Abstract: The disclosure provides compositions, methods, and kits that facilitate the characterization of omic variation in tissues while preserving spatial information related to the origin of target analytes in the tissue.

Abstract: Provided herein are methods for modification-based controlled polynucleotide translocation in nanopores for sequencing, modified nucleotides, and kits and systems for performing the disclosed methods. In some embodiments, modifications can be used to control polynucleotide translocation by modifying nucleotides on a strand of polynucleotide to carry a modification, where the modifications can arrest or slow translocation when encountering the nanopore. In some embodiments, application of a voltage can move one nucleotide and its attached modification through the nanopore at a time.

Abstract: A method for amplifying a target nucleic acid including providing a system having a crRNA or a derivative thereof, and a Cas protein or a variant thereof. The crRNA or the derivative thereof contains a target-specific nucleotide region substantially complementary to a region of the target nucleic acid, and contacting the target nucleic acid with the system to form a complex.

Abstract: An example of a nanopore sensor device includes one or more cis wells; a cis electrode; a plurality of trans wells, each of the plurality of trans wells separated from the one or more cis wells by a lipid/solid-state membrane having a nanopore; a plurality of trans electrodes, each of the plurality of trans electrodes associated with one of the plurality of trans wells; a first concentration of an electrolyte within the one or more cis wells; and a second concentration of the electrolyte within the trans wells, wherein the first concentration is higher than the second concentration.

Abstract: A composition includes a nanopore including first and second sides and an aperture, nucleotides each including an elongated tag, and a first polynucleotide that is complementary to a second polynucleotide. A polymerase can be disposed adjacent to the first side of the nanopore and configured to add nucleotides to the first polynucleotide based on a sequence of the second polynucleotide. A permanent tether can include a head region anchored to the polymerase, a tail region, and an elongated body disposed therebetween that occurs in the aperture of the nanopore. A first moiety can be disposed on the elongated body that binds to the elongated tag of a first nucleotide upon which the polymerase is acting. A reporter region can be disposed on the elongated body that indicates when the first nucleotide is complementary or is not complementary to a next nucleotide in the sequence of the second polynucleotide.

Abstract: The present disclosure provides method and systems for improving nanopore-based analyses of polymers. The disclosure provides methods for selectively modifying one or more monomeric subunit(s) of a kind a pre-analyte polymer that results polymer analyte with a modified subunit. The polymer analyte produces a detectable signal in a nanopore-based system. The detectable signal, and/or its deviation from a reference signal, indicates the location of the modified subunit in the polymer analyte and, thus, permits the identification of the subunit at that location in the original pre-analyte polymer.

Abstract: Polypeptide nanopores synthetically functionalized with positively charged species, and methods of making and using the same, are provided herein. In some examples, a polypeptide nanopore includes a first side, a second side, a channel extending through the first and second sides, and a mutated amino acid residue. The mutated amino acid residue may be synthetically functionalized with a positively charged species that inhibits translocation of cations through the channel.

Abstract: A method for amplifying a target nucleic acid including providing a system having a crRNA or a derivative thereof, and a Cas protein or a variant thereof. The crRNA or the derivative thereof contains a target-specific nucleotide region substantially complementary to a region of the target nucleic acid, and contacting the target nucleic acid with the system to form a complex.

Abstract: In an example, a sensing system includes a pH sensor. The pH sensor includes two electrodes and a conductive channel operatively connected to the two electrodes. A complex is attached to the conductive channel of the pH sensor. The complex includes a polymerase linked to at least one pH altering moiety that is to participate in generating a pH change within proximity of the conductive channel from consumption of a secondary substrate in a fluid that is exposed to the pH sensor. The at least one pH altering moiety is selected from the group consisting of an enzyme, a metal coordination complex, a co-factor, and an activator.

Abstract: The current document discusses electromechanical sequence detectors that transduce changes in the shape of a shape-change sensor component into an electrical signal from which one or more derived values are generated. In a disclosed implementation, the sequence-detection system comprises a mechanical-change sensor that changes shape when specifically interacting with entities within a target, a shape-to-signal-transduction component that transduces changes in the shape of the mechanical-change sensor into an electrical signal, an analysis subsystem that determines the types of entities within the target using the electrical signal, and a control subsystem that continuously monitors operational characteristics of the sequence-detection system and adjusts sequence-detection system operational parameters.

Abstract: Methods and compositions for characterizing a target polynucleotide, including, characterizing the sequence of the target polynucleotide, using the fractional translocation steps of the target polynucleotide's translocation through a pore.

Abstract: The current document discusses electromechanical sequence detectors that transduce changes in the shape of a shape-change sensor component into an electrical signal from which one or more derived values are generated. In a disclosed implementation, the sequence-detection system comprises a mechanical-change sensor that changes shape when specifically interacting with entities within a target, a shape-to-signal-transduction component that transduces changes in the shape of the mechanical-change sensor into an electrical signal, an analysis subsystem that determines the types of entities within the target using the electrical signal, and a control subsystem that continuously monitors operational characteristics of the sequence-detection system and adjusts sequence-detection system operational parameters.

Abstract: A composition includes a nanopore including first and second sides and an aperture, nucleotides each including an elongated tag, and a first polynucleotide that is complementary to a second polynucleotide. A polymerase can be disposed adjacent to the first side of the nanopore and configured to add nucleotides to the first polynucleotide based on a sequence of the second polynucleotide. A permanent tether can include a head region anchored to the polymerase, a tail region, and an elongated body disposed therebetween that occurs in the aperture of the nanopore. A first moiety can be disposed on the elongated body that binds to the elongated tag of a first nucleotide upon which the polymerase is acting. A reporter region can be disposed on the elongated body that indicates when the first nucleotide is complementary or is not complementary to a next nucleotide in the sequence of the second polynucleotide.

Abstract: Devices and methods of using the devices are disclosed which can provide scalability, improved sensitivity and reduced noise for sequencing polynucleotide. Examples of the devices include a biological or solid-state nanopore, a field effect transistor (FET) sensor with improved gate controllability over the channel, and a porous structure.

Abstract: Methods and compositions for characterizing a target polynucleotide, including, characterizing the sequence of the target polynucleotide, using the fractional translocation steps of the target polynucleotide's translocation through a pore.

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: The current document discusses a detection system comprising a mechanical-change sensor that exhibits one or more mechanical changes when specifically interacting with entities within a target, each entity having a type, a mechanical-change-to-signal transducer that transduces the one or more mechanical changes into a signal, and an analysis subsystem that determines the types of entities within the target using the signal.

Abstract: In one aspect, the disclosed technology relates to nanopore sequencing with a polynucleotide comprising a plurality of nucleotides, wherein each nucleotide comprises a linker construct between two positions of the nucleotide, wherein the linker construct optionally comprises a reporter moiety corresponding to the identity of the nucleotide, and wherein the linker construct is a part of the cleavable cyclic loop nucleotide comprising a cleavable site. In some embodiments, the nucleotides further comprise arresting constructs for slowing or halting the polynucleotide translocation through a nanopore.

Abstract: A sensing system includes a charge sensor including two electrodes and an electrically conductive channel connecting the two electrodes. The sensing system also includes a charged molecule attached to the electrically conductive channel. The charged molecule includes a recognition site to reversibly bind a label of a labeled nucleotide; has an unbound favored conformation associated with an unbound charge configuration; and has a favored conformation associated with a charge configuration when the recognition site is bound to the label. The charge configuration is different from the unbound charge configuration. The sensing system further includes a polymerase attached to the electrically conductive channel or to the charged molecule.

Abstract: A method for enriching or amplifying a target nucleic acid including providing a system having a guide nucleic acid, and a Cas or Argonaute protein or a variant thereof. The guide nucleic acid contains a target-specific nucleotide region substantially complementary to a region of the target nucleic acid, and contacting the target nucleic acid with the system to form a complex.