Nabsys, Inc.

Nabsys, 2.0 LLC

Brown University

John S Oliver

Franco Preparata

Barrett Bready

Peter H Goldstein

Eliezer Upfal

Xinsheng Ling

Petre Ianakiev

Jing Tang

Maryam Jouzi

Leo Petrossian

Assay methods for preparing a biomolecule analyte includes hybridizing a sequence specific oligonucleotide probe to a biomolecule template and reacting the resulting analyte with a binding moiety.

Assay methods using DNA binding proteins

Methods for enhancing the binding of oligonucleotide probes to DNA and RNA are disclosed. The methods make use of thermodynamic and kinetic effects to reduce probe mismatches and failure of complementary probes to bind to DNA and RNA templates. Mapping and sequencing of the probed DNA and RNA samples are contemplated herein.

Enhanced probe binding

Devices and methods for detecting the length of analytes and/or sequencing analytes are provided in which two or more electrical signals are obtained as an analyte traverses a fluidic channel. Detection of the relative position of probes hybridized to a biopolymer and/or the length of the analyte (e.g., a biopolymer) does not rely on the absolute time between detection events of a given electrical signal to determine a distance associated with the biopolymer. Instead, multiple signals are obtained (e.g., as functions of time) corresponding to a plurality of detector volumes at known locations along a fluidic channel through which the biopolymer passes, and the distances are determined from the multiple signals.

Devices and methods for determining the length of biopolymers and distances between probes bound thereto

Devices for detecting an analyte are provided. Devices for voltage sensing of analytes may comprise a plurality of fluidic channels defined in a substrate, each channel having a pair of sensing electrodes disposed in or adjacent to the fluidic channel and defining a detection volume for sensing voltage therein. At least one pair of electromotive electrodes for applying potential along at least one fluidic channel is provided as well.

Use of longitudinally displaced nanoscale electrodes for voltage sensing of biomolecules and other analytes in fluidic channels

Assay methods and apparatus for the analysis of biopolymers are disclosed. The assays employ nicking endonucleases to enable the generation of flaps on target biomolecules which are detected in nanopore or fluidic channel devices. Identification of flap locations enables a map of the target biomolecule to be derived.

Assay methods using nicking endonucleases

Methods for sequencing a biopolymer by forming local ternary complexes along the length of the double-stranded biopolymer target molecule using one or more probes and obtaining information about the location of the probe(s) using a detector. These methods offer particular advantage when implemented with nanopore (including micropore) detection systems.

Biopolymer Sequencing By Hybridization of probes to form ternary complexes and variable range alignment

Devices and methods for detecting the length of analytes, and/or sequencing analytes are provided in which two or more electrical signals are obtained as an analyte traverses a fluidic channel. Detection of the relative position of probes hybridized to a biopolymer and/or the length of the analyte (e.g., a biopolymer) does not rely on the absolute time between detection events of a given electrical signal to determine a distance associated with the biopolymer. Instead, multiple signals are obtained as functions of time) corresponding to a plurality of detector volumes at known locations along a fluidic channel through which the biopolymer passes, and the distances are determined from the multiple signals.

Devices and methods for detecting an analyte are provided. Devices for voltage sensing of analytes may comprise a fluidic channel defined in a substrate, a pair of sensing electrodes disposed in a fluidic channel for sensing voltage therein, and a pair of electromotive electrodes for applying potential along the fluidic channel. The pair of sensing electrodes may include a first and second sensing electrode disposed at two discrete locations along the length of the fluidic channel and the pair of electromotive electrodes may be disposed at a first end and a second end of the fluidic channel. The fluidic channel may include a nanochannel or a microchannel. Methods for detecting an analyte may include the steps of disposing the analyte in a fluidic channel; applying a potential along the fluidic channel to generate an electrophoretic force therein such that the analyte is translocated from a first end of the fluidic channel to a second end of the fluidic channel; and measuring a voltage signal between a pair of sensing electrodes disposed in the fluidic channel as the analyte moves past the sensing electrodes.

Biopolymer sequencing by hybridization of probes to form ternary complexes and variable range alignment

Devices and methods for detecting the length of analytes and/or sequencing analytes are provided in which two or more electrical signals are obtained as an analyte traverses a nanopore or fluidic channel. Detection of the relative position of probes hybridized to a biomolecule and/or the length of the analyte (e.g., a biomolecule) rely on detection events to determine a distance associated with the biomolecule. Multiple signals may be obtained (e.g., as functions of time) corresponding to a plurality of detector volumes at known locations along a fluidic channel through which the biomolecule passes, and the distances may be determined from the multiple signals.

Devices and methods for analyzing biomolecules and probes bound thereto

The systems and methods described herein relate to nucleic acid probes comprising a pattern of universal and designate nucleotides (or analogs thereof), or 'gapped' probes, and the use of sets of gapped probes in sequencing by hybridization to determine the sequence of nucleic acid sequences. The inclusion of universal nucleotides in the probes allows for efficient and rapid sequencing of longer nucleotide sequences than can be sequenced using traditional probes. The systems and methods described herein also relate to apparatus for sequencing nucleic acids which include gapped probes, as well as computer systems capable of analyzing data generated using gapped probes in such apparatus.

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Bristol, RI, United States of America

John S Oliver