Abstract: The present invention relates to droplet-based pyrosequencing including a method of identifying a base at a target position in a sample nucleic acid. The method includes: (a) providing a droplet microactuator including a first droplet including a sample nucleic acid immobilized on a bead; and (b) on the droplet microactuator: (i) contacting the first droplet with one or more reagent droplets to yield a second droplet, wherein the one or more reagent droplets include reagents for extending a double stranded portion of the sample nucleic acid by incorporating a nucleotide at the target position; (ii) splitting the second droplet to yield a third droplet including the bead and a fourth droplet lacking the bead; and (iii) assaying the third droplet to determine whether the nucleotide was incorporated at the target position.

Abstract: Methods and apparatus for direct detection of chemical reactions are provided. Electric charge perturbations of the local environment during enzyme-catalyzed reactions are sensed by an electrode system with an immobilized target molecule. The charge perturbation caused by the polymerase reaction can uniquely identify a DNA sequence. The polymerization process generates local perturbations of charge in the solution near the electrode surface and induces a charge in a polarazible gold electrode. This event is detected as a transient current by a voltage clamp amplifier. Detection of single nucleotides in a sequence can be determined by dispensing individual dNTPs to the electrode solution and detecting the charge perturbations. Alternatively, multiple bases can be determined at the same time using a mix of all dNTPs with subsequent analysis of the resulting signal.

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The invention further provides a method for withdrawing liquid comprising the steps of: (a) positioning a droplet to be withdrawn from a gap of an electrowetting device using an electrowetting array; and (b) withdrawing the droplet through a hole in a housing or substrate of the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 present technology relates generally to microfluidic devices for measuring platelet coagulation, and associated systems and methods. In some embodiments, a fluidics device includes an array of microstructures including pairs of generally rigid blocks and generally flexible posts. The fluidics device further includes at least one fluid channel configured to accept the array. The fluid channel is configured to induce fluid flow of a biological sample, such as whole blood, through the array. The fluidics device can further include a detection component configured to measure a degree of deflection of one or more of the flexible posts in the array. In some embodiments, the fluidics device comprises a handheld device and usable for point of care testing of platelet forces and coagulation.

Abstract: A microfluidic device comprising a plurality of reaction chambers in fluid communication with a flow channel formed in an elastomeric substrate, a vapor barrier for preventing evaporation from the plurality of reaction chambers, and a continuous phase fluid for isolation of each of the plurality of reaction chambers.

Abstract: A detection apparatus that includes (a) an array of responsive pads on a substrate surface; (b) an array of pixels, wherein each pixel in the array has a detection zone on the surface that includes a subset of at least two of the pads; and (c) an activation circuit to apply a force at a first and second pad in the subset, wherein the activation circuit is configured to apply a different force at the first pad compared to the second pad, and wherein the activation circuit has a switch to selectively alter the force at the first pad and the second pad.

Abstract: DNA-based temperature sensor for measuring temperature through a transition of one or more strands of DNA from a coupled configuration to a decoupled configuration at a temperature threshold, and a fluorescent dye adapted to emit fluorescence when the DNA is in the coupled configuration, includes a receptacle adapted to receive the DNA and the fluorescent dye in a solution, an imaging device adapted to acquire an image of fluorescence emitted from the solution, the image having a plurality of regions, and a processor adapted to determine a plurality of fluorescence levels corresponding to each of the plurality of regions of the image and to generate a temperature map based on the determined fluorescence levels. A method for measuring temperature and a DNA-based temperature sensing solution are also provided.

Abstract: Embodiments of the present invention are directed toward microfluidic systems, apparatus, and methods for measuring a quantity of cells in a fluid. Examples include a differential white blood cell measurement using a centrifugal microfluidic system. A method may include introducing a fluid sample containing a quantity of cells into a microfluidic channel defined in part by a substrate. The quantity of cells may be transported toward a detection region defined in part by the substrate, wherein the detection region contains a density media, and wherein the density media has a density lower than a density of the cells and higher than a density of the fluid sample. The substrate may be spun such that at least a portion of the quantity of cells are transported through the density media. Signals may be detected from label moieties affixed to the cells.

Abstract: Embodiments of the present invention relate to methods and apparatuses for the discretization and manipulation of sample volumes that is simple, robust, and versatile. It is a fluidic device that partitions a sample by exploiting the interplay between fluidic forces, interfacial tension, channel geometry, and the final stability of the formed droplet and/or discretized volume. These compartmentalized volumes allow for isolation of samples and partitioning into a localized array that can subsequently be manipulated and analyzed.

Abstract: A method for measuring a property of a binding interaction between a capture agent and a binding partner for the capture agent is provided. In certain embodiments, this method comprises: a) contacting a population of particles that are linked to a capture agent with a substrate comprising a binding partner to produce capture agent/binding partner complexes, wherein the population of particles comprises first particles that are bound to a single molecule of the capture agent and second particles that are bound to two molecules of the capture agent; b) applying a force to the bound support, wherein the force is in a direction that separates the particles from the support; and c) separately measuring the forces required to disassociate the first particles and the second particles from their respective complexes.

Abstract: Disclosed is a method for lowering the detection limit in a method of detecting a nucleic acid comprising (i) contacting a solution comprising a first PNA with a substrate having a second PNA affixed thereto, the second PNA comprising at least one trans-cyclopentane residue, wherein the first PNA has two linker-attached biotins attached thereto and the first and second PNAs being complementary to different portions of a target DNA; (ii) contacting a sample suspected of containing the nucleic acid with the first and second PNAs; and (iii) determining the presence of the reporter molecule on the substrate. Also disclosed are a detection assay and a kit for detecting a target nucleic acid.

Abstract: Rapid and uniform temperature changes in the wells of a microplate or any thin-walled plate that contains an array of reaction wells or sample receptacles are achieved by the use of heating and cooling elements with a vapor chamber interposed between such elements and the microplate. The upper surface of the vapor chamber and the underside of the sample plate in certain embodiments are complementary in shape, i.e., they have identical but oppositely directed contours in the areas around each of the sample receptacles, to provide continuous surface contact along the surface of each receptacle. In other embodiments, an intermediary plate is placed between the vapor chamber and the well plate, with the top surface of the intermediary plate being complementary in shape to the underside of the well plate.

Abstract: A multi-spot metal-capped nanostructure array nucleic acid chip for diagnosing corneal dystrophy, and more particularly to a multi-spot metal-capped nanostructure array nucleic acid chip capable of employing LSPR (localized surface plasmon resonance) optical properties, a preparation method thereof, and a multi-spot metal-capped nanostructure array nucleic acid chip for diagnosing BIGH3 gene mutations, which can diagnose various corneal dystrophies. The metal-capped nanostructure array nucleic acid chip can be combined with analysis devices, including a light source, a detector, a spectrophotometer and a computer, to provide an LSPR optical property-based optical biosensor, and the use of the multi-spot metal-capped nanostructure array nucleic acid chip for diagnosing BIGH3 gene mutations allows the simultaneous diagnosis of various corneal dystrophies that are genetic ocular diseases.

Abstract: The present invention provides a broad response single-stranded DNA-graphene chemical sensor device. The present invention also provides methods for improving the ability of graphene to work as a chemical sensor by using single-stranded DNA as a sensitizing agent.

Abstract: The present technology relates generally to devices to expose cells to fluid shear forces and associated systems and methods. In particular, several embodiments are directed toward devices to expose cells to fluid shear forces in order to measure changes in internal cell forces. In some embodiments, a fluidic device includes a flow unit configured to induce fluid flow through the device. The device further includes a fluid channel configured to accept a biological sample dispersed on an array of flexible structures. The flow unit can be configured to induce disturbed and/or laminar flow in the fluid channel. The device can further include optical or magnetic detection means configured to measure a degree of deflection of one or more flexible structures in the array.

Abstract: A personal diagnostic patch device for biological analysis includes a sample acquisition layer for obtaining a fluid sample, a fluidic processing layer including a fluidic circuit for directing fluid flow, an assay results detection layer having a detector for detecting diagnostic results derived from fluid sample analysis, and a processor and transmitter for sending diagnostic results to a remote location. The layers are situated in register with each other and operatively attached with constituent elements in alignment to form the fluidic circuit for sample processing, detection, and analysis. Related systems include a remotely located user computer for receiving a signal from the patch device when the device is provided with the transmitter. The user computer may be connected to a network including any one or more of several different medical providers. Methods include use of the patch device for specific applications, related processes, and steps for manufacturing and assembling.

Abstract: Dual mode genetics testing systems are devised about a single element testing platform. A microfluidic network and system of interconnected receiving cells and reaction vessels supports at the same time genotyping and copy number analysis where the platform may be subject to a common thermal cycle schedule to cause the proper reactions (DNA replication) necessary in both test types. Further, the microfluidic platform which includes reaction vessels for genotyping which are spatially removed from reaction vessels for copy number analysis, is coupled to optical scanner and detection systems specifically arranged to apply test specific detection routines on each of these distinct regions or portions of the dual mode test platform.

Abstract: The invention provides systems, devices, methods, and kits for performing an integrated analysis. The integrated analysis can include sample processing, library construction, amplification, and sequencing. The integrated analysis can be performed within one or more modules that are fluidically connected to each other. The one or more modules can be controlled and/or automated by a computer. The integrated analysis can be performed on a tissue sample, a clinical sample, or an environmental sample. The integrated analysis system can have a compact format and return results within a designated period of time.

Abstract: Systems and methods are provided for capturing and/or isolating target microparticles. In one aspect, a method for capturing target microparticles is disclosed. The method includes: forming a fluid including the target microparticles, non-target microparticles, and magnetic beads, the magnetic beads having a stronger affinity with the target microparticles than with the non-target microparticles; flowing the fluid through a multidirectional microchannel; and applying a magnetic field to the fluid while the fluid is flowing through at least a portion of the microchannel to effect capture of at least a portion of the target microparticles onto the magnetic beads. Such a method can further includes passing the fluid having exited from the microchannel through a separator while subjecting the fluid to a second magnetic field so as to isolate the target microparticles. In addition, devices and systems are disclosed for capturing and/or isolating target microparticles based on magnetic manipulation.

Abstract: The present invention is generally related to systems and methods for producing droplets. The droplets may contain varying species, e.g., for use as a library. In some cases, at least one droplet is used to create a plurality of droplets, using techniques such as flow-focusing techniques. In one set of embodiments, a plurality of droplets, containing varying species, can be divided to form a collection of droplets containing the various species therein. A collection of droplets, according to certain embodiments, may contain various subpopulations of droplets that all contain the same species therein. Such a collection of droplets may be used as a library in some cases, or may be used for other purposes.