Abstract: A method for fabricating hydrogel based microarrays by a nanostamping process is provided. A method of manufacturing a patterned hydrogel array is provided comprising the steps of contacting a patterned substrate with a hydrogel substrate to form a substrate complex, wherein the patterned substrate comprises a surface, a first polymer attached to the surface, and a second polymer reversibly attached to the first polymer, the hydrogel substrate comprises a polymer matrix and a plurality of attachment sites along the polymer matrix capable of attaching the second polymer, binding at least one attachment site to the second polymer, disassociating the dimer; and separating the substrate complex to obtain a patterned hydrogel array having a second polymer attached to an attachment site. Methods where the second polymer is synthesized using the first polymer as template are provided. Hydrogel arrays manufactured according to the methods of the invention are provided.

Abstract: A novel method for two-dimensionally arraying ferritin on a substrate is provided which obviates the need for a metal ion that permits linking between adjacent two ferritin particles. In a method of two-dimensionally arraying ferritin on a substrate, the surface of the substrate is hydrophilic, and the method includes the steps of: developing a solution containing a solvent and the ferritin on the substrate; and removing the solvent from the solution developed on the substrate, while the ferritin has an amino acid sequence set out in SEQ ID NO: 1 modified at its N-terminus.

Abstract: The invention relates to a printer device for producing biological test arrays by depositing an array of biofluids onto a substrate. The invention further relates to the use of such a device in the production of biological test arrays. The invention also relates to a method for producing a biological test array. The invention moreover relates to a biological test array. The method according to the invention is failure-proof, and results in biological test arrays of superior quality.

Abstract: A functionalized platform for a polymer array, comprising a substrate, and a metal oxide layer that attaches a functionalized alkyl phosphonate compound is described together with related array methods and systems.

Abstract: The invention relates to the early detection of sepsis and the use of particular sets of biomarkers. Combinations of biomarkers representing changes in expression levels of specific genes are provided and, in particular, the use of microarrays to detect such changes of expression and to provide early diagnostic information is provided.

Abstract: A system and method for producing label-free micro-array biochip based on the surface plasmon resonance in metallic nano-slit arrays, wherein the micro-array biochip of the does not utilize fluorescent labeling. Without the fluorescence labeling, the label-free micro-array substantially reduces the sample cost and can detect bio-molecular interactions in their native forms.

Abstract: Synthesis of chain molecules such as DNA is carried out in a conduit having an interior channel with an inlet end and an outlet end. At least one wall of the conduit is substantially transparent to selected wavelengths of light. Solid carrier particles are contained within the interior channel of the conduit. A plurality of controllable light sources are mounted at spaced locations along the length of the transparent wall of the conduit to allow selective illumination of separated sections of the particles within the conduit. When a light source is turned on, a photodeprotecting group is removed from the carrier particles in the section that is illuminated by the light source. A reagent containing a selected base is flowed through the conduit so that the base will attach to the carrier particles in those sections which have been exposed to light and deprotected.

Abstract: The present invention provides methods for synthesizing arrays of polymers. A barrier to a reaction is applied to select features of the array thereby limiting the reaction to the remaining features.

Abstract: A microsphere-based analytic chemistry system and method for making the same is disclosed in which microspheres or particles carrying bioactive agents may be combined randomly or in ordered fashion and dispersed on a substrate to form an array while maintaining the ability to identify the location of bioactive agents and particles within the array using an optically interrogatable, optical signature encoding scheme. A wide variety of modified substrates may be employed which provide either discrete or non-discrete sites for accommodating the microspheres in either random or patterned distributions. The substrates may be constructed from a variety of materials to form either two-dimensional or three-dimensional configurations. In a preferred embodiment, a modified fiber optic bundle or array is employed as a substrate to produce a high density array. The disclosed system and method have utility for detecting target analytes and screening large libraries of bioactive agents.

Abstract: A method of ex situ fabrication of at least one biochip, the method being of the type consisting in projecting onto a substrate a microvolume of reagent comprising at least one probe diluted in a suitable solvent so as to form, after the solvent has been eliminated, a spot comprising said probe, the method consisting in using a microprojection device comprising at least one tank in which the reagent is stored, and at least one source of gas under pressure put into communication with the tank, and in projecting the microvolume of reagent through an ejection nozzle under drive from the pressure exerted by the gas on the reagent.

Abstract: Methods and devices provide integrated synthesis of a support for analyte determination and the analyte determination. Preferred embodiments involve particles immobilized on the surface of a support to which receptors are coupled location-specifically, time-specifically or both on pre-determined positions on the support.

Abstract: A bead array chip manufacturing process for manufacturing a bead array chip having plural kinds of beads arrived in a predetermined order in, in a container having a plurality of first channels disposed substantially in parallel with each other and a second channel crossing the plurality of first channels, each of the first channels. The process including lowering a capillary inserted in the second channel and sucking and retaining one bead in one end of the capillary, lifting the capillary to position the beads retained in the one end of the capillary in a desired channel of the plurality of first channels, terminating the suction of the capillary, and generating a uniflow of a fluid in the second channel.

Abstract: The invention relates to a method for synthesizing templated molecules attached to the templated which directed the synthesis thereof. The method involves a template, a scaffold functional entity and a functional entity attached to a building block, which, in turn, is attached the template. The scaffold functional entity and the functional entity of the building block are both provided with complementary dimerization domains allowing the functional entities to come into close proximity when the complementary domains interact with to each other. The method may be used for generating libraries of templated molecules which may be selected for biological activity.

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: Random arrays of single molecules are provided for carrying out large scale analyses, particularly of biomolecules, such as genomic DNA, cDNAs, proteins, and the like. In one aspect, arrays of the invention comprise concatemers of DNA fragments that are randomly disposed on a regular array of discrete spaced apart regions, such that substantially all such regions contain no more than a single concatemer. Preferably, such regions have areas substantially less than 1 ?m2 and have nearest neighbor distances that permit optical resolution of on the order of 109 single molecules per cm2. Many analytical chemistries can be applied to random arrays of the invention, including sequencing by hybridization chemistries, sequencing by synthesis chemistries, SNP detection chemistries, and the like, to greatly expand the scale and potential applications of such techniques.

Abstract: Discrete microstructures of predefined size and shape are prepared using sol-gel phase-reversible hydrogel templates. An aqueous solution of hydrogel-forming material is covered onto a microfabricated silicon wafer master template having predefined microfeatures, such as pillars. A hydrogel template is formed, usually by lowering the temperature, and the formed hydrogel template is peeled away from the silicon master template. The wells of predefined size and shape on the hydrogel template are filled with a solution or a paste of a water-insoluble polymer, and the solvent is removed to form solid structures. The formed microstructures are released from the hydrogel template by simply melting the hydrogel template in water. The microstructures are collected by centrifugation. The microstructures fabricated by this method exhibit pre-defined size and shape that exactly correspond to the microwells of the hydrogel template.

Abstract: In a process for fabricating a nanopore device, at least one carbon nanotube catalyst region is formed on a structure. A plurality of nanopores is formed in the structure at a distance from the catalyst region that is no greater than about an expected length for a carbon nanotube synthesized from the catalyst region. Then at least one carbon nanotube is synthesized from the catalyst region. This fabrication sequence enables the in situ synthesis of carbon nanotubes at the site of nanopores, whereby one or more nanotubes articulate one or more nanopores without requiring manual positioning of the nanotubes.

Abstract: The present invention relates to methods, microarrays and kits for detecting one or more human astrovirus serotypes in a sample (e.g., a fecal sample) from an individual. The method includes amplifying nucleic acid molecules of the sample with one or more primers, to thereby obtain an amplified nucleic acid product; contacting the amplified nucleic acid product with one or more serotype specific probes having a nucleic acid sequence that is specific for only one astrovirus serotype in the group of astroviruses being assessed, wherein the nucleic acid sequence includes between about 9 and 25 nucleic acid bases (e.g., SEQ ID NO: 5-24); and detecting the hybridization complex. The presence of hybridization complexes with a serotype specific probe indicates the presence of one or more specific astrovirus serotypes, and the absence of hybridization complexes with a serotype specific probe indicates the absence of the specific astrovirus serotype.

Abstract: This invention relates generally to biosensor technology, and pertains more particularly to novel multifunctional biosensors based on ordered arrays of metallic, semiconductors and magnetic nano-islands for medical, biological, biochemical, chemical and environmental applications.

Abstract: Reference membrane components are either pre-labeled or labeled during assays for purposes of normalizing signals associated with binding or functional assays employing G-protein coupled receptor microarrays. A reference component may be included in a membrane in which the target GPCR is embedded or may be present in another membrane printed in conjunction with the target membrane on a microspot. Or, a GPCR microarray may be pre-labeled by incorporating a label on an exposed substrate in a defect in the printed microspot.

Abstract: A system for directly printing a variety of chemicals, including very large molecules on the substrate, includes a channel of nanometric dimension movable with respect to a substrate on which printing is to occur or a substrate movable with respect to the channel. Precision contact of the end aperture, or tip, of the channel with the surface deposits the chemical on the surface. Precision contact can be made by normal force atomic force microscopy or by other techniques that allow controlled contact or near contact with the surface on which the chemical is to be written with fine precision. Multiple channels with multiple orifices may be provided. The channel is connected to a suitable separation device such as a high performance liquid chromatograph and the chemicals are delivered through a probe orifice onto a substrate.

Abstract: Liquid delivery apparatus and methods, in particular for the production of high-density arrays, wherein a partial drop of liquid is deposited from a capillary (1) onto a substrate (12), the capillary (1) and substrate (12) being capable of x, y and z movements relative to one another under the control of a translation mechanism.

Abstract: A template-based system enables the assembly of macromolecules and nanostructures. The template system comprises a plurality of single strand DNA molecules which are substantially parallel, substantially inline each from one end, and substantially equally spaced apart, wherein each DNA molecule has a distinguishable length and a known sequence. The system can be used for the precise, accurate, and efficient synthesis of peptides, proteins and enzymes.

Abstract: The present disclosure relates to compositions and methods for screening a plurality of polypeptide variants.

Abstract: The present invention provides for certain polynucleotide sequences that have been correlated to AMD. These polynucleotides are useful as diagnostics, and are preferably used to fabricate an array, useful for screening patient samples. The array is used as part of a laboratory information management system, to store and process additional patient information in addition to the patient's genomic profile. As described herein, the system provides an assessment of the patient's risk for developing AMD, risk for disease progression, and the likelihood of disease prevention based on patient controllable factors.

Abstract: Disclosed are methods permitting colonies of nucleic acids produced by amplifying them in an immobilized medium to be visualized with a homogeneous fluorescence detection system which is introduced into the medium before amplification. No post-amplification steps, such as opening the gel, blotting, hybridization, and removal of unbound substrates, dyes, or probes are needed, and the growing molecular colonies can be monitored in real time. Also disclosed are methods for quantitative in situ assays of nucleic acids contained in individual cells or in tissue fragments. The methods are conveniently executed using a disposable transparent chamber containing dry matrix of the medium and equipped by inlet and outlet ports that serve for filling the chamber with a solution comprising components of amplification and detection systems, said solution being absorbed by said matrix to swell all over the inner volume of said chamber.

Abstract: Disclosed herein are novel nanoparticles, particularly metal nanoparticles, such as gold nanoparticles. According to one embodiment of a method disclosed herein nanoparticles are functionalized via ligand exchange reactions. Also disclosed is a method for controlling nanoparticle spacing to produce nanoparticle arrays having defined spacing. Such nanoparticles and arrays thereof are particularly useful in nanoelectronics, nanophotonics, catalysis, sensors, and biotaggents.

Abstract: The present invention relates to a spot pin (2) including: a liquid holding portion (21) including a tubular portion and defining a liquid holding space (27) for holding a liquid; and an upper limit position definition portion positioned in a middle of the liquid holding portion (21) in an axial direction and defining the upper limit position of the liquid held in the liquid holding portion (21). The upper limit position definition portion has one or a plurality of outside air communication holes (24) communicated with the liquid holding space (27) and opened in the circumferential surface of the liquid holding portion (21).

Abstract: The present invention provides a method of patterning, the method comprising the steps of: (a) providing a porous film; and (b) adding at least one structure to the porous film. The present invention also provides a patterned film prepared according to the method of the invention. The present invention also provides a method of preparing a porous film, and a porous film prepared according to the method of the invention.

Abstract: The present invention relates to a gene discovery system and gene expression systems specific for genes encoding ARE-containing mRNAs. In one aspect, the present invention relates to computational methods of selecting coding sequences of ARE-genes from databases using a one or more ARE search sequences. The ARE search sequences are from 10 to 80 nucleotides in length and comprise a sequence which is encompassed by one of the following two sequences: (a) WU/T(AU/TU/TU/TA)TWWW, SEQ ID NO. 1, wherein none or one of the nucleotides outside of the parenthesis is replaced by a different nucleotide, and wherein W represents A, U, or T; and (b) U/T(AU/TU/T/U/T)n, SEQ ID NO. 2 wherein n indicates that the search sequence comprises from 3 to 12 of the tetrameric sequences contained within the parenthesis. The method comprises extracting from the databases, those nucleic acids whose protein coding sequences are upstream and contiguous with a 3? untranslated region (UTR) that comprises one of the ARE search sequences.

Abstract: The present invention relates to novel methods for the quantitative detection of molecules in an array. In particular, the present invention relates to methods and apparatuses for producing a frameless array. In another embodiment, the present invention relates to a composition comprising nitrocellulose that is useful of producing a frameless array. In another embodiment, the present invention relates to a method for detecting a molecular interaction. In yet another embodiment, the present invention relates to kits useful for practicing the methods and apparatuses of the present invention. The present invention provides improved methods and apparatuses for the high throughput analysis of molecular interactions and quantitative detection.

Abstract: The present invention relates to artificial receptors and arrays or microarrays of artificial receptors or candidate artificial receptors. Each member of the array includes a plurality of building block compounds, typically immobilized in a spot on a support. The present invention also includes the building blocks, combinations of building blocks, arrays of building blocks, and receptors constructed of these building blocks together with a support. The present invention also includes methods of making and using these arrays and receptors.

Abstract: The present invention relates to artificial receptors, arrays or microarrays of artificial receptors or candidate artificial receptors, methods of and compositions for making them, and methods of using them. Each artificial receptor includes a plurality of building block compounds. In an embodiment, at least one of the building blocks includes a tether moiety. The tether can provide spacing or distance between the recognition element and the support or scaffold to which the building block is immobilized. A tether moiety can have any of a variety of characteristics or properties including flexibility, rigidity or stiffness, ability to bond to another tether moiety, and the like.

Abstract: The present inventions provides an apparatus and method for the parallel loading of multiple samples in a microarray containing a plurality of sub-arrays. The method makes use of a microarray containing multiple sub-arrays, a loading channel array, and a fluid handling robot or an assembly robot or machine.

Abstract: A diagnostic pollen array includes allergens extracted from pollen coat material. Diagnostic pollen arrays are useful to diagnose allergy in individuals, identify novel allergens, identify genetic loci responsible for allergy in hosts, and to develop treatment plans for allergy.

Abstract: A biosensor chip includes a substrate, a polymer having an anionic functional group and being arranged on a surface of the substrate, a polyamino group which is directly or indirectly bound to the anionic functional group at a surface of the polymer, and a long-chain alkyl-based group which is directly or indirectly bound to the anionic functional group at the surface of the polymer.

Abstract: The present invention relates to the field of molecular diagnostics. In particular, the present invention provided improved substrates and methods of using liquid crystals and other biophotonically based assays for quantitating the amount of an analyte in a sample. The present invention also provides materials and methods for detecting non-specific binding of an analyte to a substrate by using a liquid crystal or other biophotonically based assay formats.

Abstract: A microarray has a substrate and a plurality of three-dimensional microstructures formed on the substrate. Each of the three-dimensional microstructures is made with polymer material and has a plurality of reactive sites formed on its surface and interior pores. The polymer material is polymer gel or other porous polymer. The combination of three-dimensional microstructure and porous polymer material increases the surface area of the microstructure and density of the reactive sites on the surface of the microstructures. The higher density of reactive sites increases the luminescence, visibility or instrument detectability of the interaction between analytes and reactive microstructure sites on the microarray. A plurality of chemical groups are respectively attached to the reactive sites. The chemical groups each include at least one monomer. The chemical groups may have different chemical structures. A plurality of microchannels can be formed around the microstructures for isolation.

Abstract: Arrays and substrates comprising a material, in particular capture agents and/or detectable targets, attached to the substrates along substantially parallel lines forming a barcoded pattern and related methods and systems.

Abstract: A method of making a set of labelled compounds by the use of a preferably particulate support, comprises dividing the support into lots, performing a different chemical reaction on each lot of the support, e.g. to couple a chemical moiety to that lot of the support, tagging a fraction of each lot of the support with a different label, and combining the said lots of the support. The steps are repeated several times, preferably to build up oligomer molecules carrying labels which identify the nature and position of a monomer unit of the oligomer, and which are releasable from the support. Preferred labels, which are releasable from the compounds by cleavage to provide charged groups for analysis by mass spectrometry, are groups of the trityl (trimethylphenyl) family. Also claimed are libraries of these labels and their use in assays and nucleic acid analysis methods.

Abstract: This invention provides improved components (e.g. array “pins”, print head, substrate platen, print head platen, and the like) for microarray printing devices as well as microarray printing devices incorporating such components. In one embodiment, this invention provides a microarray print head comprising a plurality of glass or quartz spotting capillaries disposed in a support that maintains a fixed spacing between the spotting capillaries and that permits the spotting capillaries to move in a direction parallel to the long axis of the capillaries.

Abstract: The invention relates to novel silane compounds corresponding to the formula (I) below: A-E-X??(I) in which: X represents a silyl group capable of creating a covalent bond after reaction with the hydroxyl or hydride functional groups of a support; E represents an organic spacer group; A represents a group chosen from the groups of formulae below: in which: Z1 to Z5 independently represent a hydrogen atom or a halogen atom; Z6 and Z7 represent a group for protecting the phosphonic acid functional group, a hydrogen atom or a monovalent cation; Z8 to Z12 independently represent a group for protecting the carboxylic acid functional group, a hydrogen atom or a monovalent cation; and Z13 represents an imidazole, N-hydroxysuccinimide, nitrophenyl, pentafluorophenyl or acid anhydride group. Use of these silane compounds for functionalizing solid supports and for immobilizing biological molecules on these supports.

Abstract: A microfluidic device for isolating genomic DNA from human leukocytes, simultaneously capturing and measuring the DNA for simplifying genetic analysis. The device contains a fluid inlet port, a fluid outlet port, and a DNA binding channel in contact with the fluid inlet port wherein at least a portion of at least one surface within the DNA binding channel is modified with a binding reagent such that DNA is preferentially bound to the surface.

Abstract: The present invention relates to the synthesis of a beaded and cross-linked, high loading capacity polymer for solid phase synthesis, purification of reaction mixtures, chromatographic separation procedures, and the like. The invention can thus be used for the isolation of molecular entities having an affinity for the polymer beads or a chemical entity attached thereto. The beaded polymer matrix can be formed by cross-linking an optionally substituted poly(aminoalkylene), under inverse suspension or inverse emulsion polymerisation conditions, with a cross-linking unit of functionality ?2.

Abstract: An apparatus for use in fabricating structures and depositing materials from tips to surfaces for patterning in direct-write mode, providing ability to travel macroscopic distances and yet provide for nanoscale patterning. Useful in small scale fabrication and nanolithography. The instrument can be compact and used on a laboratory bench or desktop. An apparatus comprising: at least one multi-axis assembly comprising a plurality of nanopositioning stages, at least one pen assembly, wherein the pen assembly and the multi-axis assembly are adapted for delivery of material from the pen assembly to a substrate which is positioned by the multi-axis assembly, at least one viewing assembly, at least one controller. Nanopositioning by piezoelectric methods and devices and motors is particularly useful. The apparatus can include integrated environmental chambers and housings, as well as ink reservoirs for materials to be delivered. The viewing assembly can be a microscope with a long working distance.

Abstract: The present invention relates to a gene discovery system and gene expression systems specific for genes encoding ARE-containing mRNAs. In one aspect, the present invention relates to computational methods of selecting coding sequences of ARE-genes from databases using aone or more ARE search sequences. The ARE search sequences are from 10 to 80 nucleotides in length and comprise a sequence which is encompassed by one of the following two sequences: (a) WU/T(AU/TU/TU/TA)TWWW, SEQ ID NO. 1, wherein none or one of the nucleotides outside of the parenthesis is replaced by a different nucleotide, and wherein W represents A, U. or T; and (b) U/T(AU/TU/T/U/T)n, SEQ ID NO. 2, wherein n indicates that the search sequence comprises from 3 to 12 of the tetrameric sequences contained within the parenthesis. The method comprises extracting from the databases, those nucleic acids whose protein coding sequences are upstream and contiguous with a 3?untranslated region (UTR) that comprises one of the ARE search sequences.

Abstract: The present invention describes templated combinatorial chemical libraries comprised of a plurality of bifunctional molecules having both a chemical compound and a nucleic acid tag that defines the structure of the chemical compound and directs its synthesis. Also described are methods for producing, enriching and in vitro evolution of the bifunctional molecules of such libraries based on the nucleic acid tags and methods for selecting for library compounds having a desired activity.

Abstract: The invention relates to biosensors, methods for obtaining them and their use for detecting, assaying or locating, in direct immunofluorescence, a ligand such as an antigen or hapten, in a heterogeneous population. The biosensor includes (i) at least one fragment of a receptor which is protein in nature, capable of binding to a ligand via an active site, where at least one amino acid residues of the fragment located in the proximity of the active site is naturally present in the form of a cystein (Cys) residue, or is substituted with a Cys residue, and (ii) a fluorophore coupled to the Cys residue.

Abstract: This invention relates to methods of generating single stranded DNA libraries for use in amplification and sequencing reactions. In various aspects, the disclosed methods include: fragmenting DNA; polishing the fragments' ends; ligating the fragments to universal adaptors; performing strand displacement and extension of the nicked fragments; purifying the double-stranded ligation products; capturing the double-stranded ligation products onto a solid support; and isolating single stranded DNA library fragments, and binding these fragments to another solid support.

Abstract: The invention provides an ink jet device (10) for producing a biological assay-substrate by releasing a plurality of substances onto the substrate, the device comprising printing means (20), detection means (30,32,45,45?), filling means and cleaning means (120), and wherein the ink jet device further comprises control means for an automated production such that the production of the biological assay substrate is error tolerant for a multitude of error sources.