公开(公告)号：US11255809B2

公开(公告)日：2022-02-22

申请号：US16788187

申请日：2020-02-11

Applicant: Advanced Liquid Logic, Inc. ,  Duke University

Inventor： Vamsee K. Pamula ,  Vijay Srinivasan ,  Michael G. Pollack ,  Richard B. Fair

IPC: G01N27/26 ,  B01F13/00 ,  B01L3/00 ,  B01L7/00 ,  G01N35/00 ,  C12Q1/686 ,  C12Q1/6869 ,  G01N27/447 ,  G01N27/327 ,  G01N27/416 ,  B01L3/02

Abstract: The present invention relates to droplet-based surface modification and washing. According to one embodiment, a method of splitting a droplet is provided, the method including providing a droplet microactuator including a droplet including one or more beads and immobilizing at least one of the one or more beads. The method further includes conducting one or more droplet operations to divide the droplet to yield a set of droplets including a droplet including the one or more immobilized beads and a droplet substantially lacking the one or more immobilized beads.

公开(公告)号：US10809254B2

公开(公告)日：2020-10-20

申请号：US16191270

申请日：2018-11-14

Applicant: Advanced Liquid Logic, Inc.

Inventor： Vamsee K. Pamula ,  Ramakrishna Sista ,  Vijay Srinivasan ,  Michael G. Pollack ,  Allen E. Eckhardt

IPC: G01N1/40 ,  G01N1/00 ,  G01N1/10 ,  G01N1/22 ,  G01N1/18 ,  G01N35/00 ,  G01N1/38 ,  B01L3/00 ,  G01N33/543 ,  B01F11/00 ,  B01F13/00 ,  B01F13/08 ,  B01L7/00 ,  G01N35/10

Abstract: Provided herein are methods of splitting droplets containing magnetically responsive beads in a droplet actuator. A droplet actuator having a plurality of droplet operations electrodes configured to transport the droplet, and a magnetic field present at the droplet operations electrodes, is provided. The magnetically responsive beads in the droplet are immobilized using the magnetic field and the plurality of droplet operations electrodes are used to split the droplet into first and second droplets while the magnetically responsive beads remain substantially immobilized.

公开(公告)号：US20200209231A1

公开(公告)日：2020-07-02

申请号：US16811789

申请日：2020-03-06

Applicant: Advanced Liquid Logic, Inc.

Inventor： Vamsee K. Pamula ,  Michael G. Pollack ,  Ramakrishna Sista ,  Arjun Sudarsan

IPC: G01N33/543 ,  B01F11/00 ,  G01N33/561 ,  C12N15/10 ,  B03C5/00 ,  B03C1/30 ,  B03C1/28 ,  B03C1/02 ,  B01L3/00 ,  B01F13/00

Abstract: Methods are provided for separating magnetically responsive beads from a droplet in a droplet actuator. Droplet operations electrodes and a magnet are arranged in a droplet actuator to manipulate a bead-containing droplet and position it relative to a magnetic field region that attracts the magnetically responsive beads. The droplet operations electrodes are operated to control the droplet shape and transport it away from the magnetic field region to form a concentration of beads in the droplet. The continued transport of the droplet away from the magnetic field causes the concentration of beads to break away from the droplet to yield a small, concentrated bead-containing droplet immobilized by the magnet.

公开(公告)号：US10379112B2

公开(公告)日：2019-08-13

申请号：US14719731

申请日：2015-05-22

Applicant: Advanced Liquid Logic, Inc. ,  Duke University

Inventor： Ramakrishna Sista ,  Vamsee K. Pamula ,  Michael G. Pollack ,  Vijay Srinivasan ,  Allen E. Eckhardt ,  Richard B. Fair

IPC: B01L3/00 ,  G01N27/447 ,  G01N33/543 ,  C12M1/12 ,  G01N35/10 ,  G01N35/00

Abstract: A method of providing a droplet in contact with a magnetically responsive bead and having a reduced quantity of a substance. The method generally includes the steps of (a) providing a droplet actuator comprising: (i) a substrate comprising electrodes arranged for conducting droplet operations on a surface; (ii) a starting droplet comprising: (1) one or more magnetically responsive beads; (2) a starting quantity of the substance; and (3) a starting volume; (b) magnetically immobilizing the one or more magnetically responsive beads at a location which is at a distance from a target droplet splitting zone; (c) conducting one or more droplet operations comprising droplet dividing operations selected to divide the combined droplet to yield a set of droplets comprising: (i) a droplet comprising substantially all of the one or more magnetically responsive beads and having a decreased quantity of the substance relative to the starting concentration; and (ii) a droplet substantially lacking the magnetically responsive beads.

公开(公告)号：US10078078B2

公开(公告)日：2018-09-18

申请号：US15210634

申请日：2016-07-14

Applicant: Advanced Liquid Logic, Inc.

Inventor： Vamsee K. Pamula ,  Michael G. Pollack ,  Ramakrishna Sista ,  Arjun Sudarsan

IPC: G01N15/06 ,  G01N33/00 ,  G01N33/48 ,  G01N33/543 ,  B01F11/00 ,  B01F13/00 ,  B01L3/00 ,  B03C1/02 ,  B03C1/30 ,  B03C5/00 ,  G01N33/561 ,  B03C1/28 ,  C12N15/10 ,  B01L7/00 ,  G01N35/10

CPC classification number: G01N33/54333 ,  B01F11/0071 ,  B01F13/0071 ,  B01F13/0076 ,  B01L3/502715 ,  B01L3/502761 ,  B01L3/502784 ,  B01L3/502792 ,  B01L7/52 ,  B01L7/525 ,  B01L2200/027 ,  B01L2200/0647 ,  B01L2200/0668 ,  B01L2300/0654 ,  B01L2300/0816 ,  B01L2300/0861 ,  B01L2300/0864 ,  B01L2300/0867 ,  B01L2300/089 ,  B01L2300/1827 ,  B01L2400/0406 ,  B01L2400/0415 ,  B01L2400/0421 ,  B01L2400/0424 ,  B01L2400/0427 ,  B01L2400/043 ,  B01L2400/0436 ,  B01L2400/0442 ,  B03C1/02 ,  B03C1/288 ,  B03C1/30 ,  B03C5/005 ,  B03C2201/18 ,  B03C2201/26 ,  C12N15/1013 ,  G01N33/561 ,  G01N2035/1046 ,  Y10T436/11 ,  Y10T436/25 ,  Y10T436/25625 ,  Y10T436/2575

Abstract: The invention relates to bead incubating and washing on a droplet actuator. Methods for incubating magnetically responsive beads that are labeled with primary antibody, a sample (i.e., analyte), and secondary reporter antibodies on a magnet, on and off a magnet, and completely off a magnet are provided. Also provided are methods for washing magnetically responsive beads using shape-assisted merging of droplets. Also provided are methods for shape-mediated splitting, transporting, and dispensing of a sample droplet that contains magnetically responsive beads. The apparatuses and methods of the invention provide for rapid time to result and optimum detection of an analyte in an immunoassay.

公开(公告)号：US10005080B2

公开(公告)日：2018-06-26

申请号：US14538506

申请日：2014-11-11

Applicant: GENMARK DIAGNOSTICS, INC. ,  ADVANCED LIQUID LOGIC, INC.

Inventor： Jon Faiz Kayyem ,  Sean Ford ,  Vamsee K. Pamula ,  Vijay Srinivasan ,  Scott Corey ,  Brian Murphy ,  David Walter Wright ,  Dominic Aiello

IPC: B01L3/00 ,  B01L7/00

CPC classification number: B01L3/502 ,  B01L3/502792 ,  B01L3/52 ,  B01L7/525 ,  B01L2200/04 ,  B01L2200/0647 ,  B01L2200/10 ,  B01L2200/16 ,  B01L2300/021 ,  B01L2300/04 ,  B01L2300/06 ,  B01L2300/0636 ,  B01L2300/0672 ,  B01L2300/0681 ,  B01L2300/0816 ,  B01L2300/0867 ,  B01L2300/0874 ,  B01L2300/123 ,  B01L2300/1822 ,  B01L2400/0427 ,  B01L2400/043 ,  B01L2400/0481 ,  B01L2400/0487 ,  B01L2400/0683

Abstract: In one embodiment, a multiplex fluid processing cartridge includes a sample well, a deformable fluid chamber, a mixing well with a mixer disposed therein, a lysis chamber including a lysis mixer, an electrowetting grid for microdroplet manipulation, and electrosensor arrays configured to detect analytes of interest. An instrument for processing the cartridge is configured to receive the cartridge and to selectively apply thermal energy, magnetic force, and electrical connections to one or more discrete locations on the cartridge and is further configured to compress the deformable chamber(s) in a specified sequence.

公开(公告)号：US09952177B2

公开(公告)日：2018-04-24

申请号：US14795304

申请日：2015-07-09

Applicant: Advanced Liquid Logic, Inc. ,  Duke University

Inventor： Michael G. Pollack ,  Vijay Srinivasan ,  Zhishan Hua ,  Hon Lung Chu ,  Michael Hauser ,  Allen Eckhardt

IPC: G01N27/447 ,  G01N27/453 ,  B01L3/00 ,  B01L7/00

CPC classification number: G01N27/44743 ,  B01L3/502715 ,  B01L3/502792 ,  B01L7/525 ,  B01L2200/025 ,  B01L2200/027 ,  B01L2300/088 ,  B01L2300/0887 ,  B01L2300/089 ,  B01L2300/161 ,  B01L2400/0406 ,  B01L2400/043 ,  B01L2400/0457 ,  B01L2400/046 ,  G01N27/44791

Abstract: The invention is directed to a droplet actuator device and methods for integrating gel electrophoresis analysis with pre or post-analytical sample handling as well as other molecular analysis processes. Using digital microfluidics technology, the droplet actuator device and methods of the invention provide the ability to perform gel electrophoresis and liquid handling operations on a single integrated device. The integrated liquid handling operations may be used to prepare and deliver samples to the electrophoresis gel, capture and subsequently process products of the electrophoresis gel or perform additional assays on the same sample materials which are analyzed by gel electrophoresis. In one embodiment, one or more molecular assays, such as nucleic acid (e.g., DNA) quantification by real-time PCR, and one or more sample processing operations such as sample dilution is performed on a droplet actuator integrated with an electrophoresis gel. In one embodiment, an electrophoresis gel may be integrated on the top substrate of the droplet actuator.

公开(公告)号：US09861986B2

公开(公告)日：2018-01-09

申请号：US14506265

申请日：2014-10-03

Applicant: ADVANCED LIQUID LOGIC, INC.

Inventor： Michael G. Pollack ,  Prasanna Thwar ,  Vamsee K. Pamula ,  Vijay Srinivasan ,  Allen E. Eckhardt ,  Alexander Shenderov ,  Dwayne J. Allen

IPC: B01L3/00 ,  G01N27/447 ,  B01L7/00 ,  G01N35/10 ,  G01N35/00

CPC classification number: B01L3/502784 ,  B01L3/502715 ,  B01L3/502761 ,  B01L7/52 ,  B01L2200/027 ,  B01L2200/0673 ,  B01L2300/022 ,  B01L2300/023 ,  B01L2300/024 ,  B01L2300/0672 ,  B01L2300/0816 ,  B01L2300/0864 ,  B01L2300/0867 ,  B01L2400/0415 ,  B01L2400/0424 ,  B01L2400/0427 ,  B01L2400/043 ,  B01L2400/0478 ,  B01L2400/0481 ,  B01L2400/0487 ,  B01L2400/049 ,  B01L2400/0683 ,  G01N27/44704 ,  G01N35/0098 ,  G01N2035/1046 ,  Y10T436/25 ,  Y10T436/2575

Abstract: The invention provides droplet actuators and droplet actuator cassettes including reagent storage capabilities, as well as methods of making and using the droplet actuators and cassettes. The invention also provides continuous flow channel elements and techniques for using electrodes to manipulate droplets in flowing streams. The invention also discloses methods of separating compounds on a droplet actuator. Various other aspects of the invention are also disclosed.

公开(公告)号：US20170241949A1

公开(公告)日：2017-08-24

申请号：US15472248

申请日：2017-03-28

Applicant: Advanced Liquid Logic, Inc.

Inventor： Donovan Bort ,  Carrie Graham ,  Vamsee Pamula ,  Michael Pollack ,  Ramakrishna Sista ,  Vijay Srinivasan

IPC: G01N27/447 ,  B01F13/00 ,  B01L3/00 ,  B01F1/00

CPC classification number: G01N27/44791 ,  B01F1/0027 ,  B01F13/0071 ,  B01F13/0076 ,  B01F2001/0055 ,  B01F2215/0037 ,  B01L3/502761 ,  B01L3/502792 ,  B01L2200/0605 ,  B01L2200/0668 ,  B01L2200/10 ,  B01L2200/16 ,  B01L2300/0816 ,  B01L2300/0867 ,  B01L2300/089 ,  B01L2400/0406 ,  B01L2400/0418 ,  B01L2400/0427 ,  B01L2400/043 ,  B01L2400/0487 ,  B81B1/004

Abstract: A droplet actuator for manipulating a fluid using an electrical field includes a droplet arranged on or over an electrode. The droplet includes a set of beads arranged substantially in a monolayer on or over a surface of the droplet actuator.

公开(公告)号：US09511369B2

公开(公告)日：2016-12-06

申请号：US14248884

申请日：2014-04-09

Applicant: Advanced Liquid Logic, Inc.

Inventor： Vijay Srinivasan ,  Michael G. Pollack ,  Alexander Shenderov ,  Zhishan Hua ,  Arjun Sudarsan

IPC: B01L3/00

CPC classification number: B01L3/502792 ,  B01L2200/12 ,  B01L2300/0819 ,  B01L2300/089 ,  B01L2400/0415 ,  B01L2400/0421 ,  B01L2400/0427 ,  Y10T29/49826

Abstract: The invention provides a droplet actuator. The droplet actuator may include a base substrate and a top substrate separated to form a gap. The base substrate may include electrodes configured for conducting droplet operations in the gap; and the top substrate may include a glass substrate portion coupled to a non-glass portion, where the non-glass portion may include one or more openings establishing a fluid path extending from an exterior of the droplet actuator and into the gap. The invention also provides related methods of manufacturing the droplet actuator, methods of using the droplet actuator, and methods of loading the droplet actuator.

Abstract translation: 本发明提供一种液滴致动器。 液滴致动器可以包括分离以形成间隙的基底基板和顶基板。 基底基板可以包括被配置用于在间隙中进行液滴操作的电极; 并且顶部衬底可以包括联接到非玻璃部分的玻璃衬底部分，其中非玻璃部分可以包括建立从液滴致动器的外部延伸到间隙中的流体路径的一个或多个开口。 本发明还提供了制造液滴致动器的相关方法，使用液滴致动器的方法以及装载液滴致动器的方法。