Abstract: A method of using a sequencing cell includes applying an alternating signal across a nanopore of the sequencing cell. The method further includes acquiring a first set of voltage data during a first portion of a plurality of cycles of the alternating signal. The method further includes determining a shifted set of voltage data from the first set of voltage data, computing difference data values by computing differences between data points of the first set of voltage data and corresponding data points of the shifted set of voltage data, identifying a plurality of noise data points as data points having difference data values that are larger than a first threshold value, and removing the plurality of noise data points from the first set of voltage data.

Abstract: Disclosed are methods for isolating polymerase complexes from a mixture of polymerase complex components. The polymerase complexes can comprise a nanopore to provide isolated nanopore sequencing complexes. The methods relate to the positive and negative isolation of the polymerase complexes and/or nanopore sequencing complexes. Also disclosed is a nucleic acid adaptor for isolating active polymerase complexes, polymerase complexes comprising the nucleic acid adaptor, and methods for isolating active polymerase complexes using the nucleic acid adaptor.

Abstract: The invention is a method of predicting response to therapy in a colorectal cancer patient, the method comprising analysis of circulating tumor DNA from a patient's sample.

Abstract: Sequencing adaptors and methods are provided for preparation of polynucleotides for sequencing. The sequencing adaptors contain a portion of a recognition sequence for a methyl-dependent endonuclease. Unwanted adaptor dimers that form during ligation of adaptors to target polynucleotides produce a complete restriction sequence and are cleaved by the endonuclease, followed by exonuclease digestion, thereby removing the dimers.

Abstract: The invention provides methods, compositions, kits and devices for the detection of target molecules. In some embodiments, the invention allows for multiplexed target molecule detection.

Abstract: Systems and methods of polynucleotide sequencing are provided. Systems and methods optimize control, speed, movement, and/or translocation of a sample (e.g., a polynucleotide) within, through, or at least partially through a nanopore or a type of protein or mutant protein in order to accumulate sufficient time and current blocking information to identify contiguous nucleotides or plurality of nucleotides in a single-stranded area of a polynucleotide.

Abstract: The present invention is a method and compositions for primer extension target enrichment of nucleic acids and improvements thereto including simultaneously enriching for RNA and DNA and optionally sequencing the enriched products. An embodiment of the present invention includes a method comprising the steps of: hybridizing a target-specific primer to a target DNA or RNA, wherein the primer comprises a target-binding region and a region of complementarity to an adaptor; extending the primer with a DNA polymerase or reverse transcriptase to form a primer extension product; contacting the product with an adaptor comprising a longer strand with a 5?-overhang having complementarity to said primer and a shorter strand comprising a universal priming site; hybridizing the adaptor to the product; and ligating one strand of the adaptor to the product to form a ligation product.

Abstract: This disclosure provides chips, systems and methods for sequencing a nucleic acid sample. Tagged nucleotides are provided into a reaction chamber comprising a nanopore in a membrane. An individual tagged nucleotide of the tagged nucleotides can contain a tag coupled to a nucleotide, which tag is detectable with the aid of the nanopore. Next, an individual tagged nucleotide of the tagged nucleotides can be incorporated into a growing strand complementary to a single stranded nucleic acid molecule derived from the nucleic acid sample. With the aid of the nanopore, a tag associated with the individual tagged nucleotide can be detected upon incorporation of the individual tagged nucleotide. The tag can be detected with the aid of the nanopore when the tag is released from the nucleotide.

Abstract: Described herein are variants of alpha-hemolysin having at least one mutation selected from T12R, T12K, N17R, N17K or combinations of T12 and N17 mutations. The variants in some embodiments may further comprise H144A. The ?-hemolysin variants have a decreased time to thread.

Abstract: The present disclosure provides biochips and methods for making biochips. A biochip can comprise a nanopore in a membrane (e.g., lipid bilayer) adjacent or in proximity to an electrode. Methods are described for forming the membrane and inserting the nanopore into the membrane. The biochips and methods can be used for nucleic acid (e.g., DNA) sequencing. The present disclosure also describes methods for detecting, sorting, and binning molecules (e.g., proteins) using biochips.

Abstract: The present disclosure provides 3? protected nucleotides, including those 3? protected nucleotides having a detectable tag. Systems and methods of sequencing nucleic acids using the 3? protected nucleotides are also disclosed, such as the sequencing of a nucleic acid using a nanopore or the sequencing of a nucleic acid via sequencing-by-synthesis.

Abstract: The invention comprises methods and compositions for enriching for a target nucleic acid with a single primer extension and low-bias limited amplification.

Abstract: The invention relates to a method for making nanopores in thin layers or monolayers of transition metal dichalcogenides that enables accurate and controllable formation of pore within those thin layer(s) with sub-nanometer precision.

Abstract: This disclosure provides systems and methods for attaching nanopore-detectable tags to nucleotides. The disclosure also provides methods for sequencing nucleic acids using the disclosed tagged nucleotides.

Abstract: Devices for sequencing linear biomolecules (e.g., DNA, RNA, polypeptides, proteins, and the like) using quantum tunneling effects, and methods of making and using such devices, are provided. A nanofabricated device can include a small gap formed by depositing a thin film between two electrodes, and subsequently removing the film using an etching process. The width of the resulting gap can correspond with the size of a linear biomolecule such that when a part of the biomolecule (e.g., a nucleobase or amino acid) is present in the gap, a change in tunneling current, voltage, or impedance can be measured and the part of the biomolecule identified. The gap dimensions can be precisely controlled at the atomic-scale by, for example, atomic layer deposition (ALD) of the sacrificial film. The device can be made using existing integrated circuit fabrication equipment and facilities, and multiple devices can be formed on a single chip.

Abstract: Disclosed herein are apparatuses for nucleic acid sequencing, and methods of making and using such apparatuses. In some embodiments, the apparatus comprises a magnetic sensor array comprising a plurality of magnetic sensors, each of the plurality of magnetic sensors coupled to at least one address line, and a fluid chamber adjacent to the magnetic sensor array, the fluid chamber having a proximal wall adjacent to the magnetic sensor array.

Abstract: The invention is a novel method of making and using a library such as a sequencing library of single stranded circular nucleic acid templates via splint ligation. In particular, disclosed are methods of making circular target nucleic acid molecules and libraries of such molecules for downstream analysis such as nucleic acid sequencing. The method comprises the steps of adding universal sequences to nucleic acid molecules, rendering single-stranded these nucleic acid molecules with universal sequences on their ends by contacting with a probe complementary to at least a portion of the universal sequences, and allowing the hybridized probe to enable circularization and formation of single-stranded circular (sscDNA) molecules.

Abstract: Embodiments may include a method of determining a nucleic acid sequence. The nucleic acid may be DNA. The method may include forming, by a polymerase, a double-stranded nucleic acid molecule from a first nucleic acid strand and a second nucleic acid strand. Forming the double-stranded nucleic acid molecule may include adding a first compound to the second nucleic acid strand. The first compound may include a nucleotide attached to a third nucleic acid strand. The third nucleic acid strand may be attached to a moiety. The method may also include detaching the nucleotide from the third nucleic acid strand and the moiety. The method may further include measuring a change in an electrical characteristic of a transistor resulting from the moiety. Additionally, the method may include identifying the nucleotide based on the measured change in the electrical characteristic.