Arizona State University

Motorola Corporation

Columbia University

Amersham Biosciences Ab

Universal Sequencing Technology Corporation

Peiming Zhang

Stuart Lindsay

Yanan Zhao

Jin He

Kevin Reinhart

Subhadip Senapati

Shuo Huang

Shuai Chang

Saikat Manna

Sudipta Biswas

Suman Sen

Sovan Biswas

Changming Li

George N Maracas

Hao Yan

Colin P Nuckolls

John C Chaput

Vi-En Choong

Quan Qing

Xu Wang

Pei Pang

Ming Lei

Jinyao Tang

W Travis Johnson

Jaymie Robin Sawyer

Ching-wei Tsao

Jong One Im

Norman Gery Fuller

Michael Gaskin

This invention provides a system and related devices, methods, and molecular modules for electronically sequencing biopolymers.

System for sequencing biopolymers

A single molecule sensing or detecting device includes a first electrode and a second electrode separated from the first electrode by a gap. The first electrode and the second electrode have an opening formed therethrough. At least one of the first electrode and the second electrode is functionalized with a recognition molecule. The recognition molecule has an effective length L1 and is configured to selectively bind to a target molecule having an effective length L2. The size of the gap is configured to be greater than L2, but less than or equal to the sum of L1 and L2.

System and method for single molecule detection

The present disclosure provides an apparatus for synthesizing a biopolymer, a method for preparing an apparatus for synthesizing a biopolymer, and a method of synthesizing a biopolymer. The apparatus comprises (a) a substrate comprising atop surface and a plurality of wells, wherein each of the plurality of wells comprises a first electrode disposed on the bottom of the well and a linker attached to the sides of the well; and (b) a fluidic chamber system disposed on the top surface of the substrate.

Apparatus and methods for synthesizing biopolymers

A single molecule sensing or detecting device includes a first electrode and a second electrode separated from the first electrode by a gap. The first electrode and the second electrode have an opening formed therethrough. At least one of the first electrode and the second electrode is functionalized with a recognition molecule. The recognition molecule has an effective length LI and is configured to selectively bind to a target molecule having an effective length L. The size of the gap is configured to be greater than L, but less than or equal to the sum of LI and L

The present disclosure provides a method for identifying and quantifying sulfated glycosaminoglycans, including for example heparin, by passing a sample through nanopores. The glycosaminoglycans sample is measured in microliter quantities, at nanomolar concentrations with detection of impurities below 0.5%, and a dynamic range over five decades of magnitude with a trained machine learning algorithm.

Solid state nanopores aided by machine learning for identification and quantification of heparins and glycosaminoglycans

The present disclosure provides apparatus and methods for determining the sequence of a nucleic acid. The apparatus comprises electrodes that form a tunnel gap through which the nucleic acid can pass. The electrodes comprise a reagent that is capable of selectively interacting with a nucleobase of the nucleic acid sequence. When the reagent interacts with a nucleobase, a detectable signal is produced and used to identify the nucleobase of the nucleic acid. Advantageously, the apparatus of this disclosure is specific to identifying nucleic acids.

Non-hydrogen-bonding universal reader for DNA sequencing

The invention includes compositions, devices, and methods for analyzing a polymer and/or polymer unit. The polymer may be a homo or hetero-polymer such as DNA, RNA, a polysaccharide, or a peptide. The device includes electrodes that form a tunnel gap through which the polymer can pass. The electrodes are functionalized with a reagent attached thereto, and the reagent is capable of forming a transient bond to a polymer unit. When the transient bond forms between the reagent and the unit, a detectable signal is generated and used to analyze the polymer.

Controlled tunnel gap device for sequencing polymers

The present invention is directed to systems, devices and methods for identifying biopolymers, such as strands of DNA, as they pass through a constriction such as a carbon nanotube nanopore. More particularly, the invention is directed to such systems, devices and methods in which a newly translocated portion of the biopolymer forms a temporary electrical circuit between the nanotube nanopore and a second electrode, which may also be a nanotube. Further, the invention is directed to such systems, devices and methods in which the constriction is provided with a functionalized unit which, together with a newly translocated portion of the biopolymer, forms a temporary electrical circuit that can be used to characterize that portion of the biopolymer.

Trans-base tunnel reader for sequencing

A single molecule sensing or detecting device includes a first electrode and a second electrode separated from the first electrode by a gap. The first electrode and the second electrode have an opening formed therethrough. At least one of the first electrode and the second electrode is functionalized with a recognition molecule. The recognition molecule has an effective length Land is configured to selectively bind to a target molecule having an effective length L. The size of the gap is configured to be greater than 2L, but less than or equal to the sum of 2Land L

Triazole-based molecules, methods of making and using the same are provided. Triazole-based molecules may be used as reading molecules and incorporated into or operatively-linked with electrodes, for example, and used in recognition tunneling systems to identify individual and/or sequences of molecules (e.g., DNA bases, carbohydrates, proteins, peptides, and/or amino-acids).

Triazole-based reader molecules and methods for synthesizing and use thereof

An system for recognition of a translocating polymeric target molecule includes a device having at least one constriction that is sized to permit translocation of only a single copy of the molecule. A pair of spaced apart sensing electrodes border the constriction, which may be a nanopore. The first electrode is connected to a first affinity element and the second electrode is connected to a second affinity element. Each affinity element may connected to its corresponding electrode via one or more intermediary compounds, such as a linker molecule and/or an electrode attachment molecule. The first and second affinity elements are configured to temporarily form hydrogen bonds with first and second portions of the target molecule as the latter passes through the constriction. During translocation, the electrodes affinity elements and first and second portions of the target molecule complete an electrical circuit and allow a measurable electrical current to pass between the first and second electrodes. The time-varying nature of this electrical current, and the specific affinity elements employed, allow one to characterize the target molecule.

Devices and methods for target molecule characterization

Some of the embodiments of the present disclosure relate to a compound of the formula, and methods of preparing and using same. 

Linker molecule for multiplex recognition by atomic force microscopy (AFM)

Embodiments of the present disclosure are directed to methods, systems and devices, for analyzing the molecules. For example, in some embodiments, a system is provided which includes a first volume of conducting fluid, a second volume of conducting fluid, an orifice in communication with the first and second volumes of fluid, and means for applying an electric potential difference between the first and second volumes of fluid. In some such embodiments, a conjugate product is provided which includes charged polymers each having attached thereto at least one first molecule for analysis, where the product carries a predetermined charge greater than the charge on the first molecule, and upon dissolving the product in the first volume of fluid, the product is directed into the orifice.

Growing community of inventors

Gilbert, AZ, United States of America

Peiming Zhang