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 further provides a method of determining bound and free analyte in a sample using at least one photon reducing agent. The present invention also provides a method of screening test chemicals in fluorescent assays using photon reducing agents.

Abstract: Invented is a method of preparing combinatorial libraries and combinatorial libraries prepared thereby. Also invented is a method for identifying compounds having desired characteristics from a combinatorial library or a set of combinatorial libraries by the use of flow cytometry. Also invented is a method for encoding combinatorial libraries using fluorophore labeled beads.

Abstract: The present invention relates to a measuring device which comprises electrodes fabricated on porous membrane substrate in which the sample migrates chromatographically; and the method of quantifying material in the sample by using the device. The sample material for measuring can be quantified by the measuring device of this invention, which is consists pretreatment bands in the lower part of porous membrane substrate and electrodes in the upper prt of pretreatment bands, by the procedure as foolows: The sample material for measuring is chromatographically migrated in the porous membrane substrate by applying the sample on the lower part of the porous membrane substrate; and then the changes of electric signal by the material at the electrode are measured to quantify the material.

Abstract: Novel activated peptides and conjugates thereof, useful in diagnostic assays and therapeutics, and processes for the preparation thereof are disclosed.

Abstract: The present invention provides novel cyclosporine C (CsC) derivatives having improved protein conjugatibility and hydrolytic stability. The present invention further provides a CsC derivative conjugated to a carrier, e.g., a solid support. Preferably, the solid support is a latex or magnetic particle.

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 further provides a method of determining bound and free analyte in a sample using at least one photon reducing agent. The present invention also provides a method of screening test chemicals in fluorescent assays using photon reducing agents.

Abstract: The present invention relates to the field of immunoassays for metal ions. The invention presents: chelators, chelates, antibodies specific for the chelates, tracers comprising chelates conjugated to detectable labels, and immunoassays utilizing the foregoing.

Abstract: Novel sensor devices composed of a crystalline colloidal array (CCA) polymerized in a hydrogel are disclosed. The hydrogels are characterized as being capable of shrinking and swelling in response to specific stimuli applied thereto. As the hydrogels shrink or swell, the lattice structure of the CCA embedded therein changes, thereby changing the wavelength of light diffracted by the CCA. Thus by monitoring the change in diffracted wavelength, the concentration of a stimulus is determined. The gels can be modified to sense numerous different stimuli. The sensor devices are specific in that they are modified to react with only one species or family of species. These sensors have various applications in areas including, for example, environmental and chemical systems, chemomechanical systems, sensor devices and medical diagnostic tools. Various methods for making and using these devices are also disclosed.

Abstract: A method of releasing particulates from a solid matrix is provided. The method is effected adding to the solid matrix a degrading enzyme capable of degrading the solid matrix, to thereby release the particulates from the solid matrix.

Abstract: A compound having a polysaccharide binding domain such as contained by a cellulose and essentially lacking in polysaccharidase activity is purified from other ingredients in a mixture using an affinity partition system. A mixture containing the compound is contacted with a system containing as a first phase an aqueous solution of oligosaccharide polymer such as cellulose and as a second phase a solution of a polymer such as a poly(ethylene glycol)-poly(propylene glycol) copolymer. The compound petitions into the first phase and binds to the oligosaccharide polymer, preferably with a Ka of 103 to 107, to form a complex. The complex is collected, and the compound is dissociated from the oligosaccharide polymer. The compound may be formed of a non-peptide chemical moiety or a peptide moiety linked to a polypeptide having the polysaccharide binding domain.

Abstract: Devices for conducting an assay are disclosed which utilize shrink wrap as a casing material. The use of shrink wrap casings enables the preliminary fluid filtering step and the chemical detection step to be combined, provides improved control over the flow of fluids into and through the assay device and reduces the time, material, effort, expense and risk of contamination involved in conducting assays.

Abstract: An apparatus and method for chemical and biological analysis, the apparatus having an optical trapping means to manipulate the reaction substrate, and a measurement means. The optical trapping means is essentially a laser source capable of emitting a beam of suitable wavelength (e.g., Nd:YAG laser). The beam impinges upon a dielectric microparticle (e.g., a 5 micron polystyrene bead which serves as a reaction substrate), and the bead is thus confined at the focus of the laser beam by a radial component of the gradient force. Once "trapped," the bead can be moved, either by moving the beam focus, or by moving the reaction chamber. In this manner, the bead can be transferred among separate reaction wells connected by microchannels to permit reactions with the reagent affixed to the bead, and the reagents contained in the individual wells.

Abstract: An affinity chromatographic matrix for purification of a biological material is provided having an ionically charged polymeric ligand such as glycoaminoglycan non-covalently bound directly by an ionic bond to an oppositely ionically charged group on a chromatographic matrix. Having the ligand non-covalently bound to the matrix by an ionic bond, allows the ligand to be easily washed off the matrix and replaced for subsequent purifications without having to replace the matrix. A biological material in a crude mixture is purified by non-covalently binding the material to the bound ligand and dissociating the material from the ligand. Matrices that may be used include crosslinked agarose, crosslinked dextran, crosslinked cellulose, crosslinked dextran and bisacrylamide, or matrices based on silica or plastic polymers. The charged group may be a quaternary amine or diethylaminoethyl group.

Abstract: The present invention relates to a method for biotinylating a desired subset of a larger population of proteins, wherein the subset of proteins is first selectively bound to a solid phase, thereby separating it from undesired proteins of the population, and then, still bound to solid phase, it is biotinylated. Unreacted biotin may then be washed from the solid phase, and the biotinylated protein may be uncoupled from the solid phase.

Abstract: The present invention describes xanthene dyes, including rhodamines, rhodols and fluoresceins that are substituted one or more times by a sulfonic acid or a salt of a sulfonic acid. The dyes of the invention, including chemically reactive dyes and dye-conjugates are useful as fluorescent probes, particularly in biological samples.

Abstract: Disclosed are conjugates including a polymer backbone or microbead and binding molecules, such as Fv, Fab, or F(ab').sub.2 fragments of monoclonal antibodies or whole antibodies that are bound through their Fc carbohydrate moieties or have their Fc portion modified so that they cannot effect ADCC or complement-mediated cytolysis, and that are specific for a T cell surface antigen, such as CD3, TCR, CD4, CD8, or CD28 on T cells. The polymer or microbead is preferably made of cross-linked dextran, ficoll, latex, or agarose. The microbeads are preferably of 1 to 10 .mu.m in size, so that they can be suspended in in vivo fluids. These conjugates can be used to induce proliferation of T cells and immune stimulation, and to increase the antibody response against an administered antigen.

Abstract: The invention provides a biocompatible polymeric coating material, wherein the polymeric material is selected from the group consisting of linear, dendrimeric and branched polymers which contain primary, secondary, tertiary or quaternary amine groups with hydrophobic side chains and which polymers are insoluble, or only slightly soluble, in aqueous solution at a pH range between 3 and 11 and soluble in at least one organic solvent selected from the group consisting of alcohols, acetone, methyl ethyl ketone, tetrahydrofuran, dioxane, chloroform, dichloromethane, hexanes and mixtures thereof.

Abstract: A technique is disclosed for generating nonrandom combinatorial libraries on solid phase supports in which each of a set of predetermined species of test compounds is present on a predetermined number of solid phase supports, preferably on only one, and each solid phase support has only a single species of test compound. Each of the predetermined species of test compounds is prepared with absolute certainty because the technique does not employ any random division of the solid phase supports. Rather, the method is based on the stepwise division of a continuous solid phase support matrix prior to each synthetic step in which more than one type of subunit is added. Non-limiting examples of matrices of the solid phase supports include polypropylene membranes, polytetrafluoropropylene membranes and cotton thread. The combinatorial libraries made by the technique are also disclosed.

Abstract: A method of determining the concentration of a sample antigen in the presence of an interferant by(1) running two immunoassays on the sample: one assay where the interferant influences the binding of both the sample antigen and a labeled antigen and a second assay where the interferant influences the binding of the sample antigen but not the labeled antigen;(2) obtaining a plot of the possible sample antigen concentrations versus the possible interferant concentrations corresponding to the readout for the sample for each of the two immunoassays; and(3) determining the sample antigen concentration and the interferant concentration which correspond to the point that appears in both the immunoassays plots.

Abstract: A suspension of inert particles is prepared in an aqueous solution, to which an antibody or an antigen and a carrier-bound antigen or antibody, respectively, are added in any desired order. After centrifuging, the positive, weakly positive, or negative reaction can easily be recognized on the basis of a simple pattern.

Abstract: The invention provides a method of assessment of carbohydrate-deficient transferrin in a transferrin containing body fluid, said method comprising the steps of:i) obtaining a transferrin containing liquid sample of or derived from a said fluid;ii) contacting said sample with a source of iron ions;iii) subsequently contacting said sample with an anionic ion exchange resin at a pH such as to cause carbohydrate-deficient transferrin to be retained by said resin;iv) subsequently contacting said resin with an eluant serving to release carbohydrate-deficient transferrin into the eluate from said resin;v) collecting a volume of said eluate substantially free from tetra- and penta-sialo transferrin; andvi) assessing the transferrin variant content in said volume of eluate.By including at least a proportion of the trisialotransferrin in the eluate, it is possible to use relatively simple assessment techniques such as turbidimetry in the assay.

Abstract: The invention relates to a process for making a test element, such as an analytical test element. Compositions of matter, such as analyte specific receptors, are treated to carry a charge. These are then applied to test carriers treated to carry a charge opposite that of the composition of matter. Interaction of charge fixes the composition of matter to the test element.

Abstract: A multilayer dry immunoassay element comprising 1) a spreading layer having a sample application area and a signal read area and 2) a separate receptor layer residing on 3) a radiation-transmissive support characterized in that the spreading layer contains a light absorbing material.

Abstract: A stable protein-coated nickel particle useful in biological assays contains a nickel particle having removed from the surface thereof nickel oxide; a linker attached to said nickel particle, the linker having a free amino group; and a protein attached to said linker by covalently bonding to the free amino group. Methods of producing and using these oxide-free nickel-protein conjugates are disclosed.

Abstract: The present invention relates to bioassay materials useful for the detection of toxic substances and, more particularly, to packaging materials for food and other products, along with methods for their manufacture and use. The invention provides a unique composite material capable of detecting and identifying multiple biological materials within a single package. The biological material identification system is designed for incorporation into existing types of flexible packaging material such as polyolefin films, and its introduction into the existing packaging infrastructure will require little or no change to present systems or procedures.

Abstract: A two-phase partition system is provided for affinity separation of a composition containing a polysaccharide binding peptide from a mixture such as a fermentation broth. The peptide may be from an enzyme and lacking in polysaccharidase activity such as the binding domain of cellulase that binds to cellulose. The system contains a phase-forming oligosaccharide polymer such as a cellulose derivative to which the peptide binds with a Ka of 10.sup.3 M to 10.sup.7 M, and a phase inducing agent such as a polyethylene glycol polymer, or a salt present at sufficiently high concentration to induce phase separation. If the oligosaccharide polymer is thermoseparating, phase separation can be induced by heating. Using the system involves contacting a composition containing the peptide such as a fusion protein with the system, partitioning the composition into a phase containing the oligosaccharide polymer by binding to the polymer and recovering the polymer containing the bound composition.

Abstract: In a vertical down-flow fluid bed reactor, suspended particles in liquid proximal to an inlet in an uppermost part of the reactor are agitated to form a downward extending turbulent zone having vigorously moving particles and a non-turbulent zone distal to the inlet having essentially stationary particles in liquid below and adjoining the turbulent zone. In a vertical up-flow fluid bed reactor, an upward extending turbulent zone is formed proximal to an inlet in a lowermost part of the reactor and the non-turbulent zone is above the turbulent zone. The downward or upward extend of the turbulent zone is determined by the degree of agitation. The particles may contain an active substance and be in the form of a conglomerate of base particles having a desired density to control floatation or sedimentation. Particles in the turbulent and non-turbulent zones may be different such as having different specific gravities.

Abstract: The invention provides a monospecific antibody that is specifically reactive with enzymatically mediated degradation products of fibrin(ogen) (i.e., fibrin, fibrinogen, and related substances). The monospecific antibody of the invention is specifically reactive with an epitope defined by an amino acid sequence SEQ ID NO:1. The invention further provides compositions containing a monospecific antibody, optionally detectably labeled, for the performance of fibrinolytic or thrombolytic analyses. The invention further provides continuous cell lines (hybridomas) that produce monospecific antibodies as described.

Abstract: An immunoassay method in which blood can be measured even without pretreatment by a centrifuge etc. In the present invention, antibodies or antigens in a sample are subjected to agglutination reaction with insoluble carriers onto which antigens or antibodies specifically reacting with the antibodies or antigens in the sample have been imrobilized and the resulting agglutination mixture is determined for the change in its absorbance or in its scattered light by irradiation with light, wherein said sample is whole blood and the whole blood is forcibly lysed.

Abstract: A method for detecting mutations, such as a single base change or an addition or deletion of about one to four base pairs, is based on the use of an immobilized DNA mismatch-binding protein, such as MutS, which binds to a nucleic acid hybrid having a single base mismatch or unpaired base or bases, thereby allowing the detection of mutations involving as little as one base change in a nucleotide sequence. Such a method is useful for diagnosing a variety of important disease states or susceptibilities, detecting the presence of a mutated oncogene and for isolating or removing by affinity chromatography duplex DNA molecules containing mismatches such as error-containing molecules in PCR-amplified DNA samples. Also provided are kits useful for practicing the methods of the present invention.

Abstract: A method of assay for a ligand in a sample is described in which calibration occurs within the assay. This is achieved utilizing a measurement region and one or more calibration regions. In at least one of the calibration regions a non-zero signal results, either because of the presence of a calibration reagent or as a result of a binding reaction analogous to that which takes place in the measurement region.

Abstract: An immunochemical assay device comprising a base member, an array disposed on the base member, and at least one assay indicia zone. The array comprises (i) a reservoir pad to receive sample liquid, (ii) a wicking membrane, and (iii) at least one filter zone interposed between the wicking membrane and the reservoir pad. The filter zone being operable to permit passage of any specific immunocomplex to the wicking membrane while impeding passage of larger components.

Abstract: The invention provides a new method for antiglobulin testing from serum of a potential blood transfusion recipient in which warm autoantibodies are removed from serum so as to allow identification of alloantibodies present. The method involves contacting serum from a patient with one or more ligands that bind warm autoantibodies but do not bind alloantibodies, separating the non-bound serum components from the bound warm autoantibodies, and using the warm autoantibody-depleted serum in antiglobulin testing. Suitable ligands include phospholipids, the polar head groups of phosphoglycerides, and naturally occurring and synthetic analogues of these molecules.

Abstract: Combinatorial libraries are disclosed which are represented by Formula I: ##STR1## wherein: ##STR2## is a solid support; T'--L-- is an identifier residue; and --L'--II' is a ligand/linker residue. These libraries contain dihydrobenzopyrans of the formula ##STR3## which interact (i.e., as agonists or antagonists) with .alpha. adrenergic receptors, dopamine receptors, .sigma.-opiate receptors, and K.sup.+ channels and are inhibitors of carbonic anhydrase isozymes. They are useful in the treatment of ocular diseases such as glaucoma.

Abstract: Encoded combinatorial chemistry is provided, where sequential synthetic schemes are recorded using organic molecules, which define choice of reactant, and stage, as the same or different bit of information. Various products can be produced in the multi-stage synthesis, such as oligomers and synthetic non-repetitive organic molecules. Conveniently, nested families of compounds can be employed as identifiers, where number and/or position of a substituent define the choice. Alternatively, detectable functionalities may be employed, such as radioisotopes, fluorescers, halogens, and the like, where presence and ratios of two different groups can be used to define stage or choice. Particularly, pluralities of identifiers may be used to provide a binary or higher code, so as to define a plurality of choices with only a few detachable tags. The particles may be screened for a characteristic of interest, particularly binding affinity, where the products may be detached from the particle or retained on the particle.

Abstract: Antibodies that selectively bind to quadruplex nucleic acids are described. Isolated cells that produce such antibodies, and methods utilizing these antibodies, are also described.

Abstract: A method for a single-measurement quantification of multiple populations of white blood cells (WBC) is based upon the labeling of different pairs of cell populations, each pair containing mutually exclusive cell receptors which are expressed at substantially similar receptor densities with labeled ligands for each receptor. One cell population is labeled with a ligand capable of binding to a first cell surface receptor which ligand is directly conjugated to a fluorescent phycobiliprotein or tandem dye; and a second cell population is labeled with a ligand capable of binding to a second cell surface receptor, which ligand is cross-linked by an aminodextran to a fluorescent phycobiliprotein or tandem dye. The phycobiliproteins upon laser excitation produce a different detectable fluorescence intensity for each cell population. Use of such pairs of conjugates enable two populations of cells with similar receptor densities to be distinguished with the use of a single color marker.

Abstract: The invention provides a method of diagnosing Alzheimer's disease. The method utilizes presenilin-1, whose level is found to be substantially decreased in Alzheimer's patients. Included in the invention are diagnostic kits for Alzheimer's disease and methods of screening for effective therapeutics for the disease. The invention also provides a method of studying the function and regulation of presenilin-1 in brain by the use of primate retinoblastoma cells.

Abstract: A method of detecting heparin-induced antibodies to complete a diagnosis of heparin-induced thrombocytopenia (HITP) is disclosed. This method comprises the first step of attaching a glycosaminoglycan to a solid support, wherein the glycosaminoglycan is attached to the solid support only at the reducing end of the molecule (unidirectionally). Platelet factor 4 is then bound to the glycosaminoglycan forming a complex having an epitope recognizable by antibodies generated in an HITP immune response. Human blood plasma or serum from a patient suspected of having HITP is exposed to the complex and the complex is analyzed to determine if HITP-related antibodies are present. A device and kit used in performing the diagnostic assay are also disclosed.

Abstract: Encoded combinatorial chemistry is provided, where sequential synthetic schemes are recorded using organic molecules, which define choice of reactant, and stage, as the same or different bit of information. Various products can be produced in the multi-stage synthesis, such as oligomers and synthetic non-repetitive organic molecules. Conveniently, nested families of compounds can be employed as identifiers, where number and/or position of a substituent define the choice. Alternatively, detectable functionalities may be employed, such as radioisotopes, fluorescers, halogens, and the like, where presence and ratios of two different groups can be used to define stage or choice. Particularly, pluralities of identifiers may be used to provide a binary or higher code, so as to define a plurality of choices with only a few detachable tags. The particles may be screened for a characteristic of interest, particularly binding affinity, where the products may be detached from the particle or retained on the particle.

Abstract: Compounds and methods are provided for use in purification of CD34.sup.+ cells and specific surface antigens thereof. The present invention discloses methods for releasing CD34.sup.+ cells, as well as compounds having a carbohydrate epitope of the CD34 surface antigen, from an affinity matrix, using carbohydrates having the structure:Neu5Ac.alpha.2-3Gal.beta.1-4(X)wherein (X) is GlcNAc, or a monosaccharide or a cyclohexane derivative that is structurally similar to GlcNAc.

Abstract: Disclosed is apparatus for detecting the presence of an analyte of interest in a sample, comprising an immobilised binding partner comprising a solid support and a reversibly binding receptor which is capable of binding to the analyte of interest thereby causing a measurable change in a property of the immobilised partner, and detection means for detecting the measurable change and a method for detecting the presence of an analyte of interest.

Abstract: A method of using a reaction plenum in the presence or absence of paramagnetic beads to perform chemical syntheses resulting in separation and recovery of a final desired reaction product is provided. The reaction plenum comprises a reaction plate, a reaction vessel for mounting in the reaction plate, a reaction plate holder, a screw-like rod, a mounting block attached to the reaction plate holder for operably receiving the screw-like rod, a motor, a sonication region in a temperature controllable water bath and a magnetic separation region in the water bath. Paramagnetic beads having reaction sites are introduced into the reaction vessels along with the appropriate solvent and one or more reactants. The contents of the reaction vessel are sonicated, then moved to the magnetic separation region where the paramagnetic beads are tightly held against the reaction vessel while the solvent is aspirated off. Once the desired reaction product is attained, the reaction product is cleaved off the paramagnetic bead.

Abstract: Disclosed are rationally designed mixed mode resins which are useful in recovering a target compound from an aqueous solution and methods for use of such resins. The resins described herein have a hydrophobic character at the pH of binding of the target compound and a hydrophilic and/or electrostatic character at the pH of desorption of the target compound from the resin and are specifically designed to bind the target compound from an aqueous solution at both a low and high ionic strength.

Abstract: For the qualitative or/and quantitative detection of a substance to be determined in a test sample with the aid of an immunoassay or nucleic acid hybridization assay the following components are used:a) a capture reagent which enables a specific detection of the substance to be determined by means of two different binding sites 1) if desired together with further test components and 2) is bound or is capable of binding to an active solid phase via a specific binding pair one partner of which is linked to the capture reagent and the second partner of which is coupled to an active solid phaseb) an active solid phase andc) an inactive solid phase which substantially corresponds to the active solid phase but to which the capture reagent cannot bind,wherein the test sample is either firstly brought into contact with the inactive solid phase alone and only later with the active solid phase, or is simultaneously brought into contact with the active and inactive solid phase during which the capture reagent and if des

Abstract: A stent for the inhibition of restentosis. The stent is coated with an antigen which can be bound by a labelled antibody. The antibody is preferably labelled with a radioactive source. After the stent has been placed in the blood vessel of the subject, the antibody is injected. The antibody then binds to the antigen on the stent, thereby localizing the radioactive source to the area to be treated, for example for restenosis. Other biomedical devices, such as coil, artificial valve and vascular graft, could also be used in the place of the stent. The biomedical device could be placed in another biological passageway, such as the gastrointestinal tract, an airway or the genitourinary tract.

Abstract: This invention relates to an improved method for detecting and quantifying the presence of a target molecule, such as an antigen, an antibody or a polynucleotide, in a sample which method uses alkaline phosphatase as the reporter enzyme and the reduction of a tetrazolium salt to a formazan as part of the detection/signaling system.

Abstract: The present invention is a method useful for the detection of bloodgroup antigens and antibodies. The method of the present invention is envisioned for two types of assays: a direct assay and an indirect assay. The direct assay comprises adding a sample of erythrocytes to a reaction tube charged with two layers of immunoreactive particles, a first layer, preferably Sepharose, having Protein G coupled to the surface of those particles and a second layer, preferably Sephacryl S-200, having Protein A coupled to those particles in a buffer solution. Antibodies specific for the bloodgroup antigens tested for are coupled to the Protein G. The reaction tube is then centrifuged for a time sufficient to force to the bottom of the reaction tube erythrocytes that do not attach to the antibodies.

Abstract: Antivenoms to snake, spider, scorpion and jelly fish venoms are produced for treatment of humans and animals, and for analytical use. Polyvalent antivenoms are produced containing immunoglobulin which is greater than fifty percent venom reactive. Purified polyvalent antivenom is derived from a first polyvalent antivenom having two or more monovalent subpopulations, and purified such that greater than fifty percent of the monovalent subpopulations are recovered by weight. The antivenoms can be horse or avian such as chicken antivenom. Chicken antivenom is obtained using a whole venom that is not glutaraldehyde pretreated, and the antivenom contains yolk immunoglobulin. Antivenoms are purified with an antigen matrix containing a single whole venom or a plurality of whole venoms covalently attached to an insoluble support such as aldehyde-activated agarose. Preferably, the whole venoms forming the plurality of whole venoms are selected from the four whole venoms of C. atrox, B. atrox, C. adamanteus and C.

Abstract: The present application discloses dextran crosslinked, antibody-phycobiliprotein conjugates containing up to twenty phycobiliprotein per dextran molecule which conjugates are able to achieve amplification of fluorescence intensity over direct antibody-phycobiliprotein labeled cells of two fold or greater.