University of California

Affymetrix, Inc.

Leland Stanford Junior University

Dna Sciences, Inc.

Cairn Biosicences, Inc.

Richard A Mathies

Alexander N Glazer

Jingyue Ju

Adam T Woolley

Konan Peck

William H Grover

James R Scherer

Peter C Simpson

Chung N Liu

Robert Blazej

Palani Kumaresan

Erik C Jensen

Eric Lagally

Su-Chun Hung

Alison Skelley

Carolyn Ruth Bertozzi

Xiaohua C Huang

Erik Douglas

Matthew B Francis

Hiroaki Onoe

Amy Twite

Pankaj Singhal

Jungkyu Kim

Mark A Quesada

Shih-Chia Hsiao

Stephanie H I Yeung

Ravi Chandra

Charles A Emrich

Nicholas Toriello

Robert Anthony Street

Lubert Stryer

Lee W Riley

Mary J C Ludlam

David Wartmann

Amador Goodridge

Brian Paegel

Richard Novak

Lester Hutt

Robert Eugene Snyder

Toshihiro Kamei

Jin Xie

Stephen J Williams

David Wexler

Kaigin Lao

Kaiqin Lao

Austin Blanco

Chaoyang Yang

Tao Geng

Peter Ertl

Devices, systems, methods, and techniques regarding a microfluidic-enabled multiwell device with closed-loop monitoring and control of various parameters of the microfluidic environment are provided. A microfluidic-enabled multiwell device may have a removable and disposable microfluidics module layer and a reusable sensor module layer. The sensor module layer may be configured to monitor and control parameters of the environment inside the microfluidics module layer, store data regarding the parameters, and wirelessly transmit the data. The device may be configured to individually address flow of fluid to any one of a plurality of wells, using one or more pneumatic micropumps. The device may be configured to automatically execute one or more live cell cultures, assays, and/or protocols. The device may be configured to be received in a docking station and/or portable manifold adapter, and to be fluidly, pneumatically, and/or electronically coupled to the station, adapter, or other laboratory equipment.

Microfluidic-enabled multiwell cell culture devices and systems for precision culture, control and monitoring of living cells

A short tandem repeat (STR) typing method and system are developed for forensic identification of individual cells. Agarose-in-oil droplets are produced with a high frequency using a microfluidic droplet generator. Statistically dilute single cells, along with primer-functionalized microbeads, are randomly compartmentalized in the droplets. Massively parallel single-cell droplet PCR is performed to transfer replicas of desired STR targets from the single-cell genomic DNA onto a coencapsulated microbead. These DNA-conjugated beads are subsequently harvested and reamplified under statistically dilute conditions for conventional capillary electrophoresis STR fragment size analysis. The methods and systems described herein are valuable for the STR analysis of samples containing mixtures of cells/DNA from multiple contributors and for low concentration samples.

Single-cell forensic short tandem repeat typing within microfluidic droplets

The present invention provides conjugates of DNA and cells by linking the DNA to a native functional group on the cell surface. The cells can be without cell walls or can have cell walls. The modified cells can be linked to a substrate surface and used in assay or bioreactors.

DNA-cell conjugates

The present disclosure provides methods of detectingin an individual, generally involving detecting antibody to a mycobacterial lipid in a biological sample obtained from the individual. The present disclosure further provides compositions and kits for carrying out the methods.

Compositions and methods for detecting mycobacterium

The present disclosure relates to method, system for microfluidic control. One or more embodiments of the disclosure relate to pneumatically actuated 'lifting gate' microvalves and pumps. In some embodiments, a microfluidic control module is provided, which comprises a plurality of pneumatic channels and a plurality of lifting gate valves configured to be detachably affixed to a substrate. The plurality of lifting gate valves are aligned with at least one fluidic channel on the substrate when affixed to the substrate. Each of the valves comprises: a pneumatic layer, a fluidic layer, and a pneumatic displacement chamber between the pneumatic layer and the fluidic layer. The fluidic layer has a first side facing the pneumatic layer and a second side facing away from the pneumatic layer, wherein the second side has a protruding gate configured to obstruct a flow of the fluidic channel when the fluidic layer is at a resting state.

Lifting gate polydimethylsiloxane microvalves and pumps for microfluidic control

Methods and apparatus for implementing microfluidic analysis devices are provided. A monolithic elastomer membrane associated with an integrated pneumatic manifold allows the placement and actuation of a variety of fluid control structures, such as structures for pumping, isolating, mixing, routing, merging, splitting, preparing, and storing volumes of fluid. The fluid control structures can be used to implement a variety of sample introduction, preparation, processing, and storage techniques.

Fluid control structures in microfluidic devices

Methods and microfluidic circuitry for inline injection of nucleic acids for capillary electrophoresis analysis are provided. According to various embodiments, microfabricated structures including affinity-based capture matrixes inline with separation channels are provided. The affinity-based capture matrixes provide inline sample plug formation and injection into a capillary electrophoresis channel. Also provided are methods and apparatuses for a microbead-based inline injection system for DNA sequencing.

Inline-injection microdevice and microfabricated integrated DNA analysis system using same

Provided are microfluidic designs and methods for rapid generation of monodisperse nanoliter volume droplets of reagent/target (e.g., molecule or cell) mix in emulsion oil. The designs and methods enable high-throughput encapsulation of a single target (e.g., DNA/RNA molecules or cells) in controlled size droplets of reagent mix. According to various embodiments, a microfabricated, 3-valve pump is used to precisely meter the volume of reagent/target mix in each droplet and also to effectively route microparticles such as beads and cells into the device, which are encapsulated within droplets at the intersection of the reagent channel and an oil channel. The pulsatile flow profile of the microfabricated pumps provides active control over droplet generation, thereby enabling droplet formation with oils that are compatible with biological reactions but are otherwise difficult to form emulsions with.

Microfabricated droplet generator for single molecule/cell genetic analysis in engineered monodispersed emulsions

Methods and apparatus for genome analysis are provided. A microfabricated structure including a microfluidic distribution channel is configured to distribute microreactor elements having copies of a sequencing template into a plurality of microfabricated thermal cycling chambers. A microreactor element may include a microcarrier element carrying the multiple copies of the sequencing template. The microcarrier element may comprise a microsphere. An autovalve at an exit port of a thermal cycling chamber, an optical scanner, or a timing arrangement may be used to ensure that only one microsphere will flow into one thermal cycling chamber wherein thermal cycling extension fragments are produced. The extension products are captured, purified, and concentrated in an integrated oligonucleotide gel capture chamber. A microfabricated component separation apparatus is used to analyze the purified extension fragments. The microfabricated structure may be used in a process for performing sequencing and other genetic analysis of DNA or RNA.

Microfabricated integrated DNA analysis system

Membrane valves and latching valve structures for microfluidic devices are provided. A demultiplexer can be used to address the latching valve structures. The membrane valves and latching valve structures may be used to form pneumatic logic circuits, including processors.

Multiplexed latching valves for microfluidic devices and processors

Growing community of inventors

Moraga, CA, United States of America

Richard A Mathies