Abstract: A method of making a sample plate for mass spectrometric analysis of a specimen is provided comprising applying a mask to a substrate to form at least one sample site. The sample plate comprises a substrate having an electrically conductive surface, a mask applied to the electrically conductive surface. The mask has a rougher surface than the substrate. The sample site comprises a central portion formed from the electrically conductive surface and a marginal portion formed from the mask where the marginal portion is more hydrophobic than the central portion.

Abstract: The present invention describes methods and cassettes for cell-based toxin detection and organ localization. The cassettes includes an array containing cells and a matrix of openings or depressions, wherein each region of the substrate enclosed by the opening or depression in the matrix forms a domain individually addressable by microfluidic channels in the device.

Abstract: Methods are provided for detecting biomolecular interactions. The use of labels is not required and the methods can be performed in a high-throughput manner. The invention also relates to optical devices.

Abstract: An assay plate for detecting the presence of a mobile reactant that binds to a immobilized reactant and the methods of making and using the same. An assay plate according to the present invention includes a substrate and at least one dried aliquot of the immobilized reactant, the immobilized reactant being bound to the surface of the substrate. The immobilized reactant binds the mobile reactant when a solution containing the mobile reactant is brought into contact with the immobilized reactant. The mobile and immobilized reactants may be any pair of biological compounds that have a specific affinity for one another. For example the reactants may be nucleic acids or antibody-antigen pairs. The preferred embodiment of an assay plate according to the present invention includes a plurality of assay spots, each spot having a different immobilized reactant or concentration thereof.

Abstract: An improved apparatus for conducting a multiplicity of individual and simultaneous binding reactions is described. The apparatus comprises a substrate on which are located discrete and isolated sites for binding reactions. The apparatus is characterized by discrete and isolated regions that extend through a substrate and terminate on a second surface thereof, such that when a test sample is applied to the substrate, it is capable of penetrating through each such region during the course of the binding reaction. The apparatus is especially useful for sequencing by hybridization of DNA molecules.

Abstract: Provided herein are type II transmembrane serine protease 7 (MTSP7) polypeptides. Zymogen and activated forms of these polypeptides as well as single and two chain forms of the protease domain are also provided. Methods using the polypeptides to identify compounds that modulate the protease activity of an MTSP7 are provided.

Abstract: This invention provides methods of retentate chromatography for resolving analytes in a sample. The methods involve adsorbing the analytes to a substrate under a plurality of different selectivity conditions, and detecting the analytes retained on the substrate by desorption spectrometry. The methods are useful in biology and medicine, including clinical diagnostics and drug discovery.

Abstract: Provided herein are type II transmembrane serine protease 10 (MTSP10) polypeptides. Zymogen and activated forms of these polypeptides as well as single and two chain forms of the protease domain are also provided. Methods using the polypeptides to identify compounds that modulate the activity of an MTSP10 are provided.

Abstract: Provided herein are type II transmembrane serine protease 9 (MTSP9) polypeptides. Zymogen and activated forms of these polypeptides as well as single and two chain forms of the protease domain are also provided. Methods using the polypeptides to identify compounds that modulate the protease activity of an MTSP9 are provided.

Abstract: A simple easy to manufacture analytical device capable of performing membrane based immunoassays on batch of samples within 3 to 10 minutes wherein the method permits focused application of samples, costly labeled immunoassay and signal amplification reagents, said device includes an antibody-immobilized micro porous membrane, breadth corner layer of which is directly attached to a semi-rigid liquid-impervious body with water insoluble adhesive; absorbent body is provided separately and is not attached to analytical device during manufacture, absorbent body is wetted and is placed proximal to the lower surface of the membrane thereby forming networks of capillary channels with the absorbent body; flow of samples or reagents is always kept downwards and focused without application of any force to the absorbent body and the use of disposable adsorbent body permits stepwise addition of signal amplification reagents for ultra sensitive detection of diagnostically important molecules by visual examination of the m

Abstract: An efficient method for the microfabrication of electronic devices which have been adapted for the analyses of biologically significant analyte species is described. The techniques of the present invention allow for close control over the dimensional features of the various components and layers established on a suitable substrate. Such control extends to those parts of the devices which incorporate the biological components which enable these devices to function as biological sensors. The materials and methods disclosed herein thus provide an effective means for the mass production of uniform wholly microfabricated biosensors. Various embodiments of the devices themselves are described herein which are especially suited for real time analyses of biological samples in a clinical setting. In particular, the present invention describes assays which can be performed using certain ligand/ligand receptor-based biosensor embodiments.

Abstract: The present invention provides a method for reducing undesirable light emission from a sample using at least one photon producing agent and at least one photon reducing agent (e.g. dye-based photon reducing agents). The present invention further provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one collisional quencher. The present invention also provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one quencher, such as an electronic quencher. The present invention also provides a system and method of screening test chemicals in fluorescent assays using photon reducing agents. The present invention also provides compositions, pharmaceutical compositions, and kits for practicing these methods.

Abstract: The invention relates to an optical system for determining the distribution, environment, or activity of fluorescently labeled reporter molecules in cells for the purpose of screening large numbers of compounds for specific biological activity. The invention involves providing cells containing fluorescent reporter molecules in an array of locations and scanning numerous cells in each location with a fluorescent microscope, converting the optical information into digital data, and utilizing the digital data to determine the distribution, environment or activity of the fluorescently labeled reporter molecules in the cells. The array of locations may be an industry standard 96 well or 384 well microtiter plate or a microplate which is a microplate having a cells in a micropaterned array of locations. The invention includes apparatus and computerized method for processing, displaying and storing the data.

Abstract: The present invention provides a method and device for conducting a rapid in vitro enzyme immunoassay test for the direct and qualitative detection of two or more viral antigens from specimens of symptomatic patients. The method for immunoassay of viral antigens is performed on a membrane. Non-immunological capture of viral antigens takes place by absorption onto the membrane. Captured antigen binds to a detection reagent that includes a label conjugated to a specific antibody. The test is a differentiated test such that two or more viral antigens may be distinguished from each other in a single test. The invention also includes a kit for performing an assay in accordance with the method of the present invention, wherein the kit comprises the device of the present invention.

Abstract: The present invention relates to an assay for free protein S comprising the addition of a ligand specific for free protein S to a biological fluid sample to form a protein S/ligand complex, and subsequent determination of the amount of the complex formed in the sample. The ligand specific for free protein S is comprised of the C4b binding protein (C4BP), or part thereof, or a compound comprising an amino acid residue sequence that binds specifically to the binding site for C4BP in protein S. The present invention further relates to antibodies specific for free protein S, which can be used as ligands in the assay of the invention, and with protein S related polypeptides, which can be used to produce such antibodies. In addition, the present invention is related to diagnostic test systems, suitable in kit form, comprising the present ligand and at least one further reagent required in the assay for free protein S.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.

Abstract: Disclosed are devices for detecting the presence of a preselected analyte in a fluid sample. The devices comprise a substrate microfabricated to define a sample inlet port, and a mesoscale flow system that includes a sample flow channel extending from the inlet port. The mesoscale flow system further includes an analyte detection region in fluid communication with the flow channel comprised of a binding moiety for specifically binding the analyte. The detection region is constructed with a mesoscale dimension sufficiently small to enhance binding of the binding moiety and the analyte. The binding moiety may be immobilized in the detection region. The mesoscale detection systems of the invention may be used in a wide range of applications, including the detection of cells or macromolecules, or for monitoring reactions or cell culture growth.

Abstract: Devices and methods are disclosed for containing and processing samples on the surface of supports. Biopolymer features are attached to the surfaces of the supports. A device in accordance with the invention comprises a housing and a support confined by the housing. The housing comprises a well having walls and at least one wall extending from the edge of the well. The height of the walls of the well is at least great enough, and the design of the at least one wall is such, that liquid contained in the well is not drawn out of the well to any substantial degree by surface tension or small movements or small mechanical vibrations. In one embodiment, the at least one wall is designed such that corners thereof are curved or are distant from the edge of the well to substantially eliminate wicking of liquid from the well. Also disclosed are methods for mixing materials on the surface of a support. A sample is incubated with the surface of the support of the aforementioned device.

Abstract: Disclosed are devices for detecting the presence of a preselected analyte in a fluid sample. The devices comprise a substrate microfabricated to define a sample inlet port, and a mesoscale flow system that includes a sample flow channel extending from the inlet port. The mesoscale flow system further includes an analyte detection region in fluid communication with the flow channel comprised of a binding moiety for specifically binding the analyte. The detection region is constructed with a mesoscale dimension sufficiently small to enhance binding of the binding moiety and the analyte. The binding moiety may be immobilized in the detection region. The mesoscale detection systems of the invention may be used in a wide range of applications, including the detection of cells or macromolecules, or for monitoring reactions or cell culture growth.

Abstract: A method for producing arrays by spacing a dispenser a distance from a surface of a support, dispensing a volume containing a compound in a single coupling step of less than 5 nl to occupy a localized area of less than 1 cm2 of the surface of the support, allowing the compound to bind directly or indirectly to the support and repeating the steps to produce an array of at least 100 ligands at a density of 1000 per cm2 or greater.

Abstract: A system for the rapid characterization of multi-analyte fluids, in one embodiment, includes a light source, a sensor array, and a detector. The sensor array is formed from a supporting member into which a plurality of cavities may be formed. A series of chemically sensitive particles are, in one embodiment positioned within the cavities. The particles may be configured to produce a signal when a receptor coupled to the particle interacts with the analyte. Using pattern recognition techniques, the analytes within a multi-analyte fluid may be characterized.

Abstract: The invention relates to an optical system for determining the distribution, environment, or activity of fluorescently labeled reporter molecules in cells for the purpose of screening large numbers of compounds for specific biological activity. The invention involves providing cells containing fluorescent reporter molecules in an array of locations and scanning numerous cells in each location with a fluorescent microscope, converting the optical information into digital data, and utilizing the digital data to determine the distribution, environment or activity of the fluorescently labeled reporter molecules in the cells. The array of locations may be an industry standard 96 well or 384 well microtiter plate or a microplate which is a microplate having a cells in a micropaterned array of locations. The invention includes apparatus and computerized method for processing, displaying and storing the data.

Abstract: An improved microfabricated apparatus for conducting a multiplicity of individual and simultaneous binding reactions is described. The apparatus comprises a substrate on which are located discrete and isolated sites for binding reactions. The apparatus is characterized by discrete and isolated regions that extend through said substrate and terminate on a second surface thereof such that when a test sample is applied to the substrate, it is capable of penetrating through each such region during the course of said binding reaction. The apparatus is especially useful for sequencing by hybridization of DNA molecules.

Abstract: The microarrays of the present invention are prepared by using a separate fiber for each compound being used in the microarray. The fibers are bundled and sectioned to form a thin microarray that is glued to a backing.

Abstract: This invention is directed to filtrate-holder and reversible-well collection plates composed of polypropylene and Teflon®, and to their use, in connection with compatible filter units, in high-throughput screening assays for assessing the binding of small molecules to proteins.

Abstract: A microplate having a base and wells is disclosed. The base has mark parts at least on one edge thereof. Each mark part is defined by notches cut in the edge of the base. The wells are provided in the base and arranged in rows and columns. The mark parts can be used as indicia for identifying not only the microplate but also the wells so that the microplate and the wells can be easily identified without writing numerals or marks on the edges of the base with a felt pen or the like.

Abstract: A thermal cycling device for biological samples. The thermal cycling device may include a sample block, an annular plate, and a plurality of spring devices interposed between the sample block and the annular plate. The sample block has a plurality of openings for receiving sample wells of a sample well tray. The annular plate may be positioned adjacent the outer periphery of the sample block and may be configured to abut a bottom surface of the sample well tray when the sample well tray is positioned thereon. The plurality of spring device may be interposed between the sample block and the annular plate to urge the annular plate and sample well tray away from the sample block.

Abstract: A method for producing polymer arrays by spacing a dispenser a distance from a surface of a support, dispensing a volume containing a monomer in a single coupling step of less than 5 nl to occupy a localized area of less than 1 cm2 of the surface of the support, allowing the monomer to bind directly or indirectly to the support and repeating the steps to produce an array of at least 100 polymer ligands at a density of 1000 per cm2 or greater.

Abstract: The present invention recognizes that separation of components of a sample facilitate, and are often necessary for, sample analysis. Dielectrophoretic separation provides an efficient, reliable, nondisruptive, and automatable method for the separation of moieties in a sample based on their dielectric properties. The present invention provides compositions and methods for enhancing the dielectrophoretic separation of one or more moieties in a sample. A first aspect of the present invention is a solution that when mixed with a sample, modifies at least one dielectric property of one or more components of the sample and has a conductivity such that one or more moieties of the sample can be separated using dielectrophoresis. Such solutions can be used in the analysis of samples on chips, and can be used in methods that use binding partners, including microparticles that can be translocated by dielectrophoretic forces, traveling-wave dielectrophoretic forces or magnetic forces.

Abstract: The vascular endothelial growth factor (VEGF) activity in a patient's bloodstream or other biological sample can serve as a diagnostic and prognostic index for cancer, diabetes, heart conditions, and other pathologies. Antibody-sandwich ELISA method and kits for VEGF as an antigen were developed to detect VEGF levels in biological samples from animal models and human patients and are used as a diagnostic/prognostic index.

Abstract: A method for producing arrays by depositing a resist on a substrate, selectively removing a portion of the resist to expose localized areas, dispensing a monomer to occupy a localized area of less than 1 cm2 of the surface of the support, allowing the monomer to bind directly or indirectly to the support and repeating the steps to produce an array of at least 10 different polymers is formed.

Abstract: Microarrays are prepared by using a separate fiber for each compound being used in the microarray. The fibers are bundled and sectioned to form a thin microarray that is glued to a backing.

Abstract: Methods are provided for preparing nucleic acid arrays on a support. In these methods a plurality of nucleic acids are synthesized on the support and the synthesis steps include oxidizing a phosphite triester nucleic acid linkage to a phosphate triester nucleic acid linkage using a solution about 0.005 to about 0.05 M iodine in a mixture comprising water and organic solvent.

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. In particularly preferred embodiments, these compounds are attached to the solid support through a covalent interaction.

Abstract: A gelatin-based substrate for fabricating protein arrays, the substrate comprising: gelatin having at least one surface; a polymer scaffold affixed to the gelatin surface; wherein the polymer in the scaffold is rich in reactive units capable of immobilizing proteins.

Abstract: Methods and compounds are provided for detecting target molecules in a sample using specific binding assays. In particular, methods are provided for detecting a nucleic acid target in a sample. In one embodiment, the presently claimed invention provides a method of labeling a hybridized target wherein the target comprises a binding ligand. In another embodiment, the presently claimed invention provides methods of signal amplification.

Abstract: A multi-slide assembly includes various components that alone or in combination facilitate testing of test samples with minimal manipulation of assay components. Moreover, the various device components permit centrifugation, culturing and analysis of each test sample to be performed in the same assembly. A frame retains a plurality of reaction vessel assemblies between a pair of opposing channels that are configured to slidably receive the opposing ends of each reaction vessel assembly. A strip cap seals the openings in each reaction vessel using cap members having sealing rings circumscribing the external walls thereof to form compression seals with internal walls of the reaction vessels. Furthermore, in a method of making a multi-well slide assembly, an ultrasonic welding process removably bonds a plurality of wells to a slide plate to provide an adequate seal therebetween during centrifugation, yet still enable separation thereof by an operator.

Abstract: A method and apparatus for screening an array of test compounds for bioactivity by contacting an array of test compounds with a detector layer capable of detecting bioactivity, and detecting a detector layer response. The detector layer is comprised of physiologically viable cells. The method and apparatus allow a large number of test compounds to be simultaneously assayed in parallel without the need for complex fluidic devices.

Abstract: The present invention provides systems, methods, and screens to measure receptor internalization in a single step with appropriate automation and throughput. This approach involves luminescent labeling of the receptor of interest and the automated measurement of receptor internalization to a perinuclear location.

Abstract: The present invention provides systems, methods, screens, reagents and kits for optical system analysis of cells to rapidly determine the distribution, environment, or activity of fluorescently labeled reporter molecules in cells for the purpose of screening large numbers of compounds for those that specifically affect particular biological functions.

Abstract: The invention provides a novel human Mab Fab, cloned by phage display, and its use in diagnostic and therapeutic methods. In particular the invention provides a method for analyzing the OxLDL components of atherosclerotic plaques in vivo and a means to determine their relative pathology. As the method is based on a human Fab rather than a mouse Mab, the progress or regression of the disease may be monitored over time. The antibody may also be used for the analysis of surgical or serum samples ex vivo for the presence of OxLDL. The antibody may also be used to target therapeutic agents to the site of atherosclerotic plaques or may have use as a therapeutic agent itself.

Abstract: Electrokinetic devices having a computer for correcting for electrokinetic effects are provided. Methods of correcting for electrokinetic effects by establishing the velocity of reactants and products in a reaction in electrokinetic microfluidic devices are also provided. These microfluidic devices can have substrates with channels, depressions, and/or wells for moving, mixing and monitoring precise amounts of analyte fluids.

Abstract: The present invention provides imprint compositions useful for capturing, isolating, detecting and/or quantifying macromolecules in a sample, methods of making and using the same. Generally, the imprint compositions comprise a matrix material defining an imprint of a template molecule, and the template molecule typically corresponds to a portion of a macromolecule of interest.

Abstract: The present invention is a method and an apparatus to provide a dynamic matrix system for synthesizing a plurality of chemical compounds simultaneously, i.e. in parallel, and to synthesize a series of plurality of simultaneously synthesized chemical compounds sequentially, i.e. in series. The apparatus includes a base support structure, a physical chemistry teabag support structure, a plurality of physical chemistry teabags and a fixed-reactant/liquid reactant mixture shifting (changing) mechanism. The base support structure has a plurality of reaction vessels arranged in at least a two dimensional predetermined array. The physical chemistry teabag support structure is adapted to hold and support a plurality of physical chemistry teabags arranged in at least a two dimensional predetermined teabag array, at least partially coinciding with the base support structure reaction vessel array. The teabags have at least one predetermined fixed reactant thereon.

Abstract: Devices are provided which include supports upon which one or more ion-exchange materials can be disposed for purifying a sample. In various embodiments, the supports include a plurality of deformable members, for example, petal-shaped purification members, that provide binding sites for ion-exchange material and optionally biochemical species, chemicals, salts, or other materials. An apparatus and method are also provided for the insertion and removal of the purification members into respective wells of a multi-well microplate.

Abstract: Disclosed is a device and method of use for detecting polyvalent analytes such as antibody to the AIDS virus, utilizing an inverse sandwich method. The test device comprises a first substance having an epitope, bound to a label and capable of moving within the test device. The test device further comprises a second substance immobilized to the test device and spatially separated from the first substance. The second substance has an epitope substantially similar to the epitope of the first substance. Upon application to the test device, the polyvalent analyte binds to the first substance and moves within the test device to the location of the second substance with both polyvalent analyte and first substance are immobilized at location of the second substance. Polyvalent analyte is detected by the presence of the label at the location of the second substance. Also disclosed is a control substance for use with the device that can be used to determine completion of the test and viability of the device.

Abstract: A thermal cycling device for biological samples. The thermal cycling device may include a sample block, an annular plate, and a plurality of spring devices interposed between the sample block and the annular plate. The sample block has a plurality of openings for receiving sample wells of a sample well tray. The annular plate may be positioned adjacent the outer periphery of the sample block and may be configured to abut a bottom surface of the sample well tray when the sample well tray is positioned thereon. The plurality of spring device may be interposed between the sample block and the annular plate to urge the annular plate and sample well tray away from the sample block.

Abstract: This invention is directed to filtrate-holder and reversible-well collection plates composed of polypropylene and Teflon®, and to their use, in connection with compatible filter units, in high-throughput screening assays for assessing the binding of small molecules to proteins.

Abstract: The present invention concerns a high throughput electrorotation chip having an array of electrorotation units and methods of use thereof. To make the high throughput electrorotation chip, a plurality of electrorotation units (EU) are fabricated on a substrate or support and each EU is capable of producing a rotating electric field upon the application of an appropriate electrical signal. Exemplary embodiments include a row-column configuration of EUs having four electrode elements realized through two conductive-layers. The electrode elements may be linear, concave, or convex. Thin plates having one or multiple holes are bound to high-throughput electrorotation chips to form assay chambers having one or multiple wells. Particles can be introduced to the wells and electrorotation measurements can be performed on the particles.

Abstract: The invention relates to an optical system for determining the distribution, environment, or activity of fluorescently labeled reporter molecules in cells for the purpose of screening large numbers of compounds for specific biological activity. The invention involves providing cells containing fluorescent reporter molecules in an array of locations and scanning numerous cells in each location with a fluorescent microscope, converting the optical information into digital data, and utilizing the digital data to determine the distribution, environment or activity of the fluorescently labeled reporter molecules in the cells. The array of locations may be an industry standard 96 well or 384 well microtiter plate or a microplate which is a microplate having a cells in a micropaterned array of locations. The invention includes apparatus and computerized method for processing, displaying and storing the data.