Abstract: According to various embodiments, a method is provided that comprises washing an array of DNA-coated beads on a substrate, with a wash solution to remove stacked beads from the substrate. The wash solution can include inert solid beads in a carrier. The DNA-coated beads can have an average diameter and the solid beads in the wash solution can have an average diameter that is at least twice the diameter of the DNA-coated beads. The washing can form dislodged DNA-coated beads and a monolayer of DNA-coated beads. In some embodiments, first beads for forming an array are contacted with a poly(ethylene glycol) (PEG) solution comprising a PEG having a molecular weight of about 350 Da or less. In some embodiments, slides for forming bead arrays are provided as are systems for imaging the same.

Abstract: Means and methods for preparing double stranded target DNA molecules for sequencing. In embodiments double stranded backbone DNA molecules comprising 5? and 3? ends are provided that are: ligation compatible with 5? and 3? ends of the target DNA; form a first restriction enzyme recognition site when self-ligated; in a form that enables self-ligation. Methods may comprise providing, if not already present, the target DNA with 5? and 3? ends that are in a form that prevents self-ligation and that are ligation compatible with the backbone DNA 5? and 3? ends. Methods may further comprise ligating the target DNA to the backbone DNA in the presence of a ligase and a first restriction enzyme that cuts the first restriction enzyme recognition site, thereby producing at least one DNA circle comprising a backbone DNA molecule and a target DNA molecule.

Abstract: A method for characterizing or quantifying one or more proteins in visible and/or sub-visible particles formed in a sample by detecting the at least one visible or sub-visible particle in the sample, isolating and capturing the at least one visible or sub-visible particle to identify a presence of a protein, and using a mass spectrometer to characterize the protein.

Abstract: An analysis device includes a controller configured to count a pulse derived from a particles as a plural particles when a light reception level signal includes the pulse having a first extreme value point, a second extreme value point, and a third extreme value point, and the pulse fulfils a condition in which the third extreme value point is present between the first extreme value point and the second extreme value point in a pulse width direction of the pulse, the third extreme value point is present between the first extreme value point and a threshold in a pulse amplitude direction, the first extreme value point and the second extreme value point are each an extreme value point of a waveform projecting in a common direction, and the third extreme value point is an extreme value point of a waveform in a direction opposite to the common direction.

Abstract: Provided herein is a polymerase-free enzyme mix (FRAG) for fragmenting double-stranded DNA. In some embodiments the enzyme mix may comprise a double-stranded DNA nickase and at least one of a DNA ligase capable of sealing a nick within a DNA, and a single-strand specific DNA nuclease. Methods for fragmenting double-stranded DNA are also provided.

Abstract: Devices, systems, and methods for non-volatile storage include a well activation device operable to modify one or more wells from a plurality of wells of a flow cell to provide a set of readable wells. Readable wells are configured to allow exposure of a well to substances from nucleotide sequencing fluids, and prevent exposure to other substances and fluids, such as nucleotide synthesizing fluids. The well activation device may also modify wells to provide a set of writeable wells. This set of wells is configured to allow exposure to the nucleotide synthesizing fluids and substances; and prevent exposure to the nucleotide sequencing fluids and substances. There may also be provisions made for risk mitigation for data errors such as generating commands to write specified data to a nucleotide sequence associated with a particular location in a storage device, reading the nucleotide sequence and performing a comparison.

Abstract: Disclosed herein are methods for diagnosing acute cellular rejection (ACR) of an allograft by analysis of predictive gene sets and kits for practicing these methods.

Abstract: Systems and methods for releasing semiconductor devices during pick and place operations are disclosed. A representative system for handling semiconductor dies comprises a support member positioned to carry at least one semiconductor die releasably attached to a support substrate. The system further includes a picking device having a pick head coupleable to a vacuum source and positioned to releasably attach to the semiconductor die at a pick station. The system still further includes a release station having a fluid delivery device coupleable to a source of release fluid, the fluid delivery device having an exit positioned to direct release fluid toward a semiconductor die carried by the support member at the release station.

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: Various embodiments disclosed relate to a substrate. The present disclosure provides a substrate for use in both surface enhanced Raman spectroscopy and surface enhanced infrared spectroscopy. The substrate includes a flexible polymeric membrane, a plurality of metal oxide nanoparticles disposed on the polymeric membrane, and a plurality of metallic nanoparticles directly disposed on a portion of the plurality of metal oxide nanoparticles. The plurality of metal oxide nanoparticles are configured to work synergistically with metal nanoparticles upon exposure of the substrate surface to at least one of visible light or infrared radiation.

Abstract: The present disclosure discloses methods and systems for encoding digital information in nucleic acid (e.g., deoxyribonucleic acid) molecules without base-by-base synthesis, by encoding bit-value information in the presence or absence of unique nucleic acid sequences within a pool, comprising specifying each bit location in a bit-stream with a unique nucleic sequence and specifying the bit value at that location by the presence or absence of the corresponding unique nucleic acid sequence in the pool. Also disclosed are chemical methods for generating unique nucleic acid sequences using combinatorial genomic strategies (e.g., assembly of multiple nucleic acid sequences or enzymatic-based editing of nucleic acid sequences).

Abstract: A biosensor for the detection of an analyte using surface-enhanced Raman spectroscopy (SERS) is provided. The biosensor includes a SERS-active substrate and a microfludic circuit device arranged to be in fluid communication with the SERS-active substrate. Method of manufacturing a biosensor, and methods for detecting an analyte using the biosensor, wherein the analyte may be haptoglobin, are also provided.

Abstract: Embodiments of the present disclosure provide plasmonic structures, methods of making plasmonic structures, and the like.

Abstract: A plasmonic waveguide (10), a biosensor chip (100) and a system, wherein the plasmonic waveguide (10) is applied to the biosensor chip (100), and comprises a base (11) and a plasmonic structure (12) provided on the upper surface of the base (11); the plasmonic structure (12) comprises a plurality of plasmons (121) periodically arranged, the plasmons (121) being metal split rings, and the annular openings of the plasmons (121) being used for fixing antibody probes (122). The plasmon waveguide (10) is provided in the biosensor chip (100), the target biomolecules in the detection liquid flowing into a microfluidic channel (31) can be captured by means of the antibody probes (122), and the plasmonic waveguide (10) is used to enhance the signal strength of terahertz waves emitted to the biosensor chip (100), thereby enhancing the signal strength of the reflected terahertz waves detected by a terahertz analyzer (300), improving the detection sensitivity, the signal-to-noise ratio and the reliability.

Abstract: Embodiments in accordance with the present disclosure are directed to polymer beads and uses thereof, including forming libraries of compounds for screening and assay purposes. A polymer bead, in accordance with embodiments, has an interior surface and an exterior surface that are topologically segregated from one another. The interior surface includes a protecting group and the exterior surface includes a deprotected group, which can also be referred to as a deprotected functional group. The protecting group can includes a nitrobenzenesulfonamide group that protects an amine group.

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.