Abstract: The present invention related to a saccharide-based cholera toxin detection sensor for detection of Vibrio cholerae and its use. More specifically, the present invention relates to a carbohydrate chip for detection of Vibrio cholerae, a method for detecting Vibrio cholerae using the same, and a method for preparing the same, where the carbohydrate chip comprises GM1 pentasaccharide, GM2 tetrasaccharide, asialo GM1 tetrasaccharide, GM3 trisaccharide, galactose-? 1,3-N-acetylgalactosamine, lactose, and sialic acid that are immobilized on the surface of a solid substrate.

Abstract: Disclosed embodiments concern differentiating and classifying one or more targets using a perhalophenylazide-derived nanoparticle probe, or multiple such probes. Particular embodiments concern using statistical analysis to produce score plots illustrating the level of differentiation and/or classification. Also disclosed are methods for making perhalophenylazide-derived nanoparticle probes, individually or by using a microarray technique. Particular embodiments concern methods for using the per halophenylazide-derived nanoparticle probes to diagnose, detect, and/or treat a disease. Kits comprising the perhalophenylazide-derived nanoparticle probes are also disclosed.

Abstract: A process for the production of a reaction chamber assembly, wherein a flat substrate and bottomless reaction chambers are provided, the substrate is first loaded with a biological agent and then the bottomless reaction chambers are bonded glue-free to the substrate, in particular through laser bonding, and liquid-tight reaction chambers, for instance individual wells, individually connected wells, such as strips, or wells in the form of a microtiter plate, are obtained. The present invention further provides a kit comprising a substrate suitable for being loaded with at least one biological agent and at least one bottomless reaction chamber, wherein the kit is suitable for glue-free bonding of the bottomless reaction chamber to the substrate.

Abstract: The present invention relates to a protein or peptide printing method, comprising (a) a step for preparing nucleic acids and a cell-free protein synthesis system in an engraved plate composed of microscopic grooves having a specific opening shape, (b) a step for superimposing a substrate on the engraved plate so as to contact a protein or peptide to be synthesized in the microscopic grooves, and (c) a step for synthesizing the protein or peptide from the nucleic acids using the cell-free protein synthesis system in the microscopic grooves, and immobilizing the protein or peptide on the substrate along the specific opening shapes of the microscopic grooves.

Abstract: Disclosed are a structure with a nanopore and an apparatus for determining sequences of nucleic acids including the structure, the structure including three or more structures having facing surfaces, a plurality of oligonucleotides attached at one ends thereof to the surfaces, and a pore formed between the structures to which the plurality of oligonucleotides are bound, and allowing a pore of a desired size to be precisely formed by adjusting the length of a plurality of oligonucleotides.

Abstract: A device for individually analysing cells of interest, comprising (a) a channel for receiving the contents of a cell of interest, wherein the channel has an input end and an output end, and (b) a cell trapping site in proximity to the input end of the channel, wherein (i) the input end of the channel is adapted such that an intact cell of interest cannot enter the channel; and (ii) the channel contains one or more analytical components for analysing the contents of the cell of interest. In use, a cell is applied to the device, where it is trapped by the cell trapping means. The cell cannot enter the channel intact, but its contents can be released in situ to enter the channel's input end. The contents can then move down the channel, towards the output end, and they encounter the immobilised reagents, thereby permitting analysis of the cell contents.

Abstract: The present invention provides a method of forming one or more biological-binding areas on a substrate for biological-testing. The method includes activating at least a portion of a glass-ceramic substrate comprising glass and one or more metal containing compounds. The one or more metal containing compounds have a range of diameters that are less than about 300 nanometers in diameter and are spaced an average distance of at least one-half the midpoint of the diameter range apart. The one or more metals include compounds selected from metal oxides, metal nanoparticles, metal alloys, and atomic metals. The glass-ceramic substrate is heated to a temperature near the glass transformation temperature to form one or more metal nanoparticles in one or more ceramic biological-binding areas. The glass-ceramic substrate is etched to expose one or more metal.

Abstract: The present invention provide several methods of derivatizing a surface of a support with one or more linkers thus providing a suitable platform for synthesis of a polymer array, particular a nucleic acid array. Some methods derivatize a surface with a self-assembled monolayer (SAM) of a linker. The SAM confers advantages of hydrolytic stability, broad compatibility with synthesis and detection chemistries, and reduced emergence of latent functional groups during polymer array synthesis. Substrates can also be derivatized with multi-layers of SAMs providing greater hydrolytic stability. Substrates can also be derivatized by synthesizing a linker in situ on the substrate by atom transfer radical polymerization of functional and functional monomers. Appropriate selection of monomers reduces emergence of latent functional groups in subsequent array synthesis.

Abstract: A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations.

Abstract: The present invention provides compositions and methods to facilitate the identification of compounds that are capable of interacting with a biological macromolecule of interest. In one aspect, a composition is provided that comprises an array of one or more types of chemical compounds attached to a solid support, wherein the density of the array of compounds is at least 1000 spots per cm2. These compounds are typically attached to the solid support through a covalent interaction. In another aspect, the present invention provides methods for utilizing these arrays to identify small molecule partners for biological macromolecules of interest.

Abstract: A manufacturing method of a semiconductor element from a pattern formed body capable of attaining patterning efficiently with a high precision. The method includes a photoresist pattern formation step, a hydrophilicity imparting step and a photoresist pattern peeling step.

Abstract: A microarray comprises a carrier substrate and a plurality of immobilization particles configured to immobilize capture molecules. Each immobilization particle comprises a first sub-section bonded to the carrier substrate and a second sub-section which is exposed.

Abstract: The present invention relates to a device for isolating and recovering a biomolecule from a test sample. The device includes a support and at least one peelable layer deposited on at least a portion of the support. The peelable layer includes a substrate having a target component immobilized on the substrate. The device is effective for isolating and recovering a biomolecule having affinity to the target component. The present invention also relates to systems and methods of using the device. The present invention also relates to a biomolecule elution strip and related methods.

Abstract: A method of fabricating a microarray including the steps of: (a) contacting a substrate having wells with a reagent reactive with said substrate to produce a surface modification within said wells and a surface modification surrounding said wells; (b) polishing said substrate to produce a polished surface modification surrounding said wells, wherein said surface modification surrounding said wells is removed and said surface modification within said wells is retained, and (c) depositing a biopolymer onto said substrate, wherein different affinities of said surface modification within said wells and said polished surface facilitate localization of said biopolymer within said wells.

Abstract: This invention provides methods for attaching a nucleic acid to a solid surface and for sequencing nucleic acid by detecting the identity of each nucleotide analogue after the nucleotide analogue is incorporated into a growing strand of DNA in a polymerase reaction. The invention also provides nucleotide analogues which comprise unique labels attached to the nucleotide analogue through a cleavable linker, and a cleavable chemical group to cap the —OH group at the 3?-position of the deoxyribose.

Abstract: An object of the invention is to provide a metal nanoparticle array structure in which metal nanoparticle arrays are firmly bonded to the substrate thereof via chemical bonding or the like and in which the coverage with the metal nanoparticle arrays is high. The problem can be solved by using a metal nanoparticle array structure 10 that comprises a substrate 1, a immobilizing layer 2 formed on one surface 1a of the substrate 1, and metal nanoparticle arrays 3 formed on one surface 2a of the immobilizing layer 2, wherein the metal nanoparticle arrays 3 are so arrayed that multiple metal nanoparticles 4 can be at regular intervals and the metal nanoparticles 4 are bonded to each other via the modifying part 5 arranged on a surface thereof while the metal nanoparticles 4 are immobilized on one surface 2a of the immobilizing layer 2 via chemical bonds.

Abstract: There is disclosed a method of making an array for cell assays comprising the step of providing an array of structures on a substrate, each of said structures having a pre-defined topography thereon, and wherein at least one structure has a different topography from at least one other structure.

Abstract: A biochip includes a substrate, a photoresist pattern layer, a blocking layer, a bonding layer, at least one linker molecule, and a probe molecule. The photoresist pattern layer is formed on a surface of the substrate. The blocking layer is formed on the surface of the substrate at a region uncovered by the photoresist pattern layer. The bonding layer is covalently attached to the photoresist pattern layer. The at least one linker molecule is covalently bonded to the binding layer. The probe molecule is covalently bonded to the at least one linker molecule for specifically reacting with a to-be-detected molecule.

Abstract: A probe array substrate suitable for forming a probe array that has high packing density, that can hold sufficient amounts of probe molecules, and that has little variation in the amounts of probe molecules. A plurality of arrayed probe-holding portions are defined by recesses, and isolating grooves are formed between the adjacent probe-holding portions to prevent probe solutions introduced into the probe-holding portions from spreading to adjacent probe-holding portions. Inner surfaces of the probe-holding portions are made hydrophilic, whereas inner surfaces of the isolating grooves are made hydrophobic. Liquid-introducing protrusions are formed in the probe-holding portions.

Abstract: A method of manufacturing a substrate is provided. The method comprises, in some aspects, a) providing a support; b) forming a template by attaching a plurality of polymeric nanoparticles some or all having a core-shell structure to the support, wherein the core comprises a first polymer and the shell comprises a second polymer; and c) forming the metal nanoarray substrate by attaching a plurality of metallic nanoparticles to at least some of the polymeric nanoparticles of the template. A biosensor comprising a substrate manufactured by the method, and a method for the detection of an analyte in a sample by surface enhanced Raman spectroscopy (SERS) is also provided.

Abstract: A method of preparing a substrate with a composition comprising (i) an organoborane initiator and (ii) a radical curable component disposed thereon includes the step of depositing the composition onto the substrate wherein at least one of (i) the organoborane initiator and (ii) the radical curable component is deposited onto the substrate in the form of a gradient pattern. An article comprises the substrate and the gradient pattern formed on the substrate. The gradient pattern is formed from a developed composition comprising the reaction product of (i) the organoborane initiator and (ii) the radical curable component. By forming the gradient pattern on the substrate, combinatorial and high-throughput methods of generating and testing the developed composition are possible, which enable characterization of the developed composition for various physical and chemical properties.

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: The invention provides a novel array method for nucleic acid sequence detection with improved specificity which allows for detection of genetic variation, from simple SNPs (where the variation occurs at a fixed position and is of limited allelic number) to more complex sequence variation patterns (such as with multigene families or multiple genetic strains of an organism where the sequence variation between the individual members is neither fixed nor consistent). The array is comprised of short, synthetic oligonucleotide probes attached to a solid surface which are hybridized to single-stranded targets. Single stranded targets can be produced using a method that employs primers modified on the 5? end to prohibit degradation by a 5?-exonuclease that is introduced to degrade the unprotected strand. The invention further provides for printing buffers/solutions for the immobilization of oligonucleotide probes to an array surface.

Abstract: The disclosure relates to a method of forming a pattern having pattern elements with a plurality of sizes on a substrate surface with a tilted pen array that includes choosing a tilt geometry for a pen array with respect to a substrate, inducing the tilt geometry between the pen array and the substrate surface, and forming a pattern having pattern elements on the substrate surface with the titled pen array, whereby the size of the formed pattern elements varies across the substrate surface along the tilted axis or axes. For example, the tilt geometry is in reference to the substrate surface and comprises a first angle with respect to a first axis of the substrate and a second angle with respect to a second axis of the substrate, the second axis being perpendicular to the first axis, and at least one of the first and second angles being non-zero.

Abstract: A method for immobilizing a self-organizing material or fine particles on a substrate, and a substrate whereupon the self-organizing material or the fine particles are immobilized. More specifically, the method for immobilizing the fine particles including a nucleic acid (for instance, DNA or RNA) or a metal oxide on the substrate, and the substrate whereupon the nucleic acid (for example, DNA or RNA) or the metal oxide is immobilized.

Abstract: A method for drug screening is provided. An atomic force microscopy (AFM) is used to obtain quantitative difference. At least one receptor is immobilized on a probe of the AFM and at least one ligand is immobilized on chips. By flowing a candidate drug on the chips or even applying different candidate drugs to different areas of each chip, drug screening is processed through measuring the binding force between the receptor and the ligand. Multiple drugs can be screened without weakening activity of the proteins during repeated drug screening processes. The drug screening process is cost saved and has high quality. Highly effective protein chips can be developed based on the present disclosure.

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: The invention concerns a nanostructured device (100) comprising a substrate (101), an intermediate layer (102), a zone (103) consisting of multiple three-dimensional structured sites (104) made of semiconductor material, having chemical species (106) fixed to the surface of said three-dimensional nanostructured sites (104). The inventive device is useful for making a biochip and an electronic memory. The invention also concerns a method for forming an electronic memory.

Abstract: A substrate includes; a fiducial mark disposed on the substrate, an area on the substrate on which a probe material is configured to be immobilized, the area being separated from the fiducial mark, and a probe immobilization compound disposed on the area on the substrate on which the probe material is configured to be immobilized, wherein the fiducial mark has a structure which reflects irradiated light at a greater intensity than an intensity of reflected irradiated light form the area on the substrate not corresponding to the fiducial mark.

Abstract: Provided is a surface having metal regions and an interstitial region having a composition that differs from the metal regions, wherein a continuous gel layer coats the surface across the metal regions and the interstitial regions. Nucleic acids or other analytes can be attached to the continuous gel layer such that a greater amount is attached over the metal regions than over the interstitial region. Also provided are methods for making such surfaces. Methods are also provided for making an array of nucleic acids or other analytes using such surfaces.

Abstract: The present invention is directed to restricted access media (RAM), methods for preparing restricted access media, and kits for preparing restricted access media that contain protected ligand binding agents or protected enzymes. Certain RAM provided contain a plurality of protected regions of the support that contain ligand binding agents that are protected by blocking agents. Certain RAM provided contain a plurality of protected regions of the support that contain unbound ligand binding agents or enzymes that are retained in the protected regions by a capping agent.

Abstract: The invention is directed to enzyme immobilization compositions comprising: one or more enzymes, a humectant, an acrylic-based monomer, a water-soluble organic photo-initiator and a water-soluble acrylic-based cross-linker in a substantially homogeneous aqueous mixture. The invention is also directed to methods for forming sensors comprising such compositions and to apparati for forming arrays of immobilized layers on an array of sensors by dispensing such compositions onto a substrate.

Abstract: The present disclosure relates to photoactivable protecting groups containing a diarylsulfide chromophore, a method for the synthesis thereof and their use as photoactivable protecting groups using maskless photolithography based array synthesis.

Abstract: The present invention provides a method and a kit for selecting and enriching target sequences specific for a genomic region of interest or a subset of a transcriptome using a target-capturing sequence library. The target-capturing sequence library comprises random DNA fragments generated from a target sequence template encompassing all the target sequences. The present invention provides an efficient and cost-effective method of target selection for targeted genome resequencing.

Abstract: Carriers or holders for holding microfluidic devices are provided. Some of the carriers that are provided include a hydration control device and/or a source of controlled fluid pressure to facilitate use of the carrier in conducting various types of analyses.

Abstract: The present invention relates to a microarray comprising at least 50,000 oligopeptide features per cm2 where the oligopeptide features represent at least 50%, 60%, 70%, 80%, 90%, 95%, 99%, or 100% of the proteome of a virus or an organism. The present invention further relates to methods for the synthesis of such microarrays and methods of using microarrays comprising at least 50,000 oligopeptide features per cm2. In an embodiment of the invention, the oligopeptide features represent proteins expressed in the same species, wherein the oligopeptide features are presented in a tiling pattern representing at least about 5,000 to-at least about 25,000 proteins expressed in a species. In some embodiments, the oligopeptide microarray features represent proteins expressed in the same species, wherein the microarray features are present in a tiling pattern that represents at least about 5,000 to at least about 50,000 expressed proteins.

Abstract: A method of performing a fluid-material assay employing a device including at least one active pixel having a sensor with an assay site functionalized for selected fluid-assay material. The method includes exposing the pixel's sensor assay site to such material, and in conjunction with such exposing, and employing the active nature of the pixel, remotely requesting from the pixel's sensor assay site an assay-result output report. The method further includes, in relation to the employing step, creating, relative to the sensor's assay site in the at least one pixel, a predetermined, pixel-specific electromagnetic field environment.

Abstract: An oligopeptide microarray and methods for the synthesis thereof are presented. Further presented is a microarray on a solid support comprising at least about 10,000 oligopeptide features per cm2 and preferably at least about 50,000 oligopeptide features per cm2.

Abstract: A method for producing a bilayer, the method comprising: (a) providing a hydrated support and a hydrophilic body immersed in a hydrophobic medium; wherein a first monolayer of amphipathic molecules is formed on an interface between the hydrophobic medium and the hydrophilic body and a second monolayer of amphipathic molecules is formed on an interface between the hydrophobic medium and the hydrated support; and (b) bringing the first monolayer into contact with the second monolayer to form a bilayer of amphipathic molecules, wherein at least part of a cell membrane, comprising cell membrane constituents, is provided in or on the hydrated support and/or in the hydrophilic body, and such that constituents of the cell membrane incorporate into the bilayer during or after the bilayer formation. A bilayer produced by the method of the invention, and uses of the bilayer.

Abstract: An oligomer probe array with improved signal-to-noise ratio and desired detection sensitivity even when a reduced design rule is employed includes a substrate, a plurality of probe cell active regions formed on or in the substrate, each of the plurality of probe cell active regions having a three-dimensional surface and being coupled with at least one oligomer probe with its own sequence, and a probe cell isolation region defining the probe cell active regions and having no functional groups for coupling with the oligomer probes on a surface.

Abstract: Methods and reagents for site-selective functionalization of peptides and proteins. The methods most generally involve the reaction of a thioester with hydrazine. Reagents include bifunctional reagents of formula: H2N—NH—CH2-M-L-FG and salts thereof where M is a single bond or a chemical group carrying a non-bonding electron pair, such as —C(O)NR?—, where R? is H, or an alkyl or aryl group; L is an optional linker group as described above; and FG is a functional group having reactivity that is orthongonal to that of the hydrazine group. FG can, among others, be an azide, alkenyl, alkynyl, nitrile (—CN) or triazole group and is preferably an azide group (—N3). Methods and reagents can, for example, be combined with intein-mediated protein splicing to link proteins or fragments thereof to various chemical species or to a surface.

Abstract: Fluidic conduits, which can be used in microarraying systems, dip pen nanolithography systems, fluidic circuits, and microfluidic systems, are disclosed that use channel spring probes that include at least one capillary channel. Formed from spring beams (e.g., stressy metal beams) that curve away from the substrate when released, channels can either be integrated into the spring beams or formed on the spring beams. Capillary forces produced by the narrow channels allow liquid to be gathered, held, and dispensed by the channel spring probes. Because the channel spring beams can be produced using conventional semiconductor processes, significant design flexibility and cost efficiencies can be achieved.

Abstract: Described are systems, devices, and methods which related to various aspects of assays for detecting and/or determining a measure of the concentration of analyte molecules or particles in a sample fluid. In some cases, the systems employ an assay consumable comprising a plurality of assay sites. The systems, devices, and/or methods, in some cases, are automated. In some cases, the systems, devices, and/or methods relate to inserting a plurality of beads into assay sites, sealing assay sites, imaging assay sites, or the like.

Abstract: A method for producing an active-matrix, fluid-assay micro-structure including, utilizing low-temperature TFT and Si technology, establishing preferably on a glass or plastic substrate a matrix array of digitally-addressable, assay-material-specific-functionalizable pixels, and employing pixel-specific digital addressing for selected, array-established pixels, individually functionalizing these pixels.

Abstract: A method and device is disclosed for increasing droplet and micro-well reactor densities per unit area for microfluidic platforms. The device and method use controlled Height to Droplet Diameter Ratios (HDR) of the collection region which can produce different crystalline packing formations. HDR ratios above unity and less than about 2.65 are used to create a variety of three-dimensional packing schemes with increased density over conventional single layer hexagonal packing.

Abstract: The present invention provides massively parallel oligonucleotide synthesis and purification for applications that utilize large collections of defined high-fidelity oligonucleotides (e.g., from about 101 to about 105 different sequences, generally between 25-160 bases in length).

Abstract: The present invention provides a method of creating an array of features. The method can include steps of (a) providing a plurality of beads, wherein each bead in the plurality of beads includes probe content; (b) contacting the plurality of beads with a surface to produce a layer of beads on the surface; and (c) transferring the probe content from the beads to the surface to create an array of spatially discrete features on the surface, wherein each spatially discrete feature includes probe content from a bead in the plurality of beads.

Abstract: Methods for genotyping polymorphisms using a locus specific primer that is complementary to a region near a selected polymorphism are described. Methods for synthesizing pools of locus specific primers that incorporate some degenerate positions are also disclosed. A plurality of different sequence capture probes are synthesized simultaneously using degenerate oligonucleotide synthesis. The sequence of the locus specific regions of the capture probes are related in that they have some bases that are identical in each sequence in the plurality of sequences and positions that vary from one locus specific region to another. The sequences are selected based on proximity to a polymorphism of interest and because they conform to a similar sequence pattern.

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: The invention provides methods for controlling the density of different molecular species on the surface of a solid support. A first mixture of different molecular species is attached to a solid support under conditions to attach each species at a desired density, thereby producing a derivatized support having attached capture molecules. The derivatized support is treated with a second mixture of different molecular species, wherein different molecular species in the second mixture bind specifically to the different capture molecules attached to the solid support. One or more of the capture molecules can be reversibly modified such that the capture molecules have a different activity before and after the second mixture of molecular species are attached. In particular embodiments, the different molecular species are nucleic acids that are reversibly modified to have different activity in an amplification reaction.