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    Systems and methods for encapsulation and multi-step processing of biological samples
    1.
    发明授权
    Systems and methods for encapsulation and multi-step processing of biological samples 有权

    公开(公告)号：US11860076B2

    公开(公告)日：2024-01-02

    申请号：US16934045

    申请日：2020-07-21

    申请人： Vilnius University ,  Droplet Genomics

    发明人： Linas Mazutis ,  Greta Stonyte ,  Karolis Leonavicius ,  Ausra Zelvyte

    IPC分类号： G01N1/40 ,  C12Q1/68 ,  B01J13/04 ,  B01J13/20 ,  C12Q1/6806

    CPC分类号： G01N1/4077 ,  B01J13/046 ,  B01J13/206 ,  C12Q1/6806

    摘要： The present invention relates to methods and systems for isolation of species in semi-permeable capsules and processing of encapsulated species through series of steps and/or reactions. To produce capsules, first aqueous two-phase system (ATPS) droplets are generated using microfluidics system and then the hydrogel shell layer is hardened by inducing polymerization. As exemplified in this invention to achieve concentric ATPS droplet formation density-matched PEGDA and Dextran polymer solutions can be used. Once a capsule is formed, its composition can be changed by adding new reagents or replacing out old ones (e.g. by resuspending capsules in desired aqueous solution). The hydrogel shell of semi-permeable capsules can be dissolved at selected step during multi-step procedures in order to release the encapsulated species. The present invention exemplifies the isolation of individual cells within capsules and using the encapsulated cells for genotypic and phenotypic analysis. Finally, the present invention also exemplifies the use of capsules in multi-step procedures to perform complex biological reactions.

    SYSTEMS AND METHODS FOR ENCAPSULATION AND MULTI-STEP PROCESSING OF BIOLOGICAL SAMPLES
    2.
    发明公开
    SYSTEMS AND METHODS FOR ENCAPSULATION AND MULTI-STEP PROCESSING OF BIOLOGICAL SAMPLES 审中-公开

    公开(公告)号：US20240085287A1

    公开(公告)日：2024-03-14

    申请号：US18514235

    申请日：2023-11-20

    申请人： Vilnius University ,  Droplet Genomics

    发明人： Linas Mazutis ,  Greta Stonyte ,  Karolis Leonavicius ,  Ausra Zelvyte

    IPC分类号： G01N1/40 ,  B01J13/04 ,  B01J13/20 ,  C12Q1/6806

    CPC分类号： G01N1/4077 ,  B01J13/046 ,  B01J13/206 ,  C12Q1/6806

    摘要： This invention relates to methods and systems for isolation of species in semi-permeable capsules and processing of encapsulated species through series of steps and/or reactions. To produce capsules, first aqueous two-phase system (ATPS) droplets are generated using microfluidics system. Then the hydrogel shell layer is hardened by inducing polymerization. As exemplified in this invention to achieve concentric ATPS droplet formation density-matched PEGDA and Dextran polymer solutions can be used. Once a capsule is formed, its composition can be changed by adding new reagents or replacing out old ones (e.g. by resuspending capsules in desired aqueous solution). The hydrogel shell of semi-permeable capsules can be dissolved at selected step during multi-step procedures to release the encapsulated species. This invention exemplifies isolation of individual cells within capsules and using the encapsulated cells for genotypic and phenotypic analysis. This invention also exemplifies use of capsules in multi-step procedures to perform complex biological reactions.

    Systems and methods for barcoding nucleic acids
    5.
    发明授权
    Systems and methods for barcoding nucleic acids 有权

    公开(公告)号：US10596541B2

    公开(公告)日：2020-03-24

    申请号：US15723490

    申请日：2017-10-03

    申请人： President and Fellows of Harvard College ,  Vilnius University

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

    IPC分类号： B01J19/00 ,  B01L3/00 ,  B01F13/00 ,  C12Q1/6806 ,  B01L7/00

    摘要： 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.

    Systems and methods for biomimetic fluid processing
    8.
    发明授权
    Systems and methods for biomimetic fluid processing 有权

    公开(公告)号：US11566214B2

    公开(公告)日：2023-01-31

    申请号：US16792484

    申请日：2020-02-17

    申请人： BRIGHAM AND WOMEN'S HOSPITAL, INC. ,  President and Fellows of Harvard College ,  Vilnius University

    发明人： Jonathan N. Thon ,  Joseph E. Italiano ,  Linas Mazutis ,  David A. Weitz

    IPC分类号： C12M3/06 ,  C12M1/42 ,  B01L3/00 ,  C12M3/00 ,  C12N5/078

    摘要： 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.

    System and Method for a Biomimetic Fluid Processing
    9.
    发明申请
    System and Method for a Biomimetic Fluid Processing 审中-公开

    公开(公告)号：US20200316597A1

    公开(公告)日：2020-10-08

    申请号：US16904523

    申请日：2020-06-17

    申请人： The Brigham and Women's Hospital, Inc. ,  President and Fellows of Harvard College ,  Vilnius University

    发明人： Joseph Italiano ,  Linas Mazutis ,  Jonathan Thon ,  David A. Weitz

    IPC分类号： B01L3/00 ,  C12M3/06 ,  C12M1/12 ,  C12M1/34 ,  G01N33/86 ,  C12M1/00

    摘要： 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.