Abstract: Covalently modified alginate polymers, possessing enhanced biocompatibility and tailored physiochemical properties, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates are useful as a matrix for the encapsulation and transplantation of cells. Also disclosed are high throughput methods for the characterizing the biocompatibility and physiochemical properties of modified alginate polymers.

Abstract: A biologic-adsorbent, e.g., protein-adsorbent, material is prepared by forming a polymeric substrate into structures having high surface area topography whose biologic adsorbing properties can be controlled. Biologic adsorption by these structures of optimized high surface area topography is increased by mild treating of the surfaces, e.g., by oxygen plasma, without substantially altering topography. Structures can have tailored geometric features including microstructures, e.g., pillars, with a diameter from 100 nm-50 ?m and height greater than 1 ?m.

Abstract: The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

Abstract: The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

Abstract: An apparatus of manufacturing a microarray biochip including a spinning platen, at least one carrier and at least one substrate is provided. The carrier is disposed on the spinning platen and includes at least one micro-channel having an input terminal and an output terminal. The substrate is attached on the output terminal of the micro-channel of the carrier. A method of manufacturing a microarray biochip with said apparatus is also provided. A sample is injected into the micro-channel through the input or the output terminal. The spinning platen is powered-on to provide a centrifugal force to the carrier, such that the sample is flowed toward the output terminal from the input terminal, and then is immobilized on the surface of the substrate.

Abstract: A system and method of increasing productivity of OLED material screening includes providing a substrate that includes an organic semiconductor, processing regions on the substrate by combinatorially varying parameters associated with the OLED device production on the substrate, performing a first characterization test on the processed regions on the substrate to generate first results, processing regions on the substrate in a combinatorial manner by varying parameters associated with the OLED device production on the substrate based on the first results of the first characterization test, performing a second characterization test on the processed regions on the substrate to generate second results, and determining whether the substrate meets a predetermined quality threshold based on the second results.

Abstract: A metering device, a metering element, and a method for operating same, the metering element having a storage container open on one side for receiving the substances to be metered and a plunger which is axially movable and reversibly seals the opening of the storage container and which preferably has at least one centrally located metering opening for metering the substances provided in the storage container, the plunger including a separation device for particles.

Abstract: Multiplexed microarrays, multiplexed microarray cassettes, and methods for fabricating multiplexed microarrays are disclosed. In some embodiments, the multiplexed microarrays include a substrate, a chamber layer, and at least one channel layer. The topmost channel layer forms a port layer and may be compressible. The multiplexed microarrays may also include a compressible or non-compressible cover or sealing film. The multiplexed microarray cassette includes a base and may also include a cover. The base of the multiplexed microarray cassette includes a plurality of tracks to receive corresponding multiplexed microarrays.

Abstract: The invention provides molecules useful for enhancing charge transport across membranes, such as electron transport across membranes, and methods of using such molecules, for example in improving the performance of a microbial fuel cell or in staining microbes for observation. The amphiphilic molecule comprises a conjugated core with hydrophilic groups on either end. The amphiphilic molecule inserts into the membrane of a microbe and facilitates charge transfer across the membrane of the microbe.

Abstract: Analyte filter arrays and methods for making an analyte filter array are provided. The arrays are formed using a dispersion of filter particles having selected moieties attached to the surface of the particles and a microarray having complementary moieties formed in an array on a substrate, such that each filter particle is attached to a selected region of the microarray. The moiety on the substrate may be RNA or DNA or other molecule. The substrate may be a surface of a detector array, a membrane that may be placed in registration with the detector array or a stamp used to transfer the filter array to a detector array.

Abstract: The present invention is directed to the preparation and use of a collection of antibody heavy chain complementarity determining region 3 (HCDR3) members, where diversity of the collection is a function of the length of the HCDR3 members. The diversity of the collection of HCDR3 regions substantially represents the natural amino acid distribution of HCDR3 in the human repertoire. This natural amino acid distribution can be represented by biasing the complete random distribution of amino acids, accordingly, in the HCDR3 encoding DNA sequence by using trinucleotide mutagenesis (TRIM) technology. A collection of HCDR3 members of the invention each can be comprised within a variable region of an antibody (or fragment thereof) to form a library of synthetic antibodies or antibody fragments. The invention also provides nucleic acid molecules encoding such diverse collection and methods of making and using the same.

Abstract: A probe array base including probe-holding portions which are periodically arranged on a solid base member and which have grooves is prepared by anisotropically etching a single-crystalline silicon substrate. Probe solutions are supplied to the probe-holding portions by capillary action from a plurality of tank arrays having a certain cylinder period. This allows a probe array to be completed. The probe array is used as, for example, a DNA or antigen chip, has a high degree of integration, and is capable of holding a constant and sufficient number of probe molecules.

Abstract: Described are methods for producing libraries of cells expressing at least two separate single polypeptide chain binding proteins, in which the binding proteins have different target epitopes. Such libraries are made by integration of the nucleic acid sequences encoding the polypeptide chains into the genome of the host cell, and selecting for cells that have successfully integrated these nucleic acids. The selected cells are preferably subjected to a cloning step. Mixtures of binding proteins are produced without having to individually produce each of the components of the mixture. A library of cells wherein essentially each cell encodes at least two single polypeptide chain binding proteins having different target epitopes is also herewith provided, as well as methods for producing a composition comprising at least two separate single polypeptide chain binding proteins having different target epitopes.

Abstract: Methods to improve the tropism or other features of a virus are disclosed. Such methods can be used to prepare, e.g., DNA or plasmid libraries of variants of a gene encoding a viral capsid or envelope protein having a randomly inserted restriction site, libraries of viral clones with such variant genes with a randomly inserted restriction site or polypeptide sequence targeting a receptor expressed by a specific type of mammalian cells. Described are also methods to prepare mosaic viruses, i.e., viral particles wherein copies of one or more capsid or envelope proteins originate from different sources. These methods can be used to prepare mosaic viruses of a specific mixture of wild-type and mutant proteins, or of different types of mutant proteins.

Abstract: Methods for improving antibodies by a variety of DNA diversification and selection procedures are provided. Improvements include increases in affinity, alterations in specificity and effector function, as well as reduced antigenicity, e.g. humanization. Libraries of recombinant antibody sequences are provided, as are cells expressing members of such libraries. Novel phage display vectors are provided. Methods for the coevolution of an antibody and its cognate antigen are provided. Coevolution is used to evolve HIV envelope proteins with increased antigenicity and broadly neutralizing antibodies that interact therewith. Methods of improving antibodies for use in the detection of biological warfare agents are provided.

Abstract: The present invention provides a method for identifying a modulator or mediator of a biological activity, which activity includes antigenicity and or immunogenicity, said method comprising the step of: (i) producing a gene fragment expression library derived from defined nucleotide sequence fragments; and (ii) assaying the expression library for at least an amino acid sequence derived from step (i) for a biological activity wherein that activity is different from any activity the amino acid sequence may have in its native environment.

Abstract: A method of analyzing a tumor sample comprising: (a) acquiring a library comprising a plurality of tumor members from a tumor sample; (b) contacting the library with a bait set to provide selected members; (c) acquiring a read for a subgenomic interval from a tumor member from said library; (d) aligning said read; and (e) assigning a nucleotide value (e.g., calling a mutation) from said read for the preselected nucleotide position, thereby analyzing said tumor sample.

Abstract: Artificial transposon sequences having code tags and target nucleic acids containing such sequences. Methods for making artificial transposons and for using their properties to analyze target nucleic acids.

Abstract: In alternative embodiments, the invention provides phosphatidylinositol-specific phospholipase C (PI-PLC) enzymes, nucleic acids encoding them, antibodies that bind specifically to them, and methods for making and using them. Industrial methods and products comprising use of these phospholipases are also provided. In certain embodiments, provided herein are methods for hydration of non hydratable phospholipids (NHPs) within a lipid matrix. The methods enable migration of NHPs to an oil-water interface thereby allowing the NHPs to be reacted and/or removed from the lipids. In certain embodiments, provided is a method for removing NHPs, hydratable phospholipids, and lecithins from vegetable oils to produce a degummed oil or fat product that can be used for food production and/or non-food applications. In certain embodiments, provided herein are methods for hydration of NHPs followed by enzymatic treatment and removal of various phospholipids and lecithins.

Abstract: Artificial transposon sequences having code tags and target nucleic acids containing such sequences. Methods for making artificial transposons and for using their properties to analyze target nucleic acids.

Abstract: Devices and methods for producing and analyzing microarrays are disclosed. In an embodiment, a method for converting a library of beads to an array of analytes includes positioning a plurality of beads having one or more analytes bound therein on a solid support in a spatially separated manner, causing the analytes to be released from the plurality of microparticles, and localizing the released analytes in discrete spots.

Abstract: The tissue disaggregator device includes a base having a multiple well array. Each of the wells includes a screen embedded into bottom portion of the well. The device removably connects with standardized plate and allows for multiple fold increase in tissue sample preparation.

Abstract: The invention relates to a method for altering the conformational diversity of a first repertoire of polypeptide ligands, comprising a plurality of polypeptides comprising at least two reactive groups separated by a loop sequence covalently linked to a molecular scaffold which forms covalent bonds with said reactive groups, to produce a second repertoire of polypeptide ligands, comprising assembling said second repertoire from the polypeptides and structural scaffold of said first repertoire, incorporating one of the following alterations: (a) altering at least one reactive group; or (b) altering the nature of the molecular scaffold; or (c) altering the bond between at least one reactive group and the molecular scaffold; or (d) any combination of (a), (b) or (c).

Abstract: Substituted tricyclic diproline analogues of the formula (I): wherein the variables are as defined herein. Also disclosed are methods for the production thereof, the use thereof for the induction of an alpha-helix conformation in peptides and/or proteins, pharmaceuticals containing said compounds, methods for the production of a peptide library containing said compounds, and peptide libraries containing said compounds.

Abstract: Nature evolves biological molecules such as proteins through iterated rounds of diversification, selection, and amplification. The present invention provides methods, compositions, and systems for synthesizing, selecting, amplifying, and evolving non-natural molecules based on nucleic acid templates. The sequence of a nucleic acid template is used to direct the synthesis of non-natural molecules such as unnatural polymers and small molecules. Using this method combinatorial libraries of these molecules can be prepared and screened. Upon selection of a molecule, its encoding nucleic acid template may be amplified and/or evolved to yield the same molecule or related molecules for re-screening. The inventive methods and compositions of the present invention allow for the amplification and evolution of non-natural molecules in a manner analogous to the amplification of natural biopolymer such as polynucleotides and protein.

Abstract: The transformation yield of electroporation is increased by using higher DNA concentrations and DNA affinity purification. Fusion proteins of a viral coat protein variant and a heterologous polypeptide are useful in phage display systems.

Abstract: An integrated processing tool is described comprising a full-wafer processing module and a combinatorial processing module. Chemicals for use in the combinatorial processing module are fed from a delivery system including a set of first manifolds. An output of each first manifold is coupled to at least one mixing vessel. An output of each mixing vessel feeds more than one of a set of second manifolds. An output of each set of second manifolds feeds one of multiple site-isolated reactors of the combinatorial processing module.

Abstract: Described herein are RNA-protein fusion production methods which involve a high salt post-translational incubation step.

Abstract: Disclosed are methods and compositions of assessing one or more statuses of a subject. Also disclosed are methods and compositions of identifying status biomarkers associated with a status of a subject. Also disclosed are sets of one or more status biomarkers. Also disclosed are methods and compositions of producing status biomarker capture probes.

Abstract: Disclosed is a composition comprising a nucleic acid and a chemical compound, said composition forming a star structure defining 3 or more stems extending from a reaction center. The stems are formed by a nucleic acid duplex and the chemical compound has been formed in the reaction center as the reaction product of 3 or more chemical groups. The advantage of the composition is that a close proximity is provided between the chemical groups in the reaction center, thereby promoting a reaction. The invention also relates to a method for preparation of the composition. The advantage of the method is that it does not require the pre-synthesis of a large number of templates and that it is not dependent upon codon/anti-codon recognition for an encoded molecule to be formed.

Abstract: A method and apparatus are provided for performing light-directed reactions in spatially addressable channels within a plurality of channels. One aspect of the invention employs photoactivatable reagents in solutions disposed into spatially addressable flow streams to control the parallel synthesis of molecules immobilized within the channels. The reagents may be photoactivated within a subset of channels at the site of immobilized substrate molecules or at a light-addressable site upstream from the substrate molecules. The method and apparatus of the invention find particularly utility in the synthesis of biopolymer arrays, e.g., oligonucleotides, peptides and carbohydrates, and in the combinatorial synthesis of small molecule arrays for drug discovery.

Abstract: Disclosed are a biomolecule array and a method of fabricating a biomolecule array chip using the same. The present disclosure provides a simple method of fabricating a biomolecule array chip by coupling a pillar array with a well array The pillar array is provided with pillars protruded from a surface of a substrate, having a predetermined size and being arranged at a predetermined interval and is configured to apply biomolecules to a top surface of a pillar and the well array is configured so that each pillar formed in the pillar array is inserted into each well of the well array corresponding one-to-one after the biomolecule solutions are injected into each well.

Abstract: The present invention relates to a method of producing new chemical entities comprising the steps of: (i) taking a chemical entity as the template to prepare a molecularly imprinted polymer (MIP), (ii) removing the template from the MIP, (iii) using the specific binding sites of the MIP to direct, or facilitate, the syntheses of new chemical entities for the generation of compound libraries using molecularly imprinted polymers, and to a use of such compound libraries.

Abstract: The invention provides devices and methods for surface patterning the substrate of a microfluidic device, and for detection and analysis of interactions between molecules by mechanically trapping a molecular complex while substantially expelling solvent and unbound solute molecules. Examples of molecular complexes include protein-protein complexes and protein-nucleic acid complexes.

Abstract: Novel compounds are continually sought after to treat and prevent disorders. The invention relates to N-(2-oxo-1-phenylpiperidin-3-yl)sulfonamides useful for contributing to the search and identification of new lead compounds which can modulate the functional activity of a biological target.

Abstract: The present invention provides methods and compositions for performing multi-step nucleic acid mediated synthesis of a highly diverse collection of molecules, for example, small molecules and polymers. In the method, in at least two steps, multiple reaction intermediates and/or products are produced in the same step by different chemical reactions.

Abstract: New compounds are continually being sought for the treatment and prevention of disorders. The invention relates to 1-(sulfonyl)-N-phenyl-pyrrolidine 2-carboxamides which can be used in the search for, and identification of, new lead compounds that could modulate the functional activity of a biological target.

Abstract: New compounds are continually sought after for the treatment and prevention of disorders. The invention relates to 1-(sulfonyl)-N-phenylpyrrolidine-2-carboxamides which can be biologically and pharmacologically traced, in order to be used in the search for, and identification of, new lead compounds that can modulate the functional activity of a biological target.

Abstract: New compounds are continually sought after for the treatment and prevention of disorders. The invention relates to N-(2-oxo-1-phenylpiperidin-3-yl)sulfonamides which can be biologically and pharmacologically traced, in order to be used in the search for, and identification of, new lead compounds that can modulate the functional activity of a biological target.

Abstract: The present invention describes an improved method of screening of anti HCV agents that may have an efficacy for treatment of hepatitis C virus. The invention includes cryogenic hepatocyte bank, wherein the bank includes multiple hepatocytes collected from multiple HCV patients and the hepatocyte bank includes more than one genotype of HCV. The method involves the isolation and cryopreservation of HCV infected hepatocytes from multiple infected individuals. The isolated and cryopreserved hepatocytes are stored in a cryopreservation bank. These stored hepatocytes then are cultured in a culture medium, and anti-HCV screening of the hepatocytes is done by subjecting HCV infected hepatocytes in parallel to action of different anti-HCV compounds at various concentrations. Effective anti-HCV agents will lead to a decrease in HCV content in the cultures.

Abstract: Apparatus and methods are described for split synthesis combinatorial chemistry that provides candidate libraries where an even distribution of theoretical products is obtainable through even mixing during the pooling step, followed by controlled redistribution of the mixed pooled products from the prior addition step into separate synthesis columns, one for each different specie of subunit to be added.

Abstract: Provided herein are methods of isolating a polynucleotide encoding a polypeptide such as an antibody with a desired property by way of mammalian display library screening and methods of generating a library of polynucleotides encoding polypeptides such as antibodies, wherein the polynucleotides collectively encode at least 109 different polypeptides. Also provided are kits for carry out the methods described herein, polynucleotides isolated by methods described herein, libraries encoding the antibody reservoir of different species including human, mouse, rabbit, and polypeptides encoded by the polynucleotides.

Abstract: The object of this patent advances the State of the Art by the following innovations: 1st—It creates a new electrophoretic process to be carried out in fused silica capillary that was previously covered internally with neutral hydrophilic substances that reduces the seven mandatory steps of the electrophoretic process according to the State of the Art into one single electrophoretic migration in the new process, with high power of separating the “protein oligonucleotide” compound, which allows the achievement of results in which the sample protein, as well as other substances, get physically well separated from similar complexes, therefore attaining a narrow compound zone in the internally covered capillary tube, constituted of the sample protein bound to, at least, one oligonucleotide by means of the stronger and specific bound, eliminating the fraction collection window which is a typical phenomenon described in the State of the Art.

Abstract: The present invention relates generally to methods for producing normalized nucleic acid libraries in which each member of the library can be isolated with approximately equivalent probability. In particular, the present methods comprise subtractive hybridization of a nucleic acid library with haptenylated (e.g., biotinylated, avidinated or streptavidinated) nucleic acid molecules that are complementary to one or more of the nucleic acid molecules of the library, such that the variation in the abundances of the individual nucleic acid molecules in the library is reduced. The invention also relates to production of normalized nucleic acid libraries (particularly cDNA libraries) in which contaminating nucleic acid molecules have been reduced or eliminated, and to normalized nucleic acid libraries produced by such methods.

Abstract: The invention relates to a nucleic acid comprising the following contiguous elements arranged in the 5 prime to 3 prime direction; a promoter; a selectable marker; a cloning site for receipt of a nucleic acid segment, said segment comprising a candidate miRNA target sequence; and a poly adenylation signal, said elements arranged such that a transcript directed by said promoter comprises said selectable marker, said candidate miRNA target sequence, and said poly adenylation signal in that order. Suitably the miRNA test sequence is or is derived from a 3?UTR. The invention also relates to methods for making and screening libraries.

Abstract: Versions of the invention are directed to methods and apparatus for a new type of association-based linkage study technique using bi-allelic markers. The markers used in this technique are chosen so that the least common allele frequencies of the markers vary systematically over a range or subrange of least common allele frequency and the chromosomal location of the markers vary systematically over one or more chromosomal regions or chromosomes to achieve a systematic distribution of the markers over a two-dimensional region that has the orthogonal dimensions of chromosomal location and least common allele frequency. By using the two characteristics or two dimensions of marker chromosomal location and marker allele population frequency in this way, the power and systematic nature of genetic linkage studies using association-based linkage tests is greatly increased. These two-dimensional linkage study techniques increase the power of association studies to localize trait-causing polymorphisms of modest effect.

Abstract: The invention provides compounds of general formulae (I)-(IV) or pharmaceutically acceptable salts thereof: The invention also provides methods of preparing the compounds, pharmaceutical compositions comprising the compounds and use of the compounds for the preparation of medicaments intended to modulate the activity of one or more members of the G-protein coupled receptor (GPCR) class. Compounds of the invention may be used to create a compound library for use in screening for agents which modulate signalling through GPCRs.

Abstract: The present invention relates among others to a method of pooling samples to be analyzed for a categorical variable, wherein the analysis involves a quantitative measurement of an analyte, said method of pooling samples comprising providing a pool of n samples wherein the amount of individual samples in the pool is such that the analytes in the samples are present in a molar ratio of x0:x1:x2:x(n?1), and wherein x is equal to a positive value other than 1 representing the pooling factor.

Abstract: Disclosed is a combinatorial synthesis of Diamond wherein a first reactive species is produced by catalytic treatment of Acetylene, a second reactive species is produced by decomposition of a hydrocarbon source having a low Hydrogen-to-Carbon ratio using a high energy discharge, and the two reactive species so obtained are combined in the vapor phase to yield Diamond without the need of post-treatments. The reaction is efficient and affords Diamond under mild conditions with high purity such that it may be useful for producing Diamond for semiconductor and microelectronics applications.

Abstract: The invention relates to polypeptides having glucanase, e.g., endoglucanase, mannanase, xylanase activity or a combination of these activities, and polynucleotides encoding them. In one aspect, the glucanase activity is an endoglucanase activity (e.g., endo-1,4-beta-D-glucan 4-glucano hydrolase activity) and comprises hydrolysis of 1,4-beta-D-glycosidic linkages in cellulose, cellulose derivatives (e.g., carboxy methyl cellulose and hydroxy ethyl cellulose) lichenin, beta-1,4 bonds in mixed beta-1,3 glucans, such as cereal beta-D-glucans or xyloglucans and other plant material containing cellulosic parts. In addition, methods of designing new enzymes and methods of use thereof are also provided. In alternative aspects, the new glucanases e.g., endoglucanases, mannanases, xylanases have increased activity and stability at increased pH and temperature.