Abstract: Methods and apparatus relate to reduction of sequence errors generated during synthesis of nucleic acids on a microarray chip. The error reduction can include synthesis of complementary stands (to template strands), using a short universal primer complementary to the template strands and polymerase. Heteroduplex can be formed be melting and re-annealing complementary stands and template strands. The heteroduplexes containing a mismatch can be recognized and cleaved by a mismatch endonuclease. The mismatch-containing cleaved heteroduplexes can be removed from the microarray chip using a global buffer exchange. The error free synthetic nucleic acids generated therefrom can be used for a variety of applications, including synthesis of biofuels and value-added pharmaceutical products.

Abstract: Embodiments provided herein relate to methods and compositions for preparing nucleic acid libraries. Some embodiments include preparing libraries from nucleic acids obtained from degraded samples, such as ancient samples and fixed samples.

Abstract: The inventors experimentally demonstrated NO2 gas sensing performance of multilayer black phosphorous (BP) field effect transistors. The BP sensors were sensitive to NO2 concentration down to 5 ppb making them comparable in sensitivity to the best 2D material based sensors. Raman spectroscopy comparison revealed no apparent change in the spectra before and after exposure to NO2, which shows that thick BP flakes can maintain their relative stability after sensing. Moreover, the BP device sensing performance fitted well with the Langmuir Isotherm for molecules adsorbed on a surface, which confirms charge transfer as the dominant mechanism for sensing. The systematic increase in conductance with increasing NO2 concentrations suggests NO2 molecules withdraw electrons and dope BP flakes with holes. These results lay the ground work for BP to be applied to various sensing applications including chemical, gas, and bio-sensors.

Abstract: Provided herein are methods, systems, kits and compositions for identifying nucleic acids of interest from individual cells. The methods include isolating single cells on electrodes and identifying nucleic acids of interest from the isolated cells by sequencing.

Abstract: A method of determining one or more interaction parameters for the interaction between an analyte and a ligand using a biosensor, which comprises the steps of: A: providing a sensor surface having the ligand immobilized thereto, B: contacting the sensor surface with a control analyte, C: registering the sensor response from binding of the control analyte to binding sites of the ligand, D: determining the control saturation response (RmaxC) for the interaction between the control analyte and the ligand, E: transforming the control saturation response (RmaxC) to an analyte saturation response (RmaxA) using the relative molar response contribution of the analyte and the control analyte.

Abstract: The present invention provides breeding methods and compositions to enhance the germplasm of a plant by the use of direct nucleic acid sequence information. The methods describe the identification and accumulation of preferred nucleic acid sequences in the germplasm of a breeding population of plants.

Abstract: The present invention generally pertains to methods for detecting the presence or absence of a particular nucleic acid sequence. The present invention generally relates to incorporating a detector into a target nucleic acid, adding an oligonucleotide probe, polymerase enzyme and an inhibitor to the reaction, and detecting interference of the oligonucleotide probe with the inhibitor as an indication of the presence of a particular target nucleic acid sequence as well as kits encompassing the same.

Abstract: A SERS unit 1A comprises a SERS element 2 having a substrate and an optical function part 20 formed on the substrate, the optical function part 20 for generating surface-enhanced Raman scattering; a measurement board 3 supporting the SERS element 2 upon measurement; and a holding part 4 mechanically holding the SERS element 2 in the measurement board 3.

Abstract: A method of evaluating an interaction parameter for the interaction between a plurality of analytes and a ligand using a biosensor, which comprises the steps of: A: providing a sensor surface having the ligand immobilized thereto, B: contacting the sensor surface with the plurality of analytes, C: registering a sensor response curve for each one of the plurality of analytes, D: extracting interaction parameters from each sensor response curve, E: evaluating each sensor response curve according to one or more binding behavior criteria, F: displaying the interaction parameters in a diagram, wherein interaction parameters relating to response curves meeting a binding behavior criteria are graphically distinguishable from interaction parameters relating to response curves meeting another or no binding behavior criteria.

Abstract: A microdeposition pin having a contact surface with at least one concave edge for creating microarrays and the like. The microdeposition pin may be used either alone or with a plurality of microdeposition pins in conjunction with a holder. The concave edge of the pin is especially adapted for helping to control the spreading of a deposited material. By selectively controlling the spread of the reagent composition from the microdeposition pin, the flow of the reagent composition from the deposition target area may be reduced. Sensor strips having raised substrate features with limited or no spreading of the reagent composition beyond the target area are disclosed.

Abstract: A SERS unit 1A comprises a SERS element 2 having a substrate and an optical function part 20 formed on the substrate, the optical function part 20 for generating surface-enhanced Raman scattering; a measurement board 3 supporting the SERS element 2 upon measurement; and a holding part 4 mechanically holding the SERS element 2 in the measurement board 3.

Abstract: A method (200) for determining a concentration of an analyte in a fluid or fluid sample, comprises: providing (201) a SERS substrate comprising receptor molecules (107) capable of binding competitor molecules (106); contacting (202) the SERS substrate (102) with a fluid (sample) comprising analyte (108) and such competitor molecules (106); radiating (203) the SERS substrate (102) with a light source while measuring a SERS signal; and determining (205) a concentration of the analyte (108) based on the measured signal level. A corresponding device and system are also provided.

Abstract: A composite material for electromagnetic interference shielding is provided. The composite material comprises a polymer matrix with metal nanoparticles dispersed within the matrix. Methods of characterizing the nanocomposites are provided and demonstrate commercially relevant mechanical and electrical properties, particularly an electromagnetic interference shielding effectiveness in the microwave frequency. An economical process for preparing the nanocomposites is also provided.

Abstract: In some aspects, an electrically responsive device can include a composite structure having spatially modulated structural properties that includes a substrate material having a surface and defining a plane; an electrically responsive material layer formed over at least a portion of the surface of the substrate material; an electrode material over portions of the electrically responsive material; and a stiffening material disposed along the electrode material, where the stiffening material has a thickness that varies and has regions of increased thickness that correspond with the regions of the composite structure along which the electrode material is disposed. The spatially modulated structural properties can include the regions of the composite structure along which the electrode material is disposed having the increased material stiffness, exclusive of the electrode material, relative to regions of the composite structure that do not include the electrode material.

Abstract: This disclosure provides, among other things, a method for analyzing a planar cellular sample. In some embodiments, the method comprises: (a) indirectly or directly attaching nucleic acid tags to binding sites in a planar cellular sample; (b) contacting the planar cellular sample with a solid support comprising an array of spatially addressed features that comprise oligonucleotides, wherein each oligonucleotide comprises a molecular barcode that identifies the feature in which the oligonucleotides is present; (c) hybridizing the nucleic acid tags, or a copy of the same, with the oligonucleotides to produce duplexes; and (d) extending the oligonucleotides in the duplexes to produce extension products that each comprises (i) a molecular barcode and (ii) a copy of a nucleic acid tag. Other embodiments, e.g., kits and the like, are also described.

Abstract: The present invention provides methods for replication of nucleic acid molecules distributed on a surface or within a layer by transferring them to a target surface covered with oligonucleotides, and fixation of transferred molecules by hybridization to complementary sequences.

Abstract: A plurality of isolated microvessels including a plurality of encoded microvessels each having a microbody and a reservoir core. The microbody is configured to separate a biological or chemical substance in the reservoir core from an ambient environment surrounding the microbody. The microbody includes a transparent material that at least partially surrounds the reservoir core and facilitates detection of an optical characteristic of the substance within the reservoir core. The microbody of each microvessel includes an identifiable code that distinguishes individual microvessels of the plurality of encoded microvessels from each other. The plurality of isolated microvessels also includes a plurality of compartments each configured to separate individual microvessels of the plurality of encoded microvessels from each other.

Abstract: Disclosed herein are methods for detecting, diagnosing and/or prognosing a malignant adrenocortical tumor. Also disclosed are methods of treating a malignant adrenocortical tumor, such as ACC. In some examples, the method of diagnosing and/or prognosing includes obtaining a sample comprising genomic DNA from a subject at risk of acquiring or suspected to have an adrenocortical tumor; isolating genomic DNA from the sample; and measuring the level of one or more methylated genomic CpG dinucleotide sequences in one or more of the adrenocortical genomic targets in the sample, wherein an increase in the level of methylation of the one or more genomic CpG dinucleotide sequences in the sample compared to a control indicates a malignant adrenocortical tumor.

Abstract: The methods of the present invention provide methods for manufacturing a master substrate and methods for manufacturing replica arrays from the master substrate. The methods may be used, for example, directly to manufacture or “print” peptide arrays from a DNA array; however, the methods are applicable to a wide range of manufacturing applications for use any time multiple copies of an array needs to be printed.

Abstract: The present invention discloses a method of detecting T-cell proliferation in a subject comprising the steps of (a) obtaining a sample from said subject; and (b) profiling at least one parameter selected from the group consisting of: the activation level of GSK-3?, the expression level of GSK-3? and the activation or expression level of related members of pathways in which GSK-3? plays a part. It is a core aspect of the invention, wherein a significant deviation from normal values indicates cellular proliferation. The present invention further discloses kits for detecting T-cell proliferation.

Abstract: The present invention relates to systems and methods for minimizing or eliminating diffusion effects. Diffused regions of a segmented flow of multiple, miscible fluid species may be vented off to a waste channel, and non-diffused regions of fluid may be preferentially pulled off the channel that contains the segmented flow. Multiple fluid samples that are not contaminated via diffusion may be collected for analysis and measurement in a single channel. The systems and methods for minimizing or eliminating diffusion effects may be used to minimize or eliminate diffusion effects in a microfluidic system for monitoring the amplification of DNA molecules and the dissociation behavior of the DNA molecules.

Abstract: Disclosed herein are methods and compositions for purifying proteins from crude solutions.

Abstract: Disclosed is a method that includes: (i) providing a plurality of initial nucleic acid cassettes that include: a) a first coding region encoding a first immunoglobulin variable domain, b) a second coding region encoding a second immunoglobulin variable domain, and c) a ribosomal binding site disposed between the first and second coding regions for translation of the second polypeptide in a first expression system, wherein the first and second coding regions are in the same translational orientation; (ii) modifying each nucleic acid cassette of the plurality in a single reaction mixture so that it is functional in a second expression system, wherein the first and second region remain physically attached during the modifying; (iii) introducing each modified nucleic acid cassette into a mammalian cell to produce a mixture of transfected cells; and (iv) expressing each modified nucleic acid cassette in the transfected cells.

Abstract: The methods of the present invention provide methods for manufacturing a master substrate and methods for manufacturing replica arrays from the master substrate. The methods may be used, for example, directly to manufacture or “print” peptide arrays from a DNA array; however, the methods are applicable to a wide range of manufacturing applications for use any time multiple copies of an array needs to be printed.

Abstract: In a genome sequencing system and methodology, a protocol is provided to achieve precise alignment and accurate registration of an image of a planar array of nanoballs subject to optical analysis. Precise alignment correcting for fractional offsets is achieved by correcting for errors in subperiod x-y offset, scale and rotation by use of minimization techniques and Moiré averaging. In Moiré averaging, magnification is intentionally set so that the pixel period of the imaging element is a noninteger multiple of the site period. Accurate registration is achieved by providing for pre-defined pseudo-random sets of sites, herein deletion or reserved sites, where nanoballs are prevented from attachment to the substrate so that the sites of the array can be used in a pattern matching scheme as registration markers for absolute location identification.

Abstract: Plant genes regulated by transcription factors that control the gene network response to an environmental perturbation or signal are described. This class of genes responds to the perturbation of a transcription factor and the signal it transduces, but surprisingly, without stable binding of the transcription factor. These genes represent members of the “dark matter” of metabolic regulatory circuits. The invention involves the transgenic manipulation of these “response genes” and/or the genes encoding their regulatory transcription factors in plants so that their respective gene products are either overexpressed or underexpressed in the plant in order to confer a desired phenotype. The invention also relates to a rapid technique named “TARGET” (Transient Assay Reporting Genome-wide Effects of Transcription factors) for determining such “response genes” and their transcription factors by perturbation of the expression of the transcription factors of interest in protoplasts of any plant species.

Abstract: The invention relates to methods and devices for analyzing single molecules, i.e., nucleic acids. Such single molecules may be derived from natural samples, such as cells, tissues, soil, air and water without separating or enriching individual components. In certain aspects of the invention, the methods and devices are useful in performing nucleic acid sequence analysis by probe hybridization.

Abstract: Methods, systems, devices and apparatus for use in screening and/or selecting a library of nucleic acid molecules and/or nucleic acid tagged or encoded molecules for binding to or interaction with a target molecule or substance (e.g., for use in new compound or drug discovery) are described. In some embodiments the device comprises: (a) a spatially addressable array, said array comprising a plurality of separate and discrete locations thereon; (b) a plurality of different oligomers operably connected to said spatially addressable array at different ones of said separate and discrete locations; (c) a tag sequence which is complementary to, and is hybridized to, each of said oligomers; and (d) a candidate chemical operably connected to each of said tag sequences, wherein each of said discrete locations is a unique identifier for its corresponding oligomer; and wherein said tag sequence is a unique identifier for its connected candidate chemical.

Abstract: A method, system and device to identify, study and/or mimic carbohydrate-protein interactions on cell surfaces and in solution measured by a glycan microarray. In some instances the method, system and device uses very small quantities of carbohydrate as low as attomol. In some instances the system, method and device is high-throughput. The small quantity sensitivity may allow for close placement of carbohydrate array members wherein due to close proximity multivalent interactions with proteins may be identified.

Abstract: Methods for non-random loading of single analyte molecules into array structures are provided. The methods allow for distribution of a population of target molecules into a plurality of size confined regions such as wells. Sizing moieties are linked to individual target molecules. The sizing moieties are of sufficient size, relative to the size-confined reaction or observation regions, such that only a selected number of sizing moieties will fit into the size confined regions. The confined regions and the sizing moieties or target molecules comprise a selected charge that allow for controlling the loading of the sizing moities.

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: 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: Provided herein are nanostructure-based sequencing methods and systems.

Abstract: The invention relates to a carrier comprising at least one substrate, which has a coating in at least certain regions produced from individual modules by plasma polymerization, and the coating has one or more free spaces in at least certain regions for accommodating at least one solution containing a biological sample.

Abstract: The present invention relates to systems and methods for minimizing or eliminating diffusion effects. Diffused regions of a segmented flow of multiple, miscible fluid species may be vented off to a waste channel, and non-diffused regions of fluid may be preferentially pulled off the channel that contains the segmented flow. Multiple fluid samples that are not contaminated via diffusion may be collected for analysis and measurement in a single channel. The systems and methods for minimizing or eliminating diffusion effects may be used to minimize or eliminate diffusion effects in a microfluidic system for monitoring the amplification of DNA molecules and the dissociation behavior of the DNA molecules.

Abstract: A method and device for periodically perturbing the flow field within a microfluidic device to provide regular droplet formation at high speed.

Abstract: A plurality of isolated microvessels including a plurality of encoded microvessels each having a microbody and a reservoir core. The microbody is configured to separate a biological or chemical substance in the reservoir core from an ambient environment surrounding the microbody. The microbody includes a transparent material that at least partially surrounds the reservoir core and facilitates detection of an optical characteristic of the substance within the reservoir core. The microbody of each microvessel includes an identifiable code that distinguishes individual microvessels of the plurality of encoded microvessels from each other. The plurality of isolated microvessels also includes a plurality of compartments each configured to separate individual microvessels of the plurality of encoded microvessels from each other.

Abstract: A testing method of nucleic acid binding protein based on biochip, comprises the following steps: 1. puts a plurality of groups solution including nucleic acid captured probes into biological sample including a plurality of nucleic acid binding protein to be test, and thus forming nucleic acid captured probe-nucleic acid binding protein complexes; such nucleic acid captured probe includes at least a segment of binding sequence which can bind with aimed nucleic acid binding protein; 2. separates such nucleic acid captured probe-nucleic acid binding protein complexes, then recoveries nucleic acid captured probes; 3. hybridizes the nucleic acid captured probes according to step 2 with a plurality of single strand blotting probes on biochip substrate; the sequence of such blotting probe compensates with such nucleic acid captured probe or one of its strand; 4. detects the result of hybridization.

Abstract: The present invention relates to methods and products for the localized or spatial detection of nucleic acid in a tissue sample and in particular to a method for localized detection of nucleic acid in a tissue sample comprising: (a) providing an array comprising a substrate on which multiple species of capture probes are directly or indirectly immobilized such that each species occupies a distinct position on the array and is oriented to have a free 3? end to enable said probe to function as a primer for a primer extension or ligation reaction, wherein each species of said capture probe comprises a nucleic acid molecule with 5? to 3?: (i) a positional domain that corresponds to the position of the capture probe on the array, and (ii) a capture domain; (b) contacting said array with a tissue sample such that the position of a capture probe on the array may be correlated with a position in the tissue sample and allowing nucleic acid of the tissue sample to hybridize to the capture domain in said capture probes;

Abstract: The invention relates to novel photo-generated carbohydrate arrays and methods of their use to detect the presence of one or more agents in a sample. The invention also relates to a high-throughput strategy to facilitate the identification and immunological characterization of pathogen-specific carbohydrates, including those of Bacillus anthracis. The invention can be used to determine the presence of a pathogen and whether a subject has been exposed to a pathogen, such as by screening for pathogen-specific antibodies.

Abstract: The present invention is directed to a method of designing a plurality of capture oligonucleotide probes for use on a support to which complementary oligonucleotide probes will hybridize with little mismatch, where the plural capture oligonucleotide probes have melting temperatures within a narrow range. The first step of the method involves providing a first set of a plurality of tetramers of four nucleotides linked together, where (1) each tetramer within the set differs from all other tetramers in the set by at least two nucleotide bases, (2) no two tetramers within a set are complementary to one another, (3) no tetramers within a set are palindromic or dinucleotide repeats, and (4) no tetramer within a set has one or less or three or more G or C nucleotides. Groups of 2 to 4 of the tetramers from the first set are linked together to form a collection of multimer units.

Abstract: This invention provides substrates for use in various applications, including single-molecule analytical reactions. Methods for propagating optical energy within a substrate are provided. Devices comprising waveguide substrates and dielectric omnidirectional reflectors are provided. Waveguide substrates with improved uniformity of optical energy intensity across one or more waveguides and enhanced waveguide illumination efficiency within an analytic detection region of the arrays are provided.

Abstract: The present invention relates to screening methods and, in particular, to methods of screening anti-ligands libraries for identifying anti-ligands specific for differentially and/or infrequently expressed ligands. The method comprises the steps of providing a library of anti-ligands; providing a first subtractor ligand; providing a second target ligand; determining the amount of the first and second target ligands using one or more equations derived from the universal law of mass action; providing the determined amount of a first subtractor ligand; providing the determined amount of a second target ligand; providing separation means capable of use to isolate anti-ligand bound to the second target ligand from anti-ligand bound to the first subtractor ligand; exposing the library of to the first and second target ligands to permit binding of anti-ligands to ligands; and using the separation means to isolate the anti-ligand bound to second target ligand.

Abstract: Methods for the diagnosis and/or monitoring of pancreatic cancer by detection of micro-RNAs (miRNA) are provided. In certain embodiments, detection of miR-21, miR-210, miR-155, and/or miR-196a in the plasma, blood, or pancreatic juice of a subject, such as a human patient, may be used to detect, diagnose, or monitor a pancreatic cancer.

Abstract: The invention encompasses microfluidic microarray assemblies (MMA) and subassemblies and methods for their manufacture and use. In one embodiment, first and second channel plates are provided and are sealingly connected to a test chip in consecutive steps. Each plate includes microfluidic channels configured in a predetermined reagent distribution pattern. The test chip comprises a plurality of discrete test positions, each test position being located at the intersection between a first predetermined reagent pattern and a second predetermined reagent pattern, wherein at least one of said patterns is non-linear. The first channel plate allows the distribution of a first reagent on said test chip, wherein said first reagent is immobilized at said test positions. The second channel plate allows the distribution of a second reagent on said test chip, wherein said second reagent comprises a plurality of different test samples.

Abstract: This invention is directed to methods and compositions for sorting and/or determining microscopic organisms or cells. The methods and compositions are directed to the use of molecular probes to selectively stain the organisms or cells in combination with the use of binding partners to selectively immobilize the stained organisms or cells to a solid carrier. By combining the selectivity of both molecular probes and binding partners in an orthogonal method for staining and immobilization, these methods and compositions increase both the discriminating power of the assays and/or the certainty of the result obtained therefrom.

Abstract: A selective targeting method is disclosed comprising contacting a library of ligands, particularly a peptide library, with an anti-target to allow the ligands to bind to the anti-target; separating the non-binding ligands from the anti-target bound ligands, contacting the non-binding anti-target ligands with a target allowing the unbound ligands to bind with the target to form a target-bound ligand complex; separating the target-bound ligand complex from ligands which do not bind to the target, and identifying the target-bound ligands on the target-bound ligand complex wherein the target-bound ligands have a KD in the range of about 10?7 to 10?10 M. Additionally claimed are the ligands identified according to the method.

Abstract: Improved compositions, methods, apparatus, and kits for high-throughput nucleic acid amplification, detection and sequencing are disclosed. A nucleic acid cluster having an identifiable center is produced by generating on a solid support an immobilized nucleic acid complement from a template, one of which comprises a detectable label; and amplifying the complement and the template to obtain a nucleic acid cluster on the support, the cluster having a substantially central location marked by the detectable label and a surrounding region comprising immobilized copies. Also disclosed are nucleotide sequence determination in nucleic acid clusters so produced, center position annotation in the clusters, assignment of sequence information to overlapping clusters, and related compositions and methods.

Abstract: The present invention relates to novel methods for sequencing and mapping genetic markers in polynucleotide sequences using Type-IIs restriction endonucleases. The methods herein described result in the “capturing” and determination of specific oligonucleotide sequences located adjacent to Type-IIs restriction sites. The resulting sequences are useful as effective markers for use in genetic mapping, screening and manipulation.

Abstract: This invention relates to a number of bird sex-identification oligonucleotides and their use in determining the sex of birds in various families.