Louisiana State University and Agricultural & Mechanical College

The University of North Carolina at Chapel Hill

Cornell University

Northeastern University

Roche Molecular Systems, Inc.

University of Kansas

Clarkson University

Board of Supervisors of Lsu and A&m College

Univ. of N Carolina at Chapel Hill

Steven A Soper

Michael C Murphy

Robin L McCarley

Francis Barany

Sunggook Park

Collin J McKinney

John William Efcavitch

Mateusz Hupert

George Grills

George A Martin

Jen Jen Yeh

André A Adams

Dimitris Nikitopoulos

Elizabeth J Podlaha-Murphy

Dorel Moldovan

Makgorzata Witek

Robert P Hammer

Jianmin Huang

Wanjun Wang

Jack D Davies

Bikas Vaidya

Maria Da Graça Henriques Vicente

Daniel Sang-won Park

Yuli Vladimirsky

Ren Yang

Guofang Chen

Hamed Shadpour

Elizabeth Podlaha-murphy

Yu-wei Cheng

Hong Wang

Malgorzata A Witek

Serhii Pakhomov

June Feng

Timothy J Jensen

Michael W Allen

Irina V Nesterova

June Feng Schneider

Dimitris E Nikitopoulos

Robin L Mccarley

Collin J Mckinney

Juan Feng

Andre A Adams

Michael Murphy

Disclosed are nanofluidic analytical devices. The devices employ a sample processing region that includes a plurality of fluidically connected sample handling elements that, in combination, affect a physical change on a sample introduced into the sample processing region. This physical change can include, for example, purification of an analyte of interest present in the sample, concentration of an analyte of interest present in the sample, chemical modification (e.g., cleavage and/or chemical derivatization) of an analyte of interest present in the sample, or a combination thereof. The analytical devices further include a nanochannel comprising a plurality of in-plane nanopores in series fluidically coupled to the sample processing region. The in-plane nanopores can be used to detect and/or analyze analyte(s) present in the sample following processing by the sample processing region. These analytical devices can advantageously provide for the label-free detection of single molecules.

Nanofluidic analytical devices and methods of using thereof

The present invention relates to a device comprising a biomolecular processor. Each biomolecular processor has one or more bioreactor chambers defined by a solid substrate; a support structure within each bioreactor; a cleaving enzyme immobilized to the support structure and operatively positioned within the bioreactor chamber to cleave monomer or multimer units of a biopolymer molecule operatively engaged by the cleaving enzyme; and one or more time-of-flight channels formed in the solid substrate and fluidically coupled to said one or more bioreactor chambers. Each of the time-of-flight channels have two or more sensors including at least (i) a first sensor contacting the time-of-flight channel proximate to the input end of the channel and (ii) a second sensor contacting the time-of-flight channel proximate to the output end of channel. The present invention further relates to methods of sequencing and identifying biopolymer molecules using the device.

Biomolecular processing platform and uses thereof

The present invention is directed methods for identifying, in a sample, one or more target nucleotide sequences differing from other nucleotide sequences in the sample by one or more nucleotides, one or more copy numbers, one or more transcript sequences, and/or one or more methylated residues, using ligation detection reactions, polymerase mediated extension reactions, and/or cleavage reactions. The present invention is also directed to methods for identifying, in a sample, one or more nucleotides in a target nucleotide sequence.

Method for identification and enumeration of nucleic acid sequences, expression, splice variant, translocation, copy, or DNA methylation changes using combined nuclease, ligase, polymerase, terminal transferase, and sequencing reactions

The present invention is directed to methods comprising a device that comprises a biomolecular processor and one or more nanotubes. Each biomolecular processor comprises a bioreactor chamber defined by a solid substrate, a plurality of spaced support structures within said bioreactor chamber and attached to the solid substrate, one or more nanotubes defined by the solid substrate and fluidically coupled to the bioreactor chamber and one or more capture molecules immobilized to some or all of said plurality of spaced support structures, said one or more capture molecules suitable to bind to a portion of a target nucleic acid molecule in a sample. The nanotubes have a passage extending between an input end proximate to the bioreactor chamber and an output end distal to the bioreactor chamber, and comprises one or more nanopores within the passage with each nanopore having a reduced diameter relative to the passage.

Universal molecular processor for precision medicine

Microdevices are disclosed to efficiently, accurately, and rapidly isolate and enumerate rare cells, such as circulating tumor cells, from liquids such as whole blood. The system employs multiple parallel meandering channels having a width on the order of 1-2 cell diameters. The microdevices can be produced at low-cost, may readily be automated, and in many instances may be used without pre-processing of the sample. They may be used to isolate and enumerate rare cells, including for example the detection and diagnosis of cancers, cancer staging, or evaluating the effectiveness of a therapeutic intervention, or detecting pathogenic bacteria. The device may optionally be used to nondestructively capture and later to release target cells.

Microfluidic isolation of tumor cells or other rare cells from whole blood or other liquids

The present invention is directed to a device that comprises a biomolecular processor and one or more nanotubes. Each biomolecular processor comprises a bioreactor chamber defined by a solid substrate, a plurality of spaced support structures within said bioreactor chamber and attached to the solid substrate, and one or more capture molecules immobilized to some or all of said plurality of spaced support structures, said one or more capture molecules suitable to bind to a portion of a target nucleic acid molecule in a sample. The device also comprises one or more nanotubes defined by the solid substrate and fluidically coupled to the bioreactor chamber.

This invention provides methods and compositions for capturing circulating tumor cells (CTCs) as well as various divergent CTC phenotypes using seprase-specific affinity reagents. Methods of analyzing CTCs and assessing their metastatic potential in vivo and in vitro are also disclosed.

In Vitro capture and analysis of circulating tumor cells

A method is disclosed for fabricating free-standing polymeric nanopillars or nanotubes with remarkably high aspect ratios. The nanopillars and nanotubes may be used, for example, in integrated microfluidic systems for rapid, automated, high-capacity analysis or separation of complex protein mixtures or their enzyme digest products. One embodiment, preferably fabricated entirely from polymer substrates, comprises a cell lysis unit; a solid-phase extraction unit with free-standing, polymeric nanostructures; a multi-dimensional electrophoretic separation unit with high peak capacity; a solid-phase nanoreactor for the proteolytic digestion of isolated proteins; and a chromatographic unit for the separation of peptide fragments from the digestion of proteins. The nanopillars and nanotubes may also be used to increase surface area for reaction with a solid phase, for example, with immobilized enzymes or other catalysts within a microchannel, or as a solid support for capillary electrochromatography-based separations of proteins or peptides.

Polymeric nanopillars and nanotubes, their manufacture and uses

The present invention is directed to methods for capturing, amplifying and identifying one or more of a plurality of target nucleotide sequences in a sample. The present invention is further directed to a device comprising a solid support having a plurality of wells or pillars and a plurality of oligonucleotides attached to the wells or pillars. Other aspects of the invention are directed to methods of making such devices.

Methods and devices for DNA sequencing and molecular diagnostics

In vitro capture and analysis of circulating tumor cells

A method is described for the direct photochemical modification and micro-patterning of polymer surfaces, without the need to use a photoresist. For example, micropatterns of various functional chemical groups, biomolecules, and metal films have been deposited on poly(carbonate) and poly(methyl methacrylate) surfaces. These patterns may be used, for example, in integrated electronics, capture elements, or sensing elements in micro-fluidic channels.

Photoresist-free micropatterning on polymer surfaces

Asymmetrically substituted metal-phthalocyanine compounds are disclosed. These compounds and other phthalocyanine-derivatives are used in bioimaging, bioanalysis, FRET and quenching techniques, photodynamic therapy, DNA analysis for cells, proteins, tissues and other biological entities, and other applications. Near-infrared fluorescence minimizes matrix effects typically seen in other methods of analyzing biochemical entities in cells, proteins, tissues and other biological entities.

Tetraazaporphyrin-based compounds and their uses

An accurate and inexpensive integral micro-optical system for coupling and aligning optical fibers with other optical components, such as other optical fibers, diffusers, beam shapers, beam splitters, mirrors, or lenses is disclosed. The micro-optical coupler disclosed comprises one or more fiberport collimators and one or more microlens arrays, optically aligned during fabrication so that an optical fiber, or other source of light, was coupled to another optical fiber, or other light receiver, by simple inserting the optical source in one side of the micro-coupler and inserting the optical receiver in the other side of the micro-coupler. Often the fabrication process for this system can be done in a single lithography procedure. Since the optical axis of each component was aligned during the fabrication step, no subsequent alignment was required.

Integral pre-aligned micro-optical systems

Growing community of inventors

Baton Rouge, LA, United States of America

Steven A Soper