Abstract: Provided according to embodiments of the invention are nanostructured surfaces that include a substrate; and an array of metallic nanopillar islands on the substrate, wherein each metallic nanopillar island includes a metal base layer on the substrate and a plurality of metallic nanopillars on the metal base layer, and wherein portions of the substrate between adjacent metallic nanopillar islands are free of the metal base layer. Also provided according to some embodiments of the invention are nanostructured surfaces that include a non-conductive substrate; and at least one nanoelectrode defined within the non-conductive substrate, wherein the at least one nanoelectrode is sized and/or shaped to immobilize an analyte or a probe molecule. Also provided are apparatuses and methods for SERS and detection of analytes or biological binding by EDL capacitance.

Abstract: Methods and systems for processing polynucleotides (e.g., DNA) are disclosed. A processing region includes one or more surfaces (e.g., particle surfaces) modified with ligands that retain polynucleotides under a first set of conditions (e.g., temperature and pH) and release the polynucleotides under a second set of conditions (e.g., higher temperature and/or more basic pH). The processing region can be used to, for example, concentrate polynucleotides of a sample and/or separate inhibitors of amplification reactions from the polynucleotides. Microfluidic devices with a processing region are disclosed.

Abstract: A method and system are presented for fast and efficient isolation, purification and quantitation of nucleic acids from complex biological samples using isotachophoresis in microchannels. In an embodiment, a sieving medium may be used to enhance selectivity. In another embodiment, PCR-friendly chemistries are used to purify nucleic acids from complex biological samples and yield nucleic acids ready for further analysis including for PCR. In another embodiment, small RNAs from biological samples are extracted, isolated, preconcentrated and quantitated using on-chip ITP with a high efficiency sieving medium. The invention enables fast concentration and separation (takes 10s to 100s of seconds) of nucleic acids with high selectivity and using lower volumes of reagents (order of 10s of ?L to focus less than 1 pg/?L of nucleic acid).

Abstract: The invention generally relates to methods for sample multiplexing. In certain embodiments, methods of the invention obtaining a plurality of different reactant molecules, attaching a unique identifier to the reactant molecules, and forming a droplet including the reactant molecules.

Abstract: The present invention relates to a device for processing an analyte and to a method of processing and/or detecting an analyte using said device.

Abstract: A receptacle having a plurality of interconnected chambers arranged to permit multiple process steps or processes to be performed independently or simultaneously. The receptacles are manufactured to separate liquid from dried reagents and to maintain the stability of the dried reagents. An immiscible liquid, such as an oil, is included to control loading of process materials, facilitate mixing and reconstitution of dried reagents, limit evaporation, control heating of reaction materials, concentrate solid support materials to prevent clogging of fluid connections, provide minimum volumes for fluid transfers, and to prevent process materials from sticking to chamber surfaces. The receptacles can be adapted for use in systems having a processing instrument that includes an actuator system for selectively moving fluid substances between chambers and a detector. The actuator system can be arranged to concentrate an analyte present in a sample.

Abstract: A liquid-feeding chip for feeding a liquid utilizing the action of centrifugal force and gravity by rotating the chip around an axis of rotation, includes a first storage tank (1-1) into which the liquid can be introduced when rotation of the chip is stopped, and two or more liquid-feeding units arranged in a plurality of levels adjacent to each other, each liquid-feeding unit (U-1, U-2, U-3) being composed of a first holding tank (10-1, 20-1, 30-1), a second holding tank (10-2, 20-2, 30-2) positioned in the direction of gravity with respect to the first holding tank, and a channel B (B-1, B-2, B-3) which extends from the first holding tank in the direction of gravity and which connects the first holding tank and the second holding tank, the first holding tank at a first level being connected with a channel A (A-1) which extends from the first storage tank toward an outer circumferential side.

Abstract: A device for amplifying target nucleic acid in a sample can include a planar fluidic assembly including a transparent substrate, a porous material layer on a surface of the transparent substrate, and a cover over the porous material layer and sealingly affixed to the substrate. The cover may be spaced from the porous material layer and a flow channel defined between the porous material layer and the cover. The flow channel may have a uniform cross-section from a first end to a second end.

Abstract: A method and system for using spatially modulated excitation/emission and relative movement between a particle (cell, molecule, aerosol, . . . ) and an excitation/emission pattern are provided. In at least one form, an interference pattern of the excitation light with submicron periodicity perpendicular to the particle flow is used. As the particle moves along the pattern, emission is modulated according to the speed of the particle and the periodicity of the stripe pattern. A single detector, which records the emission over a couple of stripes, can be used. The signal is recorded with a fast detector read-out in order to capture the “blinking” of the particles while they are moving through the excitation pattern. This concept enables light detection with high signal-to-noise ratio and high spatial resolution without the need of expensive and bulky optics.

Abstract: A system and method for processing biological sensors. The system includes a support component configured to support a fluidic component. The fluidic component includes at least a first container and a second container. The first container is capable of holding a first volume of a first fluid, and the second container is capable of holding a second volume of a second fluid. Additionally, the system includes a hybridization component configured to perform a hybridization process on a first sensor and a second sensor. Moreover, the system includes a transport component configured to move the first sensor, directly or indirectly, from the hybridization component into the first container and in contact with the first volume of the first fluid.

Abstract: Disclosed are methods and compositions for detection and amplification of nucleic acids, wherein two DNA strands hybridized to an RNA strand are ligated. In one aspect, the disclosed methods include removal of an energy source, such as ATP, upon charging a ligase to form an enzyme-AMP intermediate, and then adding substrate, which results in one complete round of RNA-templated DNA ligation. In another aspect, the ligation reaction is accomplished by use of a mixture of at least two different ligase enzymes. The disclosed methods and compositions for RNA-templated DNA ligation may be particularly useful for detection of RNA sequence variants, for example RNA splice variants, and for quantitative expression analysis.

Abstract: The present invention describes microfluidic devices that provide novel fluidic structures to facilitate the separation of fluids into isolated, pico-liter sized compartments for performing multiplexing chemical and biological reactions. Applications of the novel devices including biomolecule synthesis, polynucleotide amplification, and binding assays are also disclosed.

Abstract: Methods 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. This technique may be adapted to other reaction determinations, such as enzymatic reactions, other electrode configurations, and other amplifying circuits.

Abstract: Embodiments of the present techniques provide systems and methods for isolating particular classes of biological molecules, for example, proteins or nucleic acids, from mixtures of biological components. The methods use solutions that react with the biological molecules to enhance their adsorption by substrates, allowing contaminants to be washed away from the targeted molecules. Embodiments include automated systems that can be used to implement the technique with no or minimal intervention. Other embodiments include separation column technologies that may be used in the techniques.

Abstract: Methods of trapping a deformed portion of a double-stranded polynucleotide in a membrane nanopassage are provided. In an aspect, the membrane has a nanopassage that defines a confine region, wherein the membrane separates a first fluid compartment from a second fluid compartment, and the nanopassage is in fluid communication with the first and second compartments. A polynucleotide is provided to the first fluid compartment and optionally a threshold voltage for the membrane and the polynucleotide is determined. A driving voltage across the membrane that is greater than the threshold voltage is applied to force a portion of the polynucleotide sequence into the nanopassage confine region, and decreased to a holding voltage bias to trap the polynucleotide portion in the nanopassage confine region. In particular, at least one nucleotide base-pair is fixably positioned in the nanopassage confine volume. In further embodiments, any of the trapping methods are used to characterize or sequence double stranded DNA.

Abstract: A receptacle having a plurality of interconnected chambers arranged to permit multiple process steps or processes to be performed independently or simultaneously. The receptacles are manufactured to separate liquid from dried reagents and to maintain the stability of the dried reagents. An immiscible liquid, such as an oil, is included to control loading of process materials, facilitate mixing and reconstitution of dried reagents, limit evaporation, control heating of reaction materials, concentrate solid support materials to prevent clogging of fluid connections, provide minimum volumes for fluid transfers, and to prevent process materials from sticking to chamber surfaces. The receptacles can be adapted for use in systems having a processing instrument that includes an actuator system for selectively moving fluid substances between chambers and a detector. The actuator system can be arranged to concentrate an analyte present in a sample.

Abstract: A new device capable of measuring the number of particles present in a colloidal suspension is disclosed, which includes a forward scatter detector, an extinction detector, a laser beam, a cylindrical lens with which to create a plane of light through which particles can pass, and the various pumps and tubing needed to pass the colloidal suspension through the plane of light. The device is particularly designed for measuring particles which have different refractive indices, and which are in the size range of between about 0.7 to 2 microns. The device can determine the presence or absence of biological particles of interest in a given sample, by incubating a sample with a given ratio of active particles and marker particles, and determining whether the ratio of active particles and marker particles has changed. Additional binding and/or non-binding particles can also be present, and kits including the particles are also disclosed.

Abstract: An apparatus and system are provided for simultaneously analyzing a plurality of analytes anchored to microparticles. Microparticles each having a uniform population of a single kind of analyte attached are disposed as a substantially immobilized planar array inside of a flow chamber where steps of an analytical process are carried out by delivering a sequence of processing reagents to the microparticles by a fluidic system under microprocessor control. In response to such process steps, an optical signal is generated at the surface of each microparticle which is characteristic of the interaction between the analyte carried by the microparticle and the delivered processing reagent. The plurality of analytes are simultaneously analyzed by collecting and recording images of the optical signals generated by all the microparticles in the planar array.

Abstract: The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences using adaptors interspersed in target polynucleotides. The sequence information can be new, e.g. sequencing unknown nucleic acids, re-sequencing, or genotyping. The invention preferably includes methods for inserting a plurality of adaptors at spaced locations within a target polynucleotide or a fragment of a polynucleotide. Such adaptors may serve as platforms for interrogating adjacent sequences using various sequencing chemistries, such as those that identify nucleotides by primer extension, probe ligation, and the like. Encompassed in the invention are methods and compositions for the insertion of known adaptor sequences into target sequences, such that there is an interruption of contiguous target sequence with the adaptors. By sequencing both “upstream” and “downstream” of the adaptors, identification of entire target sequences may be accomplished.

Abstract: The present technology provides for a microfluidic substrate configured to carry out PCR on a number of polynucleotide-containing samples in parallel. The substrate can be a single-layer substrate in a microfluidic cartridge. Also provided are a method of making a microfluidic cartridge comprising such a substrate. Still further disclosed are a microfluidic valve suitable for use in isolating a PCR chamber in a microfluidic substrate, and a method of making such a valve.