Fluidigm Corporation

California Institute of Technology

Standard Biotools Corporation

University of California

Digenomix Corporation

Fuidigm Corporation

Fluidign Corporation

Marc Alexander Unger

Hou-Pu Chou

Stephen R Quake

Axel Scherer

Todd A Thorsen

Geoffrey Richard Facer

Michael Ybarra Lucero

Neil Switz

Christopher G Cesar

Barry Clerkson

Carl L Hansen

Hany Ramez Nassef

Mark L Adams

Jake Kimball

Lincoln McBride

Yong Yi

Brian Fowler

Ian D Manger

Markus M Enzelberger

Geoffrey Facer

Jiang Huang

David Fernandes

Emerson Cheung Quan

Martin Pieprzyk

Robert Grossman

Emily Miyashita-Lin

Andrew Paul May

Jason A A West

Jing Wang

Antoine Daridon

Dominique Toppani

Myo Thu Maung

Naga Gopi Devaraju

Phillip Lam

Michael C Norris

Anja Wienecke

Hany Ramaz Nassef

Jian Liu

Geoff Facer

Dmitri A Kossakovski

Shoujun Xiao

Bernhard Zimmermann

Stephen D O'Connor

Kenneth J Livak

David Ruff

R Michael Van Dam

Lei Xi

John D Baldeschwieler

Alain Mir

Ramesh Ramakrishnan

Wayne D Volkmuth

Xiaohui Wang

Michael Van Dam

David Randall Baselt

Federico Goodsaid

Philip Lam

Cunsheng Casey Hao

Anja Weinecke

Dave Fernandes

Christian F Johnson

Dominique G Toppani

Lincoln Mcbride

Geoffrey R Facer

Ian David Manger

Bernhard G Zimmermann

Tze-Howe Charn

A microfluidic device includes an input source characterized by a source pressure, an input channel in fluid communication with the input source, and an output channel. The microfluidic device also includes a normally closed valve having a closed state and an open state. The normally closed valve is disposed between the input channel and the output channel. The microfluidic device further includes one or more release chambers coupled to a pressure source. Activation of the pressure source deforms the one or more release chambers, placing the normally closed valve in the open state.

Method and systems for microfluidic logic devices

A microfluidic system includes a substrate, a set of input ports coupled to the substrate, and a set of output ports coupled to the substrate. The microfluidic system also includes a microfluidic processing system coupled to the substrate and including a plurality of processing sites. The microfluidic processing system is coupled to the set of input ports and the set of output ports. The microfluidic system further includes one or more microfluidic logic devices coupled to the substrate and operable to control at least a portion of the microfluidic processing system.

In some embodiments, a variety of devices and methods for conducting microfluidic analyses are utilized herein, including devices that can be utilized to conduct thermal cycling reactions such as nucleic acid amplification reactions. The devices include elastomeric components; in some instances, much or all of the device is composed of elastomeric material. Amplification products (amplicons) can be detected and distinguished (whether isolated in a reaction chamber or at any subsequent time) using routine methods for detecting nucleic acids. An example of a detection method includes hybridization to arrays of immobilized oligo or polynucleotides.

Optical lens system and method for microfluidic devices

In certain embodiments, the present invention provides a way of 'digitally' marking different the alleles of different chromosomes by using a transposase to insert differently barcoded transposons into genomic DNA before further analysis. According to this method, each allele becomes marked with a unique pattern of transposon barcodes. Because each unique pattern of transposon barcodes identifies a particular allele, the method facilitates determinations of ploidy and copy number variation, improves the ability to discriminate among homozygotes, heterozygotes, and patterns arising from sequencing errors, and allows loci separated by uninformative stretches of DNA to be identified as linked loci, thereby facilitating haplotype determinations. Also provided is a novel artificial transposon end that includes a barcode sequence in two or more positions that are not essential for transposition.

Haploidome determination by digitized transposons

The present invention provides microfluidic devices and methods for using the same. In particular, microfluidic devices of the present invention are useful in conducting a variety of assays and high throughput screening. Microfluidic devices of the present invention include elastomeric components and comprise a main flow channel; a plurality of branch flow channels; a plurality of control channels; and a plurality of valves. Preferably, each of the valves comprises one of the control channels and an elastomeric segment that is deflectable into or retractable from the main or branch flow channel upon which the valve operates in response to an actuation force applied to the control channel.

Apparatus and methods for conducting assays and high throughput screening

Systems for microfluidic logic devices

A method for carrying out nucleic acid amplification reactions using a microfluidic device is described. Amplification primers and other amplification reagents are deposited at a plurality of reaction sites in the device, a sample solution containing amplifiable polynucleotides is introduced into the reaction sites, and amplification is carried out.

Thermal reaction device and method for using the same

An apparatus for imaging one or more selected fluorescence indications from a microfluidic device. The apparatus includes an imaging path coupled to least one chamber in at least one microfluidic device. The imaging path provides for transmission of one or more fluorescent emission signals derived from one or more samples in the at least one chamber of the at least one microfluidic device. The chamber has a chamber size, the chamber size being characterized by an actual spatial dimension normal to the imaging path. The apparatus also includes an optical lens system coupled to the imaging path. The optical lens system is adapted to transmit the one or more fluorescent signals associated with the chamber.

Methods, systems, and devices are described for multiple single-cell capturing and processing utilizing microfluidics. Tools and techniques are provided for capturing, partitioning, and/or manipulating individual cells from a larger population of cells along with generating genetic information and/or reactions related to each individual cell. Different capture configurations may be utilized to capture individual cells and then processing each individual cell in a multi-chamber reaction configuration. Some embodiments may provide for specific target amplification, whole genome amplification, whole transcriptome amplification, real-time PCR preparation, copy number variation, preamplification, mRNA sequencing, and/or haplotyping of the multiple individual cells that have been partitioned from the larger population of cells. Some embodiments may provide for other applications. Some embodiments may be configured for imaging the individual cells or associated reaction products as part of the processing. Reaction products may be harvested and/or further analyzed in some cases.

Methods for multiple single-cell capturing and processing using micro fluidics

The invention provides an assay method for detection and/or quantification of a plurality of nucleic acid or protein targets in a sample. In the method probes are used to associate a detectable tag sequence with each of the selected targets present in the sample. Probes or primers sufficient to identify at least 25, and preferably at least 500, different targets are used. The method involves segregating aliquots of the sample from each other and detecting the tag sequences in each aliquot.

Methods for detection and quantification of nucleic acid or protein targets in a sample

A variety of elastomeric-based microfluidic devices and methods for using and manufacturing such devices are provided. Certain of the devices have arrays of reaction sites to facilitate high throughput analyzes. Some devices also include reaction sites located at the end of blind channels at which reagents have been previously deposited during manufacture. The reagents become suspended once sample is introduced into the reaction site. The devices can be utilized with a variety of heating devices and thus can be used in a variety of analyzes requiring temperature control, including thermocycling applications such as nucleic acid amplification reactions, genotyping and gene expression analyzes.

Microfluidic device with reaction sites configured for blind filling

Methods and systems are provided for conducting a reaction at a selected temperature or range of temperatures over time. An array device is provided. The array device contains separate reaction chambers and is formed as an elastomeric block from multiple layers. At least one layer has at least one recess that recess has at least one deflectable membrane integral to the layer with the recess. The array device has a thermal transfer device proximal to at least one of the reaction chambers. The thermal transfer device is formed to contact a thermal control source. Reagents for carrying out a desired reaction are introduced into the array device. The array device is contacted with a thermal control device such that the thermal control device is in thermal communication with the thermal control source so that a temperature of the reaction in at least one of the reaction chamber is changed as a result of a change in temperature of the thermal control source.

Integrated chip carriers with thermocycler interfaces and methods of using the same

A microfabricated fluidic unidirectional valve includes a microfabricated elastomer material having a flow through channel. The microfabricated fluidic unidirectional valve also includes an elastomer flap attached to the elastomer material in the flow through channel. The elastomer flap forms a seal in the flow through channel to prevent fluid from flowing in a first direction through the flow through channel and to allow fluid flow in a second direction through the flow through channel.

Microfabricated fluidic circuit elements and applications

Methods, systems and devices for multiple single-cell capturing and processing using microfluidics

Growing community of inventors

San Mateo, CA, United States of America

Marc Alexander Unger