Bio-rad Laboratories, Inc.

454 Life Sciences Corporation

Axiomx, Inc.

Raindance Technologies, Inc.

Harvard College

Illumina Corporation

Roche Molecular Systems, Inc.

454 Lice Sciences Corporation

'454 Corporation

Michael Weiner

Jonathan Marc Rothberg

Darren Roy Link

David Marran

John Harris Leamon

Kenton L Lohman

Margaret Kiss

Jan Berka

Yi-Ju Chen

Wolfgang Hinz

Maithreyan Srinivasan

Vinod B Makhijani

John Q Lu

Gary James Sarkis

Gilbert Feke

Laurent Boitard

Jeffrey Branciforte

Yves Charles

Ahmadali Tabatabai

Steve Lefkowitz

Michael L Samuels

John Brian Hutchison

David A Weitz

Jeremy Agresti

Adam R Abate

Tony Hung

Steven M Lefkowitz

Melissa Batonick

John W Simpson

Joel S Bader

Keith McDade

Jonathan M Rothberg

Scott B Dewell

Christopher M Colangelo

Maithreyn Srinivasan

Michael T Ronan

David Marren

Brian Hutchinson

Jonathan Rothberg

Kenton Lohman

John H Leamon

The present invention provides novel microfluidic substrates and methods that are useful for performing biological, chemical and diagnostic assays. The substrates can include a plurality of electrically addressable, channel bearing fluidic modules integrally arranged such that a continuous channel is provided for flow of immiscible fluids.

Microfluidic devices

The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays and combinatorial chemistry. The invention provides for aqueous based emulsions containing uniquely labeled cells, enzymes, nucleic acids, etc., wherein the emulsions further comprise primers, labels, probes, and other reactants. An oil based carrier-fluid envelopes the emulsion library on a microfluidic device, such that a continuous channel provides for flow of the immiscible fluids, to accomplish pooling, coalescing, mixing, sorting, detection, etc., of the emulsion library.

Microfluidic devices and methods of use in the formation and control of nanoreactors

The present invention generally relates to droplet libraries and to systems and methods for the formation of libraries of droplets. The present invention also relates to methods utilizing these droplet libraries in various biological, chemical, or diagnostic assays.

Droplet libraries

The present invention provides methods and compositions for converting a first polypeptide into a chimeric polypeptide. The invention includes two vectors: a first vector including the sequence of the first polypeptide and a second vector including a second polypeptide. The vectors include complementary site-specific recombination motifs such that site-specific recombination between the two vectors results in the generation of a chimeric polypeptide including at least a portion of the first polypeptide and at least a portion of the second polypeptide. A site-specific recombination motif may be positioned within an intron or within a coding sequence on the first or second vector.

Methods and compositions for producing a chimeric polypeptide

The identification of binding moieties capable of selectively interacting with one or more target antigens is of scientific, medical, and commercial value. Disclosed herein are methods and compositions for the identification, labeling and/or retrieval of cognate binding moieties.

Methods of utilizing recombination for the identification of binding moieties

Disclosed herein is an efficient method of generating a library of variants of a sequence of interest, such as may be used in directed evolution, in one embodiment, the method includes an amplification reaction, e.g. error-prone PCR, to generate double-stranded DNA (dsDNA) variants of a sequence of interest, after which one strand of the dsDNA variants may be selectively degraded to produce single-stranded DNA (ssDNA) variants. The ssDNA variants may be hybridized to ssDNA intermediaries, e.g., uracilated circular ssDNA intermediaries, to form heteroduplex DNA, which may be transformed into cells, such ascells, yielding a library of variants. This method eliminates the inefficient sub-cloning steps and the need for costly primer sets required by many prior methods.

Methods for the production of libraries for directed evolution

Disclosed are methods for nucleic acid amplification wherein nucleic acid templates, beads, and amplification reaction solution are emulsified and the nucleic acid templates are amplified to provide clonal copies of the nucleic acid templates attached to the beads. Also disclosed are kits and apparatuses for performing the methods of the invention.

Bead emulsion nucleic acid amplification

The present invention relates to systems and methods for sequencing nucleic acids, including sequencing nucleic acids in fluidic droplets. In one set of embodiments, the method employs sequencing by hybridization using droplets such as microfluidic droplets. In some embodiments, droplets are formed which include a target nucleic acid, a nucleic acid probe, and at least one identification element, such as a fluorescent particle. The nucleic acid probes that hybridize to the target nucleic acid are determined, in some instances, by determining the at least one identification element. The nucleic acid probes that hybridize to the target nucleic acid may be used to determine the sequence of the target nucleic acid. In certain instances, the microfluidic droplets are provided with reagents that modify the nucleic acid probe. In some cases, a droplet, such as those described above, is deformed such that the components of the droplets individually pass a target area.

Systems and methods for nucleic acid sequencing

Growing community of inventors

Guilford, CT, United States of America

Michael Weiner