Harvard College

The Brigham and Women's Hospital, Inc.

The Procter Gamble Company

Massachusetts Institute of Technology

The Johns Hopkins University

University of Toronto

Basf Se Corporation

The General Hospital Corporation

Stc.unm

The Broad Institute, Inc.

Cambridge Enterprise Limited

Massachusetts Eye and Ear Infirmary

Centre National De La Recherche Scientifique

Dana-farber-cancer Institute Inc.

Bio-rad Laboratories, Inc.

David A Weitz

Adam R Abate

Jeremy Agresti

Darren Roy Link

Amy Rowat

Liang-Yin Chu

George M Church

Gautam Dantas

George M Whitesides

John R Gilbert

Jin-Woong Kim

Morten Sommer

Linas Mazutis

Zhengdong Cheng

Galder Cristobal-Azkarate

Alireza Abbaspourrad

Keunho Ahn

Tony Hung

Mark Benjamin Romanowsky

Howard A Stone

Eugenia Kumacheva

Marco Caggioni

Irina Gitlin

Andrew B Feldman

Taotao Zhu

Willow Ruth Diluzio

Jeffrey S Lin

John Christopher Wesner

Angela M Belcher

Michael Weiner

Marc W Kirschner

Seth Fraden

Pascaline Mary

David J Mooney

Aviv Regev

Joanna Aizenberg

Hongkun Park

Alexander K Shalek

Christopher Martin Dobson

Bradley Bernstein

Yanwei Jia

Robert Nicol

Jeffrey J Fredberg

Mathias Kolle

Dimiter N Petsev

Ho Cheung Shum

Hakim Boukellal

Seila Selimovic

Zongli Zheng

Tuomas Knowles

John Brian Hutchison

Jonathan N Thon

Joseph Italiano

Thomas Franke

Christian Holtze

Assaf Rotem

Manuel Marquez-Sanchez

Achim Wixforth

John Heyman

Shelley L Anna

Allon Moshe Klein

Lothar Schmid

Nathalie Bontoux

Daeyeon Lee

Chang-Hyung Choi

Piotr Garstecki

Ilke Akartuna

Andrew S Utada

Huidan Zhang

Esther Amstad

Christian Boehm

Sarah Koester

Stefanie Utech

Andrew Parsons Magyar

Steven Andrew McCarroll

Tanya Shirman

Andrew S Pekosz

James P Butler

Christiane Wobus

Nicolas Vogel

Alberto Fernandez-Nieves

Anindita Basu

Ian Burgess

Enric Santanach Carreras

Nick Carroll

Asaf Rotem

Joshua T Wolfe

Eleftherios Paschalis Ilios

Kiryakos Spiro Mutafopulos

Ramaswamy Krishnan

Ralph Alexander Sperling

Evan Macosko

Katherine Reece Phillips

Christopher B Ford

Chan Young Park

Kellogg Schwab

Angelo S Mao

Thomas Edward Kodger

Raluca Ostafe

Jared D Evans

Methods for analyzing DNA-containing samples are provided. The methods can comprise isolating a single genomic equivalent of DNA from the DNA-containing sample to provide a single isolated DNA molecule. The single isolated DNA molecule can be subjected to amplification conditions in the presence of one or more sets of unique molecularly tagged primers to provide one or more amplicons. Any spurious allelic sequences generated during the amplification process are tagged with an identical molecular tag. The methods can also include a step of determining the sequence of the one or more amplicons, in which the majority sequence for each code is selected as the sequence of the single original encapsulated target. The DNA-containing sample can be a forensic sample (e.g., mixed contributor sample), a fetal genetic screening sample, or a biological cell.

Analysis of DNA-containing samples and resolution of mixed contributor DNA samples

The present invention provides capsules having a shell of material that comprises an assembly of a protein, and the capsule is optionally provided with a network of material within the shell that is an assembly of the protein. The assembly of the protein is obtained or obtainable by the aggregation of the protein, optionally together with another protein. The assembly is a non-covalent assembly of a protein.

Protein capsules

A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.

System and method for a biomimetic fluid processing

The present invention generally relates to microfluidics and labeled nucleic acids. In one aspect, the present invention is generally directed to a method, wherein the method includes providing a plurality of droplets comprising particles, the particles comprising oligonucleotides, and attaching a nucleic acid sequence to the oligonucleotides. Certain embodiments are generally directed to systems and methods for splitting a droplet into two or more droplets. Certain embodiments are generally directed to systems and methods for sorting fluidic droplets in a liquid.

Barcoding systems and methods for gene sequencing and other applications

The present invention generally relates to microfluidic droplets and, including forming gels within microfluidic droplets. In some aspects, a fluid containing agarose or other gel precursors is transported into a microfluidic droplet, and caused to harden within the droplet, e.g., to form a gel particle contained within the microfluidic droplet. Surprisingly, a discrete gel particle may be formed even if the fluid containing the agarose or other gel precursor, and the fluid contained within the microfluidic droplet, are substantially immiscible. Other aspects of the present invention are generally directed to techniques for making or using such gels within microfluidic droplets, kits containing such gels within microfluidic droplets, or the like.

Formation of colloids or gels within droplets

The present invention generally relates to a combination of molecular barcoding and emulsion-based microfluidics to isolate, lyse, barcode, and prepare nucleic acids from individual cells in a high-throughput manner.

Droplet-based method and apparatus for composite single-cell nucleic acid analysis

Systems and methods generating physiologic models that can produce functional biological substances are provided. In some aspects, a system includes a substrate and a first and second channel formed therein. The channels extend longitudinally and are substantially parallel to each other. A series of apertures extend between the first channel and second channel to create a fluid communication path passing through columns separating the channels that extends further along the longitudinal dimension than other dimensions. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate, wherein the first channel flow rate and the second channel flow rate create a differential configured to generate physiological shear rates within a predetermined range in the channels.

Systems and methods for biomimetic fluid processing

The present invention generally relates to the manipulation of species using acoustic waves such as surface acoustic waves. In some aspects, a channel such as a microfluidic channel may be provided having two or more outlets, and acoustic waves applied to species within the channel to determine which outlet the species is directed to. For instance, surface acoustic waves may be applied to a species such as a cell or a particle to deflect it from the channel into a groove or other portion that directs it to a different outlet. In some cases, surprisingly, this deflection of species may be in a different direction than the incident acoustic waves on the channel. Other embodiments of the present invention are generally directed to kits including such systems, techniques for producing such systems, or the like.

Acoustic wave sorting

Parallel uses of microfluidic methods and devices for focusing and/or forming discontinuous sections of similar or dissimilar size in a fluid are described. In some aspects, the present invention relates generally to flow-focusing-type technology, and also to microfluidics, and more particularly parallel use of microfluidic systems arranged to control a dispersed phase within a dispersant, and the size, and size distribution, of a dispersed phase in a multi-phase fluid system, and systems for delivery of fluid components to multiple such devices.

Scale-up of microfluidic devices

The present invention is generally related to systems and methods for producing a plurality of droplets. The droplets may contain varying species, e.g., for use as a library. In some cases, the fluidic droplets may be rigidified to form rigidified droplets (e.g., gel droplets). In certain embodiments, the droplets may undergo a phase change (e.g., from rigidified droplets to fluidized droplets), as discussed more herein. In some cases, a species may be added internally to a droplet by exposing the droplet to a fluid comprising a plurality of species.

Creation of libraries of droplets and related species

The present invention generally relates to systems and techniques for manipulating fluids and/or making droplets. In certain aspects, the present invention generally relates to droplet production. The droplets may be formed from fluids from different sources. In one set of embodiments, the present invention is directed to a microfluidic device comprising a plurality of droplet-making units, and/or other fluidic units, which may be substantially identical in some cases. Substantially each of the fluidic units may be in fluidic communication with a different source of a first fluid and a common source of a second fluid, in certain embodiments. In one aspect, substantially the same pressure may be applied to substantially all of the different sources of fluid, which may be used to cause fluid to move from the different sources into the microfluidic device. In some cases, the fluids may interact within the fluidic units, e.g., by reacting, or for the production of droplets within the microfluidic device. In some cases, the droplets may be used, for example, to form a library of droplets.

Systems and methods for droplet production and/or fluidic manipulation

Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one set of embodiments, droplets may be sorted using surface acoustic waves. The droplets may contain cells or other species. In some cases, the surface acoustic waves may be created using a surface acoustic wave generator such as an interdigitated transducer, and/or a material such as a piezoelectric substrate. The piezoelectric substrate may be isolated from the microfluidic substrate except at or proximate the location where the droplets are sorted, e.g., into first or second microfluidic channels. At such locations, the microfluidic substrate may be coupled to the piezoelectric substrate (or other material) by one or more coupling regions. In some cases, relatively high sorting rates may be achieved, e.g., at rates of at least about 1,000 Hz, at least about 10,000 Hz, or at least about 100,000 Hz, and in some embodiments, with high cell viability after sorting.

Acoustic waves in microfluidics

A structurally colored pigment is described that contains a plurality of photonic crystal particles dispersed in a medium, where each photonic crystal particles contains a plurality of spectrally selective absorbing components dispersed within the photonic crystal particle. In certain embodiments, each photonic crystal particle has a predetermined minimum number of repeat units of the photonic crystal structure. The structurally colored material provides improved reflectance, long-term stability, and control of the desired optical effects. The fabrication techniques described herein also provide high throughput and high yield allowing use in wide ranging applications from cosmetics, paints, signs, sensors, to packaging material.

Structurally colored materials with spectrally selective absorbing components and methods for making the same

The present invention generally relates to microfluidics, and, in particular, to systems and methods for coalescing or fusing droplets. In certain aspects, two or more droplets within a microfluidic channel are brought together and caused to coalesce without using electric fields or charges. For example, in certain embodiments, droplets stabilized with a surfactant may be disrupted, e.g., by exposing the droplets to a solvent able to alter the surfactant, which may partially destabilize the droplets and allow them to coalesce. In some instances, the droplets may also be physically disrupted to facilitate coalesce. In addition, in some cases, the positions of one or more droplets may be controlled within a channel using a groove in a wall of the channel. For example, a droplet may at least partially enter the groove such that the position of the droplet is at least partially controlled by the groove.

Coalescence of droplets

Growing community of inventors

Bolton, MA, United States of America

David A Weitz