Abstract: A method and device for periodically perturbing the flow field within a microfluidic device to provide regular droplet formation at high speed.

Abstract: A plurality of isolated microvessels including a plurality of encoded microvessels each having a microbody and a reservoir core. The microbody is configured to separate a biological or chemical substance in the reservoir core from an ambient environment surrounding the microbody. The microbody includes a transparent material that at least partially surrounds the reservoir core and facilitates detection of an optical characteristic of the substance within the reservoir core. The microbody of each microvessel includes an identifiable code that distinguishes individual microvessels of the plurality of encoded microvessels from each other. The plurality of isolated microvessels also includes a plurality of compartments each configured to separate individual microvessels of the plurality of encoded microvessels from each other.

Abstract: A testing method of nucleic acid binding protein based on biochip, comprises the following steps: 1. puts a plurality of groups solution including nucleic acid captured probes into biological sample including a plurality of nucleic acid binding protein to be test, and thus forming nucleic acid captured probe-nucleic acid binding protein complexes; such nucleic acid captured probe includes at least a segment of binding sequence which can bind with aimed nucleic acid binding protein; 2. separates such nucleic acid captured probe-nucleic acid binding protein complexes, then recoveries nucleic acid captured probes; 3. hybridizes the nucleic acid captured probes according to step 2 with a plurality of single strand blotting probes on biochip substrate; the sequence of such blotting probe compensates with such nucleic acid captured probe or one of its strand; 4. detects the result of hybridization.

Abstract: The present invention relates to methods and products for the localized or spatial detection of nucleic acid in a tissue sample and in particular to a method for localized detection of nucleic acid in a tissue sample comprising: (a) providing an array comprising a substrate on which multiple species of capture probes are directly or indirectly immobilized such that each species occupies a distinct position on the array and is oriented to have a free 3? end to enable said probe to function as a primer for a primer extension or ligation reaction, wherein each species of said capture probe comprises a nucleic acid molecule with 5? to 3?: (i) a positional domain that corresponds to the position of the capture probe on the array, and (ii) a capture domain; (b) contacting said array with a tissue sample such that the position of a capture probe on the array may be correlated with a position in the tissue sample and allowing nucleic acid of the tissue sample to hybridize to the capture domain in said capture probes;

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 invention is directed to a method of designing a plurality of capture oligonucleotide probes for use on a support to which complementary oligonucleotide probes will hybridize with little mismatch, where the plural capture oligonucleotide probes have melting temperatures within a narrow range. The first step of the method involves providing a first set of a plurality of tetramers of four nucleotides linked together, where (1) each tetramer within the set differs from all other tetramers in the set by at least two nucleotide bases, (2) no two tetramers within a set are complementary to one another, (3) no tetramers within a set are palindromic or dinucleotide repeats, and (4) no tetramer within a set has one or less or three or more G or C nucleotides. Groups of 2 to 4 of the tetramers from the first set are linked together to form a collection of multimer units.

Abstract: This invention provides substrates for use in various applications, including single-molecule analytical reactions. Methods for propagating optical energy within a substrate are provided. Devices comprising waveguide substrates and dielectric omnidirectional reflectors are provided. Waveguide substrates with improved uniformity of optical energy intensity across one or more waveguides and enhanced waveguide illumination efficiency within an analytic detection region of the arrays are provided.

Abstract: The present invention relates to screening methods and, in particular, to methods of screening anti-ligands libraries for identifying anti-ligands specific for differentially and/or infrequently expressed ligands. The method comprises the steps of providing a library of anti-ligands; providing a first subtractor ligand; providing a second target ligand; determining the amount of the first and second target ligands using one or more equations derived from the universal law of mass action; providing the determined amount of a first subtractor ligand; providing the determined amount of a second target ligand; providing separation means capable of use to isolate anti-ligand bound to the second target ligand from anti-ligand bound to the first subtractor ligand; exposing the library of to the first and second target ligands to permit binding of anti-ligands to ligands; and using the separation means to isolate the anti-ligand bound to second target ligand.

Abstract: Methods for the diagnosis and/or monitoring of pancreatic cancer by detection of micro-RNAs (miRNA) are provided. In certain embodiments, detection of miR-21, miR-210, miR-155, and/or miR-196a in the plasma, blood, or pancreatic juice of a subject, such as a human patient, may be used to detect, diagnose, or monitor a pancreatic cancer.

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: This invention is directed to methods and compositions for sorting and/or determining microscopic organisms or cells. The methods and compositions are directed to the use of molecular probes to selectively stain the organisms or cells in combination with the use of binding partners to selectively immobilize the stained organisms or cells to a solid carrier. By combining the selectivity of both molecular probes and binding partners in an orthogonal method for staining and immobilization, these methods and compositions increase both the discriminating power of the assays and/or the certainty of the result obtained therefrom.

Abstract: A selective targeting method is disclosed comprising contacting a library of ligands, particularly a peptide library, with an anti-target to allow the ligands to bind to the anti-target; separating the non-binding ligands from the anti-target bound ligands, contacting the non-binding anti-target ligands with a target allowing the unbound ligands to bind with the target to form a target-bound ligand complex; separating the target-bound ligand complex from ligands which do not bind to the target, and identifying the target-bound ligands on the target-bound ligand complex wherein the target-bound ligands have a KD in the range of about 10?7 to 10?10 M. Additionally claimed are the ligands identified according to the method.

Abstract: Improved compositions, methods, apparatus, and kits for high-throughput nucleic acid amplification, detection and sequencing are disclosed. A nucleic acid cluster having an identifiable center is produced by generating on a solid support an immobilized nucleic acid complement from a template, one of which comprises a detectable label; and amplifying the complement and the template to obtain a nucleic acid cluster on the support, the cluster having a substantially central location marked by the detectable label and a surrounding region comprising immobilized copies. Also disclosed are nucleotide sequence determination in nucleic acid clusters so produced, center position annotation in the clusters, assignment of sequence information to overlapping clusters, and related compositions and methods.

Abstract: The present invention relates to novel methods for sequencing and mapping genetic markers in polynucleotide sequences using Type-IIs restriction endonucleases. The methods herein described result in the “capturing” and determination of specific oligonucleotide sequences located adjacent to Type-IIs restriction sites. The resulting sequences are useful as effective markers for use in genetic mapping, screening and manipulation.

Abstract: This invention relates to a number of bird sex-identification oligonucleotides and their use in determining the sex of birds in various families.

Abstract: The invention relates to novel variants that associate with Alzheimer's disease AD and their use in kits as a means for diagnosing AD; and also their use in nucleic acid molecules or cells/cell lines for identifying novel therapeutic, label of identification means.

Abstract: This invention provides methods for characterizing the amounts of nucleic acids, including plus/minus determinations, the use of different constructs, the use of a library and a reference library. Expression may also be compared in two or more samples using the methods of this invention. Also provided are heterophasic arrays comprising labeled positive copies of nucleic acids hybridized to the array and labeled negative copies of nucleic acids hybridized to the array, in which the labeled positive copies are separately quantifiable from the labeled negative copies.

Abstract: The invention provides a method for multiple cytokine detection from single cells for the purpose of generating immunological profiles of diseases.

Abstract: The present invention relates to methods for identifying compounds capable of modulating a cellular response. The methods involve attaching living cells to solid supports comprising a library of test compounds. Test compounds modulating a cellular response, for example via a cell surface molecule may be identified by selecting solid supports comprising cells, wherein the cellular response of interest has been modulated. The cellular response may for example be changes in signal transduction pathways modulated by a cell surface molecule.

Abstract: A microplate for use within an interrogation system and a method of using the microplate are disclosed. The microplate contains within the bottom of each well, an optical waveguide grating based sensor. Approximate to each sensor is a mask having an aperture of predetermined size. The aperture regulates the light that enters and exits the sensor upon successive scans and ensures repeatable readings from the sensor. In an extended embodiment, a method of detection is disclosed that utilizes a launch and receive system while employing the aforementioned microplate.

Abstract: The invention is directed to an isolated genomic nucleic acid molecule fragment that encodes human RhoC, vectors and hosts containing the fragment and fragments hybridizing to noncoding regions as well as antisense oligonucleotides to these fragments. The invention is further directed to methods of using these fragments to obtain human RhoC and to diagnose, treat, prevent and/or ameliorate a pathological disorder.

Abstract: A method for identifying from an HLA library an HLA complex that specifically binds to a compound. This method can be relied on to assess whether a compound is likely to induce an adverse drug reaction and, if so, in which human population.

Abstract: The invention provides methods for sequencing a polynucleotide comprising stopping an extension cycle in a sequence by synthesis reaction before the reaction has run to near or full completion.

Abstract: The present invention provides novel polypeptides having the scaffold structure of a C-type lectin-like domain (CTLD) and a randomized loop region for specifically binding a variety of target compounds and also provides nucleic acids encoding the polypeptides. The present invention further provides combinatorial CTLD libraries, methods for constructing the libraries, and methods for screening the libraries to identify and isolate the novel CTLD polypeptides. Specifically, the invention provides libraries of nucleic acids encoding polypeptides having a scaffold CTLD with a randomized loop region, as well as nucleic acid sequences, vectors, and methods for preparing and expressing the libraries. Exemplary nucleic acids useful in the combinatorial libraries are derived from tetranectin and other proteins having a CTLD.

Abstract: Multiplexed affinity purification and thermal dissociation prior to biochip hybridization simplifies uncharacterized sample admixtures, thereby minimizing or eliminating sample interferents, improving hybridization specificity on a microarray detector, and minimizing or eliminating the need for post-hybridization thermal dissociation analysis. An integrated thermo-affinity sample preparation sub-circuit for sample purification and enrichment is described that is consistent with a field-portable form factor and analytical processes. Thermo-affinity sample preparation on model admixtures of varying complexity was efficacious.

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 building block molecule that is a peptide of Formula: R1R2N—R3—(R4)n—X—(R5)m—Y—C(O)—R6, Tether-R1NH—Z-Ala-Gly-Ala-Gly-X-Ala-Y—C(O)—R6, R1R2NH—Z-Ala-Gly-Ala-Gly-X-Ala-Y—C(O)-Tether, Linker-R1NH—Z-Ala-Gly-Ala-Gly-X-Ala-Y—C(O)—R6, or R1R2NH—Z-Ala-Gly-Ala-Gly-X-Ala-Y—C(O)-Linker.

Abstract: A method is provided for identifying complexes between a transcription factor and another protein, such as another different transcription factor. The method includes the steps of isolating from a biological sample transcription factor complexes based on whether the transcription factor complexes include a particular type of transcription factor; and identifying which of the multiple different proteins are present in the isolated transcription factor complexes.

Abstract: The invention relates to materials and methods for detecting interactions between lipid complexes and lipid binding agents. More specifically, the invention provides materials and methods for displaying lipid complexes, particularly those containing two or more different lipid molecules, on a hydrophobic surface so as to mimic their in vivo environment more closely than in other analytical methods. This allows more accurate detection of lipid complexes and even identification of lipid complexes which are not detected by other methods. The invention lends itself particularly well to array or microarray formats.

Abstract: Combinations, called matrices with memories, of matrix materials with remotely addressable or remotely programmable recording devices that contain at least one data storage unit are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The matrix materials may additionally include fluophors or other luminescent moieties to produce luminescing matrices with memories. The data storage units are non-volatile antifuse memories or volatile memories, such as EEPROMS, DRAMS or flash memory. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.

Abstract: T cells are profiled with respect to their expression of antigen receptor. The cells are arrayed on a planar or three-dimensional substrate through binding to immobilized or partially diffused MHC-antigen complexes. The cells may further be characterized with respect to their ability to respond to external stimulus in the microenvironment. External stimuli include cell-cell interactions, response to factors, and the like.

Abstract: The invention relates to compounds comprising a photolabile protecting group and to the use thereof as coupling agents for the functionalisation of solid supports. The invention also relates to the solid supports functionalised by said compounds and to the use of same for the immobilisation of biological molecules of interest, such as nucleic acid molecules.

Abstract: The present invention provides a method for the isolation and analysis of a target nucleic acid, the target nucleic acid being present in a sample of genomic DNA, comprising the steps of a) fragmentation of the genomic DNA, b) hybridization of the genomic DNA on a nucleic acid solid support, the solid support comprising a plurality of oligonucleotide probes, the probes being characterized in that each probe is at least partially complementary to the sequence of the target nucleic acid or its complement, under hybridization conditions, characterized in that the plurality of probes hybridizes to fragments of the target nucleic acid but does not hybridize to other nucleic acids which are present in the sample, c) stripping off the target molecules hybridized to the nucleic acid array, d) overlap extension synthesis in order to generate double stranded overlap extension synthesis product, e) fragment polishing, and f) adaptor ligation.

Abstract: Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials or, alternatively, allowing the components to interact to form at least two different materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, nonbiological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc.

Abstract: The invention describes a process for filter selection of anti-angiogenesis antibody fragments from a large combinatorial repertoire; the invention further relates to the anti-angiogenesis antibody fragments thus obtained.

Abstract: A method for electrochemical removal of acid-labile protecting groups on an electrode microarray using an organic solution is disclosed. The solution comprises a hydrazine derivative and a salt in an organic solvent. The hydrazine derivative has at least one hydrazine group having at least one hydrogen. The hydrazine derivative provides acidic reagent when an electrode is active and isolates the acidic reagent to the area around the active electrode. The salt is an organic salt or ionic liquid having a concentration sufficient to provide electrochemical conductivity under an applied voltage. During the applied voltage, acidic reagent is generated, which removes acid-labile protecting groups thereby allowing continued addition of monomers to build a custom microarray of oligonucleotides, peptides, or other polymers.

Abstract: A method of identifying an analyte. The method includes providing a plurality of microparticles. The microparticles have optically detectable codes extending along bodies of the corresponding microparticle. The microparticles have the chemical probes attached thereto. Each of the chemical probes is associated with a corresponding one of the codes. The method also includes selectively binding target analytes to the chemical probes on the microparticles to produce labeled microparticles and distributing the labeled microparticles to random locations of a substrate. The method also includes determining the codes for the labeled microparticles in the random array and code positions of the codes in the random array. The method further includes detecting the label on the labeled microparticles in the random array and label positions of the labels in the random array. The method also includes using the code positions and the label positions to analyze the target analyte.

Abstract: The invention provides a method of selecting a representational sample of nucleic acid sequences from a complex mixture. The method includes: (a) contacting a complex mixture of nucleic acids under conditions sufficient for hybridization with a population of capture probes complementary to one or more nucleic acids comprising a predetermined portion of the sequence collectively present in the complex mixture to form hybridization complexes of the one or more nucleic acids with the population of probes, the population of capture probes being attached to a solid support, and (b) removing unhybridized nucleic acids to select a representational sample of nucleic acids having a complexity of less than 10% but more than 0.

Abstract: The present invention provides compositions including peptide display scaffolds that present at least one candidate peptide and at least one detectable moiety in at least one of the N-terminal and C-terminal candidate peptide presenting domains that when expressed in a cell are accessible at a surface of the cell outermembrane. In addition, the present invention also provides kits and methods for screening a library of cells presenting the candidate peptides in peptide display scaffolds to identify a ligand for an enzyme.

Abstract: Single nucleotide polymorphic site at position 11646 of the bovine FGF2 gene is associated with improved fertilization rate and/or improved embryo survival rate, as well as improved milk production. Also disclosed are nucleic acid molecules, kits, methods of genotyping and marker assisted bovine breeding methods.

Abstract: The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences using adaptors interspersed in target polynucleotides. The sequence information can be new, e.g. sequencing unknown nucleic acids, re-sequencing, or genotyping. The invention preferably includes methods for inserting a plurality of adaptors at spaced locations within a target polynucleotide or a fragment of a polynucleotide. Such adaptors may serve as platforms for interrogating adjacent sequences using various sequencing chemistries, such as those that identify nucleotides by primer extension, probe ligation, and the like. Encompassed in the invention are methods and compositions for the insertion of known adaptor sequences into target sequences, such that there is an interruption of contiguous target sequence with the adaptors. By sequencing both “upstream” and “downstream” of the adaptors, identification of entire target sequences may be accomplished.

Abstract: The present invention is concerned with improvements to methods of imaging nucleotides incorporated into polynucleotides and in particular with improved methods of determining the sequence of template nucleic acid molecules using multiple cycle nucleic acid “sequencing-by-synthesis” reactions.

Abstract: Methods, compositions, and kits for the cell-free production and analysis of proteins are provided. The invention allows for the production of proteins from prokaryotic sequences or eukaryotic sequences, including human cDNAs using PCR and IVT methods and detecting the proteins through fluorescence or immunoblot techniques. This invention can be used to identify optimized PCR and WT conditions, codon usages and mutations. The methods are readily automated and can be used for high throughput analysis of protein expression levels, interactions, and functional states.

Abstract: The disclosure provides methods of capturing target nucleic acids (e.g., gene or gene fragments) onto a solid support for further analysis. The disclosed methods utilize a capture probe that selectively circularizes only the target nucleic acid. Following the circularization of the target, the linear, non-target, nucleic acids are removed from the sample. Next, the circularized target is linearized and bound to a solid support. To allow for linearization, the capture probe may include a cleavage site that can be a noncanonical nucleotide(s) (e.g., uracil in DNA) and/or a rare-cutter site (e.g., the Not I restriction site). In some embodiments, the target nucleic acid is captured onto a support without an intermediate amplification step.

Abstract: The invention provides methods for highly-specific detection of hybridization of single stranded nucleic acids. The invention also provides methods for target identification which rely on this highly-specific hybridization detection. Targets suitable for detection include, but are not limited to, nucleic acid biomarkers. The methods of the invention can employ an on-chip, DNA polymerase-dependent labeling scheme termed primer extension (PEX) to couple biotinylated deoxyribonucleotide triphosphate (dNTP) molecules to nucleic acid hybrids bound to a solid substrate, allowing for subsequent recognition by biotin-binding-protein-labeled photoinitiators. Surface-initiated polymerization from these surface bound photoinitiators can lead to the formation of macroscale amounts of polymeric material, thereby amplifying the signal from the initial molecular recognition event.

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: Methods arrays and systems that facilitate contig assembly during nucleic acid sequencing are provided. Geographical locations of analyte molecules on an array are correlated with subsequence relationships within larger nucleic acids.

Abstract: The present disclosure provides methods for determining a nucleic acid sequence by performing successive cycles of duplex extension along a single stranded template. The cycles typically comprise steps of extension, ligation, and cleavage. In certain embodiments, the methods make use of extension probes containing phosphorothiolate linkages and agents capable of cleaving such linkages. Methods of determining information about a sequence using at least two distinguishably labeled probe families are provided, as are methods of performing multiple sequencing reactions on a single template. Automated sequencing systems, flow cells, image processing methods, and computer-readable media that store computer-executable instructions and/or sequence information that can be used in accordance with such methods are also provided. In certain embodiments, blocking oligonucleotides are provided to facilitate sequencing using disclosed methods.

Abstract: The invention relates to the identification and selection of sequences which demonstrate particular advantage in identifying individuals having osteoarthritis (OA). The invention also provides a selection of sequences particularly useful in diagnosing the degree of advancement of osteoarthritis of an individual and in the identification of novel therapeutic targets for OA. The invention further provides for the use of these sequences as a tool to diagnose disease progression and to monitor the efficacy of therapeutic regimens.

Abstract: A testing method of nucleic acid binding protein based on biochip, comprises the following steps: 1. puts a plurality of groups solution including nucleic acid captured probes into biological sample including a plurality of nucleic acid binding protein to be test, and thus forming nucleic acid captured probe-nucleic acid binding protein complexes; such nucleic acid captured probe includes at least a segment of binding sequence which can bind with aimed nucleic acid binding protein; 2. separates such nucleic acid captured probe-nucleic acid binding protein complexes, then recoveries nucleic acid captured probes; 3. hybridizes the nucleic acid captured probes according to step 2 with a plurality of single strand blotting probes on biochip substrate; the sequence of such blotting probe compensates with such nucleic acid captured probe or one of its strand; 4. detects the result of hybridization.

Abstract: The present invention is directed to methods and compositions for acquiring nucleotide sequence information of target sequences using adaptors interspersed in target polynucleotides. The sequence information can be new, e.g. sequencing unknown nucleic acids, re-sequencing, or genotyping. The invention preferably includes methods for inserting a plurality of adaptors at spaced locations within a target polynucleotide or a fragment of a polynucleotide. Such adaptors may serve as platforms for interrogating adjacent sequences using various sequencing chemistries, such as those that identify nucleotides by primer extension, probe ligation, and the like. Encompassed in the invention are methods and compositions for the insertion of known adaptor sequences into target sequences, such that there is an interruption of contiguous target sequence with the adaptors. By sequencing both “upstream” and “downstream” of the adaptors, identification of entire target sequences may be accomplished.