Abstract: The present invention provides methods for adsorbing a protein onto a conductive solid substrate, comprising the application of an external potential to the solid substrate greater than +500 mV vs. the Ag/AgCl/Cl?SAT reference electrode, in the presence of a solution comprising the protein, wherein the solution has a pH within ±2 units of the isoelectric point of the protein, and wherein the protein adsorbs to the conductive solid substrate upon application of the external potential. Some embodiments are directed to a process of protein adsorption on a solid surface mediated by an applied potential that can be affected significantly by altering a number of variables such as protein concentration, flexibility, charge, molecular weight, pH, and charge of substrate.

Abstract: Methods and compositions are disclosed relating to the localization of nucleic acids to arrays such as silane-free arrays, and of sequencing the nucleic acids localized thereby.

Abstract: Systems and methods interconnect cell culture devices and/or fluidic devices by transferring discrete volumes of fluid between devices. A liquid-handling system collects a volume of fluid from at least one source device and deposits the fluid into at least one destination device. In some embodiments, a liquid-handling robot actuates the movement and operation of a fluid collection device in an automated manner to transfer the fluid between the at least one source device and the at least one destination device. In some cases, the at least one source device and the at least one destination device are cell culture devices. The at least one source device and the at least one destination device may be microfluidic or non-microfluidic devices. In some cases, the cell culture devices may be microfluidic cell culture devices. In further cases, the microfluidic cell culture devices may include organ-chips.

Abstract: Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one aspect, the invention relates to systems and methods for making droplets of fluid surrounded by a liquid, using, for example, electric fields, mechanical alterations, the addition of an intervening fluid, etc. In some cases, the droplets may each have a substantially uniform number of entities therein. For example, 95% or more of the droplets may each contain the same number of entities of a particular species. In another aspect, the invention relates to systems and methods for dividing a fluidic droplet into two droplets, for example, through charge and/or dipole interactions with an electric field. The invention also relates to systems and methods for fusing droplets according to another aspect of the invention, for example, through charge and/or dipole interactions. In some cases, the fusion of the droplets may initiate or determine a reaction.

Abstract: Durable asymmetric composite membranes consisting essentially of a film of cross-linked sulfonated poly(ether ether ketone) adhered to a sheet of hydrophilicitized microporous poly(ethylene) are disclosed. The membranes have application in the recovery of water from feed streams where the ability to clean in situ is desirable, for example in dairy processing. Methods of preparing cross-linked sulfonated poly(ether ether ketone) suitable for use as the rejection layer and hydrophilicitized sheets of microporous poly(ethylene) suitable for use as the support layer of such membranes are also disclosed.

Abstract: Disclosed are devices and methods for detecting analytes from a sample.

Abstract: Method for manufacturing microarrays and verifying the quality of said microarrays, wherein the method comprises: a) providing at least one reagent, b) loading said at least one reagent in a dispensing print head, in a predetermined arrangement, c) in a first print pass, generating instructions for the print head and moving said print head with respect to a substrate to print said at least one reagent on the substrate to obtain microarrays, d) obtaining an image of the printed microarrays by means of a camera, e) processing the obtained images of the printed microarrays, to calculate parameters indicative for the quality of the printed microarrays, f) comparing, at the end of the first print pass, the calculated parameters for the printed microarrays with predetermined criteria for the microarrays, to identify possible printing defects, g) comparing, for the printed microarrays, the identified printing defects of step f), h) using the outcome of the comparison of step g) to select a corrective action to impro

Abstract: One or more liquids are transferred from a source array to one or more remotely positioned destination sites such as chambers by utilizing one or more movable transfer elements, such as contact pins or capillaries. The source array may include a predetermined organization of addresses at which materials are positioned. One or more materials may be selected for transfer. Based on the selection, one or more addresses may be accessed by the transfer element(s). The addresses may correspond to spots on a surface of the source array. Each spot may be a feature containing one or more (bio)chemical compounds. At the chamber(s), the material(s) may be processed, such by reaction with one or more reagents. The reaction(s) may entail synthesis of one or more desired products. Alternatively, reaction(s) may be performed at the source array, and the product(s) then transferred to the chamber(s).

Abstract: The disclosure generally relates to a deoxyribonucleic acid (DNA) sequencing circuit having a controllable pore size and a lower membrane capacitance and noise floor relative to biological nanopore devices. For example, design principles used to fabricate a fin-shaped field effect transistor (FinFET) may be applied to form, on a first wafer, a nanopore that has a desired pore size in a silicon-based membrane. Electrodes and an interconnect embedded with an amplifier and analog-to-digital converter (ADC) may be formed on a separate second wafer, wherein the first wafer and the second wafer may then be bonded and further processed to form a sensing device that includes appropriate wells and pores to be used in a DNA sequencing circuit.

Abstract: A method for authenticating an item of interest. A nucleic acid tag comprised of a nucleotide-support platform attached to a first nucleic acid molecule is added to the item of interest, where information about the item of interest is contained within the first nucleic acid molecule. A portion of an item is sampled for the presence of the nucleic acid tag, where the item is potentially the item of interest. The presence of the nucleic acid tag is detected in the sample, where the presence of the first nucleic acid tag authenticates the item as the item of interest.

Abstract: A disposable screen-printed microchip based on an organic membrane sensitive layer is presented. The microchip is highly responsive for the determination of Lead(II). The microchip is composed of a composite sensitive material which comprises carbon nano-tubes “CNTs” and titanium (IV) oxide nano-particles embedded in a PVC membrane which was deposited on the surface of a plastic screen printed micro-electrode using a new methodology. The prepared disposable microchip provides a linear response for Pb2+ ions covering the concentration range of 1×10?6 to 1×10?1 mole L?1 with high sensitivity (49 mV), a long life span (>4 months) and short response time (10 s). The merits offered by the micro-sensor or microchip include small size, simple fabrication, mass production, integration feasibility and cost effectiveness and automation.

Abstract: The present invention provides a method for purifying an intended substance, a kit for purifying the intended substance, and a silicon oxide-binding tag for use in the method and the kit. In the present invention, a complex of a silicon oxide-binding tag and a substance is caused to specifically bind to silicon oxide in a solution for binding, to which solution no salt is added, and binding between the silicon oxide-binding tag and the silicon oxide is broken with use of arginine.

Abstract: Magnetic actuators comprising at least one linear subarray are presented. Systems comprising such magnetic actuators and methods for using such magnetic actuators to isolate magnetic particles in a fluid are also presented. Magnetic actuators comprising at least four uniform magnets are also presented, as are systems comprising such magnetic actuators and methods for using such magnetic actuators to isolate magnetic particles in a fluid.

Abstract: Provided are a microfluidic platform for cell culturing and a cell culturing method using the same. By applying a structure of a compartment which surrounds at least a portion of an annular reservoir and moving cells to be cultured to a site adjacent to a microchannel via rotation, a probability of observing cells that grew after culturing may increase and a probability of causing cells, particularly neurons, to grow so as to correspond to a signal transfer direction may increase.

Abstract: The invention provides a method for increasing the order of an array of polymeric micelles or of nanoparticles on a substrate surface comprising a) providing an ordered array of micelles or nanoparticles coated with a polymer shell on a substrate surface and b) annealing the array of micelles or nanoparticles by ultrasonication in a liquid medium which is selected from the group comprising H2O, a polar organic solvent and a mixture of H2O and a polar organic solvent. In a related aspect, the invention provides the highly ordered arrays of micelles or nanoparticles obtainable by the methods of the invention.

Abstract: Methods, compositions and arrays for non-random loading of single analyte molecules into array structures are provided. For example, methods are presented for providing a surface comprising the plurality of array regions by exposing the surface to a solution comprising polymerase enzymes where each polymerase enzyme is bound to a binding structure having several functional moieties. The functional moieties of the binding structure react with the binding elements on the array regions such that the functional moieties on the binding structure react with other available binding sites in an array region, preventing other polymerase-binding structures from loading, and resulting in a single polymerase molecule bound to each of these regions.

Abstract: Methods are described for phototransferring a compound from a first surface to a second surface. Compounds are described with photocleavable linkers. Compounds attached to a first surface through a photocleavable linker are put in proximity (or contact) with a second surface, and then phototransferred to the second surface upon exposure to electromagnetic radiation. Illuminating the compound with radiation photocleaves the compound from the first surface and transfers the compound to the second surface.

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 probe-immobilized carrier for detecting a target substance is manufactured such that a spot is prevented from being contaminated with another spot and a probe is prevented from nonspecifically adsorbing a background area in the manufacture of the probe-immobilized carrier and nonspecific adsorption cannot be occurred even after the formation of an array. A substrate containing a reactive group for immobilizing a probe thereon is used and the steps of: (i) supplying a liquid droplet containing a probe on the substrate; (ii) inactivating a reactive group existing in an area other than a supplying area of the substrate, and (iii) removing an unreacted probe existing in the supplied liquid droplet are carried out.

Abstract: Provided are methods for performing patterned chemistry and arrays prepared thereby.

Abstract: The present invention provides methods and compositions for analyzing nucleic acid sequences. In some aspects, the methods utilize clonal objects, such as DNA balls, that have been captured on beads. Using the methods described here, compositions are fabricated wherein a bead and one clonal object are affinity bound or hybridized to each other through an affinity binding patch or hybridization patch on the surface of the bead. The invention also provides a population of beads having affinity bound or hybridized clonal objects at a ratio of 1:1. The invention additionally provides methods for amplifying a target nucleic acid molecule utilizing the compositions described herein.

Abstract: Methods are disclosed relating to generating a silene-free slide comprising the steps of providing a plastic substrate; providing a solution of acrylamide comprising N-(5-bromoacetamidylpentyl) acrylamide (BRAPA); contacting the acrylamide/BRAPA solution with a polymerizing agent; contacting the acrylamide/BRAPA solution with an oxidizing agent; and contacting the acrylamide/BRAPA/polymerizing agent/oxidizing agent to the plastic substrate.

Abstract: Micropatterns of glycan-bearing brush polymers generated by the initiation of oligomerization of acrylate and methacrylate monomers from thiol-terminated surfaces. Chain lengths are controlled in situ by varying exposure time, and these multivalent glycan scaffolds detect glycan binding proteins at sub-micromolar concentrations.

Abstract: The disclosure of this Description includes: a step of preparing a solid-phase body provided with a detection probe having a predetermined nucleotide sequence; a step of preparing a signaling target nucleic acid having a signal generating part for detecting the target nucleic acid; a step of bringing the signaling target nucleic acid, the detection probe, and an oligonucleotide being a mediator having a first site that hybridizes specifically with the target nucleic acid and a second site (preferably 20 to 50 nucleotides or more preferably 20 to 25 nucleotides in length) that hybridizes specifically with a part having the predetermined nucleotide sequence of the detection probe into contact with one another so that a hybridization product of these components can be formed; and a step of obtaining data based on the signal generating part of the signaling target nucleic acid on the solid-phase body.

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 invention provides a method of printing, onto a substrate (12), an array (14) of spots of reagent compositions for use in a chemical and/or biochemical analysis. The method includes displacing an array of reagent composition containing capillary tubes (22) arranged alongside one another from an inoperative position to an operative position in which open ends of the capillary tubes (22) simultaneously impinge against a substrate and thereafter displacing the array of tubes (22) from the operative position back to the inoperative position. The invention extends to a printing apparatus (10), a method of printing a layered array of spots of reagent compositions, a method of introducing reagent compositions into the tubes, a reagent introducing device for introducing reagent compositions into the tubes and a printing installation which includes the printing apparatus (10) and the reagent introducing device.

Abstract: The present invention provides kits and assay methods for the early detection of pathogens, precise identification of the etiologic agent, and improved disease surveillance. More specifically, the present invention discloses an immunoassay leading to the rapid and simultaneous detection of antibodies to a wide range of infectious pathogens in biological fluids of infected patients. This immunoassay involves the covalent and oriented coupling of fusion proteins comprising an AGT enzyme and a viral antigen on an identifiable solid support (e.g. fluorescent microspheres), said support being previously coated with an AGT substrate. This coupling is mediated by the irreversible reaction of the AGT enzyme on its substrate. The thus obtained antigen-coupled microspheres show enhanced capture of specific antibodies as compared to antigen-coupled microspheres produced by standard amine coupling procedures.

Abstract: Disclosed is a spotter device and methods for the formation of microassays, biochips, biosensors, and cell cultures. The spotter may be used to deposit highly concentrated spots of protein or other materials on a microarray slide, wafer, or other surface. It may also be used to perform various chemistry steps on the same spots. The spotter increases the surface density of substances at each spot by directing a flow the desired substance (or a solution thereof) over the spot area until surface saturation is accomplished. The spotter may be loaded by well plate handling equipment. The spotter uses wells, microfluidic conduits, and orifices to deposit proteins, other biomolecules, or chemicals on a spot on, a separate surface. Each orifice is connected to two wells via microconduits. When the spotter contacts a surface, a seal is formed between the orifices and the surface. The same or different substances may be flowed across each orifice. Any number of orifices may be incorporated into a spotter.

Abstract: The invention provides a method for immobilization of biological molecules such as nucleic acids, peptides and proteins onto the surface of a glass or plastic solid support.

Abstract: A method of making an assay device comprising providing micro-elements in the form of micro-particles or micro-length tube detection elements and thereafter with an automated tool, picking and placing the micro-elements into open-sided microfluidic channels in a body.

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: Methods of producing substrates having selected active chemical regions by employing elements of the substrates in assisting the localization of active chemical groups in desired regions of the substrate. The methods may include optical, chemical and/or mechanical processes for the deposition, removal, activation and/or deactivation of chemical groups in selected regions of the substrate to provide selective active regions of the substrate.

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: The present invention is drawn to the generation of micropatterns of biomolecules and cells on standard laboratory materials through selective ablation of a physisorbed biomolecule with oxygen plasma. In certain embodiments, oxygen plasma is able to ablate selectively physisorbed layers of biomolecules (e.g., type-I collagen, fibronectin, laminin, and Matrigel) along complex non-linear paths which are difficult or impossible to pattern using alternative methods. In addition, certain embodiments of the present invention relate to the micropatterning of multiple cell types on curved surfaces, multiwell plates, and flat bottom flasks. The invention also features kits for use with the subject methods.

Abstract: Methods are disclosed relating to localizing nucleic acids to arrays such as silane-free arrays, and of sequencing the nucleic acids localized thereby.

Abstract: De novo synthesized large libraries of nucleic acids are provided herein with low error rates. Further, devices for the manufacturing of high-quality building blocks, such as oligonucleotides, are described herein. Longer nucleic acids can be synthesized in parallel using microfluidic assemblies. Further, methods herein allow for the fast construction of large libraries of long, high-quality genes. Devices for the manufacturing of large libraries of long and high-quality nucleic acids are further described herein.

Abstract: A microarray substrate including a piece of fluoropolymer whose surface is modified with polydopamine, in which the polydopamine forms an array of microspots on the surface of the fluoropolymer piece, and allows immobilization of molecules or cells. A microarray including the substrate, a microfluidic system designed for dispensing reagents onto selected locations on the surface of substrates, and a method for preparing the substrate and the microarray, in which a dopamine solution is dispensed onto the fluoropolymer piece using the microfluidic system, and forms an array of polydopamine microspots serving as the reaction sites for microarray analysis.

Abstract: A method, apparatus, or system for generating a pattern of polynucleotides on a substrate. The method includes providing a substrate having a hydrophobic surface. The method further includes conjugating a polystyrene moiety to a polynucleotide and applying a polystyrene-polynucleotide conjugate to create a plurality of reaction spots on the hydrophobic surface of the substrate. An apparatus includes a substrate with at least one polystyrene-polynucleotide conjugate on a surface of the substrate. A system can analyze a polystyrene-polynucleotide conjugate and the system may perform PCR.

Abstract: A device for quantitatively determining an analyte is provided to conspicuously improve the performance of the quantitative determination. This device is equipped with a flow channel, an analyte detecting unit for capturing and detecting the analyte, and a quantitative measurement unit for quantitatively determining the analyte, wherein a signal generated when the analyte detecting unit has detected the analyte is divided into a plurality of parts in the direction of the flow in the flow channel at the quantitative measurement unit for processing. Also provided are technologies including one for controlling the density of molecules attached to the surface of a solid. In these technologies, when molecules are attached to a substrate, the density of attached molecules is controlled, by having an electrolyte also present in a solution containing the molecules to adjust the screening effect by the electrolyte, and by taking into consideration the effective size of a molecule.

Abstract: The present invention provides a method for the generation of novel libraries of encoded magnetic particles from sub-libraries of by the generation of novel sub-libraries of magnetic nanoparticles and encoded particles. The sub-libraries are functionalized on demand are useful in the formation of arrays. The present invention is especially useful for performing multiplexed (parallel) assays for qualitative and/or quantitative analysis of binding interations of a number of analyte molecules in a sample.

Abstract: The present invention provides a method of manufacturing biomedical molecular detection platform, comprising providing a plurality of reagent droplets on a first surface of a substrate; forming a plurality of hydrophilic regions and a water-repellant region on a second surface of a test paper, and the plurality of hydrophilic regions separated individually by the water-repellant region; and contacting the first surface of the substrate with the second surface of the test paper for transferring each reagent droplet on the substrate to each hydrophilic region of the test paper. The present invention also provides a biomedical molecular detection platform manufactured therefrom. The method of present invention can rapidly manufacture large quantity of biomedical molecular detection platforms, and the biomedical molecular detection platform can be used to any test that use pigmentation to determine results.

Abstract: The invention relates to a method of preparing a library of template polynucleotides with uniform sequence representation and to use of a library of templates prepared using this method for solid-phase nucleic acid amplification. In particular, the invention relates to a method of preparing a library of template polynucleotides which have common sequences at their 5? ends and at their 3? ends, which contains even representation of all the fragments present in a starting sample of nucleic acid before fragmentation. The invention is especially applicable to the preparation of short insert libraries, where the sample fragments are less than 150 base pairs in length.

Abstract: Methods are described for phototransferring a compound from a first surface to a second surface. Compounds are described with photocleavable linkers. Compounds attached to a first surface through a photocleavable linker are put in proximity (or contact) with a second surface, and then phototransferred to the second surface upon exposure to electromagnetic radiation. Illuminating the compound with radiation photocleaves the compound from the first surface and transfers the compound to the second surface.

Abstract: Surface modifications to sensors in an array give the sensors different functionalities for adsorbing or binding molecules. A first sensor in the array includes a first resonating member having a first surface comprising a polymer receptor material coated over a first underlying material. A second sensor includes a second resonating member having a second surface comprising the polymer receptor material coated over a second underlying material that is different than the first underlying material. The first underlying material, the second underlying material, and the polymer receptor material are selected such that the first resonating member, having a combination of the polymer receptor material and the first underlying material, has a different ability to adsorb or bind a mass of one or more analytes than does the second resonating member having a combination of the polymer receptor material with the second underlying material. Methods for fabricating sensors with surface modifications are also provided.

Abstract: Multi-biotinylated reactants are provided which can be used in divalent complexes for various applications such as colocalization, labeling, immobilization, and purification. Methods for constructing, purifying, and using the bis-biotinylated reactants are also provided. In certain embodiments, two bis-biotinylated reactants are bound to a single streptavidin tetramer to provide a complex having a 1:1 stoichiometry with respect to the bis-biotinylated reactants.

Abstract: A differentially coated device for conducting a plurality of nano-volume specified reactions, the device comprising a platen having at least one exterior surface modified to a specified physicochemical property, a plurality of nano-volume channels, each nano-volume channel having at least one interior surface in communication with the at least one exterior surface that is selectively coated with an optionally dissolvable coating agent physisorbed to at least one interior surface, wherein the optionally dissolvable coating agent comprises a coating agent and a first component for the plurality of specified reactions. Methods for preparing and using such devices are also provided, as well as a method of registering a location of a dispenser array in relation to a microfluidic array. A first one of the dispenser array and the microfluidic array is movable in relation to the frame, and the other of the first one of the dispenser array and the microfluidic array is fixed relative to the frame.

Abstract: An electrochemical method for measuring the activity of enzymes using nanoelectrode arrays fabricated with vertically aligned carbon nanofibers. Short peptide substrates specific to disease-related enzymes are covalently attached to the exposed nanofiber tips. A redox moiety, such as ferrocene, can be linked at the distal end of the nanofibers. Contact of the arrays with a biological sample containing one or more target enzymes results in cleavage of the peptides and changes the redox signal of the redox moiety indicating the presence of the target enzymes.

Abstract: A biochip is provided that suppresses nonspecific adsorption or bonding of a detection target substance without coating with an adsorption inhibitor and that has excellent detection sensitivity. The constitution is such that it has a macromolecular substance containing a phosphorylcholine group and an active ester group on a substrate surface of a biochip substrate.

Abstract: Provided herein is technology relating to depositing and/or placing a macromolecule at a desired site for an assay and particularly, but not exclusively, to methods and systems for transporting a macromolecule such as a protein, a nucleic acid, or a protein:nucleic acid complex to an assay site, such as the bottom of a nanopore, a nanowell, or a zero mode waveguide.

Abstract: Methods and apparatuses for generating microscopic patterns of macromolecules such as proteins on a solid surface are described. Pulsed laser light is used to alter surface portions of a solid surface substrate in a predetermined pattern, by removing macromolecules from surface portions of the substrate where the light is focused. The same wavelength light at lower intensity can be used to visualize the removal by its reflection from the specimen surface along the path to the detector. Select macromolecules introduced to the substrate selectively adhere to select surface portions, thereby depositing macromolecules in the predetermined pattern on the solid surface.