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: A supported polyionic hydrogel is prepared by impregnating a support matel with a solution of anionic polysaccharide and a solution of cationic polysaccharide where the anionic polysaccharide and cationic polysaccharide react with each other to form a polyionic hydrogel impregnated in the support material. The hydrogel may be dried such as by lyophilization. Preferably, the anionic polysaccharide is xanthan, dicarboxystarch or dicarboxycellulose and the cationic polysaccharide is chitosan. Especially preferred is a polyionic hydrogel formed from xanthan and chitosan. A paper material or a textile material can be used as the support material. A dry supported polyionic hydrogel can be formed as a bandage without active material incorporated therein. The supported polyionic hydrogel may be formed containing a biologically active material by having the active material in either polysaccharide solution or in another solution impregnated into the support material.

Abstract: A cellulose binding domain (CBD) having a high affinity for crystalline cellulose and chitin is disclosed, along with methods for the molecular cloning and recombinant production thereof. Fusion products comprising the CBD and a second protein are likewise described. A wide range of applications are contemplated for both the CBD and the fusion products, including drug delivery, affinity separations, and diagnostic techniques.

Abstract: Methods are disclosed for measuring the accumulation of advanced glycosylation endproducts (AGEs), which are predicated on the discovery that such AGEs are present in tobacco and its byproducts. More particularly, the methods focus on the observation that individuals who smoke or otherwise use tobacco have increased levels of AGEs over non-smoking individuals. The present methods relate to the measurement of AGE levels in both individuals and in tobacco and its byproduct, smoke. Methods are also disclosed for the evaluation of the tobacco products to determine their storage status and organoleptic capacity and potential, as well as for the treatment of the ambient to lower AGE levels. For example, air or other samples may be taken and evaluated by a dosimeter or like device, to determine whether AGE levels exceed normal, after which measures could be implemented to remediate the ambient condition. All such methods and corresponding materials are contemplated and included.

Abstract: The invention provides a method of diagnosing Alzheimer's disease in a human patient by measuring the amount of p33 present in a biological sample from a patient who may have Alzheimer's disease relative to the amount of p33 in a control sample from an unaffected human. Also included in the invention are diagnostic kits for Alzheimer's disease and methods of screening for effective therapeutics for Alzheimer's disease.

Abstract: Disclosed are novel compositions of morphogenic proteins constituting soluble forms of these proteins, antibodies that distinguish between soluble and mature forms, and method for producing these morphogenic proteins and antibodies.

Abstract: The present invention provides a novel class of polyethylene glycol modified ceramide lipids. The lipids can be used to form liposomes optionally containing various biological agents or drugs, such as anti-cancer agents. In addition, methods of use for the liposomes are provided.

Abstract: Combinatorial libraries are disclosed which are represented by Formula I:(T'--L).sub.q --S--C(O)--L'--II' Iwherein:S 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: ##STR1## 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: A method is provided for producing a sterile and pyrogen-free column containing coupled protein for use in removing a predetermined substance from the blood of a human subject. The method abrogates sterilization of the finished protein-containing product by providing sterile and pyrogen-free raw materials at each production step. The method provides a pathogen-free, purified solution of protein which binds to a predetermined substance in human blood such as LDL or immunoglobulin. Typically, the protein is anti-human LDL immunoglobulin or anti-human Ig immunoglobulin. The method also provides a sterile and pyrogen-free column matrix material such as an agarose which is chemically activated, either using CNBr and triethylamine or using 1,1'-carbonyldiimidazole.

Abstract: This invention is related to a process for the enhanced immobilization of a ligand to solid supports to be used for a biochemical detection method. The enhanced immobilization of the ligand was obtained by coating the surface of the solid support with the adhesive polyphenolic protein isolated from mussels. The bound ligand is reacted with a solution containing an antiligand whereby the antiligand becomes bound to the immobilized ligand. After removing the excess or unbound antiligand, the antiligand bound to the immobilized ligand is detected by using an enzyme-linked immunoassay.

Abstract: A new method for immobilization of small molecules on solid supports via a macromolecular spacer has been developed. A protein or another macromolecule is first immobilized in an aqueous medium, and the solid support is than washed with an organic solvent. The small molecule is coupled in an organic medium, followed by organic medium washes. The new solid phases are useful for affinity purifications, immunoassays and other binding assays, and for selection of binders by panning procedures.

Abstract: The present invention features stable bulking agents and blocking agents for solid phase materials containing proteins. The proteins have thiol groups which are blocked or chemically inert, preventing the formation of aggregates. Chemical solutions wherein thiol groups, if present, are blocked or chemically inert, are particularly useful in analytical applications and in diagnostic reagents utilizing solid phase materials or particles.

Abstract: A method and device is described for direct removal of heparin from whole blood during extracorporeal therapy. In clinical situations where the blood is heparinized to prevent clotting in the extracorporeal circuit containing e.g., a hemodialysis cartridge or a heart-lung machine, it would be desirable to eliminate the systemic heparinization of the patients. The extracorporeal circuit contains a device having antithrombin III immobilized and inserted between the outlet port of the primary extracorporeal device, such as the hemodialysis cartridge or heart-lung machine and the patient. When the heparinized blood comes in contact with the immobilized antithrombin III, heparin is removed and the reperfused blood is substantially free of heparin. The advantage of the system lies in the fact that heparin is removed from the blood rather than neutralized. This helps overcome the adverse reactions and side effects associated with the use of heparin anticoagulation.

Abstract: The invention describes reactive dyes having an alkyl spacer attached via a sulfonamide bond to a sulforhodamine 101 fluorophore, and a variety of useful conjugates prepared therefrom. The increased length of the covalent linkage due to the alkyl spacer results in dye-conjugates having a number of surprisingly advantageous properties relative to previous sulforhodamine 101-labeled conjugates, including enhanced solubility and increased fluorescence. The reactive dyes of the present invention are more stable than the known compound sulforhodamine 101 sulfonyl chloride. Novel reactive dyes are described for selective modification of groups other than amines, including thiols and photoreactive derivatives.

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: 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 method of assaying for CAT in a fluid involves the use of a complex of chloramphenicol with a member of a specific binding pair such as a hapten or biotin. Biotinylated chloramphenicol is claimed as new. A scintillation proximity assay involves use of this reagent with tritiated acetyl coenzyme A and streptavidin coated SPA beads.

Abstract: Gelatin and aminodextran coated polymer core particles useful in immunoassays and methods of making the same are disclosed. The preparation of aminodextrans having varying amounts of amine groups is also described, as is a method of crosslinking gelatin and aminodextran without the use of a stabilizer.

Abstract: A method for interfering with the binding between p53 and MDM2 or a protein having a p53 binding site analogous to that of MDM2, which method comprises administering a effective amount of a compound, selected from the group consisting of a peptide having up to twenty eight amino acids which is able to disrupt or prevent binding between p53 and MDM2, or a functional peptide analogue thereof.Compounds for use in the method, methods for detecting such compounds and their application in the diagnosis and treatment of tumours is also described and claimed.

Abstract: Antibodies made to a flanking region GPR(31-98) in human gastrin-releasing peptide (GRP) precursor. Since the antibodies have high affinity to GRP precursor, and the GPR precursor is highly stable in the blood, then lung cancer, especially small cell lung cancer can be diagnosed with high reliability by detecting or measuring GRP precursor in the blood of a patient using the present antibodies.

Abstract: A combinatorial library is disclosed which is represented by Formula ##STR1## wherein: ##STR2## is a solid support; T'-L- is an identifier residue; and -L'-II' is a ligand/linker residue. This library contains hydroxypropylamines of the formula:Aa.sup.1 -Aa.sup.2 -(CH.sub.2 Ar.sup.1)-CH.sub.2 CHOH-CH.sub.2 XR.sup.1IIwherein:Aa.sup.1 and Aa.sup.2 is each an amino acid joined to each other through an amide bond;Ar.sup.1 is an aromatic ring system;--CH.sub.2 Ar.sup.1 is attached to N on Aa.sup.2 ; andR.sup.1 is H, C.sub.1-20 alkyl, alkenyl, alkynyl, aryl, heteroaryl, aryl or heteroaryl fused to a 3- or 4-membered moiety to form a non-aromatic second ring, or substituted C.sub.1-20 alkyl, alkenyl, or alkynyl.

Abstract: Particles comprising an energy donor as a first component and a fluorescent dye as a second component positioned in said particles at an energy exchanging distance from one another, wherein the two components have a Stokes shift of greater than or equal to 50 nm, said particle having bound on its surface, a protein, polypeptide, nucleic acid, nucleotide or protein containing ligand analogue are disclosed and claimed. In addition, novel fluorescent dyes are described which exhibit intramolecular energy transfer for use to label various molecules, proteins, polypeptides, nucleotides and nucleic acids or to incorporate into particles.

Abstract: An immunoagglutination reagent includes liposomes, as a carrier, with a covalently bound antigen or antibody immobilized thereon. The reagent is used to assay an antibody or an antigen on the basis of agglutination. The assaying can be done at a high sensitivity in the short wave region where the change in turbidity caused by the agglutination is enhanced. An antibody or an antigen is immobilized onto the surface of the liposome, and a water-soluble polymer compound or a gelled compound is entrapped in the liposomes. The substance entrapped in the immunoagglutination reagent enhances the change in turbidity via the agglutination caused by the antigen-antibody reaction.

Abstract: Disclosed is a method for determining the concentration of an analyte in a liquid test sample. The method involves the use of colloidal sized metal particles, which exhibit a spectral response in the agglomerated state which is detectably different than in their unagglomerated state, which bear specific binding partners for the analyte in question on their surface. The specific binding partner treated colloidal particles are combined in a buffered, aqueous medium with a destabilizer material capable of destabilizing the specific binding partner-colloidal particle conjugates thereby permitting the particles to agglomerate. Also included in the liquid medium is a polymer bearing multiple analyte or analyte analog molecules along its surface which serves to protect the specific binding partner coated metal particles from dissociation by the destabilizing agent.

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: 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 ore 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: The invention relates to a method of detection, a sensor and a test-kit which find application in immunological detection (e.g., immunoassay). The invention provides, inter alia, a method of detection, suitable for use in immunological detection of an entity, which method includes the use of a secondary species (as defined in the specification), the use of a first detectable species, and the use of a second detectable species. The method may include, for example, the use of a primary species, a secondary species, a first detectable species and a second detectable species. The primary species may be, for example, an antibody or a ligand. The secondary species may be, for example, an auxiliary species such as an auxiliary binder or an auxiliary ligand, or a species which has a part which is an auxiliary function. The entity to be detected may be an analyte species as such or may be an entity which carries or includes analytes species.

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: This invention relates to polymers labeled with fluorescent dye to the point that significant fluorescence quenching occurs, such that degradation of the polymer results in fluorescence enhancement. The resulting fluorescence enhancement is useful for measuring the degradation of such polymers, for example as a result of enzymatic hydrolyis of a protein, carbohydrate, nucleic acid, or other natural or synthetic polymer.

Abstract: A dry immunoassay analytical element, for assaying a ligand is disclosed. The element comprises, in the following order, (a) a layer containing a labeled ligand, (b) a bead spreading layer, c) a cross-linked hydrophilic polymer layer and d) a support; wherein(i) a fixed concentration of an immobilized receptor for the labeled ligand is located in a zone at the interface of layers (b) and (c); and(ii) the receptors are immobilized by being covalently bonded to polymeric beads that are smaller than the beads in layer (c).

Abstract: The invention relates generally to colloidal particle having a core material and a gelatin/aminodextran coating with pendent functional groups attached thereto. Biological substances or molecules, especially monoclonal antibodies, may be attached to said particles. The monoclonal antibody containing particles are useful in a variety of positive and negative biological assays.

Abstract: A technique 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: Assays that are prognostic for patients that will develop nephritis have been developed where patient serum is screened for the presence of anti-dsDNA antibodies that are cross reactive with A and D SnRNP proteins. The assays are based on the use of either peptides containing epitopes bound by the anti-dsDNA antibodies, or the antigens for the antibodies, A and D SnRNP proteins. Therapeutic compositions have also been developed using either antibodies that block the pathogenicity of the anti-dsDNA antibodies, such as the naturally occurring anti-La/SSB and anti-U.sub.1 RNP antibodies that are cross reactive with the anti-dsDNA or using the peptides or A and D proteins to induce tolerance.

Abstract: A method for increasing the binding activity of specific binding members bound to a solid phase material, e.g., a particle, that has been sterically stabilized. This increase in binding activity is brought about by degrading a steric stabilizer on the surface of the solid phase material. The method involves both immobilizing a specific binding member on the surface of a solid phase material and degrading a steric stabilizer on the surface of that solid phase material. In the preferred embodiment, the method involves the immobilization of a specific binding member on the surface of the sterically stabilized solid phase material, with subsequent degradation of the steric stabilizer.

Abstract: A method for detecting a target substance which includes collecting a substance sample; introducing the substance sample into a substance card having at least one reagent responsive to the presence of the target substance and having a light-transmissive chamber; inserting the substance card into a substance detector device having a photosensor and adapted to receive the substance card; mixing the substance sample with the reagents for a preselected mixing period, thus producing a measurand having a target substance reaction; streaming the measurand through the light-transmissive chamber and illuminating the measurand with a quantity of light for a selectable analysis period, an optical characteristic of the measurand can be measured with the photosensor; and selecting the target substance reaction as a positive reaction or a negative reaction, responsive to the optical characteristic. If the target substance reaction is a negative reaction, the device operator is signalled thereof.

Abstract: A method is provided for measuring an analyte in a sample comprising adding substantially transparent particles to a sample in solution or suspension, said particles having an affinity for said analyte; fractionating the particles from the solution or suspension to form a particle-rich fraction and a substantially particle-free fraction; optically reading the particle-rich fraction at a first and a second wavelength; optically reading the substantially particle-free fraction at at least the first wavelength; and correlating the readings through the particle-rich fraction and the substantially particle-free fraction of the sample, with similar measurements in a particle-containing "blank" to obtain a quantitative determination of the analyte originally present in the sample.

Abstract: The invention relates to activated support materials which comprise epoxy-substituted poly(meth)acrylamides, characterized in that:a) the base support contains aliphatic hydroxyl groups,b) the covalently bonded polymers are bonded to the support via a terminal monomer unit,c) the polymers contain monomer units of the formula I,d) the monomer units are linearly linked, ##STR1## in which R.sup.1, R.sup.2 and R.sup.3 independently of one another are H or CH.sub.3,R.sup.4 is H or alkyl having 1-5 carbon atomsandn is an integer between 1 and 5 and to the use thereof.

Abstract: This invention presents novel assay devices employing capture reagents, involving a specific binding member attached to a charged substance, and porous material containing a capture or reaction zone that is oppositely charged with respect to the charged substance included in the capture reagent. In one embodiment, a test sample suspected of containing the analyte of interest is contacted with the capture reagent to form a charged capture reagent/analyte complex. The complex is then contacted to the oppositely charged capture or reaction zone to attract, attach, and immobilize the capture reagent/analyte complex. With an appropriate indicator reagent, both sandwich and competitive assays can be performed.

Abstract: The present invention is a method and apparatus useful for the detection of bloodgroup antigens and antibodies. There are two preferred embodiments of the method: a direct assay and an indirect assay. The direct assay comprises adding a sample of erythrocytes to a reaction tube charged with a column of immunoreactive particles having an immunoglobulin binding ligand selected from the group consisting of Protein A, Protein G, Protein A/G or a universal kappa light chain binding protein coupled to the surface of the particles. Antibodies specific for bloodgroup antigens tested for are coupled to the ligand on the particles. 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 on the particles.

Abstract: The invention describes the use of novel aminodextran compounds containing about 5-20% by weight amine groups to bind a plurality of monoclonal antibodies. The resulting antibody-aminodextran compounds may be used to induce the activation and proliferation of selected mammalian cells. Specific examples are given using an anti-CD3 monoclonal antibody conjugated two aminodextrans containing about 5% and 16%, respectively, by weight amine groups as an agent for inducing the activation and proliferation of T cells.

Abstract: In assays of the type which comprise contacting the sample containing the analyte to be detected with a solid phase surface supporting a ligand capable of binding the analyte, undesired binding to the surface is prevented to a substantial degree by adding to the sample one or more components of the material forming the ligand supporting solid phase surface, which components are in at least partially soluble form and capable of interacting with constituents of the sample medium.

Abstract: A fluorescent labelling composition comprises a linear polysaccharide backbone molecule having a plurality of target-binding molecules, such as antibodies or nucleic acids, attached at spaced-apart intervals thereon. Each of the target-binding molecules, in turn, includes a multiplicity of fluorescent dye molecules bound thereto. In this way, fluorescent signal introduced to a single target-site on a solid phase surface may be increased without loss of binding activity.

Abstract: A supported polyionic hydrogel containing biologically active material is epared by impregnating into a porous support material a solution of anionic polysaccharide, a solution of cationic polysaccharide and a biologically active material. The anionic polysaccharide and the cationic polysaccharide react with each other to form a hydrogel containing the biologically active material. The hydrogel may be dried such as by lyophilization. The biologically active material can be in either polysaccharide solution or in another solution impregnated into the porous support material. A paper material or a textile material may be used as the porous support material. Preferably, the anionic polysaccharide is xanthan, dicarboxystarch or dicarboxycellulose and the cationic polysaccharide is chitosan. Especially preferred is a hydrogel formed from xanthan and chitosan.

Abstract: The invention relates to the use of collagen as solid binding substrate for a sensor called ligand or refining agent, capable of reacting specifically with an element to be detected in a biological medium, to form a specific complex.Preferably, the solid substrate comprises atelocollagen or a mixture of atelocollagen and of polyholoside.The invention thus makes it possible to provide a biological reactant of high specificity and of which the constituents are of natural origin. It can be used easily and quickly.

Abstract: A method of separating bound labeled indicator from free labeled indicator in a layer of a test element for immunoassay. The method comprisesa) depositing sample containing a target immunoanalyte capable of binding to the labeled indicator or to an immobilized antibody in competition with the labeled indicator, onto an exterior surface of a test element in the presence of the labeled indicator andb) adding an amount of wash liquid to the exterior surface to form a pool of the liquid having a meniscus on the surface, the liquid penetrating the surface over an area bounded by a closed intersect edge formed between the pool meniscus and the surface, so that penetrating liquid can push free labeled indicator away from bound labeled indicator in a volume of the layer below the bounded area.

Abstract: Gelatin and aminodextran coated polymer core particles useful in immunoassays and methods of making the same are disclosed. The preparation of aminodextrans having varying amounts of amine groups is also described, as is a method of crosslinking gelatin and aminodextran without the use of a stabilizer.

Abstract: New and useful methods of producing stabilized enzyme antibody conjugates are disclosed which are particularly useful in forming multi-layer immunoassay test devices. In particular, the invention concerns the formation of a manganese ion and enzyme-antibody conjugate in aqueous solution and drying the solution to produce a dry stabilized enzyme-antibody conjugate. Further, this stabilized enzyme-antibody conjugate can be formed on a continuous web and dried in a heat tunnel. This continuous manufacturing process allows for the more efficient production of multi-layer test strips.

Abstract: The present invention relates to a process for determining complexes of .alpha.-1-antichymotrypsin and cathepsin G in a sample comprising adsorbing the cathepsin G portion of the complex to a solid phase coated with non-specific binding protein or gelatin, and detecting the .alpha.-1 portion of the complex with a detectably labelled anti-.alpha.-1-antichymotrypsin antibody. A diagnostic kit comprising the solid phase coated with non-specific binding protein or gelatin and the labelled anti-.alpha.-1-antichymotrypsin antibody is also provided.

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.