Abstract: Provided herein are compositions and methods for sequencing using at least altering electrical characteristics of polymer bridges. In some examples, the bridges may span the space between first and second electrodes and may include first and second polymer chains that are hybridized to one another. A plurality of nucleotides may be coupled to corresponding labels. A polymerase may be coupled to the bridge and may add nucleotides to a first polynucleotide using at least a sequence of a second polynucleotide. The labels corresponding to those nucleotides respectively may alter hybridization between the first and second polymer chains. Detection circuitry may detect a sequence in which the polymerase adds the nucleotides to the first polynucleotide using at least changes in an electrical signal through the bridge, the changes being responsive to the respective alterations of hybridization using the labels corresponding to those nucleotides.

Abstract: The technology disclosed relates to state-based base calling. In particular, the technology disclosed relates to incorporating state information about data from previous sequencing cycles into the analysis of data from a current sequencing cycle when generating a base call for the current sequencing cycle. For example, when generating a base call for an Nth sequencing cycle, the technology disclosed can incorporate into the base calling logic state information about data from sequencing cycles 1 to N?1.

Abstract: Artificial intelligence driven signal enhancement of sequencing images enables enhanced sequencing by synthesis that determines a sequence of bases in genetic material with any one or more of: improved performance, improved accuracy, and/or reduced cost. A training set of images taken at unreduced and reduced power levels used to excite fluorescence during sequencing by synthesis is used to train a neural network to enable the neural network to recover enhanced images, as if taken at the unreduced power level, from unenhanced images taken at the reduced power level.

Abstract: The disclosed embodiments concern methods, apparatus, systems and computer program products for determining sequences of interest using unique molecular index sequences that are uniquely associable with individual polynucleotide fragments, including sequences with low allele frequencies and long sequence length. In some implementations, the unique molecular index sequences include variable-length nonrandom sequences. In some implementations, the unique molecular index sequences are associated with the individual polynucleotide fragments based on alignment scores indicating similarity between the unique molecular index sequences and subsequences of sequence reads obtained from the individual polynucleotide fragments. System, apparatus, and computer program products are also provided for determining a sequence of interest implementing the methods disclosed.

Abstract: Provided is a method, including stretching a polynucleotide over a substrate including a plurality of equally spaced cleavage regions including a plurality of transposases, cleaving the polynucleotide with two or more of the plurality of transposases to form a plurality of polynucleotide fragments, and separating, within the plurality of polynucleotide fragments, a population of longer polynucleotide fragments from a population of shorter polynucleotide fragments. Also provided is a method including stretching a polynucleotide over a substrate including a plurality of equally spaced cleavage regions including a plurality of transposases, cleaving the polynucleotide with two or more of the plurality of transposases to form a plurality of polynucleotide fragments, and separating, within the plurality of polynucleotide fragments, a population of longer polynucleotide fragments from a population of shorter polynucleotide fragments.

Abstract: Embodiments of the present disclosure include methods and compositions for functionalizing molecules, such as oligonucleotides, with functional groups, including polyhistidine tags useful in affinity methods. Some embodiments include methods for modifying and purifying complex mixtures of molecules by exchange of functional tags.

Abstract: Degradable polyester bead are described comprising a plurality of transposome complexes immobilized to the surface thereof, wherein each transposome complex comprises a transposase bound to a first polynucleotide and a second polynucleotide, wherein the first polynucleotide comprises a 3? portion comprising a transposon end sequence and a tag, and the second polynucleotide comprises a 5? portion that is complementary to and hybridized to the transposon end sequence, and wherein the polyester bead has a melting point of from 50° C. to 65° C. Flow cells and methods related to these polyester beads are described. Also described herein are compositions comprising a bead and at least one nanoparticle and methods of use of such compositions comprising transposome complexes immobilized to nanoparticles.

Abstract: The present invention includes methods and materials for use in the detection preeclampsia and/or determining an increased risk for preeclampsia in a pregnant female, the method including identifying in a biosample obtained from the pregnant women a plurality of circulating RNA (C-RNA) molecules.

Abstract: A variety of different types of targeted transposome complexes are described herein that may be used to mediate sequence-specific targeted transposition of nucleic acids.

Abstract: The technology disclosed relates to artificial intelligence-based base calling. The technology disclosed relates to accessing a progression of per-cycle analyte channel sets generated for sequencing cycles of a sequencing run, processing, through a neural network-based base caller (NNBC), windows of per-cycle analyte channel sets in the progression for the windows of sequencing cycles of the sequencing run such that the NNBC processes a subject window of per-cycle analyte channel sets in the progression for the subject window of sequencing cycles of the sequencing run and generates provisional base call predictions for three or more sequencing cycles in the subject window of sequencing cycles, from multiple windows in which a particular sequencing cycle appeared at different positions, using the NNBC to generate provisional base call predictions for the particular sequencing cycle, and determining a base call for the particular sequencing cycle based on the plurality of base call predictions.

Abstract: Flow cells and corresponding methods are provided. The flow cells may include a support frame with top and back sides, and at least one cavity extending from the top side. The flow cells may include at least one light detection device with an active area disposed within the at least one cavity. The flow cells may include a support material disposed within the at least one cavity between the support frame and the periphery of the at least one light detection device coupling them together. The flow cells may include a lid extending over the at least one light detection device and coupled to the support frame about the periphery of the at least one light detection device. The lid and at least a top surface of the at least one light detection device form a flow channel therebetween.

Abstract: A system includes a droplet actuator having a droplet-operation gap between top and bottom substrates, a reservoir(s) external to and coupled to the droplet actuator, the reservoir(s) sized for a large-volume fluid, and pressure source(s) external to the droplet actuator and coupled to the at least one reservoir. Operation of the system includes filling the reservoir(s) with a large volume of fluid(s), dispensing droplet(s) of the fluid(s) to the droplet-operation gap using the pressure source(s) as part of performing a droplet operation(s). Movement of the droplet(s) may be effectuated by activating the droplet actuator.

Abstract: A method for spatially tagging nucleic acids of a biological specimen, including steps of (a) providing a solid support comprising different nucleic acid probes that are randomly located on the solid support, wherein the different nucleic acid probes each includes a barcode sequence that differs from the barcode sequence of other randomly located probes on the solid support; (b) performing a nucleic acid detection reaction on the solid support to locate the barcode sequences on the solid support; (c) contacting a biological specimen with the solid support that has the randomly located probes; (d) hybridizing the randomly located probes to target nucleic acids from portions of the biological specimen; and (e) modifying the randomly located probes that are hybridized to the target nucleic acids, thereby producing modified probes that include the barcode sequences and a target specific modification, thereby spatially tagging the nucleic acids of the biological specimen.

Abstract: The disclosure provides detection apparatus having one or more nanopores, methods for making apparatus having one or more nanopore and methods for using apparatus having one or more nanopores. Uses include, but are not limited to detection and sequencing of nucleic acids.

Abstract: Artificial intelligence driven enhancement of motion blurred sequencing images enables enhanced sequencing that determines a sequence of bases in genetic material with any one or more of: improved performance, improved accuracy, and/or reduced cost. A training set of images taken after unreduced and reduced movement settling times during sequencing is used to train a neural network to enable the neural network to recover enhanced images, as if taken after the unreduced movement settling time, from unenhanced images taken after the reduced movement settling time.

Abstract: A method includes engaging a well of a cartridge with a flow sensor of an instrument. The cartridge includes: a rotary valve including a rotatable port and a center port; the well in fluid communication with a channel, the channel including a channel port that the rotatable port is to align to in order to receive fluid from the well; and a flowcell including an inlet gasket in fluid communication with the center port. A source of pressurized air is connected to the flow sensor in order to establish a mass flow of air through a flow path. The flow path extends through one of the flow sensor, the channel, the rotary valve, and the flowcell. The mass flow of air through the flow path is measured with the flow sensor. It is determined if there is one of an air leak and an air blockage within the flow path.