Abstract: Actuation systems and methods for use with flow cells. An example apparatus includes a flow cell assembly including a flow cell including at least one channel, a flow cell inlet, and a flow cell outlet. The flow cell assembly includes a gasket assembly operatively fluidically coupled to the flow cell and having a flow cell inlet gasket and a flow cell outlet gasket. The flow cell inlet gasket having a through bore and being fluidically coupled to the flow cell inlet. The flow cell outlet gasket having a through bore and being fluidically coupled to the flow cell outlet. The apparatus includes a reagent cartridge adapted to receive the flow cell assembly and including a pair of reagent cartridge ports adapted to be fluidly coupled to the flow cell inlet gasket and the flow cell outlet gasket.

Abstract: An instrument includes a reagent management system. The reagent management system includes a plurality of reagent wells, each reagent well operable to contain a reagent of a plurality of reagents positioned therein. The reagent management system is operable to select a flow of reagent from one of the plurality of reagents. A flexible connection includes a laminate stack and includes a first flexible channel in fluid communication with the reagent management system. The first flexible channel is operable to route the flow of reagent therethrough. A flow cell includes a flow channel in fluid communication with the first flexible channel. The flow channel is operable to route the flow of reagent over analytes positioned in the flow channel. The flexible connection enables the flow cell to be moved by the instrument relative to a fixed reference point in the instrument.

Abstract: Some examples relate to a method for characterizing polynucleotides in a sample. First polynucleotides coupled to a first substrate may be hybridized to second polynucleotides in a sample. First labeled nucleotides may be added to the first polynucleotides using a sequence of the second polynucleotides. A first signal intensity from the first labeled nucleotides is measured. Second labeled nucleotides are added to the first polynucleotides using the sequence of the second polynucleotides. A second signal intensity from the second labeled nucleotides is measured. The first signal intensity is normalized using the second signal intensity. The normalized first signal intensity characterizes the second polynucleotides in the sample.

Abstract: Disclosed herein are flow cells and methods of sequencing using flow cells. In some examples, the flow cells include a first surface that includes a first set of capture primers and a second set of capture primers, and a second surface that includes a first set of capture primers and a second set of capture primers.

Abstract: Provided is a surface having metal regions and an interstitial region having a composition that differs from the metal regions, wherein a continuous gel layer coats the surface across the metal regions and the interstitial regions. Nucleic acids or other analytes can be attached to the continuous gel layer such that a greater amount is attached over the metal regions than over the interstitial region. Also provided are methods for making such surfaces. Methods are also provided for making an array of nucleic acids or other analytes using such surfaces.

Abstract: The technology disclosed relates to splice site prediction and aberrant splicing detection. In particular, it relates to a splice site predictor that includes a convolutional neural network trained on training examples of donor splice sites, acceptor splice sites, and non-splicing sites. An input stage of the convolutional neural network feeds an input sequence of nucleotides for evaluation of target nucleotides in the input sequence. An output stage of the convolutional neural network translates analysis by the convolutional neural network into classification scores for likelihoods that each of the target nucleotides is a donor splice site, an acceptor splice site, and a non-splicing site.

Abstract: Provided herein include various examples of an apparatus, a sensor system and examples of a method for manufacturing aspects of an apparatus, a sensor system. The apparatus may include a die. The apparatus may also include a substrate comprising a cavity. The die may be oriented in a portion of the cavity in the substrate, where the orientation defines a first space in the cavity adjacent to a first edge of the upper surface of the die and a second space in the cavity adjacent to the second edge of the upper surface of the die. The apparatus may further include fluidics fan-out regions comprising a first cured material deposited in the first space and the second space, a surface of the fluidics fan-out regions being contiguous with the upper surface of the die.

Abstract: Nucleotide sequencing methods for sequencing an oligonucleotide strand while the oligonucleotide strand is a part of a double-stranded complex. At least one strand of the double-stranded complex is immobilized on a surface. Sequencing primers may not be immobilized on a surface. Double stranded sequencing methods may employ an enzyme that has nick-translation activity.

Abstract: Fluidic device includes a manifold body having first and second body sides. The first body side has receiving ports forming a port array that defines a reaction region. The second body side has open-sided recesses forming reaction chambers when the fluidic device is mounted onto a sample substrate. The reaction chambers form a chamber array that defines a fluid-delivery region. The reaction region is greater than the fluid-delivery region. The manifold body also includes vent openings that open to an exterior. The fluidic device also includes upstream channels extending through the manifold body. Each of the upstream channels fluidly couples a corresponding receiving port of the port array to a corresponding reaction chamber of the chamber array. The fluidic device also includes venting channels extending through the manifold body. Each of the venting channels fluidly couples a corresponding reaction chamber of the chamber array to a corresponding vent opening.

Abstract: Presented herein are methods and compositions for targeted amplification of DNA and sample identification. The methods are particularly useful in validation and quality control of samples and to confirm that WGS sequence data is properly paired with a patient sample prior to delivering sequence data to a physician or to a patient.

Abstract: A closure for an apparatus comprises: a plurality of light sources; a lightguide to distribute light from the plurality of light sources, the lightguide having a first primary surface opposite a second primary surface, wherein the first primary surface has a first surface treatment, and wherein light emitted from the lightguide indicates a status of the apparatus; and a frame supporting the plurality of light sources and the lightguide for selective movement of the closure vertically or horizontally relative to the apparatus.

Abstract: An imprinting apparatus includes a silicon master having a plurality of nanofeatures defined therein. An anti-stick layer coats the silicon master, the anti-stick layer including a molecule having a cyclosiloxane with at least one silane functional group. A method includes forming a master template by: depositing a formulation on a silicon master including a plurality of nanofeatures defined therein, the formulation including a solvent and a molecule having a cyclosiloxane with at least one silane functional group; and curing the formulation, thereby forming an anti-stick layer on the silicon master, the anti-stick layer including the molecule. The method further includes depositing a silicon-based working stamp material on the anti-stick layer of the master template; curing the silicon-based working stamp material to form a working stamp including a negative replica of the plurality of nanofeatures; and releasing the working stamp from the master template.

Abstract: Presented herein are methods and compositions for multiplexed single cell gene expression analysis. Some methods and compositions include the use of droplets and/or beads bearing unique barcodes such as unique molecular barcodes (UMI).

Abstract: Methods of making barriers including nanopores and crosslinked amphiphilic molecules, and barriers made using the same, are provided herein. In some examples, a method of forming a barrier between first and second fluids includes forming at least one layer comprising a plurality of amphiphilic molecules, wherein the amphiphilic molecules comprise reactive moieties. The method may include using first crosslinking reactions of the reactive moieties to only partially crosslink amphiphilic molecules of the plurality to one another. The method may include, after using the first crosslinking reactions, inserting the nanopore into the at least one layer. The method may include, after inserting the nanopore, using second crosslinking reactions of the reactive moieties to further crosslink amphiphilic molecules of the plurality to one another.

Abstract: An interposer for a flow cell comprises a base layer having a first surface and a second surface opposite the first surface. The base layer comprises black polyethylene terephthalate (PET). A first adhesive layer is disposed on the first surface of the base layer. The first adhesive layer comprises methyl acrylic adhesive. A second adhesive layer is disposed on the second surface of the base layer. The second adhesive layer comprises methyl acrylic adhesive. A plurality of microfluidic channels extends through each of the base layer, the first adhesive layer, and the second adhesive layer.

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: Presented herein are techniques for determining microsatellite instability. The techniques include generating a reference sample dataset representative of or mimicking a hypothetical matched sample for an individual sample of interest. The reference sample dataset may be generated from a set of reference normal samples that are not matched to the sample of interest. For samples of interest lacking a matched sample, the reference sample dataset may be used to determine microsatellite instability and to provide an indication of a presence, absence, or degree of microsatellite instability of the sample of interest. The reference sample dataset may be generated such that individual microsatelliate regions associated with a high degree of variability between ethnic groups are filtered out, masked, or otherwise not considered.

Abstract: Substrates comprising a functionalizable layer, a polymer layer comprising a plurality of micro-scale or nano-scale patterns, or combinations thereof, and a backing layer and the preparation thereof by using room-temperature UV nano-embossing processes are disclosed. The substrates can be prepared by a roll-to-roll continuous process. The substrates can be used as flow cells, nanofluidic or microfluidic devices for biological molecules analysis.

Abstract: A circuit with electrical interconnect for external electronic connection and sensor(s) on a die are combined with a laminated manifold to deliver a liquid reagent over an active surface of the sensor(s). The laminated manifold includes fluidic channel(s), an interface between the die and the fluidic channel(s) being sealed. Also disclosed is a method, the method including assembling a laminated manifold including fluidic channel(s), attaching sensor(s) on a die to a circuit, the circuit including an electrical interconnect, and attaching a planarization layer to the circuit, the planarization layer including a cut out for the die. The method further includes placing sealing adhesive at sides of the die, attaching the laminated manifold to the circuit, and sealing an interface between the die and fluidic channel(s).