Advanced Liquid Logic, Inc.

Duke University

Leland Stanford Junior University

Baebies, Inc.

Genmark Diagnostics, Inc.

Vamsee K Pamula

Michael G Pollack

Vijay Srinivasan

Richard B Fair

Allen E Eckhardt

Ramakrishna Sista

Philip Y Paik

Arjun Sudarsan

Prasanna Krishnan Thwar

Ryan A Sturmer

Alexander Shenderov

Dwayne J Allen

Hong Ren

Zhishan Hua

Jeremy Rouse

Peter B Griffin

Gregory F Smith

Keith R Brafford

Brian P Murphy

Jon Faiz Kayyem

David W Wright

Scott Corey

Sean Ford

Dominic Aiello

Theodore M Winger

Carrie A Graham

Tih-Hong Wang

Richard M West

Jennifer Elderbroom

Jennifer Foley

Rainer Ng

Abigail Jackson

Tong Wang

Daniel Wu

Yalin Xiong

Ning Wu

Richard Gell

Stefan Burde

Sanjay Saha

Gajendrasinh Raolji

Donovan Bort

Raveendra Dayam

Lavern Pope

The subject matter relates generally to performing polymerase chain reaction (PCR) in microfluidics devices and more particularly to a microfluidics system, device, and methods for performing rapid polymerase chain reaction (PCR) protocols. In some embodiments, the presently disclosed subject matter provides a microfluidics system including a microfluidics instrument housing a microfluidics cartridge (or device) along with any supporting components. Further, the microfluidics cartridge may be, for example, any fluidics device or cartridge, microfluidics device or cartridge, DMF device or cartridge, droplet actuator, flow cell device or cartridge, and the like.

Microfluidics system, device, and methods for performing rapid polymerase chain reaction (PCR) protocols

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.

Droplet-based surface modification and washing

A method comprising effecting a change in a shape of a droplet, wherein the droplet is disposed over a substrate in sensing proximity to a sensor and the droplet has a starting surface area exposed to the sensor; and producing an expanded surface area of the droplet in the sensing proximity exposed to the sensor, wherein the expanded surface area exposed to the sensor is greater than the starting surface area exposed to the sensor.

Droplet actuator devices and methods employing magnetic beads

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.

Manipulation of beads in droplets and methods for manipulating droplets

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.

Bead incubation and washing on a droplet actuator

A point-of-birth system and instrument, biochemical cartridge, and methods for newborn screening is disclosed. Namely, a point-of-birth system is provided that includes a point-of-birth instrument for receiving and processing a biochemical cartridge for performing newborn screening. Further, a portable smart device, such as a smartphone or tablet, is in communication with point-of-birth instrument, wherein the smart device may include a newborn screening (NBS) mobile app. In one example, the point-of-birth system and point-of-birth instrument support newborn biological screening only. However, in another example, the point-of-birth system and point-of-birth instrument support both newborn biological screening and newborn physiological screening.

Point-of-birth system and instrument, biochemical cartridge, and methods for newborn screening

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.

A method, circuit and apparatus for detecting capacitance on a droplet actuator, inter alia, for determining the presence, partial presence or absence of a droplet at an electrode on a droplet actuator by: (a) providing a droplet actuator comprising: (i) a substrate comprising electrodes arranged on the substrate for conducting droplet operations on a surface of the substrate; (ii) a capacitance detection circuit for detecting capacitance at the droplet operations surface at one or more of the electrodes; (b) detecting capacitance at the droplet operations surface at one or more of the electrodes; and (c) determining from the capacitance the presence, partial presence or absence of a droplet at the droplet operations surface at the electrode.

Capacitance detection in a droplet actuator

The invention provides a method of circulating magnetically responsive beads within a droplet in a droplet actuator. The invention also provides methods for splitting droplets. The invention, in one embodiment, makes use of a droplet actuator with top and bottom substrates, a plurality of magnetic fields respectively present proximate the top and bottom substrates, wherein at least one of the magnet fields is selectively alterable, and a plurality of droplet operations electrodes positioned along at least one of the top and bottom surfaces. A droplet is positioned between the top and bottom surfaces and at least one of the magnetic fields is selectively altered.

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.

Methods are provided for manipulating droplets. The methods include providing the droplet on a surface comprising an array of electrodes and a substantially co-planer array of reference elements, wherein the droplet is disposed on a first one of the electrodes, and the droplet at least partially overlaps a second one of the electrodes and an intervening one of the reference elements disposed between the first and second electrodes. The methods further include activating the first and second electrodes to spread at least a portion of the droplet across the second electrode and deactivating the first electrode to move the droplet from the first electrode to the second electrode.

Droplet manipulation device

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.

Instrument and cartridge for performing assays in a closed sample preparation and reaction system employing electrowetting fluid manipulation

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Cary, NC, United States of America

Vamsee K Pamula