Caliper Life Sciences, Inc.

Caliper Technologies Corporation

Lockheed Martin Corporation

Other

Callper Life Sciences, Inc.

Andrea W Chow

Anne R Kopf-Sill

J Wallace Parce

Michael R Knapp

Michael A Spaid

Tammy Burd Mehta

Steven A Sundberg

Theo Teofanov Nikiforov

Ring-Ling Chien

Benjamin N Wang

Robert S Dubrow

Morten Juel Jensen

Luc J Bousse

Colin B Kennedy

Jill M Baker

Steve Gallagher

John Wallace Parce

H Garrett Wada

Michael J Kennedy

Peter C Jann

Stephane Mouradian

Jeffrey A Wolk

John C Owicki

Javier Anibal Farinas

Carlton F Brooks

Marja Liisa Alajoki

Claudia B Cohen

Yevgeny Yurkovetsky

Samuel D H Chan

Calvin Y H Chow

Allen R Boronkay

Josh Molho

Steven James Gallagher

Seth Stern

Susan P Ermer

Bahram Fathollahi

Anubhav Tripathi

Claudia B Jaffe

Claudia L Poglitsch

Steven A Sunberg

Ronald F May

David W Peters

Scott A Ranger

Jonathan K Ma

Hope B Warren

Ken Swartz

Walter Ausserer

Matthew B Kerby

Anne Kopf-sill

Embodiments of the invention comprise microfluidic devices, instrumentation interfacing with those devices, processes for fabricating that device, and methods of employing that device to perform PCR amplification. Embodiments of the invention are also compatible with quantitative Polymerase Chain Reaction ('qPCR') processes. Microfluidic devices in accordance with the invention may contain a plurality of parallel processing channels. Fully independent reactions can take place in each of the plurality of parallel processing channels. The availability of independent processing channels allows a microfluidic device in accordance with the invention to be used in a number of ways. For example, separate samples could be processed in each of the independent processing channels. Alternatively, different loci on a single sample could be processed in multiple processing channels.

Method and apparatus for use in temperature controlled processing of microfluidic samples

Methods are provided for detecting low copy nucleic acids of interest in a sample. In one method, a sample comprising a nucleic acid of interest is aliquotted into a plurality of reaction mixtures, at least two of which are single-copy reaction mixtures. The reaction mixtures are subjected to one or more amplification reactions while flowing through a channel of a microfluidic device. At least one of the reaction mixtures is formulated in an aqueous phase of an emulsion comprising aqueous droplets suspended in an immiscible liquid. The nucleic acid of interest is present as a single copy in at least one aqueous droplet of the aqueous phase prior to performing the amplification reaction(s). Amplification is performed on the reaction mixture when it is formulated in the emulsion. The nucleic acid is continuously flowed during a plurality of steps of the method.

Methods of detecting low copy nucleic acids

An array of transportable particle sets is used in a microfluidic device for performing chemical reactions in the microfluidic device. The microfluidic device comprises a main channel and intersecting side channels, the main channel and side channels forming a plurality of intersections. The array of particle sets is disposed in the main channel, and the side channels are coupled to reagents. As the particle sets are transported through the intersections of the main channel and the side channels, reagents are flowed through the side channels into contact with each array member (or selected array members), thereby providing a plurality of chemical reactions in the microfluidic system.

Manipulation of microparticles in microfluidic systems

The present invention provides novel methods for performing pulsed field mobility shift assays in microfluidic devices. In particular, the methods of the invention utilize differences between electrophoretic mobilities (e.g., as between reactants and products, especially in non-fluorogenic reactions) in order to separate the species and thus analyze the reaction.

High throughput mobility shift

The invention provides methods and apparatuses that allow a protein sample to undergo reduction, alkylation, and digestion in a continuous flow process carried out within a microfluidic device. Methods and apparatuses in accordance with the invention can be employed as part of an automated proteomics analysis carried out in an integrated proteomics system.

Method and apparatus for performing peptide digestion on a microfluidic device

Systems for differentiating the lengths of nucleic acids of interest in a sample are provided. The system includes a microfluidic device, a detector, and a software system. The microfluidic device includes an amplification microchannel or microchamber containing a reaction mixture under conditions that provide one or more amplicons of the nucleic acid of interest. The detector is integral with or proximal to the microfluidic device and is configured to detect the amplicons as one or more signals from a homogenous mixture. The software system interprets one or more coincidentally detected signals to indicate lengths of one or more individual nucleic acid molecules of interest, thereby differentiating the lengths of the nucleic acids of interest.

System for differentiating the lengths of nucleic acids of interest in a sample

The present invention provides novel microfluidic devices and methods for performing pulsed field mobility shift assays in microfluidic devices. In particular the devices and methods of the invention utilize differences between electrophoretic mobilities (e.g., as between reactants and products, especially in non-fluorogenic reactions) in order to separate the species and thus analyze the reaction.

The present invention provides novel methods for controlling/manipulating materials flowing in a fluidic device. In particular, the methods of the invention create and utilize differences between dispersion rates and/or average velocity of materials in order to manipulate the materials.

Channel cross-section geometry to manipulate dispersion rates

The present invention provides novel microfluidic devices and methods for preventing/ameliorating formation of precipitate blockages in microfluidic devices. In particular, the devices and methods of the invention utilize microchannels of specific cross-sectional configuration and of specific arrangement as well as application of AC current orthogonal to the direction of fluid flow, in order to prevent/ameliorate formation of precipitate blockages in microfluidic devices.

Prevention of precipitate blockage in microfluidic channels

Methods for determining nucleic acid fragmentation status are provided. A nucleic acid of interest in a reaction mixture is contacted with two or more different probes complementary to sites separated by a point of potential fragmentation. The probes each comprise a detectable marker. The nucleic acid of interest is flowed into a detection region, where two or more coincident detectable marker signals from the probes are detected. Fragmentation status of the nucleic acid of interest is determined, coincident detection of signals from two or more of the different probes indicating the nucleic acid of interest is not fragmented between the probes.

Determining nucleic acid fragmentation status by coincident detection of two labeled probes

Nucleotides and nucleotide analogs are used in various sequencing by incorporation/sequencing by synthesis methods. Nucleotide analogs comprising 3'-blocking groups are used to provide reversible chain-termination for sequencing by synthesis. Typical blocking groups include phosphate groups and carbamate groups. Fluorescent nucleotides are used to perform sequencing by synthesis with detection by incorporation of the fluorescently labeled nucleotide, optionally followed by photobleaching and intercalating dyes are used to detect addition of a non-labeled nucleotide in sequencing by synthesis with detection by intercalation. Microfluidic devices, including particle arrays, are used in the sequencing methods.

Sequencing by incorporation

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Los Altos, CA, United States of America

Andrea W Chow