Abstract: Methods for identifying polypeptides which coordinate to select metals, chemosensors comprising polypeptides which coordinate to select metals and methods for selectively detecting the presence of metals using these chemosensors are disclosed.

Abstract: The invention relates to methods of performing a binding assay for an analyte of interest present in a sample based upon electrochemiluminescence at an electrode of interest. Particles are employed in the method, which are then collected in a zone at which electrochemiluminescence can be induced, wherein the amount of induced electrochemiluminescence is related to the amount of analyte in the sample.

Abstract: A mixture of recombinant mono- and poly-epitope proteic materials able to fully replace the viral antigens when used in an enzyme immunoassay (EIA) is disclosed; the mixture includes a poly-epitope fusion protein having a first region formed by an amino acid sequence (H10) corresponding to that of the last 233 amino acids of the COOH terminus of the viral protein p52 or to a part thereof, a second region formed by an amino acid sequence (F3) corresponding to that of the last 43 amino acids of the COOH terminus of viral protein pp150 or to a part thereof, and a third region formed by an amino acid sequence (A1C2) corresponding to that taken from aa 595 to aa 614, proceeding in direction 5'.fwdarw.3', of the same viral protein pp150; and, in combination, a second fusion protein including a sequence of amino acids corresponding to that taken, proceeding in direction 5'.fwdarw.

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: This disclosure relates to novel antibodies specific to the recently discovered receptor to human interleukin 12 (IL-12R). The antibodies to IL-12R, most preferably, the monoclonal antibodies to that protein, are useful in determining the status of the human immune system and as diagnostic reagents or potential therapeutic reagents for conditions involving imbalances in IL-12 levels or cell types sensitive to IL-12 activation.Further aspects of the disclosure relate to methods of producing and purifying such novel antibodies and hybridoma cell lines capable of their production. Another aspect of the disclosure relates to an immunoprecipitation assay for the detection of solubilized IL-12R which employs, in a preferred embodiment, monoclonal antibodies to the receptor of the present invention covalently bound to Protein G-Sepharose resin.

Abstract: Disclosed is an improvement to the method of determining the concentration of a hemoglobin adduct in a blood sample by the steps of assaying the blood sample for the total amount of hemoglobin, assaying the blood sample for the hemoglobin adduct, and dividing the hemoglobin adduct concentration by the total hemoglobin concentration. The improvement involves normalizing the measurement of the hemoglobin adduct to the total amount of hemoglobin in the blood sample.

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: Methods of calculating the platelet count of an individual, by measuring the amount of a released platelet granule protein of interest in a sample of whole blood or of platelet-rich plasma from the individual, are described. The platelet granule protein of interest is either thrombospondin or .beta.-thromboglobulin. The amount of released platelet granule protein of interest in the whole blood sample or platelet-rich plasma sample is measured using an enzyme-linked immunosorbent assay; radioimmunoassay; sandwich assay; a quantitative immunochromatographic assay; or non-solid phase nephelometry. The platelet count is directly related to the amount of released platelet granule protein of interest in the sample, and can be determined from the amount of platelet granule protein of interest that is released from a known number of platelets.

Abstract: A method for identifying a toxicant in an environmental water or soil sample comprising (a) adding to the sample an antibody known to form a complex with a toxicant suspected to be present in the sample; (b) incubating the antibody with the sample for a time and under conditions sufficient to allow complexes to form between the antibody and the toxicant; and (c) comparing the toxicity of the sample treated as in the step (b) with the toxicity of the sample prior to the step (a), whereby a reduced amount of toxicity of the treated sample compared with the untreated sample indicates the presence of the toxicant in said sample. The method described herein provides unexpected and important advantages by providing more accurate correlations between predicted and observed toxicity of a sample than previous methods.

Abstract: The invention relates to fluorescent dyes that are substituted or unsubstituted derivatives of 1-(isoindolyl)methylene-isoindole that are bound through both isoindole nitrogens to a boron difluoride moiety, forming a fluorescent dibenzopyrrometheneboron difluoride compound ##STR1## that is further substituted by bathochromic substituents that are aryl or heteroaryl moieties further substituted by an additional aryl or heteroaryl, that is itself optionally further substituted by an additional aryl or heteroaryl. These aryl and heteroaryl groups are separated by a covalent bond, or by an ethenyl, butadienyl or hexatrienyl linkage. The dyes of the invention are particularly useful as labels for carriers, particularly polymeric microparticles. The resulting microparticles have a long-wavelength fluorescence emission, and possess utility for tracing flow in biological systems, particularly in tracing blood flow.

Abstract: An apparatus in the form of a test strip is useful for determining the presence of one or more components in a fluid sample. The test strip can be used by itself or in conjunction with an associated housing assembly. The test strip provides a rapid volume, timing and temperature independent visually readable strip for the semi-quantitative detection of a component, such as an analyte.

Abstract: Assay methods utilizing the response of a magnetically responsive reagent to the influence of a magnetic field to qualitatively or quantitatively measure binding between specific binding pair members. According to the invention, the presence of an analyte mediates whether or not the magnetically responsive reagent binds to a mobile solid phase reagent. The extent of binding will modulate the response of the magnetically responsive reagent or that of the mobile solid phase reagent, or both, to the influence of a magnetic field. Hence, by measuring the response to the magnetic field of the magnetically responsive reagent, or that of the mobile solid phase reagent, the presence or amount of analyte contained in a test sample can accurately be determined. The invention utilizes various devices to carry out the assay methods described.

Abstract: The invention relates to an immunochemical method for the detection and determination of rheumatoid factors using immune complexes as specific binding partners as well as to the preparation of reagents that are suitable for these methods.

Abstract: A biologically recognizing layer on a solid phase consisting of biologically recognizing molecules comprising regions which recognize a substance to be analyzed and regions which do not recognize a substance to be analyzed.The biologically recognizing molecules are aligned on a suitably modified surface by means of molecular regions which do not recognize the substance to be analyzed. The biologically recognizing molecules are cross-linked with the aligning surface and are consequently covalently altered. The molecular regions recognizing the substance to be analyzed are not altered by the covalent bonding and retain their bonding activity.The layer is produced in a novel two-stage method. In the first step, the biologically recognizing molecules, the aligning molecules and carrier molecules are adsorbed. In the second step, the molecules are covalently anchored by cross-linking. Cross-linking is brought about by photolytic activation of a water soluble reagent bonded to the carrier molecules.

Abstract: Stabilized particle reagents suitable for use in turbidimetric immunoassays are disclosed. The stabilized particle reagents contain functionalized polymer particles in which the surface of the particle has been modified with a molecular surface modifier having the structure:R(OCH.sub.2 CH.sub.2).sub.n NH.sub.2in which: R is --H, --CH.sub.3 or --CH.sub.2 CH.sub.3, and n is an integer between 2 and 10, inclusive. The stabilized particle reagents are resistant to premature or spontaneous aggregation during preparation or storage.

Abstract: An apparatus and method for immunomagnetic separation and concentration of target biological materials is disclosed. The immunomagnetic separation is performed by a magnetic flow cell, or filter block, as part of an automated mostly continuous immunomagnetic assay system. The magnetic flow cell has two bundles of ferromagnetic rods or pins positioned inside an internal chamber so that a fluid sample flowing through the flow cell passes through the pins. A pair of cobalt magnets flank the flow cell so that the pins concentrate and sufficiently increase the magnetic fields so that even nanometer size magnetic beads can be captured. The overall system combines a reaction subsystem for reacting coated magnetic beads with a sample, a collection subsystem for capturing magnetic beads, a rinsing subsystem for removing debris and a filtering subsystem for removing captured magnetic beads from the collection subsystem. The new magnetic flow filter is the key component for the collection and filtering subsystems.

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: A test strip for a rapid immunoassay containing specific immunochemical reagent zones (7, 8, 9) is described. The test strip (10) has a backing sheet (1) and attached thereto a receiving end pad (3) and at a distance therefrom a finishing end pad (5). A test membrane (2) is provided between said pads (3, 5). Said membrane (2) is positioned in parallel relationship to said backing (1) at a distance therefrom so that said backing (1) and said membrane (2) limit between themselves an air gap (4) which is open at its edges. Said gap (4) functions as a sheltered reaction chamber for the immunolgical reaction taking place as a liquid is made to flow through said membrane (2). The test strip is simple to manufacture by lamination and easy to use and it is suitable for both diagnostic and environmental immunoassays.

Abstract: The invention relates to methods, apparatus, reagents, and kits for performing a binding assay for an analyte of interest present in a sample based upon electrochemiluminescence at an electrode of interest. In the method, reagents and kits particles can be employed; for instance, for settling upon the electrode surface by gravity, centrifugation or magnetic attraction. The apparatus can include a magnet for generating a magnetic field in a region proximate the electrode.

Abstract: An analytical device for use in determining the presence of an analyte species of interest in a liquid state includes a chromatographic membrane support along which the liquid may travel, a plurality of first detectable particles associated with a sampling region of the device at which the liquid is to be applied, the particles being capable of being moved along the support by the liquid travel and having immobilised thereon a first binding agent capable of forming a first complex with the analyte species, a threshold region provided downstream of the sampling region in the direction of liquid travel, the threshold region being provided with a second binding agent which is capable of binding to non-complexed first binding agent on the particles, and which is present in an amount, such that a detectable number of the particles only pass the threshold region if the amount of analyte species in the sample is above a predetermined level, and a detection region downstream of the threshold region in the direction o

Abstract: The invention provides a method for determining platelet function in a mammal comprising providing platelets from the mammal, contacting the platelets in suspension with at least one immobilised ECM protein or an effective fragment or analog thereof while applying to the platelets an effective mechanical stimulus for an effective period of time and determining the platelet activation produced.The invention provides a method for monitoring the efficacy of pharmacological agents affecting platelet function in vivo and in vitro.

Abstract: A stable colloidal particle comprises a colloidal-sized core substrate having amine-reactive functional groups thereon with an aminodextran coating over its peripheral surface and a layer of colloidal-sized metallic solid overlaying the aminodextran coating. A linker comprising aminotrithiolate attached to the metallic solid has a free amino group to which a protein is attached by covalent bonding to the free amino group. Such novel particles are useful in flow cytometry, particularly useful in the simultaneous analyses of subpopulations of leukocytes. Methods of preparation of such particles, as well as methods of use are provided. These conjugates enable the simultaneous analyses of at least two different mutually exclusive subsets of white blood cells, based on the binding affinity of the conjugated protein.

Abstract: Apparatus and method for detection of low levels of about 1 ppb of analyte in samples using an enclosed permeable membrane enrichment device and agglutination reaction slide test apparatus.

Abstract: The invention addresses a method of preparing a dry polymer bead preparation. To achieve this, the polymer beads are coated with a layer of an easily soluble substance which dissolves again in a liquid when the polymer beads are resuspended. The resuspension is thus largely free of agglomerates.

Abstract: Novel analogs of phencyclidine (PCP) are disclosed. The analogs are capable of reacting with anti-PCT antibodies and are useful in immunoassays.The following analogs are described: ##STR1## wherein wherein X is --OH or a reporter molecule selected from the group consisting of aminofluorescein and aminomethylfluorescein and n is an integer between 1 and 10, inclusive.

Abstract: The invention relates to methods of performing a binding assay for an analyte of interest present in a sample based upon electrochemiluminescence at an electrode of interest. Particles are employed in the method, which are then collected in a zone at which electrochemiluminescence can be induced, wherein the amount of induced electrochemilurninescence is related to the amount of analyte in the sample.

Abstract: The present invention relates to a dry immunoassay analytical element for assaying a ligand, comprising a support bearing: (a) a label zone comprising an enzyme labeled ligand or an enzyme labeled receptor; (b) a spreading zone; (c) a receptor zone comprising a fixed concentration of an immobilized receptor for the ligand; and (d) a gravure zone comprising a diaryl telluride. A prefered embodiment of the present invention further comprises a vanadyl salt. The present invention further relates to a method for performing an assay using an element as described above.

Abstract: A process for the qualitative and/or quantitative determination of an analyte in a sample. The process includes providing a sample containing an analyte of interest in a liquid phase, providing at least one reagent having super-paramagnetic reactive metal particles linked to a substance that binds to the analyte, contacting the sample and the reagent to allow binding of the analyte in the sample and the reagent, applying a magnetic field to the mixture of sample and reagent, and detecting the presence of the analyte in the sample. The device includes a support for the sample and reagent, means for contacting the sample and reagent, magnetic means for confining and separating the analyte from the other components of the sample, and detection means for qualitative and/or quantitative measurement of the analyte.

Abstract: Methodology which avoids the problems associated with interference from whole blood is provided for instrumented determination of platelet binding function. Particularly, small particles to which fibrinogen is bound, and which contain an infrared light absorbing dye, are used to determine the binding of platelets in a whole blood sample to the fibrinogen. Agglutination of the platelets with the coated particles is determined by a change in infrared light absorption characteristics.

Abstract: Specific binding ligands can be detected with an assay which utilizes an immobilized receptor for the ligand, an immobilized reporter enzyme, an inhibitor antibody and a a water-soluble conjugate of the ligand and an anti-inhibitor antibody. Both antibodies are specific for the reporter enzyme, but the antibodies affect enzymatic activity differently. The inhibitor antibody effectively shuts down the activity of the reporter enzyme when it is complexed thereto. The anti-inhibitor antibody binds to the reporter enzyme, does not affect the enzymatic activity, but prevents the binding of the inhibitor enzyme. This assay provides a direct correlation of the generated signal to the target specific binding ligand.

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: A granular polymer composite comprising polymeric granules having coated on a surface thereof a calcium phosphate compound, at least a part of the particles of the calcium phosphate compound penetrates into the polymeric granules. The composite has a high bonding strength between the polymeric granules as a matrix and a coating of the calcium phosphate compound and also can fully exhibit the functions of a calcium phosphate compound. Using the granular polymer composite, a diagnostic agent which comprises of an antigen or antibody is adsorbed and immobilized on the composite and is therefore useful in diagnostic tests utilizing an antigen-antibody reaction for a number of infectious diseases.

Abstract: Apparatus and method for detection of low levels of about 1 ppb of hydrophobic analyte in environmental samples using an enclosed permeable membrane enrichment device and agglutination reaction slide test apparatus.

Abstract: The object of this invention is an improved method for biospecific multiparameter assay method based on the use of different categories of microparticles as solid support for different bioaffinity reagents. This invention allows the use of microparticles of small size and with very moderate monodispersity and conventional short decay time fluorescent labels for labelling the biospecific reactants. The high sensitivity of this method is based on the use of confocal excitation and detection, or alternatively, two-photon excitation for measurement of the biospecific reaction. The identification of the category of the microparticle is based on the use of fluorescent or Raman scattering indicators associated with the microparticles representing different analytes.

Abstract: Compounds are quickly selected from a combinatorial library by contacting the library with a target (e.g., receptor), separating non-binding compounds from compound-target complexes, and analyzing the complexes or eluted compound by mass spectroscopy. SAR information is obtained by performing this selection at two or more different ratios of compound to target.

Abstract: A first monoclonal antibody which specifically reacts with a human .alpha..sub.2 -plasmin inhibitor complex (PIC) and a human plasminogen; a second monoclonal antibody which reacts with PIC and also with a human .alpha..sub.2 -plasmin inhibitor; a third monoclonal antibody which reacts with PIC, but does not react with a human plasminogen and a human .alpha..sub.2 -plasmin inhibitor; hybridomas which secrete the first to third monoclonal antibodies, and an immunoassay using the first to third monoclonal antibodies.

Abstract: A nucleic acid sample is mixed with a nucleotide reagent under hybridizing conditions. The nucleotide reagent contains nucleotides each combined at 3'- and 5'-terminals thereof with particles. After cleaving double strands of hybridization products, at least ones of particles separated from each other by the cleaving and particles held in the unreacted reagent and subjected to no cleavage are detected for measuring nucleic acids in the sample. Since the particles separated from each other by the cleaving and the particles held in the unreacted reagent and subjected to no cleavage are different in size of particle masses from each other, these two groups of particles can be discriminated and detected. Therefore, a labeling substance in the unreacted reagent is no longer required to be washed and separated, enabling nucleic acids to be quickly measured with high sensitivity.

Abstract: A method is provided for differentiating leukocyte subpopulations, immunophenotyping of lymphocytes and counting white blood cells. The method preserves leukocyte morphology and surface markers without using fixatives. In addition, the method finds utility in determination of hemoglobin concentration without using cyanide. The stable hemoglobin chromogen formed is measured at approximately 540 nm.

Abstract: A solid phase system for use in ligand-receptor assays, particularly immunoassays using monoclonal antibodies, is disclosed. The solid phase system comprises a porous matrix in which microspheres, bound with a receptor capable of capturing a target ligand, are entrapped. Preferably, the microspheres are entrapped within a discrete zone or zones of the porous matrix.

Abstract: A homogeneous high throughput assay is described which screens compounds for enzyme inhibition, or receptor or other target binding. Inhibition (or binding) by the library compounds causes a change in the amount of an optically detectable label that is bound to suspendable cells or solid supports. The amounts of label bound to individual cells or solid supports are microscopically determined, and compared with the amount of label that is not bound to individual cells or solid supports. The degree of inhibition or binding is determined using this data. Confocal microscopy, and subsequent data analysis, allow the assay to be carried out without any separation step, and provide for high throughput screening of very small assay volumes using very small amounts of test compound.

Abstract: This invention relates to a method of detecting an analyte in a test liquid by means of agglutination, with the test liquid being brought into contact with an agglutinin and a reaction between the analyte and the agglutinin determined. In addition, reaction vessels and reagents for implementing the method of the invention are disclosed.

Abstract: There is provided a method for immobilizing a ligand by reacting a solvent-insoluble carrier having aldehyde group with a compound shown by the general formula: ##STR1## wherein X is --S-- or --O--, R.sup.1, R.sup.2 and R.sup.6 are the same or different, each of which is hydrogen atom or an alkyl group having 1 to 4 carbon atoms, R.sup.3 is hydrogen atom or a substituent wherein an atom adjacent to nitrogen atom shown in the above-mentioned general formula has no unsaturated bond, R.sup.4, R.sup.5 and R.sup.7 are arbitrary substituents; provided that only one partial chemical structure of HX--C--C--NHR.sup.3 wherein X and R.sup.3 are the same as defined above or HX--C--C--C--NHR.sup.3 wherein X and R.sup.3 are the same as defined above is contained in one compound described above by which, a ligand or a compound to which a ligand is bonded can react specifically and effectively with aldehyde group in a solvent-insoluble carrier at a prescribed position to form a stable bond.

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 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 needed 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: Disclosed is an assay for determining the presence of at least one analyte in a sample, which involves the steps of: (a) mixing the sample and predetermined amounts of first test microparticles having disposed thereon a binding molecule which binds a first analyte, and inert reference microparticles to form a reaction mixture, and to allow for the first binding molecule to bind the first analyte; b) counting the numbers of the non-reacted first test microparticles and the reference microparticles; and (c) comparing the number of non-reacted first test microparticles to the reference microparticles to thereby establish a first test value so that the presence of the first analyte in the sample may be determined. In a preferred embodiment, the first test value is compared to a control value for a non-reactive sample, and a change value is calculated therefrom.

Abstract: The present invention provides a process for the determination of a specifically bindable substance by incubation of the sample solution with at least three receptors R.sub.1, R.sub.2 and R.sub.3, of which R.sub.1 and R.sub.2 are bindable with one another and R.sub.3 is specifically bindable with the substance to be determined and measurement of the agglutination which takes place in the case of the reaction, wherein, as receptor R.sub.1, there is used a conjugate of a partner of a specifically binding pair P and of a substance S which corresponds to the substance to be determined or is a derivative thereof and has at least one epitope of the substance to be determined, as receptor R.sub.2 there is used a receptor which has at least two binding positions for P and as receptor R.sub.3 there is used a receptor which has at least two binding positions, of which at least one binds specifically with an epitope of the substance to be determined or of S.

Abstract: A system for assaying a fluid sample for one or more types of analytes, which employs at least one class of finely divided polystyrene spheroidal particles, each class being limited to a predetermined specific narrow range of particle diameters, the particles of each such class being coated with a specific reactant unique for that class. After the coated particles are mixed with the sample to specifically react to form conjugates of the particles and any of the analyte present, the mixture is irradiated with bursts of ultrasound swept over a range of frequencies resonant to the expected conjugate sizes. The presence of the conjugates and therefore the analyte is detected directly by measuring any selective absorption or scattering of waves of frequencies to which the conjugates are resonant.

Abstract: A novel technique is disclosed for the prevention of false positive reactions in immunological testing which are caused by interference of C.sub.1 and C.sub.1q. The method is based on heating a sample of a body fluid at a temperature of 59.degree.-64.degree. C. in the presence of a particular neutral salt. A method for screening for rheumatoid factor is also disclosed.

Abstract: The invention provides phospholipid coated particles capable of specifically binding antiphospholipid antibodies and a method for preparing such particles. Methods are also provided for determining antiphospholipid antibodies in a serum or plasma. Also provided are methods for isolating antiphospholipid antibodies from a fluid and for raising specific antiphospholipid antibodies.