Abstract: The present invention relates to droplet-based surface modification and washing. According to one embodiment, a method of providing a bead-containing droplet with a reduced concentration of a substance is provided, the method including providing a droplet microactuator including a droplet having a starting volume and including one or more beads and a starting concentration and starting quantity of the substance. The method further includes conducting one or more droplet operations to merge a wash droplet with the droplet provided in the above step to yield a combined droplet and including one or more droplet operations to divide the combined droplet to yield a set of droplets including a droplet including substantially all of the one or more beads and having a decreased concentration of the substance relative to the starting concentration and a droplet which is substantially lacking in the beads.

Abstract: The present invention relates to a droplet-based nucleic acid amplification apparatus and system. According to one embodiment, a droplet microactuator is provided made using a first substrate including a fluorescing material and including a detection region for detecting a fluorescence signal from a droplet, which detection region is coated with a light absorbing, low fluorescence or non-fluorescing material.

Abstract: A refill droplet facilitates the extraction of a droplet laterally from a channel in a microfluidic apparatus. Such extraction allows a discrete band of separated particles or solute molecules to be excised from a fluid stream and processed and analyzed separately. An extraction point is located along the length of the channel and includes an EWOD surface or similar microfluidic technology to extract a droplet. An opening in the channel opposite the extraction means is equipped with microfluidic technology to transport a refill droplet to the opening. The refill droplet is moved into the channel or column to occupy the area previously occupied by the extracted droplet. This prevents distortion or mixing of the bands of particles or molecules within the channel and prevents the draining of any portion of the fluidic system.

Abstract: The invention provides droplet actuators with droplet operations surfaces for manipulating droplets, e.g., by conducting droplet operations. The droplet operations surfaces are typically exposed to a droplet operations gap. One or more regions of a droplet operation surface may include patterned topographic features. The invention also provides a droplet actuator in which one or both gap-facing droplet operations surfaces is formed using a removable film. The removable film may, in various embodiments, also include other components ordinarily associated with the droplet actuator substrate, such as the dielectric layer and the electrodes. Further, the invention provides droplet actuator devices and methods for coupling and/or sealing substrates of a droplet actuator, such as techniques for self-aligning assembly of droplet actuator substrates.

Abstract: Alternative approaches to fabricating printed circuit boards for use in droplet actuator operations are provided. In one embodiment, a method of manufacturing a droplet actuator for conducting droplet operations includes positioning a dielectric material between a first metal layer configured to include an electrode and a second metal layer configured to include an interconnect pad. The method additionally includes forming a connection between the first and second metal layers. Droplet actuators and methods of fabricating and supporting printed circuit boards of droplet actuators are also provided.

Abstract: The present invention relates to droplet-based surface modification and washing. According to one embodiment, a method of modifying a surface on a droplet microactuator is provided, wherein the method includes executing one or more droplet operations to bring a droplet comprising a surface-modifying agent into contact with the surface. According to another embodiment, a droplet microactuator is provided and includes a sample or reagent immobilized on a surface thereof and arranged such that a droplet on the droplet microactuator may contact the surface.

Abstract: Devices, configurations and methods for improving absorbance detection are provided. For example, methods and devices are provided for determining the absorbance of a droplet, e.g., a droplet on a droplet actuator, by providing an elongated light path through the droplet.

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 provides a method for dispensing liquid, comprising the steps of: (a) positioning a droplet to be dispensed in a gap of an electrowetting device using an electrowetting array; and (b) dispensing the droplet through a hole in a housing or substrate of the electrowetting device. The invention further provides a method for withdrawing liquid comprising the steps of: (a) positioning a droplet to be withdrawn from a gap of an electrowetting device using an electrowetting array; and (b) withdrawing the droplet through a hole in a housing or substrate of the electrowetting device.

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: A microfluidic device having a substrate with an electrically conductive element made using a conductive ink layer underlying a hydrophobic layer.

Abstract: Sample processing droplet actuators, systems and methods are provided. According to one embodiment, a stamping device including a droplet microactuator is provided and includes: (a) a first plate including a path or network of control electrodes for transporting droplets on a surface thereof; (b) a second plate mounted in a substantially parallel orientation with respect to the first plate providing an interior volume between the plates, the second plate including one or more stamping ports for transporting some portion or all of a droplet from the interior volume to an exterior location; (c) a port for introducing fluid into the interior volume between the plates; and (d) a path or network of reference electrodes corresponding to the path or network of control electrodes. Associated systems and methods including the stamping device are also provided.

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: The invention provides a droplet actuator device, as well as systems, methods and devices making use of the droplet actuator device. The droplet actuator device may include a substrate having electrodes arranged for conducting one or more droplet operations. The droplet actuator device may include a substrate having a reactor path with a wash region associated with a magnet for immobilizing mobilizing beads during bead washing operations. The droplet actuator device may include nucleotide base reservoirs and dedicated nucleotide base electrode paths arranged for transporting nucleotide base droplets from nucleotide base reservoirs to the reactor path. The droplet actuator device may include one or more wash buffer reservoirs associated with electrode paths arranged for transporting wash buffer droplets from wash buffer reservoirs to the reactor path.

Abstract: The invention relates to a droplet actuator with a substrate comprising electrodes arranged for conducting droplet operations on a droplet operations surface of the substrate; a filler fluid phase in contact with the droplet operations surface at least partially surrounding a droplet phase comprising a droplet arranged on one or more of the electrodes, the droplet comprising: (i) a target substance susceptible to loss from the droplet phase into the filler fluid phase; and (ii) an additive which reduces loss of the target substance to the filler fluid phase relative to a corresponding droplet not comprising the additive. The invention also relates to various compositions and methods.

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: 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: The present invention provides modified droplet actuator systems, software, and software-executed methods for use in droplet actuator operation and droplet actuator systems that are configured and programmed to execute such software. An aspect of the software components of the invention is an interface description file for each hardware component of a microfluidics system that allows hardware components to be changed without modifying the program for performing droplet operations protocols. Another aspect of the software components of the invention is the establishment of electrode-to-electrode relationships and other aspects of droplet actuator configurations, which may be used when programming droplet operations protocols. Another aspect of the software components of the invention is a physical design library of predefined electrode elements that may be used by a droplet actuator designer when constructing a layout of electrodes.

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: 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.