Cornell University

USA As Represented by Secretary of the Navy

Naval Research Laboratory

Cytequest, Inc.

Sandia Corporation

Navel Research Laboratory

Harold G Craighead

Stephen Wilson Turner

Watt W Webb

Jonas Korlach

Michael Levene

Jeevak M Parpia

Maxim K Zalalutdinov

Mathieu Foquet

Robert B Reichenbach

Harvey C Tian

Brian H Houston

Bojan Robert Ilic

Jun Kameoka

Keith Aubin

Benjamin Ryan Cipriany

David Alan Czaplewski

David M Lin

Stephen Levy

Paul Soloway

Jeffrey W Baldwin

Juraj Topolancik

Bojan (Rob) Ilic

Leon M Bellan

Jose Manuel Moran-Mirabal

Samuel M Stavis

Joshua B Edel

Kevan T Samiee

Christopher Wallin

Robert H Hall

Jongyoon Han

Dustin Wade Carr

John T Lis

George Malliaras

Thomas N Corso

Anatoli Olkhovets

Jason D Slinker

Abdullah Ozer

Adam J Bisogni

Parijat Bhatnagar

Kylan Szeto

Joshua D Cross

Christine Tan

Sarah Reinholt

Lidija Sekaric

David Erickson

Darren W Branch

Yung-fu Chang

Hector D Abruna

Theodore G Clark

Jason Spector

Cindy K Harnett

Elizabeth Strychalski

Geoff Coates

Yun Suk Huh

Darren Robert Southworth

Alan T Zehnder

David R Latulippe

Keith L Aubin

Huizhong Xu

Pangshun Zhu

Seung-min Park

Héctor D Abruna

Grant D Meyer

Aline Cerf

John T Mannion

Reid N Orth

Jennifer Gaudioso

Jeeak M Parpia

Warren Wright

Maxim Zalalutidinov

A method for isolating one or more distinct analyte component from a cell sample is disclosed, as well as processes for testing and analyzing the distinct analyte components. The distinct analyte components include: (i) a total protein fraction; (ii) a plasma membrane protein fraction; (iii) a total RNA fraction; (iv) a cytosolic RNA fraction; (v) a cytosolic protein fraction; (vi) a nuclear RNA fraction; (vii) a nuclear protein fraction; (viii) a chromatin fraction comprising genomic DNA (gDNA); (ix) a gDNA markers fraction. This method involves the use of microfluidic device having a cell capture component and a nucleic acid entanglement component, where the cell capture component includes a cell capture array having a plurality of cell capture micropillars, where the nucleic acid entanglement component includes a nucleic acid entanglement array having a plurality of nucleic acid entanglement micropillars, and where the microfluidic device operates under continuous flow conditions.

Multiomic analysis of cell analytes using microfluidic systems

A microfluidic chip for on-chip detection of the presence or absence of a target nucleic acid region in an isolated nucleic acid sample is disclosed. The microfluidic chip includes a nucleic acid entanglement array, an isolated nucleic acid sample immobilized in the nucleic acid entanglement array, and at least one probe specific to a target nucleic acid region. Systems and methods of using the microfluidic chip are disclosed. An integrated microfluidic cell processing system is disclosed, which includes: a multiplexed microfluidic flow directing system having a plurality of reconfigurable microfluidic layers that form a plurality of reconfigurable microfluidic channels, where the multiplexed microfluidic flow directing system function to assist in directing flow of materials into, through, and out of the integrated cell processing system; and at least one microfluidic chip functionally integrated into at least one layer of the multiplexed microfluidic flow directing system, and operates under continuous flow conditions.

Systems and methods for on-chip analysis of nucleic acids and for multiplexed analysis of cells

The present invention relates to a microfluidic device for extracting and isolating DNA from cells. The device includes a support having an inlet port for receiving a sample containing a cell, an outlet port for dispensing DNA isolated from the cell, and a microfluidic channel disposed within the support and extending from the inlet port to the outlet port. The microfluidic channel includes a micropillar array, an inflow channel disposed between the inlet port and the micropillar array, and an outflow channel disposed between the micropillar array and the outlet port. The micropillar array includes micropillars spatially configured to entrap, by size exclusion, the cell, to immobilize DNA released from the cell, and to maintain the immobilized DNA in elongated or non-elongated form when hydrodynamic force is applied to the microfluidic channel. Systems and methods of making and using the device are also provided herein.

Microfluidic device for extracting, isolating, and analyzing DNA from cells

A system, device and method for electroporation of living cells and the introduction of selected molecules into the cells utilizes a fluidic system where living cells and biologically active molecules flow through a channel that exposes them to electric fields, causing the molecules to be transferred across the cell membrane. The device is structured in a manner that allows precise control of the cells location, motion, and exposure to electric fields within the flow channel device. The method is particularly well suited for the introduction of DNA, RNA, drug compounds, and other biologically active molecules into living cells.

System, device and method for electroporation of cells

The present invention relates to, inter alia, a microfluidic device for capturing target cells and analyzing genomic DNA isolated from the target cells while under flow conditions. The microfluidic device includes a cell microchannel and a nucleic acid microchannel that intersect in an orthogonal manner, thereby forming a cell capture intersection region. The microfluidic device also includes a cell capture array and a nucleic acid entanglement array. The cell capture array includes a plurality of cell capturing micropillars and is located in the cell capture intersection region. The nucleic acid entanglement array includes a plurality of nucleic acid entanglement micropillars that function to physically entangle and maintain thereon genomic DNA isolated from the one or more target cell, and is located in a portion of the nucleic acid microchannel that is adjacent to and downstream of the cell capture intersection region. Methods of using the microfluidic device are also disclosed.

Multifunctional microfluidic device for capturing target cells and analyzing genomic DNA isolated from the target cells while under flow conditions

The present invention relates to, inter alia, a microfluidic device for performing single cell genomic DNA isolation and amplification under flow. The microfluidic device comprises a solid substrate having one or more microfluidic channel system formed therein. Each microfluidic channel system of the microfluidic device comprises: (a) an intake region comprising a single microchannel; (b) a plurality of cell segregation microchannels; (c) a cell capture site located downstream of each cell segregation microchannel; and (d) a DNA capture array positioned downstream of the cell capture site and comprising a plurality of micropillars. Also disclosed is a whole genome amplification system that includes the microfluidic device of the present disclosure, as well as a method for conducting single cell DNA analysis via on-chip whole genome amplification while under flow, and a method for multiple displacement amplification (MDA) reactions of one or more nucleic acid sequence isolated single cells.

Single cell whole genome amplification via micropillar arrays under flow conditions

An electrical detector is provided that comprises a nanofluidic channel with an integrated nanoscale charge sensor. The charge sensor can be an unfunctionalized nanowire, nanotube, transistor or capacitor and can be of carbon, silicon, carbon/silicon or other semiconducting material. The nanofluidic channel depth is on the order of the Debye screening length. Methods are also provided for detecting charged molecules or biological or chemical species with the electrical detector. Charged molecules or species in solution are driven through the nanofluidic channel of the electrical detector and contact the charge sensor, thereby producing a detectable signal. Methods are also provided for detecting a local solution potential of interest. A solution flowing through the nanofluidic channel of the electrical detector contacts the charge sensor, thereby producing a detectable local solution potential signal.

Nanofluidic channels with integrated charge sensors and methods based thereon

The present invention relates to a microcolumn device for selecting nucleic acid aptamers for single and multiple target molecules, as well as a method for making the microcolumn device. The present invention also relates to a system for selecting nucleic acid aptamers for single and multiple target molecules. The present invention further relates to methods of using the microcolumn device for selecting nucleic acid aptamers for multiple target molecules. Kits that include one or more microcolumn device and/or system of the present invention are also disclosed.

Multiplexed microcolumn devices and processes for selection of nucleic acid aptamers

The present invention relates to a device for isolating and recovering a biomolecule from a test sample. The device includes a support and at least one peelable layer deposited on at least a portion of the support. The peelable layer includes a substrate having a target component immobilized on the substrate. The device is effective for isolating and recovering a biomolecule having affinity to the target component. The present invention also relates to systems and methods of using the device. The present invention also relates to a biomolecule elution strip and related methods.

Device for recovery and isolation of biomolecules

Provided herein are methods and devices for single object detection. The methods and devices can be used to identify a plurality of epigenetic markers on a genetic material, or a chromatin, encompassing fragments thereof. The invention provides for the characterization of the genetic material flowing through a channel in a continuous body of fluid based on detection of one or more properties of the genetic material. The methods and systems provided herein allow genome-wide, high-throughput epigenetic analysis and overcome a variety of limitations common to bulk analysis techniques.

Device and methods for epigenetic analysis

The present invention relates to methods and arrays for use in high resolution imaging of individual nucleic acid molecules and chromatin fragments, including native chromatin fragments. In one aspect, the present invention relates to a chromatin array that includes a transfer platform having a support and a transfer surface layered on the support. The chromatin array also includes a plurality of elongated individual native chromatin fragments coupled to the transfer surface in an orderly pattern suitable for high resolution imaging of the plurality of native chromatin fragments. The native chromatin fragments of the chromatin array include both DNA and histones.

Methods and arrays for controlled manipulation of DNA and chromatin fragments for genetic and epigenetic analysis

The present invention generally relates to microcolumn affinity chromatography devices, systems that include the microcolumn affinity chromatography devices of the present disclosure, methods of using the devices and the systems of the present disclosure, and methods of making the devices and the systems of the present disclosure. In certain embodiments, the microcolumn affinity chromatography device is suitable for conducting affinity chromatography in multiple microcolumns in parallel and/or in series.

Programmable and reconfigurable microcolumn affinity chromatography device, system, and methods of use thereof

Growing community of inventors

Ithaca, NY, United States of America

Harold G Craighead