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    Rapid production of droplets
    61.
    发明授权
    Rapid production of droplets 有权

    公开(公告)号：US10151429B2

    公开(公告)日：2018-12-11

    申请号：US14890817

    申请日：2014-05-14

    Applicant: President and Fellows of Harvard College

    Inventor： David A. Weitz ,  Esther Amstad

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

    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.

    Valves and other flow control in fluidic systems including microfluidic systems
    62.
    发明授权
    Valves and other flow control in fluidic systems including microfluidic systems 有权

    公开(公告)号：US10029256B2

    公开(公告)日：2018-07-24

    申请号：US15148955

    申请日：2016-05-06

    Applicant: President and Fellows of Harvard College

    Inventor： Adam R. Abate ,  David A. Weitz

    IPC: B01L3/00 ,  F16K99/00 ,  B01L3/02

    Abstract: Articles and methods for controlling flow in fluidic systems, especially in microfluidic systems, are provided. In one aspect, a microfluidic system described herein includes a configuration such that the actuation of a single valve can allow the switching of fluids from a first fluid path (e.g., a first channel section) to a second fluid path (e.g., a second channel section). This may be achieved, for example, by incorporating a valve with a first channel section, which may have a lower hydrodynamic resistance than a second channel section prior to actuation of the valve. Actuation of the valve can cause only the hydrodynamic resistance of the first channel section to increase, thereby redirecting fluid flow into the second channel section (which now has a relatively lower hydrodynamic resistance). In some embodiments, the valve comprises a control channel for introducing a positive or reduced pressure, and is adapted to modulate fluid flow in an adjacent channel section by constricting or expanding the channel section. For example, the valve and/or the channel section may be formed in a flexible material and actuation of the valve may be achieved by applying a positive or reduced pressure to the valve to cause deformation of both the valve and the channel section. Another aspect of the invention includes articles and methods associated with manipulation of multiphase materials (e.g., dispersions). For instance, one or more valves may be combined with a flow focusing system so as to form droplets of different volumes and/or frequencies without the need to vary flow rates of the fluids when they are introduced into the fluidic system.

    SYSTEMS AND METHODS FOR NUCLEIC ACID SEQUENCING
    64.
    发明申请
    SYSTEMS AND METHODS FOR NUCLEIC ACID SEQUENCING 审中-公开

    公开(公告)号：US20180057875A1

    公开(公告)日：2018-03-01

    申请号：US15670885

    申请日：2017-08-07

    Applicant: President and Fellows of Harvard College

    Inventor： David A. Weitz ,  Jeremy Agresti ,  Michael P. Weiner ,  Adam R. Abate ,  Tony Hung

    IPC: C12Q1/68

    CPC classification number: C12Q1/6874 ,  C12Q2537/143 ,  C12Q2563/149

    Abstract: 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.

    ASSAY AND OTHER REACTIONS INVOLVING DROPLETS
    66.
    发明申请
    ASSAY AND OTHER REACTIONS INVOLVING DROPLETS 审中-公开

    公开(公告)号：US20180023109A1

    公开(公告)日：2018-01-25

    申请号：US15670977

    申请日：2017-08-07

    Applicant: President and Fellows of Harvard College

    Inventor： David A. Weitz ,  Jeremy Agresti ,  Liang-Yin Chu ,  Jin-Woong Kim ,  Amy Rowat ,  Morten Sommer ,  Gautam Dantas ,  George Church

    IPC: C12P19/34 ,  B01J13/00 ,  B01F3/08 ,  B01F13/00 ,  C12Q1/68

    Abstract: The present invention generally relates to droplets and/or emulsions, such as multiple emulsions. In some cases, the droplets and/or emulsions may be used in assays, and in certain embodiments, the droplet or emulsion may be hardened to form a gel. In some aspects, a heterogeneous assay can be performed using a gel. For example, a droplet may be hardened to form a gel, where the droplet contains a cell, DNA, or other suitable species. The gel may be exposed to a reactant, and the reactant may interact with the gel and/or with the cell, DNA, etc., in some fashion. For example, the reactant may diffuse through the gel, or the hardened particle may liquefy to form a liquid state, allowing the reactant to interact with the cell. As a specific example, DNA contained within a gel particle may be subjected to PCR (polymerase chain reaction) amplification, e.g., by using PCR primers able to bind to the gel as it forms. As the DNA is amplified using PCR, some of the DNA will be bound to the gel via the PCR primer. After the PCR reaction, unbound DNA may be removed from the gel, e.g., via diffusion or washing. Thus, a gel particle having bound DNA may be formed in one embodiment of the invention.

    SYSTEMS, METHODS, AND KITS FOR AMPLIFYING OR CLONING WITHIN DROPLETS
    68.
    发明申请
    SYSTEMS, METHODS, AND KITS FOR AMPLIFYING OR CLONING WITHIN DROPLETS 审中-公开

    公开(公告)号：US20180016622A1

    公开(公告)日：2018-01-18

    申请号：US15544942

    申请日：2016-01-22

    Applicant: President and Fellows of Harvard College

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

    IPC: C12Q1/68 ,  C12N15/10 ,  B01L3/00 ,  B01L7/00

    Abstract: The present invention generally relates to droplet-based microfluidic devices, including systems, methods, and kits for amplifying or cloning within droplets. In some embodiments, the present invention is generally directed to systems, methods, or kits for amplifying a plurality of nucleic acids, e.g., without substantially selectively amplifying some nucleic acids over others. The nucleic acids may be contained within the droplets. In addition, in some embodiments, a plurality of microfluidic droplet containing a species of interest, such as a nucleic acid, may be mixed with microfluidic droplets free of the species, then pipetted or otherwise transferred such that, on average, a predetermined number of droplets containing species of interest is transferred.

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