Western Digital Technologies, Inc.

Sandisk Technologies Inc.

New York University

Daniel Bedau

Patrick Braganca

Justin Kinney

Andrew David Kent

Huanlong Liu

Michael Grobis

Derek Stewart

Christopher John Petti

Gerardo Bertero

Alan Kalitsov

Richard Leo Galbraith

Kurt A Rubin

Weldon Mark Hanson

Niranjay Ravindran

Iouri Oboukhov

Wen Ma

Tung Thanh Hoang

Pradhan Bellam

A method of performing nucleic acid sequencing may comprise using a disintegrator situated in a fluidic channel of a sequencing device to cleave off a portion of a nucleic acid molecule in the fluidic channel; applying an electrostatic force to divert the portion of the nucleic acid molecule through a nanopore; detecting an ionic current through the nanopore; and determining an identity of at least one nucleotide of the portion of the nucleic acid molecule based at least in part on the ionic current. A system for sequencing nucleic acids may comprise an array comprising a plurality of sequencing devices, each comprising a fluidic channel, a disintegrator embedded in the fluidic channel, and a nanopore coupled to an exit end of the fluidic channel; and detection circuitry coupled to the array and configured to detect ionic currents through the nanopores.

Methods and systems for nucleic acid sequencing using nanopores

Disclosed herein are devices, systems, and methods for controlling the movement of at least one molecule in a first fluid having a first viscosity. The system includes a fluid region defined by at least one fluid-retaining surface, a field-responsive fluid situated in the fluid region, and a field generator for generating a magnetic or electric field across the fluid region. The fluid region is traversable by the at least one molecule. In response to a magnitude of the magnetic or electric field across the fluid region exceeding a threshold magnitude, a viscosity of the field-responsive fluid is greater than the first viscosity.

Devices, systems, and methods of using smart fluids to control molecule speeds

A system for controlling a translocation speed of a molecule through a nanopore may include a fluid chamber containing a solution with a magnetic susceptibility that is different from the magnetic susceptibility of the molecule, a nanopore situated in the fluid chamber, and at least one magnetic component configured to create a magnetic field gradient within the solution to control the translocation speed of a molecule through the nanopore. A system for controlling a translocation speed of a molecule through a nanopore may include a nanopore at least one magnetic component situated to create a magnetic field that causes the molecule to experience a rotational torque as it passes through the nanopore.

Magnetic control of molecule translocation speed through a nanopore

Disclosed herein are methods of using detection devices. A detection device comprises a fluidic channel configured to receive a plurality of molecules to be detected, a plurality of temperature sensors, and an insulating material encapsulating the plurality of temperature sensors and providing a barrier between the plurality of temperature sensors and contents of the fluidic channel. A surface of the insulating material within the fluidic channel provides a plurality of sites for binding the plurality of molecules to be detected. Each of the plurality of temperature sensors is configured to detect, in the presence of an alternating magnetic field, a temperature change indicating presence or absence of one or more magnetic nanoparticles (MNPs) coupled to at least one of the plurality of molecules to be detected at a respective subset of the plurality of sites.

Thermal sensor array for molecule detection and related detection schemes

Disclosed herein are devices, systems, and methods can improve the signal-to-noise ratio of measurements made in biological applications. In some embodiments, an amplifier circuit that comprises a three-terminal device is situated in a configuration (e.g., a common-base or similar configuration) that allows the circuit to detect current through a nanopore while providing feedback to the sense electrode to reduce parasitic capacitance between the sense electrode and the counter electrode. The amplifier circuit may include, for example, a bi-polar junction transistor (BJT), a diamond transistor, a CMOS transistor, an operational transconductance amplifier, a voltage-controlled current source, a transconductor, a macro transistor, and/or a second-generation current conveyor (CCII+).

Amplifiers for biological sensing applications

A method of sensing molecules using a detection device, the detection device comprising a plurality of magnetoresistive (MR) sensors and at least one fluidic channel, comprising adding a plurality of molecules to be detected to the at least one fluidic channel, wherein at least some of the plurality of molecules to be detected are coupled to respective magnetic nanoparticles (MNPs), detecting a characteristic of a magnetic noise of a first MR sensor of the plurality of MR sensors, wherein the characteristic of the magnetic noise is influenced by a presence of one or more MNPs in a vicinity of the first MR sensor, and determining, based on the detected characteristic, whether the first MR sensor detected the presence of one or more MNPs in the vicinity of the first MR sensor.

Magnetoresistive sensor array for molecule detection and related detection schemes

A device includes arrays of Non-Volatile Memory (NVM) cells. Reference sequences representing portions of a genome are stored in respective groups of NVM cells. Exact matching phase substring sequences representing portions of at least one sample read are loaded into groups of NVM cells. One or more groups of NVM cells are identified where the stored reference sequence matches the loaded exact matching phase substring sequence using the arrays at Content Addressable Memories (CAMs). Approximate matching phase substring sequences are loaded into groups of NVM cells. One or more groups of NVM cells are identified where the stored reference sequence approximately matches the loaded approximate matching phase substring sequence using the arrays as Ternary CAMs (TCAMs). At least one of the reference sequence and the approximate matching phase substring sequence for each group of NVM cells includes at least one wildcard value when the arrays are used as TCAMs.

Devices and methods for genome sequencing

A method is provided that includes reading a plurality of resistance-switching memory cells comprising a block of data, decoding the block of data using an error correction code decoder, and based on results of the decoding, selectively performing an overwrite-read process to read the block of data. The overwrite read process determines a change in resistance of the resistance-switching memory cells in response to a write pulse.

Overwrite read methods for resistance switching memory devices

Disclosed herein are detection methods that use magnetic nanoparticles (MNPs) to allow molecules to be identified. Embodiments of this disclosure include methods of using magnetic sensors (e.g., magnetoresistive sensors) to detect temperature-dependent magnetic fields (or changes in magnetic fields) emitted by MNPs, and, specifically to distinguish between the presence and absence of magnetic fields emitted, or not emitted, by MNPs at different temperatures selected to take advantage of knowledge of how the MNPs' magnetic properties change with temperature. Embodiments disclosed herein may be used for nucleic acid sequencing, such as deoxyribonucleic acid (DNA) sequencing.

Based on thermal stabilities of magnetic nanoparticles

Disclosed herein are molecular storage systems and methods of reading molecules that include integrity markers. A molecular storage system may comprise read hardware configured to read molecules storing data, and at least one processor coupled to the read hardware. The processor is configured to determine whether a molecule being read by the read hardware includes an expected integrity marker, and, in response to a determination that the molecule being read by the read hardware does not include the expected integrity marker, instruct the read hardware to abandon a read operation associated with the molecule being read by the read hardware. The partial readback can be placed in a buffer and used in an assembly process only if an intact molecule is not available.

Encoding and integrity markers for molecular storage applications

Disclosed herein are devices, systems, and methods that can improve the SNR of nanopore measurements by mitigating the effect of parasitic capacitance between the sense electrode and the counter electrode. In some embodiments, a feedback circuit is used to inject a charge into the sense electrode to at least partially cancel the parasitic capacitance between the sense electrode and the counter electrode. In some embodiments, bootstrapping of a signal from the amplifier output or from the sense electrode is used to inject a charge on the counter electrode to substantially cancel the parasitic capacitance.

Low noise amplifiers with feedback for nanopore applications

Disclosed herein are systems and devices for detecting molecules. In some embodiments, a system for detecting molecules comprises an amplifier and a nanopore unit, wherein the nanopore unit comprises a nanopore, a sense electrode, a counter electrode, and a shield situated between the sense electrode and the counter electrode and coupled to an output of the amplifier. The shield may be recessed from a hole in the nanopore. A system or device may include an array of nanopore units that may share some components, such as a read amplifier, a digitizer, drive circuitry, control logic, and/or a multiplexer.

Low noise amplifiers with shields for nanopore Applications

Disclosed herein are improved methods and systems for sequencing nucleic acid that exploit the temperature-dependence of the emitted intensity of fluorescent dyes. The temperature of the sequencing reaction is adjusted during each sequencing cycle, and the emission, or lack of emission, of light meeting or exceeding a threshold by the fluorescent dyes at different temperatures, or within different temperature ranges, is used to detect the fluorescent labels of the incorporated dNTPs and thereby sequence the nucleic acid. The disclosed methods enable a determination of the dNTP incorporated at any given site with a reasonable number of chemistry steps without the complex optics necessary for prior-art systems.

Enhanced optical detection for nucleic acid sequencing using thermally-dependent fluorophore tags

Disclosed herein are devices, systems, and methods for controlling a translocation speed of a molecule through a nanopore. In some embodiments, a speed-control device comprises at least one fluid-retaining surface, a fluid region, a field-responsive fluid coupled to the fluid-retaining surface and situated in the fluid region. In some embodiments, a system comprises the nanopore, the speed-control device, and a field generator for generating a magnetic or electric field across the fluid region. The viscosity of the field-responsive fluid is dependent on a magnitude of the magnetic or electric field across the fluid region and can be controlled by changing a magnitude of the magnetic or electric field across the fluid region.

Devices, systems, and methods of using smart fluids to control translocation speed through a nanopore

A system includes at least one waveguide with optical interaction portions that represent a sequence of reference symbols based on the order of the optical interaction portions in the at least one waveguide. At least one light source sends photons of one or more predetermined wavelengths into the at least one waveguide representing a string of query symbols. A detector detects photons received from the at least one waveguide that result from optical interactions between photons sent into the at least one waveguide and one or more corresponding optical interaction portions with an interaction between photons and an optical interaction portion indicating a match between a query symbol and a reference symbol. An analyzer determines one or more respective relative locations of the one or more corresponding optical interaction portions indicating one or more relative locations of the string of query symbols in the reference sequence.

Growing community of inventors

San Jose, CA, United States of America

Daniel Bedau