Abstract: This disclosure provides methods and compositions for sample processing, particularly for sequencing applications. Included within this disclosure are bead compositions, such as diverse libraries of beads attached to large numbers of oligonucleotides containing barcodes. Often, the beads provides herein are degradable. For example, they may contain disulfide bonds that are susceptible to reducing agents. The methods provided herein include methods of making libraries of barcoded beads as well as methods of combining the beads with a sample, such as by using a microfluidic device.

Abstract: Disclosed herein are methods of method of making a substrate for performing a chemical synthesis reaction.

Abstract: There is provided a microarray comprising a plurality of active agents immobilized onto an array of porous nanostructures, wherein each nanostructure has a network of pores that extends throughout the thickness of said nano structure.

Abstract: A method of forming a lipid membrane attached linker comprises contacting a lipid membrane with an oligonucleotide having a first strand and a second strand of nucleic acid and two or more hydrophobic anchoring moieties located in its terminal ends. The two strands are hybridized to each other in a duplex section in a manner that the first strand terminal end is not a part of the duplex section and free from a hydrophobic anchoring moiety and the two or more hydrophobic anchoring moieties are covalently attached to the adjacent terminal ends of the first strand and the second strand of said oligonucleotide, thereby accomplishing a direct attachment of the oligonucleotide by the moieties on the same membrane.

Abstract: The invention relates to methods of generating templates for a nucleic acid sequencing reaction which comprise: providing at least one double-stranded nucleic acid molecule, wherein both strands of the double-stranded nucleic acid molecule are attached to a solid support at the 5? end, cleaving one or both strands of the double-stranded nucleic acid molecule, and subjecting the cleaved strand(s) to denaturing conditions to remove the portion of the cleaved strand(s) not attached to the solid support, thereby generating a partially or substantially single-stranded template for a nucleic acid sequencing reaction,

Abstract: Disclosed herein are formulations, substrates, and arrays. Also disclosed herein are methods for manufacturing and using the formulations, substrates, and arrays. Also disclosed are methods for identifying peptide sequences useful for diagnosis and treatment of disorders, and methods for using the peptide sequences for diagnosis and treatment of disorders, e.g., celiac disorder. In certain embodiments, substrates and arrays comprise a porous layer for synthesis and attachment of polymers or biomolecules.

Abstract: The present invention is directed to tube-in-a-tube electronic materials and electronic chemical sensors comprising tube-in-a-tube configurations such as covalently functionalized double-walled carbon nanotubes.

Abstract: The present invention provides a formulation to link protein to a solid support that comprises one or more proteins, Oligo-dT and one or more non-volatile, water-soluble protein solvents, solutes or combination thereof in an aqueous solution. Further provided is a method of attaching a protein to a surface of a substrate. The formulations provided herein are contacted onto the substrate surface, printed thereon and air dried. The substrate surface is irradiated with UV light to induce thymidine photochemical crosslinking via the thymidine moieties of the Oligo-dT.

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: A chemical sensor comprising: a hydrogel layer, comprising one or more molecular recognition agents and a 2DPC self-assembling array; and a mirror layer. A method for analyzing a sample or bodily fluid, comprising: obtaining a sample or bodily fluid; placing an amount of the sample or bodily fluid onto a chemical sensor, comprising: a hydrogel layer, comprising a molecular recognition agent and a 2DPC self-assembling array; a tethering hydrogel layer; a mirror layer; and a membrane filter layer, allowing the bodily fluid to interact with the hydrogel layer; and allowing ambient or artificial light to pass through the hydrogel layer onto the mirror layer and observing a change in diffraction versus a control.

Abstract: The disclosure relates to the field of candidate drug testing and drug development. A method is provided for providing a compound composed of at least one molecule attached via at least two linkages to a molecular scaffold, the method comprising providing a scaffold comprising at least a first and a second reactive group; providing at least one molecule capable of reacting with the at least first and second reactive group; contacting the scaffold with at least one molecule to form at least two linkages between the scaffold and the at least one molecule in a coupling reaction, wherein the formation of a linkage accelerates the formation of a consecutive linkage, preferably wherein the coupling reaction is performed in solution, more preferably in an aqueous solution. Furthermore, a method is provided for selecting a candidate drug compound comprising providing a library of compounds hereof and determining the binding of a target molecule to the compounds.

Abstract: A protein chip including at least a substrate having a plurality of steps which are regularly arranged on one surface thereof; a plurality of metallic microstructures arranged in the steps; and a lipid vesicle in which an outer surface thereof is modified by a functional group and a protein is present in a lipid bilayer thereof. The metallic microstructures and the lipid vesicle are bound via the functional group to provide the protein on the substrate.

Abstract: A method of patterning a surface of a substrate comprising: (a) applying a coating to the surface to form a coated surface, and (b) treating the coated surface with a patterned microplasma comprising a plurality of localised microplasma discharges such that localised regions of the coated surface are selectively exposed to the localised microplasma discharges to form exposed localised regions and unexposed regions that have not been substantially exposed to a microplasma discharge; wherein the coating at the exposed localised regions is modified by the patterned microplasma and the coating at the unexposed regions is substantially unmodified to form a patterned surface on the substrate.

Abstract: A protein-immobilizing solid phase is a protein-immobilizing solid phase comprising an mRNA-nucleic acid linker-protein complex, obtained by linking the mRNA and the protein encoded by that mRNA through the nucleic acid linker, immobilized on the solid phase, wherein the nucleic acid linker has a photocleavage site and a solid phase binding site.

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: The present invention relates to methods and devices for amplifying nucleic acid, and, in particular, amplifying so as to generate products on a surface without the use of emulsions. In a preferred embodiment, a plurality of groups of amplified product are generated on the surface, each group positioned in different (typically predetermined) locations on said surface so as to create an array.

Abstract: This disclosure provides microwell capsule array devices. The microwell capsule array devices are generally capable of performing one or more sample preparation operations. Such sample preparation operations may be used as a prelude to one more or more analysis operations. For example, a device of this disclosure can achieve physical partitioning and discrete mixing of samples with unique molecular identifiers within a single unit in preparation for various analysis operations. The device may be useful in a variety of applications and most notably nucleic-acid-based sequencing, detection and quantification of gene expression and single-cell analysis.

Abstract: Polymer Pen Lithography is used to induce bioorthogonal reactions between treated surfaces and functionalized inks create a soft matter layer. Fluorescent and redox-active inks were used to demonstrate that the molecules were immobilized covalently and achieves precise control over ligand orientation and density within each feature. Finally, the utility was demonstrated by creating functional arrays of biologically active probes.

Abstract: Solid supports comprising polymers covalently bound to a solid substrate are provided. The polymers find utility in any number of applications including immobilizing analyte molecules to solid supports for high throughput assays.

Abstract: The present invention provides microarrays that can be analysed by more than one technique using a non-covalent ligand attachment strategy to solid supports such as indium tin oxide (ITO) covered transparent glass slides. This provides, inter alia, glycan arrays on a micrometer scale which allow multimodal readout by MALDI-Tof-MS, fluorescence and optical microscopy. Glycans functionalized with a C5-aminolinker were attached in situ on a picomolar scale to a hydrophobic tag bound to this surface, thus avoiding the wasteful off-chip ligand tagging of other approaches. Glycan arrays prepared using this methodology were analysed both with a fluorescence scanner and by on-chip MALDI-mass spectrometry in a series of glycomics experiments specifically requiring a multimodal readout.

Abstract: Surface chemistries for the visualization of labeled single molecules (analytes) with improved signal-to-noise properties are provided. To be observed, analyte molecules are bound to surface attachment features that are spaced apart on the surface such that when the analytes are labeled adjacent analytes are optically resolvable from each other. One way to express this concept is that binding elements should be spaced apart such that the Guassian point spread functions of adjacent labels do not overlap. Another way of expressing this concept is that the surface binding elements should be spaced apart by a distance equal to at least the diffraction limit for an optical label attached to the bound analytes.

Abstract: The present invention relates generally to cinnamate crosslinkers. Specifically, the present invention relates to gels, biochips, and functionalized surfaces useful as probes, in assays, in gels, and for drug delivery, and methods of making the same using a newly-discovered crosslinking configuration.

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: A multi-spot metal-capped nanostructure array nucleic acid chip for diagnosing corneal dystrophy, and more particularly to a multi-spot metal-capped nanostructure array nucleic acid chip capable of employing LSPR (localized surface plasmon resonance) optical properties, a preparation method thereof, and a multi-spot metal-capped nanostructure array nucleic acid chip for diagnosing BIGH3 gene mutations, which can diagnose various corneal dystrophies. The metal-capped nanostructure array nucleic acid chip can be combined with analysis devices, including a light source, a detector, a spectrophotometer and a computer, to provide an LSPR optical property-based optical biosensor, and the use of the multi-spot metal-capped nanostructure array nucleic acid chip for diagnosing BIGH3 gene mutations allows the simultaneous diagnosis of various corneal dystrophies that are genetic ocular diseases.

Abstract: Provided is an array including a solid support having a surface, the surface having a plurality of wells, the wells containing a gel material, the wells being separated from each other by interstitial regions on the surface, the interstitial regions segregating the gel material in each of the wells from the gel material in other wells of the plurality; and a library of target nucleic acids in the gel material, wherein the gel material in each of the wells comprises a single species of the target nucleic acids of the library. Methods for making and using the array are also provided.

Abstract: Described herein are RNA arrays, and compositions and methods for generating RNA arrays, particularly high density RNA arrays. The disclosed methods for generating RNA arrays utilize template DNA arrays and RNA polymerase to generate RNA arrays. In some embodiments, the disclosed methods use an RNA polymerase and modified ribonucleosides to generate modified RNA arrays for various applications, e.g. RNA arrays having higher nuclease resistance, more conformationally stable RNA arrays, and higher binding affinity RNA aptamer arrays. In some embodiments, the disclosed methods are used to generate RNA bead arrays.

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: An article such as a biomolecular detector or biosensor having a nonfouling surface thereon includes: (a) a substrate having a surface portion; (b) a linking layer on the surface portion; and (c) a polymer layer formed on the linking layer; and (d) a first member of a specific binding pair (e.g., a protein, peptide, antibody, nucleic acid, etc.) bound to the polymer layer. Methods of making and using the articles are also described.

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: A method for manufacturing a biochip is provided. First, a first self-assembled monolayer is coated on a substrate. Next, a plurality of first biomedical molecular dots are formed on the first self-assembled monolayer by micro-titration technique. After the bonding reaction between the first biomedical molecular point and the first self-assembled monolayer, a second self-assembled monolayer is deposited on the surface of the first self-assembled monolayer by evaporation. The second self-assembled monolayer attached on the plurality of first biomedical molecular dots and the first self-assembled monolayer not bonded to the substrate are removed, so that the first biomedical molecular dots immobilized on the first self-assembled monolayer are exposed. Finally, a second biomedical molecular layer is immobilized on the exposed portions of the first biomedical molecular dots.

Abstract: A microarray is disclosed comprising a reaction zone and a labeling zone, wherein the at least one labeling zone contains a marker, such as an alphanumerical code, a binary code, a barcode, a 2D code, a colour code or a triplet code and wherein the marker allows the identification of the microarray.

Abstract: A microarray is designed capture one or more molecules of interest at each of a plurality of sites on a substrate. The sites comprise base pads, such as polymer base pads, that promote the attachment of the molecules at the sites. The microarray may be made by one or more patterning techniques to create a layout of base pads in a desired pattern. Further, the microarrays may include features to encourage clonality at the sites.

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: Embodiments of the invention are directed to a one-bead-two-compound method for the creation of encoded cyclic peptoid libraries. This scheme is useful for the creation of cyclic peptoid microarrays since only the cyclic peptoid, not the linear encoding molecule, contains an attachment residue and thus can be spotted onto an activated substrate.

Abstract: The present disclosure provides apparatuses, systems, and methods involving a spotter for depositing a substance on a submerged surface. The spotter comprises an outlet cavity defined at least in part by a spotting orifice, a first opening, and a second opening. The spotter also comprises a first conduit fluidly coupled to the first opening and a second conduit fluidly coupled to the second opening. The spotter is adapted so that fluid flowing through the first conduit and the second conduit is communicated among the first opening, the second opening, and a submerged deposition surface when the sealing orifice is sealed against the submerged deposition surface to form a deposition spot on the submerged deposition surface. The submerged deposition surface is within a liquid such that the liquid covers the deposition spot upon removal of the orifice from the deposition surface.

Abstract: Disclosed are compositions, devices, and methods for loading molecules of interest onto a substrate by contacting beads having molecules of interest attached to them with the substrate, for example by providing a field that brings the beads into proximity or contact with the substrate and moves the beads with respect to the substrate. Such molecules of interest can be deposited onto substrates for single-molecule analysis.

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: Methods for screening and arranging microorganisms such as viruses in an array using subtractive contact printing are provided. In one embodiment, a method for forming an array of receptors for microorganisms comprises: patterning an array of structures on a first substrate to form a template on a surface of the first substrate; applying a receptor material to a face of a second substrate; and contacting the face of the second substrate with the template to remove a portion of the receptor material from the second substrate, thereby forming an array of receptors on the second substrate.

Abstract: Methods for screening and arranging microorganisms such as viruses in an array using subtractive contact printing are provided. In one embodiment, a method for forming an array of receptors for microorganisms comprises: patterning an array of structures on a first substrate to form a template on a surface of the first substrate; applying a receptor material to a face of a second substrate; and contacting the face of the second substrate with the template to remove a portion of the receptor material from the second substrate, thereby forming an array of receptors on the second substrate.

Abstract: Methods and systems for label-free multiple analyte sensing, biosensing and diagnostic assay chips consisting of an array of photonic crystal microcavities along a single photonic crystal waveguide are disclosed. The invention comprises an on-chip integrated microarray device that enables detection and identification of multiple species to be performed simultaneously using optical techniques leading to a high throughput device for chemical sensing, biosensing and medical diagnostics. Other embodiments are described and claimed.

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

Abstract: The present 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 invention relates to a device and a method for the generation of molecular microarrays. The invention relates therefore to a universal approach for the generation of protein microarrays, DNA microarrays and RNA microarrays (in general nucleic acid microarrays), by production of an output molecule from a template molecule microarray via enzymatic or chemical processes and transfer of the output molecule onto the desired molecular microarray.

Abstract: The invention provides methods, apparatuses, and compositions for high-throughput amplification sequencing of specific target sequences in one or more samples. In some aspects, barcode-tagged polynucleotides are sequenced simultaneously and sample sources are identified on the basis of barcode sequences. In some aspects, sequencing data are used to determine one or more genotypes at one or more loci comprising a causal genetic variant.

Abstract: Guided cell patterning arrays for single cell patterning are disclosed. The arrays include a plurality of cell adhesion sites that are individually isolated on an inert surface. Each cell adhesion site has one or more cell adhesion peptides having affinity to a cell surface receptor. The inert surface is resistant to cell adhesion.

Abstract: A bifunctional linker and method of use is provided that has a spacer molecule with a functional group on one end configured to couple to the surface of a substrate and a function group on the other end that is configured couple to a biomolecule and methods of use. The preferred bifunctional linker has a poly(ethylene glycol) spacer ranging from 3 to 20 ethylene glycol units that has a silane functional group to react with a substrate and an azide functional group that can couple to a biomolecule that includes an alkyne group. The preferred linker can produce an azide-derivatized glass surface in one step and the azide functional group of the spacer can in sequence conjugate with a biomolecule using click chemistry, which can be conducted at low temperature and in aqueous solution.

Abstract: A combinatorial elastic modulus-modified microenvironment microarray (eMEArray) platform and methods for cell-based functional screening of interactions with combinatorial microenvironments. The platform and methods allow for simultaneous control of the molecular composition and the elastic modulus, and combines the use of microarray and micropatterning technologies. The eMEArrays have been used to show that the microenvironment has effects on drug-cell interactions and contributes to therapeutic response.

Abstract: A system and method for electrically detecting a target material in a sample without the need for labeling is described. A probe supporting member defining at least one hole is functionalized with target specific probe material and a change in the hole area on binding of target material is detected as a change in an ionic current through the hole. In some embodiments, an electro-chemical cell comprising an electrode having a conducting layer and a porous insulating layer is provided. In some embodiments, an electrically addressable array is provided for detection of a potentially large number of target materials in a sample.

Abstract: A microarray formed in a planar surface of a moldable slab, the microarray including a plurality of microwell sets comprising a plurality of microwells formed in the planar surface of the moldable slab, each microwell being sized to contain at least a single cell, and a plurality of microchannels formed in the planar surface of the moldable slab, the plurality of microchannels being configured to permit liquid from a first region of the microarray to transit to a second region of the microarray.