for optically probing a sample. The beam shaping group is configured to adjust one or more properties of the shaped beam over time to generally uniformly heat the objective over a region of incidence for the shaped beam.

Abstract: Polynucleotide sequencing using ionophores is provided herein. In some examples, a sequencing method includes inhibiting current flow across a barrier; contacting a polymerase with a first polynucleotide, a second polynucleotide, and a fluid comprising a first nucleotide coupled to a first ionophore; while the polymerase adds the first nucleotide to the second polynucleotide based on a sequence of the first polynucleotide, providing a first current flow across the barrier using the first ionophore; and identifying the first nucleotide using an electrical characteristic of the first ionophore.

Abstract: The present disclosure relates to systems and methods for the amplification of nucleic acids, including, but not limited to, the amplification of nucleic acid libraries and whole genome amplification.

Abstract: Apparatus and methods for transmitting light are disclosed. In an implementation, an apparatus includes a collimator at an input end positioned to receive an input beam from a fiber beam source and to produce a collimated beam. The apparatus further includes a beam shaping group having one or more optical elements and positioned to receive the collimated beam from the collimator and format the collimated beam into a shaped propagation beam having a substantially rectangular cross-section in a far field. The apparatus further includes an objective stage for optically probing a sample, such as a flow cell, using substantially rectangular cross-section sampling beam, where fluorescence from the sample is captured by a line sensor for detecting properties of the sample, such as chemical reactions therein.

Abstract: The technology disclosed processes input data through a neural network and produces an alternative representation of the input data. The input data includes per-cycle image data for each of one or more sequencing cycles of a sequencing run. The per-cycle image data depicts intensity emissions of one or more analytes and their surrounding background captured at a respective sequencing cycle. The technology disclosed processes the alternative representation through an output layer and producing an output and base calls one or more of the analytes at one or more of the sequencing cycles based on the output.

Abstract: Some examples herein provide a sequencing flowcell that includes an imaging sensor; a hydrogel disposed on the imaging sensor and comprising a moiety; and a first complex non-covalently coupled to the moiety, the first complex comprising a first oligonucleotide. A method of using the sequencing flowcell may include decoupling the first complex from the moiety; and coupling a second complex to the moiety, the second complex comprising a second oligonucleotide. Methods of forming the flowcell are also provided.

Abstract: The technology disclosed relates to training a convolutional neural network (CNN) to identify and classify images of sections of an image generating chip resulting in process cycle failures. The technology disclosed includes creating a training data set of images of dimensions M×N using labeled images of sections of image generating chip of dimensions J×K. The technology disclosed can fill the M×N frames using horizontal and vertical reflections along edges of J×K labeled images positioned in M×N frames. A pretrained CNN is further trained using the training data set. Trained CNN can classify a section image as normal or depicting failure. The technology disclosed can train a root cause CNN to classify process cycle images of sections causing process cycle failure. The trained CNN can classify a section image by root cause of process failure among a plurality of failure categories.

Abstract: A polymer is disposed through a nanopore that encodes a polynucleotide's sequence and includes monomer units that encode nucleotides and include first and second reporter moieties and first and second arresting constructs. The first reporter moiety is translocated into the nanopore's aperture, where a first value of an electrical property of the first reporter moiety is measured while the first arresting construct pauses translocation. The second reporter moiety is translocated into the aperture, where a second value of an electrical property of the second reporter moiety is measured while the second arresting construct pauses translocation. The first value and the second value for each monomer unit is used to identify the nucleotide encoded by that monomer unit; and distinguish the nucleotide encoded by that monomer unit from the nucleotides encoded by adjacent monomer units, including by those that encode the same type of nucleotide as that monomer unit.

Abstract: In some examples, a hybrid particle for use in capturing a polynucleotide may include a scaffold molecule including a seeding primer and a plurality of first moieties, and a nanoparticle including a plurality of second moieties. The scaffold molecule is coupled to the nanoparticle via interactions between the plurality of first moieties and the plurality of second moieties.

Abstract: Hardware acceleration may be leveraged for performing secondary analysis. The hardware acceleration may be implemented by utilizing a plurality of field programmable gate arrays (FPGAs) installed on a device. Requests may be made from client processes for performing secondary analysis of sequencing data at a computing device. Each FPGA may be configured with an engine, or set of engines, configured to perform the secondary analysis to service the requests from client process. An FPGA may be configured with a plurality of engines configured for performing secondary analysis. The FPGA may be configured with a single instance comprising different types of engines for performing different types of secondary analysis. The FPGA may be configured with multiple instances of an engine, or set of engines, configured to perform the same or similar type of secondary analysis. The FPGA may share its resources with multiple client processes using one or more shared engines.

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: An image sensor structure includes an image layer having an array of light detectors disposed therein. A device stack is disposed over the image layer. An array of light guides is disposed in the device stack. Each light guide is associated with a light detector. An array of nanowells is disposed over the device stack. Each nanowell is associated with a first light guide of the array of light guides. A first primer set is disposed throughout a first well region of each nanowell. A second primer set is disposed throughout a second well region of each nanowell. The second well region is adjacent the first well region. The first and second primer sets are operable to attach a forward strand cluster of forward polynucleotide strands in the first well region and a reverse strand cluster of reverse polynucleotide strands in the second well region.

Abstract: In some examples, a dendritic molecule may include a dendritic core; a seeding primer coupled to the dendritic core; and a plurality of dendrons, each of the dendrons comprising an inert, elongated polymer comprising a first end coupled to the dendritic core and a second end coupled to a first functional group, wherein the first functional group is to react with a second functional group to form a covalent bond. In other examples, a dendritic molecule may include a dendritic core; a single-stranded polynucleotide covalently bonded to the dendritic core; and a plurality of dendrons, each of the dendrons comprising an inert, elongated polymer comprising a first end coupled to the dendritic core and a second end.

Abstract: Provided are methods and systems for sample quality control in CNV detection using test samples comprising cell-free nucleic acid fragments originating from a mother and a fetus. The method involves determining an exclusion region defined by at least a fetal fraction limit of detection (LOD) curve. The fetal fraction LOD curve varies with coverage values and indicates minimum values of fetal fractions needed to achieve a detection criterion given different coverages.