Abstract: The invention relates to a microfluidic platform and methods of using the platform for conducting enzyme assays using a droplet actuator. The enzyme assays of the invention are useful for, among other things, identifying and/or characterizing disorders resulting from conditions in which enzymes are defective or are produced in inappropriate amounts. Enzyme assays of the invention may, for example, be used to detect altered activity of a particular enzyme in a sample, which may serve as an indicator of a particular disease. Altered activity may, for example, be caused by conditions which result in the increased or reduced production of a certain enzyme or its substrate and/or conditions which result in defective enzymes and/or substrates exhibiting increased or decreased effectiveness relative to corresponding normal enzymes and/or substrates.

Abstract: 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, droplet actuators are used to conduct genetic analysis using polymerase chain reaction (PCR) techniques. The invention addresses the need for improved methods of performing PCR on a droplet actuator that provide for optimum amplification and detection of a sample target.

Abstract: 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.

Abstract: A droplet actuator drive including a detection apparatus for sensing a property of a droplet on a droplet actuator; circuitry for controlling the detection apparatus electronically coupled to the detection apparatus; a droplet actuator cartridge connector arranged so that when a droplet actuator cartridge electronically is coupled thereto: the droplet actuator cartridge is aligned with the detection apparatus; and the detection apparatus can sense the property of the droplet on a droplet actuator; circuitry for controlling a droplet actuator coupled to the droplet actuator connector; and the droplet actuator circuitry may be coupled to a processor.

Abstract: Protein crystallization screening and optimization droplet actuators, systems and methods are provided. According to one embodiment, a screening droplet actuator is provided and includes: (a) a port for introduction of one or more crystallization reagents and/or one or more protein solutions; and (b) a substrate including: (i) an array of two or more mixing wells; and (ii) electric field mediated microfluidics for moving droplets comprising the crystallization reagents and protein solutions into the mixing wells. Optimization droplet actuators, systems including screening droplet actuators, methods of screening protein crystallization conditions, and methods of testing conditions for growing a crystal are also provided.

Abstract: Multiwell droplet actuators, systems and methods are provided. According to one embodiment, a substrate is provided and comprises: (a) one or more input ports for introduction of one or more reagents and/or samples; (b) a regular array of processing wells; and (c) a network of droplet transport pathways comprising pathways that provide direct or indirect droplet transport from each of the input ports to each of the one or more processing wells. Varying droplet actuators and systems related thereto are also provided.

Abstract: The invention is directed to droplet actuator devices and assay methods. The method may include, among other things, a method of conducting enzymatic assays using umbelliferone substrates with cyclodextrins in droplets in oil, the method including incubating a droplet in oil, the droplet preferably comprising an umbelliferone substrate, a sample, and a cyclodextrin compound. The methods may further include a method of substantially eliminating cross-contamination between droplets in enzymatic containing substrate-based bioassays. The method may include immobilization of the enzymatic substrate including forming an inclusion complex with the substrate for stabilizing the substrate within an aqueous environment, wherein the inclusion complex may be formed using cyclodextrins. In yet another embodiment, the invention may provide a method of enhancing hydrolysis of enzymatic substrates.

Abstract: A series of microactuators for manipulating small quantities of liquids, and methods of using these for manipulating liquids, are disclosed. The microactuators are based on the phenomenon of electrowetting and contain no moving parts. The force acting on the liquid is a potential-dependent gradient of adhesion energy between the liquid and a solid insulating surface.

Abstract: A droplet actuator with cartridge is provided. According to one embodiment, a sample analyzer is provided and includes an analyzer unit comprising electronic or optical receiving means, a cartridge comprising self-contained droplet handling capabilities, and a wherein the cartridge is coupled to the analyzer unit by a means which aligns electronic and/or optical outputs from the cartridge with electronic or optical receiving means on the analyzer unit. According to another embodiment, a sample analyzer is provided and includes a sample analyzer comprising a cartridge coupled thereto and a means of electrical interface and/or optical interface between the cartridge and the analyzer, whereby electrical signals and/or optical signals may be transmitted from the cartridge to the analyzer.

Abstract: Methods of improving microfluidic assays are disclosed. Assays can be improved (better signal to noise ratio) by using sessile drop evaporation as an analyte concentration step (enhanced signal) and repeated passes of wash droplets as a means to reduce non-specific binding (noise reduction). In addition multiple massively parallel analyses improve the statistical precision of the analyses.

Abstract: The present invention relates to droplet-based particle sorting. According to one embodiment, a droplet microactuator is provided and includes: (a) a suspension of particles; and (b) electrodes arranged for conducting droplet operations using droplets comprising particles. A method of transporting a particle is also provided, wherein the method includes providing a droplet comprising the particle and transporting the droplet on a droplet microactuator.

Abstract: The present invention relates to a droplet-based nucleic acid amplification method and apparatus.

Abstract: Systems for controlling a droplet microactuator are provided. According to one embodiment, a system is provided and includes a controller, a droplet microactuator electronically coupled to the controller, and a display device displaying a user interface electronically coupled to the controller, wherein the system is programmed and configured to permit a user to effect a droplet manipulation by interacting with the user interface. According to another embodiment, a system is provided and includes a processor, a display device electronically coupled to the processor, and software loaded and/or stored in a storage device electronically coupled to the controller, a memory device electronically coupled to the controller, and/or the controller and programmed to display an interactive map of a droplet microactuator.

Abstract: The present invention relates to a droplet microactuator system. According to one embodiment, the droplet microactuator system includes: (a) a droplet microactuator configured to conduct droplet operations; (b) a magnetic field source arranged to immobilize magnetically responsive beads in a droplet during droplet operations; (c) a sensor configured in a sensing relationship with the droplet microactuator, such that the sensor is capable of sensing a signal from and/or a property of one or more droplets on the droplet microactuator; and (d) one or more processors electronically coupled to the droplet microactuator and programmed to control electrowetting-mediated droplet operations on the droplet actuator and process electronic signals from the sensor.

Abstract: A droplet actuation system is provided including a droplet actuation device including a substrate that includes electrodes for conducting droplet operations; temperature control means for heating and/or cooling a region of the droplet actuation device and arranged such that a droplet can be transported on the electrodes to a region for heating; and a means for effecting a magnetic field in proximity to one or more of the electrodes sufficient to immobilize magnetically responsive beads in a droplet on the substrate during droplet operations. The system further includes a processor for controlling the electrodes and temperature control means, wherein the processor is programmed, and electrodes and magnetic field are arranged, to cause the electrodes to split a droplet including the magnetically responsive beads yielding a first daughter droplet which includes the magnetically responsive beads and a second daughter droplet without a substantial amount of the magnetically responsive beads.

Abstract: 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.

Abstract: Methods of using protein crystallization droplet actuators are provided. Protein sample droplets and reagent droplets are dispensed, transported, and merged to yield an array of crystallization conditions by electrowetting droplet operations in a gap comprising oil filler fluid. The oil filler fluid is doped with a surfactant that enhances droplet operations using the protein sample.

Abstract: The present invention relates to a droplet microactuator and to systems, apparatuses and methods employing the droplet microactuator for executing various protocols using droplets. The invention includes a droplet microactuator or droplet microactuator system having one or more input reservoirs loaded with reagents for conducting sequencing protocols, such as the reagents for conducting a pyrosequencing protocol. The invention also includes a droplet microactuator or droplet microactuator system, having one or more input reservoirs loaded with a sample for conducting a pyrosequencing protocol.

Abstract: The present invention is directed to droplet actuators with droplet retention structures, and methods related thereto. In an exemplary embodiment, the invention provides a droplet actuator with one or more substrates arranged to form a droplet operations gap comprising gap-facing surfaces; droplet operations electrodes configured to conduct droplet operations in the droplet operations gap; at least one barrier included on at least one of the substrate surfaces and having dimensions selected to: permit droplet transport from atop a first droplet operations electrode to a second droplet operations electrode when the second droplet operations electrode is activated; and prevent movement of a droplet from atop a first droplet operations electrode when the first and second droplet operations electrodes are inactive.