Abstract: The invention relates to a method for quantitating the level of a preselected analyte in a sample of blood of a human or animal patient by incubating the test sample with an antibody specific to the analyte to form an immunocomplex, which then interacts with the white blood cell fractions and result in the production of oxidants. Oxidants are detected using chemiluminescent reagents. In addition, the white blood cell oxidant response may be enhanced by the inclusion of certain agents such as opsonized zymosan. As part of the assay, separate blood samples are also maximally stimulated with a maximal stimulatory amount of exogenously-added antigen, and corresponding antibody, to form immunocomplexes, to provide a response factor used in the quantitation of analyte.

Abstract: A sample is prepared from blood in a manner which makes it possible to further analyze proteins in the sample, e.g. to detect prions in the sample. Blood is extracted, allowed to clot and subjected to separation processing (e.g. centrifugation) to obtain serum. The serum is treated with a complexing agent which agent binds prions in the sample forming an agent/protein complex which makes it possible to concentrate the complex. Concentration of the complex results in a sample which can be successfully analyzed, e.g. assayed using a range of different types of assay methodologies for detecting prions.

Abstract: The invention relates to a method for staging sepsis in a patient by concurrently measuring in a sample of the patient's blood four parameters which are indicative of the stage of sepsis: 1) the level of microbial product level in the blood; 2) the level of tumor necrosis factor (TNF) response reserve; 3) the maximum oxidant production by neutrophils, and 4) the responsiveness of the patient's neutrophils to immunocomplexes. Based on determining the stage of sepsis, appropriate treatment for the patient may be identified.

Abstract: The present invention is directed to the use of a soluble polyvalent support for the preparation of combinatorial libraries of compounds. The resultant combinatorial libraries are useful in screening for biologically active moieties in the drug discovery process or in developing compounds with desired physical and chemical properties.

Abstract: A method of indirect agglutination immunoassay includes, allowing particles of a reagent for immunoassay to precipitate in bottoms of at least one well, inclining the well at a specified angle to form a precipitation pattern due to a flow of the particles in the bottom of the well due to a flow of the particles, relatively moving the well and a sensor in the direction of substantially vertical to a flow direction of the formed precipitation pattern, measuring the lengths of the formed precipitation pattern at a plurality of sections within the scope of the well, and judging the occurrence of an immunoreaction based on the values of the measured length of the precipitation patterns.

Abstract: The invention provides methods for separating bound label from unbound label within an assay mixture, for predispensing assay reactants in self-contained assay vessels, as well as for detecting the presence and/or amount of an analyte within a fluid sample. In addition, a reusable detection vessel for use therein and with specific binding assays in general is disclosed. In the methods, generally an analyte within a sample is detected or measured by forming an assay mixture containing sample, analyte binding components and label, placing the assay mixture in contact with an immisable primary layer, subjecting the assay mixture to conditions that separate the analyte bound with binding components and label from unbound binding components and label, and subsequently detecting bound label.

Abstract: A hemoglobin derivative-containing sample is treated with a treating reagent containing 2-butanol and then immunologically analyzed to determine the quantity of the hemoglobin derivative. By the treatment with 2-butanol, the immunological determination for the hemoglobin derivative, particularly HbA.sub.1c, can be attained with high sensitivity by a simple procedure. Since 2-butanol-containing treating reagent does not affect the enzymatic activity, the homogeneous enzyme immunoassay with high sensitivity is realized.

Abstract: A method is provided, in one embodiment, for the determination of an analyte in a biological fluid sample in the presence of a substance interfering with an assay for the analyte. This embodiment is implemented by using antibodies to cause the selective immunoreaction of at least one of the analyte or the interfering substance and then conducting an assay for the analyte in at least one of the immunoreactants or the non-reactants. Another embodiment provides a disposable reaction device to implement the method. The invention is applicable to the detection of a wide variety of analytes, including cholesterol in a targeted lipoprotein class in the presence of cholesterol in another class; to targeted isozymes of enzymes such as creatine kinase, lactate dehydrogenase, amylase, and alkaline or acid phosphatases in the presence of other isozymes; as well as to targeted immunoglobulins in the presence of non-targeted immunoglobulins.

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: The present invention relates to novel methods and devices for detecting non-complexed prostate specific antigen (free PSA), which is used in conjunction with total PSA tests to identify patients having either benign prostatic diseases (BPD), such as benign prostatic hyperplasia, prostatitis, or glandular atrophy or prostatic adenocarcinoma (CAP). In a biological sample, one can find not only free PSA, but also prsotate specific antigen (PSA) which has formed a complex with .alpha.1-antichymotrypsin (ACT). The present invention removes complexed PSA (PSA-ACT) from a fluid sample, thereby removing any possible interference due to binding of complexed PSA to an allegedly free PSA specific antibody in an immunoassay for free PSA.

Abstract: A method of concentrating a disease-related conformation of a protein such as the PrP.sup.Sc in a sample is disclosed. The method comprises liquefying the sample and adding a complexing agent such as phosphotungstic acid (PTA) which complexes preferentially or exclusively with the PrP.sup.Sc. After the complex is formed the composition is centrifuged until the complex settles at the bottom. Thereafter, the supernatant is poured away. The remaining pellet may be resuspended in an aqueous solution containing a protease inhibitor for storage. The PTA stains the PrP.sup.Sc making the resulting concentrated PrP.sup.Sc susceptible to further analysis, making it possible to quickly and efficiently determine the presence of PrP.sup.Sc and its concentration in a sample. The method can be used to render a sample non-infectious by removing all or substantial of the infectious form of a protein from a sample.

Abstract: In a method for immunoassay of a trace component in a sample derived from a living body on the basis of a change of turbidity or scattered light intensity caused by antigen-antibody reaction, when the antigen-antibody reaction is carried out in the presence of magnesium ions previously added, an analyte can be measured rapidly and easily with high precision and reproducibility.

Abstract: A method of performing immunoassay to detect the level of target proteins common to various malignancies including metallopanstimulin or metallopanstimulin-like materials as well as complement components, in a biologic sample is provided wherein the protein molecules in the patient sample compete with radiolabeled peptide for sites on the Anti-peptide-specific antibody. The amount of radioactivity measured is inversely proportional to the concentration of protein molecules present in the patient sample, which is determined from a standard curve. Another method includes determining the presence of a protein elevated in the serum of patients with neoplasms by the detection of the interference of binding or precipitation of a first antibody by a second antibody by the target protein.

Abstract: A method of assessing glycated blood protein in a sample which comprises separating glycated and non-glycated protein using a liquid phase precipitation reagent, contacting the sample with a signal forming agent capable of binding preferentially to the glycated protein, and assessing the signal forming agents.

Abstract: A sample of liquid with suspended particles is contained in a tube and subjected to a standing wave ultrasound field transverse to the tube, the standing wave exhibiting a progressive change in pressure amplitude transverse to the tube, so that particles in suspension are displaced transversely of the tube to one or more predetermined regions; exposure of the sample to the standing wave is then terminated and the particles are allowed to settle, and inspected to determine whether they remain aggregated or whether they dissociate. The ultrasound field is produced by a transducer of tubular form encircling the tube. The invention may be used for agglutination of particles or cells via cross-bridging molecules in immuno-agglutination assays.

Abstract: A chromatographic assay device for use with immunoassays allows rapid and convenient assays of analytes of biological interest, and permits extractions to be carried out in situ, avoiding the use of separate extraction vessels. The device has a wide dynamic range and avoids interference from particulates or colored components. In one form, the device comprises: (1) a first opposable component comprising a sample preparation zone adapted to receive a sample to be assayed; (2) a second opposable component comprising a chromatographic medium; and (3) a conductive barrier attached to the second opposable component. The first and second opposable components can be brought into opposition so as to cause the sample preparation zone to apply the sample to be tested to the chromatographic medium. Preferably, the analyte is detected with a visually detectable label. Other variations of the device vary the arrangement of components to provide optimal chromatography for a variety of analytes.

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: The present invention provides methods for detecting the presence of or determining the amount of a ligand in a fluid sample. The methods comprise providing a first reagent comprising a sol particle having a detectable physical property bound to the ligand or ligand analogue (in a competitive format) or a substance capable of specifically coupling with the ligand (in a sandwich format), providing a second reagent having a detectable physical property comprising a sol particle bound to a substance capable of specifically coupling with the ligand and/or ligand analogue, if present, combining the first reagent, second reagent and the fluid sample and detecting before, during or after the reaction, a change in the physical property of the sol particles, which provides a qualitative or quantitative indication of the ligand in the fluid sample.

Abstract: The invention relates to the area of protein determinations in homogeneous solution by means of antigen-mediated precipitation by antibodies or using latex materials coated with antibodies and subsequent optical measurement of the precipitation reaction by a nephelometric or turbidimetric measurement.

Abstract: A method for quantitatively determining cholesterol in high density lipoproteins, in which, prior to the determination of cholesterol by an enzymatic method, a surfactant and a substance which forms a complex with lipoproteins other than high density lipoproteins are added to a sample containing lipoproteins.The method does not require any pretreatments such as centrifugal separation. With a simple operation, cholesterol in HDLs can be measured effectively. Also, this method can be adopted in a variety of automated analyzers, and thus is very useful in the field of clinical assays.

Abstract: The invention provides novel labelled boronic acid conjugates of formula ##STR1## (wherein V is a reporter moiety; W.sup.2 is a bond or an organic linker moiety;W.sup.1 is a *SO.sub.2 NR.sup.2, *CONR.sup.2 or *CH.sub.2 N.sup..sym. R.sup.2.sub.2 group bound at the *-marked atom to the phenyl ring;R.sup.1 is hydrogen or an electron withdrawing substituent group; andeach R.sup.2 independently is hydrogen or an optionally hydroxylated and optionally C.sub.1-6 -alkoxylated C.sub.1-6 -alkyl group) and salts thereof, e.g. for use in assays for cis-diols such as glycated blood proteins, having enhanced water-solubility and storage stability.

Abstract: Trace components in samples can be measured rapidly with high precision by applying interaction between an analyte to be measured and an affinity substance and using a membrane having specific separating capability.

Abstract: A sample of liquid with suspended particles is contained in a tube and subjected to a standing wave ultrasound field transverse to the tube, the standing wave exhibiting a progressive change in pressure amplitude transverse to the tube, so that particles in suspension are displaced transversely of the tube to one or more predetermined regions; exposure of the sample to the standing wave is then terminated and the particles are allowed to settle, and inspected to determine whether they remain aggregated or whether they dissociate. The ultrasound field is produced by a transducer of tubular form encircling the tube. The invention may be used for agglutination of particles or cells via cross-bridging molecules in immuno-agglutination assays.

Abstract: A multi-purpose on-line or field-portable system and method for monitoring the presence and concentration of selected antigen-antibody reactions singly or in combination that result from the presence of specific microorganisms or free antigens present or suspended in aqueous solutions, during a given time period. The detection system comprises a detection column and two sensors mounted around the detection column. Each sensor consists of an electromagnetic radiation source and an appropriate detector for the electromagnetic radiation. The reacted analyte tends to accumulate at the sensor located at the bottom detection column. The lower sensor continually nulls against the upper sensor to subtract any optical effects due to non-reactants in the aqueous process or environmental stream. The response from the detector sensors drive an electric circuit, which provides an output signal. In the on-line automatic version, the signal can drive elements of a process system by switching automated valves.

Abstract: A method for verifying that an assay methodology is properly performed, that assay reagents employed possess the necessary potency for accurately performing such assay methodology, and whether or not test samples or assay reagents have been tampered with or are adulterated, is described. The method is performed by employing an assay verification sample, comprising a positive analyte component and the test sample under analysis, wherein the assay verification sample is analyzed employing the same assay reagents and essentially the same assay methodology employed to analyze the test sample. The method is particularly useful for performing heterogeneous immunoassays on an automated continuous and random access analytical system.

Abstract: The present invention concerns a multivalent dextran reagent for use in a precipitation test for the determination of a specifically bindable substance comprising dextran to which several molecules of a receptor R.sub.1 which is capable of specific binding to the substance to be determined or of the specifically bindable substance or of an analogue of this substance are bound or can be bound.

Abstract: A method of dispensing wash solution to separate free from bound labels in a slide immunorate assay. The method comprises dispensing wash first as separate drops spaced to allow complete absorption prior to the next drop, followed by a time at which the rate of dispensed wash exceeds the rate of fluid uptake of the slide, to form a continuous stream. The first phase of this wash method provides a more complete separation of bound from free under the dispense tip than occurs if only a continuous stream is used throughout.

Abstract: A method, composition, and kit for isolating biomolecules from a biological sample wherein the sample is mixed with a soluble, linear polymer, such as polyvinylpyrrolidone, to form a precipitate. The biomolecule of interest is found in the precipitate or is isolated from the supernatant.

Abstract: The present invention provides a substantially pure integrin characterized in that it consists of an .alpha..sub.v and a .beta..sub.1 subunit. The receptor binds to fibronectin and GRGDSPK but does not bind to vitronectin. The .alpha..sub.v .beta..sub.1 receptor can be used to determine the presence of ligands for the receptor.

Abstract: Inter alia, a process for the selective removal of salivary .alpha.-amylase from a sample comprising salivary .alpha.-amylase and pancreatic .alpha.-amylase characterized in that there is used a monoclonal antibody against salivary .alpha.-amylase, which is immobilized or is coupled to a physically separable or seperate support and which exhibits a binding affinity towards salivary .alpha.-amylase of at elast 1.times.10.sup.7 l/m and a cross-reactivity with pancreatic .alpha.-amylase of less than 1% is disclosed. The remaining pancreatic .alpha.-amylase may be assayed.

Abstract: The present invention provides a process for the determination of low density lipoproteins (LDL) in body fluids, wherein high density lipoprotein (HDL) antibodies are added to a sample to be investigated, insolubles formed are separated off and the LDL or one of its components is determined in the supernatant. The present invention also provides a reagent for the determination of the LDL fraction in body fluids, wherein it contains HDL antibodies.

Abstract: A method and composition for isolating biomolecules from a biological sample wherein the sample is mixed with a soluble, linear polymer, such as polyvinylpyrrolidone, to form a precipitate. The biomolecule of interest is found in the precipitate or is isolated from the supernatant.

Abstract: A method of assessin glycated blood protein in a sample which comprises separating glycated and non-glycated protein using a liquid phase precipitation reagent, contacting the sample before or during the separation with a signal forming agent capable of binding preferentially to the glycated protein, and assessing the signal forming agents.

Abstract: The peptide N-terminal pro-ANF, which is present in body fluids such as plasma, has been found to be an effective predictor of heart failure and the invention provides prediction and screening methods based upon in vitro assaying of N-terminal pro-ANF in body fluids.

Abstract: A method of determining the presence and quantity of an analyte of interest in a particulate-containing sample is disclosed, as is a construct for use in the method. The method is particularly useful for determining an analyte in whole blood and in fermentation suspensions. The construct is comprised of a first moiety, which is a particulate-binding moiety and a second moiety, which binds the analyte of interest.

Abstract: The present invention relates to the measurement of glycated hemoglobin by fluorescence quenching. The present invention uniquely involves performing two sequential fluorescent quenching measurements: one measurement of the fluorescent quenching due to total hemoglobin in the sample and a second measurement of the fluorescent quenching due to glycated hemoglobin present in the sample after the non-glycated hemoglobin is removed. Glycated hemoglobin and non-glycated hemoglobin can be separated by a variety of methods as described herein, including ion capture and phase separations.

Abstract: The subject invention concerns a selective, sensitive, and highly reliable immunoassay for detecting human IL-1 .beta. in cultured mononuclear cells or human body fluids. It is a competitive immunoassay which is useful in diagnostic work to detect IL-1.beta. selectively, for the first time, from among similar lymphokines and other substances known to interfere with bioassays for IL-1.

Abstract: The present invention includes novel assays employing a capture reagent, involving a first specific binding member conjugated to a polymeric anion such as carboxymethylamylose, and a solid phase material containing a reaction site comprising a polymeric cation substance. A test sample suspected of containing the analyte of interest may be contacted with the capture reagent to form a charged capture reagent/analyte complex. The complex is then contacted to/ the oppositely charged solid phase to attract, attach, and immobilize the capture reagent/analyte complex. The use of carboxymethylamylose to prepare a suitably charged capture reagent provides a superior capture reagent that is capable of binding and retaining the analyte on the solid phase even in the presence of polyanionic non-specific binding blockers.

Abstract: Disclosed is a primary chromatographic support containing an immobilized flocculating agent for use as a separation media for a secondary support consisting of microparticles used in affinity separation and heterogeneous immunoassays. In a specific embodiment, a flocculating agent such as polyethyleneimine is immobilized on a chromatographic resin packed in a column. The column so formed is then used to trap microparticles having an affinity ligand or binder for the ligand affixed thereon. Such microparticles are used as a solid support for the affinity reaction involved in a variety of immunoassay formats.

Abstract: The present invention relates to an apparatus for conducting a variety of assays that are responsive to a change in the viscosity of a sample fluid and relates to methods of conducting such assays. In particular, the present invention is related to the use of a cartridge for conducting one or more coagulation assays or, conversely, fibrinolysis assays. The disclosed device enjoys simplicity and is adaptable to the point-of-care clinical diagnostic area, including use in accident sites, emergency rooms, surgery or intensive care units.

Abstract: A novel non-competitive immunoassay technique has been developed which not only improves sensitivity, but also is convenient and less susceptible to interfering factors. It is compatible with existing instruments and is an assay that can be run in one test tube. The analyte is reacted with labeled specific binder, after which the mixture is reacted with (1) an insoluble material attached to an analyte derivative and (2) a solid phase carrying a binder. The solid phase is then separated, and the label attached to the solid phase is measured.

Abstract: An improved method for performing immunoassays whereby specific binding proteins for vitamin B12, folate and other target analytes are utilized with antibodies with different specificities for the binding proteins. Antibodies bridge the specific binding protein directly or indirectly to a capturable material.

Abstract: The subject invention provides an antigen characterized as having a molecular weight of approximately 68 kD, being reactive with autoantibodies associated with mental illness especially schizophrenia, being located in neuronal cells, and co-migrating with a protein band in SDS-PAGE which is recognized by rabbit antibodies which react with the peptide whose sequence is Ala-Lys-Xaa-Val-Lys-Phe-Gly-Ala-Asp-Ala-Xaa-Ala-Leu-Met-Leu (SEQ ID NO: 2). The invention also provides methods for detecting in a sample from a subject the presence of an antibody to the neuronal antigen, determining the propensity of a subject toward a psychiatric disease, diagnosing and treating a subject having mental illness.

Abstract: Disclosed is a primary chromatographic support containing an immobilized flocculating agent for use as a separation media for a secondary support consisting of microparticles used in affinity separation and heterogeneous immunoassays. In a specific embodiment, a flocculating agent such as polyethyleneimine is immobilized on a chromatographic resin packed in a column. The column so formed is then used to trap microparticles having an affinity ligand or binder for the ligand affixed thereon. Such microparticles are used as a solid support for the affinity reaction involved in a variety of immunoassay formats.

Abstract: The present invention provides a process for the determination of low density lipoproteins (LDL) in body fluids, wherein high density lipoprotein (HDL) antibodies are added to a sample to be investigated, insolubles formed are separated off and the LDL or one of its components is determined in the supernatant.The present invention also provides a reagent for the determination of the LDL fraction in body fluids, wherein it contains HDL antibodies.

Abstract: A method is provided, in one embodiment, for the determination of an analyte in a biological fluid sample in the presence of a substance interfering with an assay for the analyte. This embodiment is implemented by using antibodies to cause the selective immunoreaction of at least one of the analyte or the interfering substance and then conducting an assay for the analyte in at least one of the immunoreactants or the non-reactants. Another embodiment provides a disposable reaction device to implement the method. The invention is applicable to the detection of a wide variety of analytes, including cholesterol in a targeted lipoprotein class in the presence of cholesterol in another class; to targeted isozymes of enzymes such as creatine kinase, lactate dehydrogenase, amylase, and alkaline or acid phosphatases in the presence of other isozymes; as well as to targeted immunoglobulins in the presence of non-targeted immunoglobulins.

Abstract: Disclosed are a method and device for performing sequential analytical reactions involving a first dry reagent and a second dry reagent comprised of two or more components having different rates of solubilization. The invention enables one to fully solubilize the components of the second reagent before they are brought into contact with each other to thereby avoid interference with the reaction kinetics which result when one or both of the components are not fully dissolved prior to their being brought into contact. The invention is especially useful in conjunction with immunoassay formats involving latex bound antibodies and polymeric agglutinators.

Abstract: Disclosed is a primary chromatographic support containing an immobilized flocculating agent for use as a separation media for a secondary support consisting of microparticles used in affinity separation and heterogeneous immunoassays. In a specific embodiment, a flocculating agent such as polyethyleneimine is immobilized on a chromatographic resin packed in a column. The column so formed is then used to trap microparticles having an affinity ligand or binder for the ligand affixed thereon. Such microparticles are used as a solid support for the affinity reaction involved in a variety of immunoassay formats.

Abstract: The invention includes an agglutinant complex which is useful for the investigation of the antigens present on erythrocytes, and which results from affinity couplings between nonagglutinant IgG type antibodies specific for the antigen to be identified, a protein capable of binding to at least two sites on the Fc part of antibodies and an anti-immunoglobulin antibody or its fragments.

Abstract: Reactivity between alloantigen and alloantigen-specific ligand, such as HLA and anti-HLA antibody, is detectable in a sample by separating from the sample a portion of a targeted class of ligands (including such ligands complexed with alloantigen) and measuring the amount of alloantigen in such complex containing fractions. In another embodiment of the invention, reactivity between a plurality of samples is detected by measuring soluble alloantigen in at least first and second biological samples and in a mixture of the samples. Since the formation of alloantigen immune-complexes in the mixture alters the physical and immunological behavior of soluble alloantigen, a divergence between the measured and expected concentration of the mixture indicates reactivity.