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: 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: 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: 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.

Abstract: A catalytically active substance includes a copper (I) sulfide mineral particle, and an alkyne functionalized molecule bound to a surface of the copper (I) sulfide mineral particle. In an example method, a copper (I) sulfide mineral is reacted with an alkyne functionalized molecule to form a catalytically active substance. The catalytically active substance is reacted with an azide functionalized molecule to couple the catalytically active substance with the azide functionalized molecule.

Abstract: A cartridge for use with chemical or biological analysis systems, as well as methods of using the same, is provided. The cartridge may include a floating microfluidic plate that is held in the cartridge using one or more floating support brackets that incorporate gaskets that may seal against fluidic ports on the microfluidic plate. The floating support brackets may include indexing features that may align the microfluidic plate with the seals.

Abstract: Provided herein are compositions that include nucleic acid fragments produced from double-stranded template nucleic acids, such as cell free DNA. The compositions can be used as positive or negative controls for quality of library preparation methods, calibration of an instrument such as a sequencing instrument, and/or a validation for a nucleic acid sequencing test. Also provided are methods for making the nucleic acid fragments.

Abstract: The present invention is concerned with compositions and methods for improving the rate of correct sample identification in indexed nucleic acid library preparations for multiplex next generation sequencing by modifying or blocking 5? and 3? ends of pooled indexed polynucleotides from multiple samples, with an optional exonuclease treatment, prior to amplification and sequencing.

Abstract: Versions of a sequencing system may be monitored to enable changing of a version of a server subsystem operating the sequencing system to service requests from client subsystems for performing analysis of sequencing data. A monitor subsystem may be utilized for receiving and authorizing requests from client subsystems. The monitor subsystem may identify a version associated with a server subsystem operating the sequencing system to be implemented for servicing the request. The monitor subsystem may allow the server subsystem to be accessed for servicing the request from the client subsystem when the version associated with the client subsystem is compatible with the version associated with the server subsystem. The monitor subsystem may prevent the server subsystem from being accessed when the version associated with the client subsystem is incompatible with the version associated with the server subsystem.

Abstract: The disclosure provides methods for creating long oligonucleotide reagents that include barcodes and other element for sequencing library preparation, where the oligonucleotides are created by multiple tiers of ligation of shorter oligos. The disclosed methods work to extend short oligos that are attached to particles, thereby allowing one to create particles that carry large number of long sample preparation oligonucleotides without being required to synthesize those full-length molecules with a polymerase.

Abstract: The disclosure provides a structured illumination imaging system that utilizes an image sensor (e.g., an active pixel sensor) in an active plane of a patterned sample to increase image resolution. The imaged sample may be patterned and/or aligned over an image sensor such that each light sensor (e.g., pixel) of the image sensor has a respective plurality of features formed and/or mounted above it. In response to illumination, each of the features may emit fluorescent light that is collected by a pixel of the image sensor. During imaging, each pixel of the image sensor may be spatially multiplexed using structured illumination such that only a subset (e.g., one or two) of the features aligned over the pixel are illuminated with structured light during an image read.

Abstract: Resolution of images used in processes such as sequencing by synthesis may be increased by structuring sites that would emit signals in the images to have different elevations. Differences in focus caused by these differences in elevation may be used to filter out background illumination, thereby providing an image in which in focus sites may be resolved even though the separation between any site and its nearest neighbor may be below the diffraction limit of the light that would be emitted.

Abstract: Temperature-controllable reagent cartridges and systems for controlling the temperature in such reagent cartridges are provided. An example such system may include a reagent cartridge having reagent reservoirs located at least in part within an interior plenum volume of a cartridge housing. In such an example system, each reagent reservoir may be defined, in part, by a sidewall, and a first reagent reservoir may be spaced apart from a second reagent reservoir to form a fluid flow passage between corresponding sidewalls thereof. A fluid inlet through the cartridge housing may be provided that fluidically connects the interior plenum volume with a fluid supply port of a temperature control system of an analysis instrument when the reagent cartridge is received by the analysis instrument; a fluid outlet through the cartridge housing that fluidically connects the interior plenum volume with a fluid return port of the temperature control system may also be provided.

Abstract: An example sensor includes a flow cell, a detection device, and a controller. The flow cell includes a passivation layer having opposed surfaces and a reaction site at a first of the opposed surfaces. The flow cell also includes a lid operatively connected to the passivation layer to partially define a flow channel between the lid and the reaction site. The detection device is in contact with a second of the opposed surfaces of the passivation layer, and includes an embedded metal layer that is electrically isolated from other detection circuitry of the detection device. The controller is to ground the embedded metal layer.

Abstract: A flow cell assembly is provided that includes a support layer of low-background material, a film of anodized metal oxide (AMO) material adhered to the support layer, and a substrate formed, in part, by one or more patterns imparted in the AMO material. A flow cell assembly herein may include a support layer of low-background material, a film of AMO material adhered to the support layer, and a substrate surface comprising one or more patterns imparted in the AMO material. Each pattern may comprise an array of nanowell features surrounded by interstitial regions of featureless AMO film.