公开(公告)号：US10471016B2

公开(公告)日：2019-11-12

申请号：US15915686

申请日：2018-03-08

Applicant: President and Fellows of Harvard College

Inventor： David J. Mooney ,  David A. Weitz ,  Stefanie Utech ,  Radivoje Prodanovich ,  Esther Amstad ,  Raluca Ostafe ,  Angelo S. Mao ,  Connie Chang Wilking ,  Huanan Wang

IPC: A61K9/50 ,  A61K9/16 ,  A61K35/00

Abstract: The invention relates to microparticles comprising a crosslinked gel and methods for making and using same.

公开(公告)号：US20190255530A1

公开(公告)日：2019-08-22

申请号：US16400401

申请日：2019-05-01

Applicant: Brandeis University ,  President and Fellows of Harvard College

Inventor： Seth Fraden ,  Hakim Boukellal ,  Yanwei Jia ,  Seila Selimovic ,  Amy Rowat ,  Jeremy Agresti ,  David A. Weitz

IPC: B01L3/00 ,  G01N1/28 ,  F17D1/12 ,  G01N15/02 ,  G01N15/14

Abstract: Microfluidic structures and methods for manipulating fluids, fluid components, and reactions are provided. In one aspect, such structures and methods can allow production of droplets of a precise volume, which can be stored/maintained at precise regions of the device. In another aspect, microfluidic structures and methods described herein are designed for containing and positioning components in an arrangement such that the components can be manipulated and then tracked even after manipulation. For example, cells may be constrained in an arrangement in microfluidic structures described herein to facilitate tracking during their growth and/or after they multiply.

公开(公告)号：US10371699B2

公开(公告)日：2019-08-06

申请号：US15331445

申请日：2016-10-21

Applicant: President and Fellows of Harvard College ,  Medical Research Council

Inventor： Andrew David Griffiths ,  David A. Weitz ,  Darren Roy Link ,  Keunho Ahn ,  Jerome Bibette

IPC: B01L3/00 ,  G01N33/543 ,  B01F3/08 ,  B01F5/02 ,  B01F5/06 ,  B01F13/00 ,  G01N33/50 ,  B01J19/00 ,  C12Q1/42 ,  G01N15/14 ,  G01N21/64 ,  G01N33/573 ,  C40B50/08

Abstract: The invention describes a method for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, comprising the steps of: a) compartmentalizing the compounds into microcapsules together with the target, such that only a subset of the repertoire is represented in multiple copies in any one microcapsule; and b) identifying the compound which binds to or modulates the activity of the target; wherein at least one step is performed under microfluidic control. The invention enables the screening of large repertoires of molecules which can serve as leads for drug development.

公开(公告)号：US20190160445A1

公开(公告)日：2019-05-30

申请号：US16315245

申请日：2017-07-07

Applicant: President and Fellows of Harvard College ,  Massachusetts Eye and Ear Infirmary

Inventor： David A. Weitz ,  Huidan Zhang ,  Nai Wen Cui ,  Fengyang Lei ,  Eleftherios Paschalis llios

IPC: B01J13/00 ,  B01J2/08 ,  B01L3/00

Abstract: 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.

公开(公告)号：US20190127789A1

公开(公告)日：2019-05-02

申请号：US16094766

申请日：2017-04-19

Applicant: President and Fellows of Harvard College

Inventor： David A. Weitz ,  Huidan Zhang ,  John Heyman

IPC: C12Q1/6855

Abstract: The present invention generally relates to microfluidics and labeled nucleic acids. Certain aspects are generally directed to containing cells in gels, such as agarose gels, and determining nucleic acids within the cells, e.g., while contained within the gels. The nucleic acids may be, for example, genomic DNA, mRNA, transcriptomes, or the like. In some embodiments, for instance, both genomic DNA and RNA (e.g., as in a transcriptome) from a cell may be determined. In some cases, the nucleic acids may be attached to beads for sequencing or other purposes. Such systems may be useful, for example, for high-throughput sequencing or other applications.

公开(公告)号：US20190118182A1

公开(公告)日：2019-04-25

申请号：US16093178

申请日：2017-04-14

Applicant: President and Fellows of Harvard College

Inventor： David A. Weitz ,  Kiryakos S. Mutafopulos ,  Thomas Hufnagel

IPC: B01L3/00

Abstract: The present invention generally relates to microfluidic devices. In some aspects, various entities, such as droplets or particles, may be contained within a microfluidic device, e.g., within collection chambers or other locations within the device. In some cases, the entities may be released from such locations, e.g., in a sequential pattern, or an arbitrary pattern. In some cases, the entities may be imaged, reacted, analyzed, etc. while contained within the collection chambers. Other aspects are generally directed to methods of making or using such devices, kits involving such devices, or the like.

公开(公告)号：US20190086034A1

公开(公告)日：2019-03-21

申请号：US16175395

申请日：2018-10-30

Applicant: President and Fellows of Harvard College

Inventor： David A. Weitz ,  Esther Amstad

IPC: F17D1/20 ,  B01L3/02 ,  B01F3/08 ,  B01F5/04 ,  B01F13/00 ,  B01L3/00 ,  F15D1/02

Abstract: The present invention generally relates to the production of fluidic droplets. Certain aspects of the invention are generally directed to systems and methods for creating droplets by flowing a fluid from a first channel to a second channel through a plurality of side channels. The fluid exiting the side channels into the second channel may form a plurality of droplets, and in some embodiments, at very high droplet production rates. In addition, in some aspects, double or higher-order multiple emulsions may also be formed. In some embodiments, this may be achieved by forming multiple emulsions through a direct, synchronized production method and/or through the formation of a single emulsion that is collected and re-injected into a second microfluidic device to form double emulsions.

公开(公告)号：US20180304222A1

公开(公告)日：2018-10-25

申请号：US15991600

申请日：2018-05-29

Applicant: President and Fellows of Harvard College ,  Vilnius University

Inventor： David A. Weitz ,  Allon Moshe Klein ,  Ilke Akartuna ,  Linas Mazutis ,  Marc W. Kirschner

IPC: B01J19/00 ,  B01F13/00

CPC classification number: B01J19/0046 ,  B01F13/0062 ,  B01J2219/00585 ,  B01J2219/00722 ,  B01L3/502761 ,  B01L3/502776 ,  B01L3/502784 ,  B01L7/52 ,  B01L2200/0652 ,  B01L2300/021 ,  B01L2300/0663 ,  B01L2300/0858 ,  B01L2300/0867 ,  B01L2300/0883 ,  C12Q1/6806 ,  C12Q2563/149 ,  C12Q2563/159 ,  C12Q2565/514

Abstract: The present invention generally relates to microfluidics and labeled nucleic acids. For example, certain aspects are generally directed to systems and methods for labeling nucleic acids within microfluidic droplets. In one set of embodiments, the nucleic acids may include “barcodes” or unique sequences that can be used to distinguish nucleic acids in a droplet from those in another droplet, for instance, even after the nucleic acids are pooled together. In some cases, the unique sequences may be incorporated into individual droplets using particles and attached to nucleic acids contained within the droplets (for example, released from lysed cells). In some cases, the barcodes may be used to distinguish tens, hundreds, or even thousands of nucleic acids, e.g., arising from different cells or other sources.

公开(公告)号：US20180272299A1

公开(公告)日：2018-09-27

申请号：US15922292

申请日：2018-03-15

Applicant: President and Fellows of Harvard College ,  Medical Research Council

Inventor： Andrew David Griffiths ,  David A. Weitz ,  Darren Roy Link ,  Keunho Ahn ,  Jerome Bibette

IPC: B01F13/00 ,  B01F5/06 ,  B01J19/00 ,  B01L3/00 ,  B82Y10/00 ,  B82Y30/00 ,  C07K1/04 ,  C40B40/06 ,  C40B40/10 ,  C40B50/08 ,  B01F3/08 ,  G01N35/10

CPC classification number: C40B40/08 ,  B01F3/0807 ,  B01F5/0646 ,  B01F5/0647 ,  B01F5/0655 ,  B01F13/0071 ,  B01F13/0076 ,  B01J13/025 ,  B01J19/0046 ,  B01J2219/00497 ,  B01J2219/005 ,  B01J2219/00576 ,  B01J2219/00585 ,  B01J2219/00596 ,  B01J2219/00599 ,  B01J2219/00707 ,  B01J2219/00722 ,  B01J2219/00725 ,  B01J2219/00743 ,  B01J2219/00853 ,  B01J2219/0086 ,  B01J2219/00889 ,  B01L3/5025 ,  B01L3/5027 ,  B01L3/50273 ,  B01L3/502746 ,  B01L3/502761 ,  B01L3/502784 ,  B01L2200/0605 ,  B01L2200/0673 ,  B01L2300/0864 ,  B01L2300/0867 ,  B01L2400/0406 ,  B01L2400/0415 ,  B01L2400/0487 ,  B01L2400/084 ,  B82Y10/00 ,  B82Y30/00 ,  C07K1/047 ,  C12N15/1096 ,  C12Q2600/16 ,  C40B40/06 ,  C40B40/10 ,  C40B50/08 ,  G01N2035/1034 ,  H05K999/99

Abstract: The invention describes a method for the synthesis of compounds comprising the steps of: (a) compartmentalising two or more sets of primary compounds into microcapsules; such that a proportion of the microcapsules contains two or more compounds; and (b) forming secondary compounds in the microcapsules by chemical reactions between primary compounds from different sets; wherein one or both of steps (a) and (b) is performed under microfluidic control; preferably electronic microfluidic control The invention further allows for the identification of compounds which bind to a target component of a biochemical system or modulate the activity of the target, and which is co-compartmentalised into the microcapsules.

公开(公告)号：US20180265922A1

公开(公告)日：2018-09-20

申请号：US15965452

申请日：2018-04-27

Applicant: President and Fellows of Harvard College ,  The General Hospital Corporation

Inventor： David A. Weitz ,  Assaf Rotem ,  Oren Ram ,  Bradley E. Bernstein

IPC: C12Q1/6869 ,  B01F13/00

CPC classification number: C12Q1/6869 ,  B01F13/0071 ,  B01L3/502784 ,  C12Q2521/301 ,  C12Q2523/301 ,  C12Q2525/131 ,  C12Q2525/161 ,  C12Q2563/179 ,  C12Q2565/629 ,  C12Q2563/159

Abstract: The present invention generally relates to microfluidics and/or epigenetic sequencing. In one set of embodiments, cells contained within a plurality of microfluidic droplets are lysed and the DNA (e.g., from nucleosomes) within the droplets are labeled, e.g., with adapters containing an identification sequence. The adapters may also contain other sequences, e.g., restriction sites, primer sites, etc., to assist with later analysis. After labeling with adapters, the DNA from the different cells may be combined and analyzed, e.g., to determine epigenetic information about the cells. For example, the DNA may be separated on the basis of certain modifications (e.g., methylation), and the DNA from the separated nucleosomes may be sequenced using techniques such as chromatin immunoprecipitation (“ChIP”). In some cases, the DNA sequences may also be aligned with genomes, e.g., to determine which portions of the genome were epigenetically modified, e.g., via methylation.