Iridia, Inc.

Life Technologies Corporation

California Institute of Technology

University of Southern California

Curate Biosciences LLC

Paul F Predki

Timothy Updyke

Maja Cassidy

Emil Paskalev Kartalov

Tad Decatur Simons

Shimon Spector

Itay Sela

Jennifer Miller

Randall Lowe

John Stuart Foster

Cheng-Chung Lee

Evangeline Gonzalez

Stefen Boehme

Timothy Vale Updyke

The disclosure provides novel topoisomerases which exhibit weakened ability to form a covalent bond to the 5'-(C/T)CCTT-3′recognition site in the presence of increased NaCl concentrations relative to wild-type, together with novel methods for synthesizing DNA in the 3′ to 5′ direction using the novel topoisomerase; and other compounds, compositions, methods and devices comprising or utilizing topoisomerases which exhibit reduced covalent bond formation to the 5′-(C/T)CCTT-3′ recognition site in the presence of increased NaCl concentrations, relative to wild-type.

Enzymes and systems for synthesizing DNA

A system and method of storing and reading digital data, including providing a nanopore polymer memory (NPM) device having at least one memory cell comprising at least two addition chambers each arranged to add a unique chemical construct (or codes) to a polymer (or DNA) string when the polymer enters the respective addition chamber, the data comprising a series of codes; successively steering the polymer from deblock chambers through the nanopore into the addition chambers to add codes to the polymer to create the digital data pattern on the polymer; and accurately controlling the bit rate of the polymer using a servo controller. The device may have loading chamber(s) to load (or remove) the polymer into/from the deblock chambers through at least one 'micro-hole'. The cell may be part of a memory system that stores and retrieves “raw” data and allows for remote retrieval and conversion. The cell may store multi-bit data having a plurality of states for the codes.

Systems and methods for writing and reading data stored in a polymer

The disclosure provides a novel system and method of storing multi-bit information, including providing a nano-channel-based polymer memory device, the device having at least one memory cell comprising at least two addition nano-channels, each of the addition nano-channels arranged to add a unique chemical construct (or codes) to the polymer when the polymer enters the respective addition nano-channel, the polymer having a bead or origami on a non-writing end of the polymer; each nano-channel having a nano-port constriction having a port width which allows the polymer to pass through the nano-port, and does not allow the bead or origami to pass through and does not allow addition or deblocking enzymes (or beads attached thereto) to pass through the nano-port; successively steering the polymer through the nanopore into the addition nano-channels to add the codes to the polymer based on a predetermined digital data pattern to create the digital data pattern on the polymer.

Systems and methods for writing and reading data stored in a polymer using nano-channels

The disclosure provides novel topoisomerases which exhibit weakened ability to form a covalent bond to the 5'-(C/T)CCTT-3&#x2032; recognition site in the presence of increased NaCl concentrations relative to wild-type, together with novel methods for synthesizing DNA in the 3&#x2032; to 5&#x2032; direction using the novel topoisomerase; and other compounds, compositions, methods and devices comprising or utilizing topoisomerases which exhibit reduced covalent bond formation to the 5&#x2032;-(C/T)CCTT-3&#x2032; recognition site in the presence of increased NaCl concentrations, relative to wild-type.

A system and method of storing and reading digital data, including providing a nanopore polymer memory (NPM) device having at least one memory cell comprising at least two addition chambers each arranged to add a unique chemical construct (or codes) to a polymer (or DNA) string when the polymer enters the respective addition chamber, the data comprising a series of codes; successively steering the polymer from deblock chambers through the nanopore into the addition chambers to add codes to the polymer to create the digital data pattern on the polymer; and accurately controlling the bit rate of the polymer using a servo controller. The device may have loading chamber(s) to load (or remove) the polymer into/from the deblock chambers through at least one 'micro-hole'. The cell may be part of a memory system that stores and retrieves 'raw' data and allows for remote retrieval and conversion. The cell may store multi-bit data having a plurality of states for the codes.

The disclosure provides a novel system of storing information using a charged polymer, e.g., DNA, the monomers of which correspond to a machine-readable code, e.g., a binary code, and which can be synthesized and/or read using a novel nanochip device comprising nanopores; novel methods and devices for synthesizing oligonucleotides in a nanochip format; novel methods for synthesizing DNA in the 3' to 5&#x2032; direction using topoisomerase; novel methods and devices for reading the sequence of a charged polymer, e.g., DNA, by measuring capacitive or impedance variance, e.g., via a change in a resonant frequency response, as the polymer passes through the nanopore; and further provides compounds, compositions, methods and devices useful therein.

Systems and methods for writing, reading, and controlling data stored in a polymer

The disclosure provides methods of synthesizing DNA using topoisomerase-mediated ligation, by adding single nucleotides or oligomers to a DNA strand in the' to&#x2032; direction.

Methods of synthesizing DNA

Methods, systems and devices for reading data stored in a polymer (e.g., DNA) and for verifying the sequence of a polymer synthesized in situ in a nanopore-based chip, include providing a resonator having an inductor and a cell, the cell having a nanopore and a polymer that can traverse through the nanopore, the resonator having an AC output voltage frequency response at a probe frequency in response to an AC input voltage at the probe frequency, providing the AC input voltage having at least the probe frequency, and monitoring the AC output voltage at least at the probe frequency, the AC output voltage at the probe frequency being indicative of the data stored in the polymer at the time of monitoring, wherein the polymer includes at least two monomers having different properties causing different resonant frequency responses.

Methods, compositions, and devices for information storage

The disclosure provides a novel system of storing information using a charged polymer, e.g., DNA, the monomers of which correspond to a machine-readable code, e.g., a binary code, and which can be synthesized and/or read using a novel nanochip device comprising nanopores; novel methods and devices for synthesizing oligonucleotides in a nanochip format; novel methods for synthesizing DNA in the 3' to 5&#x2032; direction using topoisomerase; novel methods and devices for reading the sequence of a charged polymer, e.g., DNA, by measuring capacitive variance as the polymer passes through the nanopore; and further provides compounds, compositions, methods and devices useful therein.

Provided herein are devices and methods for the micro-isolation of biological cellular material. A micro-isolation device described can comprise a photomask that protects regions of interest against DNA-destroying illumination. The micro-isolation device can further comprise photosensitive material defining access wells following illumination and subsequent developing of the photosensitive material. The micro-isolation device can further comprise a chambered microfluidic device comprising channels providing access to wells defined in photosensitive material. The micro-isolation device can comprise a chambered microfluidic device without access wells defined in photosensitive material where valves control the flow of gases or liquids through the channels of the microfluidic device. Also included are methods for selectively isolating cellular material using the devices described herein, as are methods for biochemical analysis of individual regions of interest of cellular material using the devices described herein. Further included are methods of making masking arrays useful for the methods described herein. The micro-isolation devices can comprise a unique combination of barcodes in each microfluidics well, allowing two-dimensional mapping of genetic information.

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Carlsbad, CA, United States of America

Paul F Predki