Roswell Biotechnologies, Inc.

Life Technologies Corporation

Semicon Bio

Roswell Me Inc.

Roswell Blotechnologies, Inc.

Paul Mola

Barry L Merriman

Tim Geiser

Chulmin Choi

Sungho Jin

Venkatesh Alagarswamy Govindaraj

Gina Costa

Eskild Timme Hansen

Mark S Gardner

Darryl Rideout

Anders Lassen

Calvin James Gardner

In various embodiments, synthetic bridge molecules are disclosed, usable in molecular electronics sensors. In various aspects, bridge molecules comprise fused ring polycyclic aromatic hydrocarbon structures in the shape of a long and narrow ribbon, with end groups on opposite short ends for selective binding to metal electrodes, one or more substituents near the midpoint of a long edge for binding to a probe molecule, and one or more additional substituent groups for solubility or other effects. In various embodiments, the bridge molecules herein are conducting, and provide a closed circuit in a sensor when forming a bridge between gapped electrodes.

Polycyclic aromatic bridges for molecular electronic sensors

In various embodiments a molecular circuit is disclosed. The circuit comprises a negative electrode, a positive electrode spaced apart from the negative electrode, and an enzyme molecule conductively attached to both the positive and negative electrodes to form a circuit having a conduction pathway through the enzyme. In various examples, the enzyme is a polymerase. The circuit may further comprise molecular arms used to wire the enzyme to the electrodes. In various embodiments, the circuit functions as a sensor, wherein electrical signals, such as changes to voltage, current, impedance, conductance, or resistance in the circuit, are measured as substrates interact with the enzyme.

Enzymatic circuits for molecular sensors

A structure usable in a molecular sensor device comprises a substrate defining a substrate plane and spaced apart pairs of reducible metal oxide or metal nitride sheets attached to the substrate at an angle to the substrate plane. The structure further includes intervening dielectric sheets. Fabrication methods for manufacturing structures for molecular sensors are disclosed comprising oblique angle deposition of reducible metal oxide or metal nitride and dielectric layers, planarization of the resulting stack, and reduction of portions of the reducible metal oxide or metal nitride sheets to the corresponding base metal.

Methods of fabricating nanoscale structures usable in molecular sensors and other devices

A sequencing device is disclosed. The sequence device includes an array of conducting electrode pairs, each pair of electrodes comprising a source and a drain electrode arrangement separated by a nanogap, the electrode array deposited and patterned on a dielectric substrate; at least one transition metal dichalcogenide (TMD) layer disposed on each pair of electrodes, wherein the TMD layer connects each source and drain electrode within each pair, and bridges each nanogap of each pair of electrodes; and a dielectric masking layer disposed on the TMD layer and comprising at least one opening that defines an exposed TMD region, wherein the at least one opening is sized so as to allow a single biomolecule to fit therein and to attach on to the exposed TMD region. In embodiments of the disclosure, the TMD layer be a defective TMD layer.

Solid state sequencing devices comprising two dimensional layer materials

In various embodiments of the present disclosure, a molecular electronics sensor array chip comprises: (a) an integrated circuit semiconductor chip; and (b) a plurality of molecular electronic sensor devices disposed thereon, each of said sensor devices comprising: (i) a pair of nanoscale source and drain electrodes separated by a nanogap; (ii) a gate electrode; and (iii) a bridge and/or probe molecule spanning the nanogap and connecting the source and drain electrodes, wherein the molecular electronic sensor devices are organized into an electronically addressable, controllable, and readable array of sensor pixels.

Methods and apparatus for measuring analytes using polymerase in large scale molecular electronics sensor arrays

A method of genotyping includes applying a sample solution including a plurality of copies of a sample polynucleotide to an array of sensors. The sample polynucleotide includes a region associated with an allele. The method further includes measuring using a plurality of sensors of the array of sensors a characteristic of the region of the plurality of copies of the sample polynucleotide and determining using a computational circuitry and the measured characteristics a statistical value indicative of the allele.

Methods for analysis of DNA fragments

A DNA or genome sequencing structure is disclosed. The structure includes an electrode pair, each electrode having a tip-shaped end, the electrodes separated by a nanogap defined by facing tip-shaped ends; at least one conductive island deposited at or near each tip-shaped end; and a biomolecule having two ends, each end attached to the conductive islands in the electrode pair such that one biomolecule bridges over the nanogap in the electrode pair, wherein nucleotide interactions with the biomolecule provides electronic monitoring of DNA or genome sequencing without the use of a fluorescing element.

Massively parallel DNA sequencing apparatus

A method of manufacturing a device useable in DNA or genome sequencing comprises disposing pairs of electrodes on a substrate, the electrodes within each pair separated by a nanogap; depositing a resist layer over the electrodes; patterning the resist layer to create an exposed region on each electrode at or near each nanogap; roughening the electrode surface within each exposed region using various methods; and exposing the exposed regions to biomolecules, wherein one biomolecule bridges each nanogap of each electrode pair, with each end of each biomolecule bound to the electrodes at each exposed region.

Electronic label-free DNA and genome sequencing

A processive enzyme molecular sensor for use in a DNA data storage system is disclosed that can extract digital information suitably encoded into a synthetic DNA molecule. In various aspects, such sensors are provided in a high-density chip-based format that can provide the high throughput, low-cost and fast data extraction capability required for large scale DNA data storage systems. The sensor for reading the digital data stored in DNA molecules processes individual encoded DNA molecules directly, eliminating the need for complicated sample preparation such as making copies of DNA or clonal populations of such molecules.

Processive enzyme molecular electronic sensors for DNA data storage

In various embodiments a molecular circuit is disclosed. The circuit comprises a negative electrode, a positive electrode spaced apart from the negative electrode, and a binding probe molecule conductively attached to both the positive and negative electrodes to form a circuit having a conduction pathway through the binding probe. In various examples, the binding probe is an antibody, the Fab domain of an antibody, a protein, a nucleic acid oligomer hybridization probe, or an aptamer. The circuit may further comprise molecular arms used to wire the binding probe to the electrodes. In various embodiments, the circuit functions as a sensor wherein electrical signals, such as changes to voltage, current, impedance, conductance, or resistance in the circuit, are measured as targets interact with the binding probe. In various embodiments, the circuit provides a means to measure the presence, absence, or concentration of an analyte in a solution.

Binding probe circuits for molecular sensors

In various embodiments, amplification-free DNA information methods, apparatus and systems are disclosed. A method of amplification-free information storage and retrieval comprises encoding digital data such as binary into nucleotide sequence motifs using an encoding scheme, and synthesizing replicate DNA molecules using an amplification-free DNA writing process. The amplification-free process of decoding the information stored in the DNA comprises exposing at least one of the replicate DNA molecules to a molecular electronics sensor that generates distinguishable signals in a measured electrical parameter of the sensor, wherein the distinguishable signals correspond to the sequence motifs, providing decoding back to the digital data.

Methods, apparatus and systems for amplification-free DNA data storage

DNA sequencer with split hexagonal element

In various embodiments, an information storage system comprises: a writing device for synthesizing a nucleotide sequence that encodes a set of information; and a reading device for interpreting the nucleotide sequence by decoding the interpreted nucleotide sequence into the set of information, wherein the reading device comprises a molecular electronics sensor, the sensor comprising a pair of spaced apart electrodes and a molecular complex attached to each electrode to form a molecular electronics circuit, wherein the molecular complex comprises a bridge molecule and a probe molecule, and wherein the molecular electronics sensor produces distinguishable signals in a measurable electrical parameter of the molecular electronics sensor, when interpreting the nucleotide sequence.

Growing community of inventors

San Diego, CA, United States of America

Paul Mola