Advanced Liquid Logic, Inc.

University of Michigan

Duke University

Zhishan Hua

Michael G Pollack

Vijay Srinivasan

Arjun Sudarsan

Vamsee K Pamula

Allen E Eckhardt

Alexander Shenderov

Rohit Pal

Mark A Burns

Erdogan Gulari

Onnop Srivannavit

Michael Hauser

Hon Lung Chu

Philip Y Paik

Ramakrishna Sista

Prasanna Krishnan Thwar

Dwayne J Allen

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.

Integrated droplet actuator for gel electrophoresis and molecular analysis

Methods of concentrating beads in a droplet and/or loading beads on a fluidic device are provided, including among other things, a method of concentrating beads in a droplet, the method comprising: (a) providing a droplet actuator comprising: (i) an interior droplet operations volume; and (ii) a reservoir exterior to the interior volume; (iii) a droplet established in a liquid path extending from the reservoir into the interior volume; (b) providing magnetically responsive beads in the portion of the droplet which is in the reservoir; (c) magnetically attracting the magnetically responsive beads through the liquid path into the portion of the droplet which is in the interior volume; and (d) forming a droplet comprising one or more of the magnetically responsive beads in the interior volume.

Method of concentrating beads in a droplet

A droplet actuator with a droplet formation electrode configuration associated with a droplet operations surface, wherein the electrode configuration may include one or more electrodes configured to control volume of a droplet during formation of a sub-droplet on the droplet operations surface. Methods of making and using the droplet actuator are also provided.

Droplet actuator configurations and methods of conducting droplet operations

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.

Droplet actuator with improved top substrate

A microactuator may be configured by activating a source of electromagnetic radiation to heat and melt a selected set of phase-change plugs embedded in a substrate of the microactuator, pressurizing a common pressure chamber adjacent to each of the plugs to deform the melted plugs, and deactivating the source of electromagnetic radiation to cool and solidify the melted plugs.

Reconfigurable microactuator and method of configuring same

Integrated droplet actuator for gel; electrophoresis and molecular analysis

The present invention is directed to a droplet actuator and methods of making and using the droplet actuator including one or more substrates configured to form a droplet operations gap and including a physical or chemical feature that may be provided at a predetermined locus within or exposed to the droplet operations gap and configured to retain a bubble in position within the droplet operations gap.

Bubble formation techniques using physical or chemical features to retain a gas bubble within a droplet actuator

The invention provides a droplet actuator comprising a base substrate and a top substrate separated to form a gap, wherein: (a) the base substrate comprises electrodes configured for conducting droplet operations in the gap; and (b) the top substrate comprises a first portion coupled to second portion, where the second portion comprises 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.

Droplet actuators for conducting droplet operations, such as droplet transport and droplet dispensing, are provided. In one embodiment, the droplet actuator may include a substrate including, droplet operations electrodes arranged for conducting droplet operations on a surface of the substrate; and reference electrodes associated with the droplet operations electrodes and extending above the surface of the substrate. Other embodiments of droplet actuators and methods of loading and using such droplet actuators are also provided.

Droplet actuator configurations and methods

The invention relates to certain novel approaches to reducing or eliminating the movement of contaminants from one droplet to another on a droplet actuator via liquid filler fluid. In one application, a method of detecting an analyte is provided and includes providing in a detection window a droplet including a signal-producing substance indicative of the presence and/or quantity of an analyte and one or more magnetically responsive beads which may interfere with signal produced by the signal producing substance. The method further includes using a magnetic field for magnetically removing the magnetically responsive beads from the detection window and/or magnetically restricting the magnetically responsive beads from entering the detection window while transporting and/or retaining the droplet in the detection window. The method additionally includes detecting a signal produced by the signal-producing substance.

Growing community of inventors

Durham, NC, United States of America

Zhishan Hua