Abstract: Staphylococcus aureus virulence genes are identified, thereby allowing the identification of novel anti-bacterial agents that target these virulence genes and their products, and the provision of novel S. aureus mutants useful in vaccines.

Abstract: The invention provides monoclonal antibodies which are reactive with fibrin(ogen) degradation products (FDPS) generated by matrix metalloproteinases (MMPs), such as MMP-3, MMP-7, and membrane-type 1, MT1-MMP proteolysis of fibrinogen and cross-linked fibrin (and not plasmin or other proteases). Monoclonal antibodies of the invention include, but are not limited to, H5, F2, 90/2, 90/5, B4, 13, C6, A6, G6, E6, 197-1 and 197-2. This invention also provides methods of using monoclonal antibodies for detection of FDPs generated by proteolysis of fibrin(ogen) by MMPs, such as MMP-3, MMP-7, and MT1-MMP. In addition, the present invention provides methods for diagnosing rheumatoid arthritis, osteoarthritis, and synovitides, as well as angiogenesis, atherosclerosis, renal diseases, malignancy and inflammation.

Abstract: Integrated systems, apparatus, software, and methods for performing biochemical analysis, including DNA sequencing, genomic screening, purification of nucleic acids and other biological components and drug screening are provided. Microfluidic devices, systems and methods for using these devices and systems for performing a wide variety of fluid operations are provided. The devices and systems of are used in performing fluid operations which require a large number of iterative, successive or parallel fluid manipulations, in a microscale, or sealed and readily automated format.

Abstract: The invention concerns a device and a method for carrying out fluorescence immunoassays, wherein from at least one light source light is directed onto a surface at one end of a light waveguide and with the light coupled into the light waveguide by evanescent field excitation at the surface of the light waveguide fluorescence of at least one labelling substance bound to a chemical or biochemical partner of a general receptor-ligand system is excited. The solution according to the invention is here to provide a possible way of carrying out fluorescence immunoassays with high accuracy of measurement at low cost and within a short time. To achieve this object, the fluorescent light is decoupled from the light waveguide and directed via an optical system onto an optical detector with which the intensity of the fluorescent light is measured.

Abstract: Invention performs an assay to determine presence or quantity of specific analyte in fluid sample. Representative device has two separate flow paths established sequentially in device with a single user activation step. First flow path delivers sample, and conjugate soluble binding reagents to solid phase. If analyte is present, an analyte:conjugate complex is formed and immobilized. Sample volume delivered by first path determined by absorbent capacity of solid phase, and not by amount of sample added to device. User need not measure sample volume. Sample/conjugate mixture is prevented from entering second flow path because capillary and surface energy of second flow path prevent it from being wetted by this mixture. Second flow path allows wash reagent to remove unbound conjugate and sample from solid phase to the absorbant, and optionally deliver detection reagents.

Abstract: Active ingredient combinations of cyclodextrins and biotin and/or one or more biotin derivatives for use in cosmetic or dermatological formulations.

Abstract: The invention concerns the stabilization and amplification of electrochemiluminescence signals in detection methods.

Abstract: A method for detecting the presence of a target analyte comprising binding a target analyte to a binding ligand comprising at least a first electron donor moiety and a second electron acceptor moiety; and detecting the electron transfer between the donor and acceptor, wherein there is a change in the amount of electron transfer between the donor and acceptor as a result of altering the structured state of the donor and acceptor caused by a conformational change in the binding ligand upon binding of the target ligand.

Abstract: A prenatal screening method for Down's syndrome involves assaying for hyperglycosylated gonadotropin in biological test samples such as urine, plasma or serum obtained from pregnant women. Hyperglycosylated gonadotropin comprises a variant population of chorionic gonadotropin, chorionic gonadotropin-free &bgr;-subunit, &bgr;-core fragment, and/or free &agr;-subunit exhibiting differences in the carbohydrate content from what is observed in samples obtained from pregnant women carrying normal fetuses. Qualitative or quantitative observation of differences in the carbohydrate content of the hyperglycosylated gonadotropin population from corresponding control samples containing a normal gonadotropin population, or direct observation of the variant species seen in Down's syndrome, indicates that the woman's fetus has Down's syndrome. Typical screens involve carbohydrate analyses, immunoassays, or combinations of these methods.

Abstract: This invention relates to an improved method and system for sensing of one or more analytes. A host molecule, which serves as an adapter/carrier, is used to facilitate interaction between the analyte and the sensor element. A detectable signal is produced reflecting the identity and concentration of analyte present.

Abstract: A method for the generation of chemical libraries using machine-readable passive tagging systems is described. The preferred embodiment uses radiofrequency tags or one- or two-dimensional bar codes to track vials and the contents therein throughout the course of the synthesis. This abrogates the need for specialized combinatorial chemistry equipment, allowing the use of standard laboratory baths, ovens, shakers and racks, as well as manual fluid handling techniques.

Abstract: A method for determining the presence and/or concentration of a water treatment polymer in an aqueous sample, comprising producing a polyclonal or monoclonal antibody to the water treatment polymer, and using the antibody so produced as a reagent in an immunoassay, conducted on the aqueous sample.

Abstract: An assay for an analyte in a sample, wherein the sample is contacted with an array of ligands including a ligand specific for the analyte, additionally comprises including a scavenger material that binds the analyte and thereby reduces its available concentration.

Abstract: The present invention relates, in general, to presenilin 2 proteolytic fragments. In particular, the present invention relates to a purified 20 kDa presenilin 2 C-terminal fragment (PS2-CTF); purified nucleic acid molecules coding for the 20 kDa PS2-CTF protein; cells containing the nucleic acid molecules; non-human organisms containing the nucleic acid molecule; antibodies having specific binding affinity to the 20 kDa PS2-CTF; hybridomas containing the antibodies; methods of detecting 20 kDa PS2-CTF in a sample; diagnostic kits; methods for screening compounds that inhibit proteolytic processing of presenilin 2 in a cell, isolated compounds that inhibit proteolytic processing of presenilin 2 in a cell, and a method of inhibiting apoptotic cell death by preventing proteolytic cleavage of presenilin 2 at a cleavage site which generates a 20 kDa C-terminal fragment.

Abstract: A process for carrying out a specific binding assay (for example an immunoassay) in which (a) a sample under assay, possibly containing a substance being tested for, is reacted with (b) a specific binding partner for the substance being tested for, immobilised on a solid support, and (c) a specific binding partner for the substance being tested for which is conjugated to a detectable marker, thereby to form a complex by reaction between whatever quantities are present of the substance being tested for with reagents (b) and (c), in which the marker is immobilised to the support via the substance being tested for, and is detected or assayed as an index of the quantity present in the sample (a) of any of the substance being tested for; characterised in that reaction ingredients (a), (b) and (c) are all mixed in a single step for reaction in a single reaction liquid, and competitive interference between the binding reactions of the substance being tested for and reagents (b) and (c) is avoided either by use of an

Abstract: The Invention relates to a method for providing at least one selected sequence in a nucleic acid with interstrand cross-links. The method comprises hybridizing at least one selected single strand sequence with a complementary single strand nucleic acid or a functional analogue thereof. The selected sequence or complementary nucleic acid or both comprise a cross-linking agent. The invention also relates to a method, referred to as COBRA, for the labeling of a set of at least two bio-organic molecules with a set of at least two colors, comprising generating said set of colors through combining ratio labeling with binary labeling.

Abstract: Protein arrays and protein-coated substrates for the parallel, in vitro screening of biomolecular activity are provided. Methods of using the protein-coated substrates and protein arrays are also disclosed. A plurality of different members of a single protein family may be immobilized on the protein-coated substrate or array. The protein-coated substrates and protein arrays are particularly useful in high-throughput drug screening and clinical diagnostics.

Abstract: A method and apparatus for urine self testing wherein the apparatus is placed directly into the toilet after urination which avoids the direct placement and retention of an apparatus in the stream of urine as is common with urine testing devices. The apparatus detects the presence of certain chemicals in dilute urine such as the presence of human chorionic gonadotropin (hCG) in the urine of a pregnant woman. An opening in the apparatus is fitted with a fluid absorption device which acts to concentrate the diluted urine on an indicator strip which contains antibodies, enzymes and antibody blockers which will provide a reactive change, usually of color, when subjected to a predetermined chemical such as hCG. The apparatus functions in dilute urine when placed in a toilet after urination and is largely constructed of biodegradable materials so that it can be flushed into the sewage system or a septic tank.

Abstract: The invention relates to the removal of viruses from aqueous solutions, as a rule protein solutions, by ultrafiltration. This entails the viruses to be removed being increased in size by incubation with a high molecular weight receptor binding thereto, preferably a specific antibody, so that, on the one hand, the separation effect is improved and, on the other hand, a larger pore diameter which can now be chosen for the filters used also makes it possible for smaller viruses to be separated from larger protein molecules present in protein solutions, and, where appropriate, the filtration rate is increased.

Abstract: Water soluble hybrid phthalocyanine derivatives useful in competitive and noncompetitive assays immunoassays, nucleic acid and assays are disclosed and claimed having (1) at least one donor subunit with a desired excitation peak; and (2) at least one acceptor subunit with a desired emission peak, wherein said derivative(s) is/are capable of intramolecular energy transfer from said donor subunit to said acceptor subunit. Such derivatives also may contain an electron transfer subunit. Axial ligands may be covalently bound to the metals contained in the water soluble hybrid phthalocyanine derivatives. Ligands, ligand analogues, polypeptides, proteins and nucleic acids can be linked to the axial ligands of the dyes to form dye conjugates useful in immunoassays and nucleic acid assays.

Abstract: The present invention provides a method for the quantification and assessment of platelet activation in whole blood samples and monitoring of antiplatelet pharmacologic agents. The method for quantifying platelet activation includes exposing platelets to a physiological concentration of an agonist that activates some of the platelets, resulting in the formation of at least one binding site on the surface of the activated platelets, and measuring the activated platelets. The present invention provides a method of assessing specific components of platelet activation.

Abstract: Disclosed herein are methods and reagent kits for the quantitative in vitro determination of the functional determination of multi-drug resistance in cells, as well as for the clinical screening of potential modulators of multi-drug resistant transport activity in cells. The method of the invention is based on the measurement of the accumulation rate of free calcein within the cells of the specimen (advantageously by fluorescence measurement), after exposing the cells in vitro to a cell permeable form of calcein that is a good substrate for MDR proteins present in the sample. The cell permeable form of calcein is converted within the cell by intracellular enzymes to free calcein. Comparison of free calcein accumulation in the presence and absence of a potential inhibitor of transport activity permits the rapid screening of such inhibitors.

Abstract: The invention relates to the removal of viruses from aqueous solutions, as a rule protein solutions, by ultrafiltration. This entails the viruses to be removed being increased in size by incubation with a high molecular weight receptor binding thereto, preferably a specific antibody, so that, on the one hand, the separation effect is improved and, on the other hand, a larger pore diameter which can now be chosen for the filters used also makes it possible for smaller viruses to be separated from larger protein molecules present in protein solutions, and, where appropriate, the filtration rate is increased.

Abstract: A kit for testing male fertility comprises a vessel, a base unit, a liquid supply containing liquid and two filters. The first filter is a sample separation filter which forms a hindrance to transmission of spermatozoa. The second filter of the kit is a spermatozoa detection filter comprising a reagent for identifying spermatozoa. Activation of the kit is prevented until a transport medium, such as the liquid, fills a gap allowing spermatozoa to transmit to a detection zone. The kit may be of one-piece construction and utilizes a thin piece of filter material to separate motile from non-motile spermatozoa.

Abstract: The invention relates to a method of evaluating the immunological status of a subject comprising the steps of 1) determining the content of an antibody in a liquid sample from the subject using an immunoassay, wherein the reaction between the antibody of the sample and a ligand in the form of an antigen, an antibody or a hapten, the ligand being directed to the Fab region of the sample antibody, is carried out in the presence of other constituents of the sample to obtain a measurement 1, 2) determining the content of an antibody in the liquid sample using an immunoassay, wherein the reaction between the antibody of the sample and a ligand in the form of an antigen, an antibody or a hapten, the ligand being directed to the Fab region of the sample antibody, is carried out in the absence of other constituents of the sample to obtain a measurement 2, and 3) interrelating measurements 1 and 2 to express the interference and using the interference as a parameter for evaluating the immunological status of the subje

Abstract: Compositions, formulae, devices and methods for the detection of target microorganisms, such as by visual immunoprecipitate assay, enzyme linked immunoassay, chemiluminescence, immunoblotting, or similar detection technology, wherein detection requires the discrimination among closely related genera, species and strains of antigenically related microorganisms based on immunological reactivity of a highly conserved antigen epitopes with a reagent system comprised of an antibody linked to a detecting reagent. The invention permits a detectable event to occur by exposing inaccessible but highly conserved and specific antigen epitopes to the detecting reagent. Exposure of such antigen epitopes without inactivating microbial metabolism allows for specific detection.

Abstract: The present invention provides a monoclonal antibody useful for immunoassay of human serum amyoloid A (SAA), which can be used as a marker for inflammations based on the agglutination reaction, as well as a reagent for immunoassay comprising the monoclonal antibody, and a method for immunoassay utilizing the monoclonal antibody. In a preferred embodiment, the monoclonal antibody recognizes at least one epitope of human amyloid A and it agglutinates with human serum amyloid A. The present invention improves the specificity of immunoassay by utilizing the agglutination reaction of SAA and monoclonal antibody in the presence or absence of other monoclonal antibodies recognizing SAA.

Abstract: A method of monitoring the amount of primary or secondary ligand in a cell, using a green fluorescent protein complex and fluorescence resonance energy transfer between two GFP molecules to monitor the primary or secondary ligand, is disclosed. Further disclosed is a method of screening a molecule, such as a peptide, for primary ligand-binding activity, which also uses a green fluorescent protein complex and fluorescence resonance energy transfer between two GFP molecules, to screen the molecule or peptide. A green fluorescent protein complex having a first green fluorescent protein, a primary ligand-binding peptide, and a second green fluorescent protein, is also disclosed.

Abstract: Magnetic particles for separating biological mixtures consist of nacreous luster pigments with magnetic properties coated with a biological polymer.

Abstract: An ultrasonic energy source is used to provide a variable force for measuring the binding forces between molecular entities and for sensing the presence of an analyte in a test sample. The device includes a surface that has a first binding member attached thereto and one or more particles that have a second binding member attached thereto. A reaction vessel is provided for exposing the surface to the particles whereby, if the first binding member has a binding affinity for the second binding member, a complex is formed between individual first binding members and individual second binding members and the particles thereby become immobilized with respect to the surface. The ultrasonic energy source is positioned for applying a variable ultrasonic force onto the surface, and the position of the particles is monitored as the intensity of the ultrasonic force is varied.

Abstract: Arrays of protein-capture agents useful for the simultaneous detection of a plurality of proteins which are the expression products, or fragments thereof, of a cell or population of cells in an organism are provided. A variety of antibody arrays, in particular, are described. Methods of both making and using the arrays of protein-capture agents are also disclosed. The invention arrays are particularly useful for various proteomics applications including assessing patterns of protein expression and modification in cells.

Abstract: A highly sensitive assay is disclosed which combines immunomagnetic enrichment with multiparameter flow cytometric and immunocytochemical analysis to detect, enumerate and characterize carcinoma cells in the blood. The assay can detect one epithelial cell or less in 1 ml of blood and has a greater sensitivity than conventional PCR or immunohistochemistry by 1-2 orders of magnitude. In addition, the assay facilitates the biological characterization and staging of carcinoma cells.

Abstract: A composition comprising a hydrogel matrix and a particulate magnetic material within the matrix may be employed to entrap different agents, including biological entities such as antibodies and antigens, whereby the composition may be employed in immunoseparation and in diagnostic procedures.

Abstract: The invention relates to a microfabricated device for the rapid detection of DNA, proteins or other molecules associated with a particular disease. The devices and methods of the invention can be used for the simultaneous diagnosis of multiple diseases by detecting molecules (e.g. amounts of molecules), such as polynucleotides (e.g., DNA) or proteins (e.g., antibodies), by measuring the signal of a detectable reporter associated with hybridized polynucleotides or antigen/antibody complex. In the microfabricated device according to the invention, detection of the presence of molecules (i.e., polynucleotides, proteins, or antigen/antibody complexes) are correlated to a hybridization signal from an optically-detectable (e.g. fluorescent) reporter associated with the bound molecules. These hybridization signals can be detected by any suitable means, for example optical, and can be stored for example in a computer as a representation of the presence of a particular gene.

Abstract: The invention concerns an immunological process for the determination of prostate-specific antigen (PSA), particularly for the determination of free PSA, the total concentration of PSA and the concentration of PSA-serpin complexes by incubation of the sample with at least one antibody specifically binding to free PSA but not to complex PSA. The process is characterized in that especially before the determination of the total PSA concentration a nucleophile containing amine is added to the sample. Furthermore, the invention concerns the use of amine-containing nucleophiles for the production of free PSA as well as a procedure for preparing free PSA from complex PSA by incubation of a sample containing complex PSA with a nucleophile containing amine.

Abstract: A method for measuring the end point and for monitoring the real time kinetics of a bioaffinity reaction in biological fluids and suspensions, employing microparticles as bioaffinity binding solid phase, biospecific reagent labelled with a fluorescent label and a fluorescence detection system which is based on two-photon fluorescence excitation, contacting the analyte, the labelled reagent and the solid phase simultaneously, focusing a two-photon exciting laser beam into the reaction suspension and measuring the fluorescence signal emitted by the microparticles from one particle at a time when they randomly float through the focal volume of the laser beam. In this method the signal is monitored kinetically to obtain information about the analyte concentration before the reaction approaches the highest point of the response. Since the growth rate of the signal intensity is directly proportional to the analyte concentration, the analyte concentration can be predicted in the initial phase of the reaction.

Abstract: The invention pertains to novel genes which function in the regulation of DNA replication and/or entry of a cell into mitosis. Tile invention also pertains to novel proteins encoded by the genes described herein, antibodies which bind the encoded protein, and homologs of the novel genes which function in regulation of DNA replication and/or entry of a cell into mitosis find hybridize to the DNA sequence of the novel genes. The invention also includes methods for determining the presence of a proliferative disorder comprising determining the presence of level of hscdc6.

Abstract: The present invention provides methods and kits for determining the identity of a nucleotide at a variant site in a target nucleic acid of interest, including, for example, point mutations and single nucleotide polymorphisms. The methods involve conducting template-dependent extension reactions in the presence of a mixture of nucleotides that include at least one labeled extendible nucleotide and at least one labeled non-extendible nucleotide that are selected to be complementary to the nucleotides that potentially occupy the variant site. The particular labeled nucleotide incorporated into the extension products is characteristic of the nucleotide at the variant site.

Abstract: The present invention provides a method of biasing the immune response of a mammal toward a desired epitope of a chosen antigen, particularly a functionally-relevant epitope. In preferred embodiments, the epitope-biasing method leads to fully-human antibodies of defined specificity with affinities of 10 nM to 50 pM. The invention further provides antibody libraries biased to tissues and to cell types, for use in generating epitope expression profiles useful for characterizing unknown genes. When all aspects of the present invention are combined, they result in an integrated system for defining critical epitopes on newly discovered gene products and rapidly devloping therapeutic grade antibodies to those critical epitopes.

Abstract: An assay device and method are provided which allow the determination of the presence or absence of at least one analyte in a test sample, while providing specific identification of the test subject. The assay device includes a reaction medium having at least one reaction zone and at least one control zone, which is capable of providing a pattern suitable for identifying the test subject. The pattern suitable for identifying the test subject is preferably a fingerprint. In a preferred embodiment of the invention, the reaction zone and the control zone include at least one member of a ligand/receptor pair.

Abstract: Novel bipyridyl-osmium complex conjugates, their preparation, and their use in electrochemical assays are described. The redox reversible-osmium complexes can be prepared to exhibit unique reversible redox potentials and can thus be used in combination with other electroactive redox reversible species having redox potentials differing by at least 50 millivolts in electrochemical assays designed for use of multiple electroactive species in the same cell and in the same sample without interference between the two or more redox coupled conjugate systems.

Abstract: A methodology for screening libraries of compounds for desirable biological/therapeutic activities, preferably using an automated system for the microinjection of compound(s) of interest into the open circulatory system (i.e., hemolymph) of Drosophila larvae genetically modified to sensitize a particular signaling pathway related to a human disease either by expression of a human disease gene or by the activation of a Drosophila gene that in the adult fly results in the development of an easily detectable phenotypes such that compounds that selectively interfere with this specific signaling pathway will modify or suppress the phenotype and can be identified rapidly and efficiently.

Abstract: A set of contiguous and partially overlapping RNA sequences and polypeptides encoded thereby, designated as PS190 and transcribed from prostate tissue is described. These sequences are useful for the detecting, diagnosing, staging, monitoring, prognosticating, preventing or treating, or determining the predisposition of an individual to diseases and conditions of the prostate, such as prostate cancer. Also provided are antibodies which specifically bind to PS190-encoded polypeptide or protein, and agonists or inhibitors which prevent action of the tissue-specific PS190 polypeptide, which molecules are useful for the therapeutic treatment of prostate diseases, tumors or metastases.

Abstract: The present invention relates to methods for identifying nucleic acid molecules encoding (poly)peptides that interact with target molecules. The method of the present invention is particularly characterized by an in vitro translation step under conditions that allow formation of polysomes in the presence of antisense oligonucleotides complementary to the tag-coding sequence of ssrA-RNA. The present invention further relates to kits that are useful for carrying out the method of the invention.

Abstract: The present invention relates to an assay apparatus for detecting a product in a sample. The assay apparatus comprises a fluid pathway with an input of the sample and an input for a reagent with a detectable moiety which transports the sample to a detecting means via a barrier arranged to prevent a product-reagent complex passage but allow passage of unbound reagent and sample. The apparatus also includes supply means for supplying a substance adapted to breakdown the complex into a detectable moiety which can flow through the barrier to the detecting means.

Abstract: A biphase immunoassay method is provided in which a water immiscible liquid is qualitatively or quantitatively measured by mixing a sample of the water immiscible liquid with an aqueous solution containing a specific binding partner of the analyte. Binding occurs at or across the interface between the respective liquids and the degree of association of the analyte with its binding partner is dependent upon the concentration ratio rather than absolute quantities. The degree of association may be determined and used to determine the presence and/or concentration of analyte in the sample.

Abstract: A homogeneous biospecific assay method for an analyte in solution or in a biological suspension, in which a biospecific reagent competitively binding an analyte and a ligand labeled with a fluorescent molecule, is reacted with and bound to a solid phase, and in which the free labeled ligand is extracted is excited with two-photon excitation by focusing a laser beam suitable for two-photon excitation into the sample volume; and the concentration of the analyte is calculated based on the photon emission contributed by the free labeled ligand.

Abstract: The present invention relates to a method for at least one of detecting, quantifying or isolating at least one analyte from a liquid medium in which the analyte is distributed and comprises providing a reagent comprised of particles having a receptor for an analyte fixed to the particles distributed in the medium and a capturing means having an exposed surface defining an active zone. An intermediate reagent is formed by the complex of the reagent with the analyte. A second receptor is fixed in the active zone to capture either the analyte bound by the reagent or the receptor (capture partners). The active zone serves as a site of isolation and concentration of the capture partners.

Abstract: Diagnosis of overt, subclinical or potential autoimmune adrenal disease, by contacting a sample of body fluid with: (i) at least one epitope region of 21-hydroxylase which epitope region is essential for binding monoclonal or polyclonal antibodies to 21-hydroxylase and/or autoantibodies to 21-hydroxylase; and (ii) monoclonal or polycolonal antibodies to 21-hydroxylase. The degree of binding of the autoantibodies present in the sample to the relevant epitope region is monitored.

Abstract: This invention provides modified phycobilisomes and phycobilisome complexes that are supramolecular complexes with diverse spectral properties, and which may optionally be immobilized on a manufactured solid support. The invention provides a versatile set of highly sensitive signal-generating systems and conjugates that may be used as highly detectable tracers and labels, or in biotransducers comprising phycobilisomes or phycobilisome complexes, and also provides methods for performing specific binding assays using signal-generating systems comprising phycobilisomes as detectable labels. The embodiments of the invention provide the art with an extremely sensitive, nonisotopic detection means for assaying analytes and for sensing molecular events and environmental conditions.