Abstract: In a method for assaying an anticardiolipin antibody in a sample utilizing .beta.2-glycoprotein I, a polypeptide having the same amino acid sequence as domain IV of .beta.2-glycoprotein I or a polypeptide partially different therefrom but functionally equivalent thereto is used in place of .beta.2-glycoprotein I itself. According to this method, an autoantibody from patients with antiphospholipid syndrome can be accurately assayed in a simple manner.

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

Abstract: This invention provides methods, compositions, and kits for detecting the presence of toxigenic strains of C. difficile in a biological sample. One embodiment provides methods for C. difficile detection that involve assaying for both C. difficile glutamate dehydrogenase and C. difficile toxin A or toxin B. In another embodiment, the invention provides a highly sensitive assay for C. difficile toxin A that is useful for determining whether a C. difficile strain is toxigenic. This embodiment involves binding of toxin A to a moiety that reversibly binds to a capture moiety present on a magnetic bead. A magnetic field is applied to the sample to concentrate the toxin A, after which the magnetic beads are dissociated and removed from the solution to obtain a highly concentrated preparation of toxin A, thus making possible a very sensitive assay.

Abstract: Methods of preparing a boronate-antigen complex for immunization of animals, a monoclonal antibody specific for the same, an immunoassay method for detection of the complex and a method of calculating the amount of a target glycated protein within the sample useful in the diagnostic monitoring of diabetes are disclosed. An immunoassay kit based on this reagent is also disclosed.

Abstract: Biomaterial such as an enzyme, cell, antigen or antibody is immobilized by covalent bonding to a substrate having an Si.sub.3 N.sub.4 surface containing Si--NH.sub.2 groups that provide reactive NH.sub.2 groups. A heterobifunctional cross-linking agent having an NH.sub.2 -reactive group and a biomaterial-reactive group is reacted with the NH.sub.2 groups of the surface and then with the biomaterial or the heterobifunctional cross-linking agent is reacted with the biomaterial and then with the NH.sub.2 groups of the surface. The Si.sub.3 N.sub.4 surface containing Si--NH.sub.2 groups can be formed by precipitating on a substrate a 10-1000 nm thick Si.sub.3 N.sub.4 layer from a SiH.sub.4 /NH.sub.3 mixture, and providing reactive NH.sub.2 groups on the surface of the layer by subjecting the surface to hydrolyzing cleaning.

Abstract: Method for detecting an analyte of interest, comprising the steps of providing a detection device comprising a light reflective or transmissive substrate supporting one or more layers comprising an adhering attachment layer to which is affixed a receptive material which specifically interacts with the analyte of interest; reacting the device with a sample potentially comprising the analyte under conditions in which the analyte binds to the receptive material; and reacting bound analyte with a reagent which creates a mass change on the surface of the device.

Abstract: Methods are provided for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A 2-aminoalcohol moiety of a biomolecule is oxidized with a periodate to an aldehyde moiety which is reacted with an amine moiety on the surface of a medical device to form an imine moiety, and the imine moiety is reduced to form an amine linkage immobilizing a coating of the biomolecule on the surface. In another method, a biomolecule coating containing an amine moiety and a 2-aminoalcohol moiety is immobilized on the surface of a medical device, the 2-aminoalcohol moiety is oxidized with a periodate to an aldehyde moiety which is reacted with the amine moiety to form an imine moiety, and the imine moiety is reduced to form a secondary amine and crosslink the coating.

Abstract: Methods are provided for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A biomolecule having a negatively charged moiety is combined with a medical device surface having a positively charged guanidino moiety to form an ionic bond immobilizing a coating of the biomolecule on the surface. In another method, the medical device surface contains an amine moiety that is combined with a guanidino forming agent to form a positively charged guanidino moiety that is combined with the negatively charged moiety to form the ionic bond. In a further embodiment, the medical device surface contains a negatively charged moiety, and a biomolecule containing an amine moiety is combined with a guanidino forming agent to form a positively charged guanidino moiety that is combined with the negatively charged moiety to form the ionic bond.

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

Abstract: Methods are provided for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A biomolecule such as a glycoprotein having an unsubstituted amide moiety is combined with an amine forming agent to form an amine-functional biomolecule. The amine-functional biomolecule is combined with a medical device surface having a chemical moiety such as aldehyde, epoxide, isocyanate, 1,2-dicarbonyl, phosphate, sulphate or carboxylate to form a chemical bond immobilizing the biomolecule on the surface. The chemical bond may be combined with a reducing agent or a stabilizing agent. The aldehyde moiety may be formed by combining a periodate with a 2-aminoalcohol moiety or a 1,2-dihydroxy moiety. Alternatively, an amine-functional medical device surface is combined with a biomolecule having a chemical moiety that reacts with an amine moiety.

Abstract: The invention relates to a dye-labeled antibody conjugate comprising an antibody conjugate and a cyanine dye. The dye-labeled antibody conjugate is prepared by polymerizing an antibody such as mouse IgG in phosphate buffer using a polyfunctional reagent such as dithiobis(sulfosuccinimidylpropionate), and stirring the antibody and a cyanine dye represented by Formula I . The dye-labeled antibody conjugate is more sensitive to antigens than conventional dye-labeled antibodies because it has many reactive sites to antigens.

Abstract: A method combining the techniques of immunoaffinity separation and continuous flow centrifugal separation is provided for selective separation of a nucleated heterogeneous cell population from a heterogeneous cell mixture. The heterogeneous cell mixture is intimately contacted to promote binding thereto by particles having attached a substance that actively binds to a specific desired type of cell out of the cell mixture. The particles are selected so that the sedimentation velocity of the particle/cell conjugate differs sufficiently from those of other cells in the cell mixture to allow its separation by means of a continuous flow cell separator.

Abstract: Use of an anti-cardiolipin antibody, anti-lipoprotein antibody or anti-.beta.2-glycoprotein I antibody together with an immobilized antibody thereof enables to accurately assay for a complex of .beta.2-glycoprotein I and an oxidized lipoprotein in a blood sample, according to a sandwich immunoassay. Thus, the oxidized lipoprotein in blood can be detected, whereby diagnosis of arteriosclerotic disease is enabled.

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

Abstract: 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: The present invention encompasses a capture membrane comprising a porous filter membrane having a hapten bound directly or indirectly to the membrane wherein complexes formed by specific binding having an anti-hapten bound to a binding member of the specifically binding complex are removed from a solution by the hapten as the solution passes through the membrane. In the preferred embodiment biotin is the hapten and avidin or streptavidin is the anti-hapten.

Abstract: A solid support for the solid-phase synthesis of peptides or proteins in high yield and in high purity, suited both to the synthesis of a single peptide or protein and to the parallel and substantially simultaneous synthesis of a plurality thereof, is based on a cross-linked polyolefin, especially polyethylene, substrate, the cross-linking having been obtained by irradiation with high energy electrons or .gamma. radiation or treatment with organic peroxide such as benzoyl peroxide, to which substrate are grafted polymer chains such as polystyrene chains which are functionalized with a chemical functionality facilitating the formation of an anchoring linkage between the polymer moiety and another chemical species. The solid support is also suited for use in solid-phase biosystems, notably bioassays, such as immunoassays, DNA hybridization assays or PCR amplification.

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: Method for the determination of chlamydial or gram negative bacterial antigen comprising contacting a sample potentially containing extracted antigen with an optically active surface comprising an attachment layer, and a layer of non-specific protein.

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: A solid phase magnetic support having a hydrophilic surface, a method of making the support, and a method of using the support for peptide synthesis are provided. The solid phase magnetic support is synthesized from a starting material which is a magnetic polystyrene polymer bead which has a plurality of polystyrene coated metal oxide particles randomly distributed in a polystyrene matrix having chloromethyl groups. Hydrophilic long chain hydrocarbon spacer arms, such as polyalkylene diamine molecules are coupled with sonication to the chloromethyl groups. Each spacer arm is provided with a terminal amine for linking to a first amino acid. Preferably, the terminal amine on the spacer arm is provided by a low molecular weight linker molecule which can be acid cleaved from the spacer arm. However, the spacer arm may be derivatized and linked to a first amino acid which cannot be acid cleaved from the spacer arm.

Abstract: A method for immunologically determining antistreptolysin O antibody comprises contacting a test sample solution containing antistreptolysin O antibody with a binding agent to selectively bind the antistreptolysin O antibody to the binding agent, and determining an amount of the bound antistreptolysin O antibody, wherein the binding agent comprises a streptolysin O-immobilized carrier obtained by contacting a solution containing streptolysin O with a carrier having immobilized thereon at least one steroid represented by formula (1): ##STR1## wherein R.sup.1 is a side chain moiety of cholesterol or a side chain moiety of cholic acid, wherein each of the side chain moieties is independently unsubstituted or substituted and independently saturated or unsaturated; R.sup.2 is hydrogen or hydroxyl; and each dashed line independently represents a single bond or no bond.

Abstract: A method is provided for enhancing the stability and increasing the activity of polymer particle reagents by incubating a polymer particle which has been covalently bound to a compound of biological interest, such as a drug, with a modifying agent that will place a negative charge on the surface of the polymer particle and reduce residual functional groups. The modifying agent is preferably an anionic nucleophile selected from the group consisting of .beta.- mercaptoacetic acid and the thiosulfates.

Abstract: A trifunctional conjugate is provided having three chemical moieties attached through a spacer moeity. At least two of the chemical moieties are relatively small molecules, usually less than about 7,000 Daltons in size. The spacer moiety is selected to impart certain steric properties to the conjugate. In one embodiment, the binding of a macromolecular specific binding partner to one of the chemical moieties sterically inhibits the binding of a different macromolecule to another chemical moiety. In another embodiment, the binding of a first chemical moiety to a macromolecule restricts the subsequent binding of a second chemical moiety to a proximate location on the same macromolecule. The three chemical moieties are preferably a nitrophenylazido residue, a phenyl boronic acid residue, and a solid support or a label such as biotin. The spacer is preferably cysteine, lysine, glutamic acid, pyroglutamic acid, S-acetylmercaptosuccinic anhydride or .omega.-carbobenzoxylysine.

Abstract: A new class of phenylboronic acid complexing reagents are provided capable of binding with phenylboronic acids is disclosed having one of the following structures: ##STR1## wherein group X is selected from H, CH.sub.3 and C.sub.6 H.sub.5 ; and groups Y and Z are selected from O and CH.sub.2 ; group Q is a spacer which is from 2 to 12 carbon equivalents in length, and which may contain intermediate amide and/or ether functionalities; and group R is a reactive electrophilic moiety suitable for conjugation of a phenylboronic acid complexing reagent with a biological macromolecular species, low molecular weight species or solid phase support having a reactive pendant nucleophilic moiety. The phenylboronic acid complexing reagents are utilized in conjunction with phenylboronic acid reagents to facilitate chemical conjugation without the use of intermediary biological macromolecules. The method of making and using such reagents is also disclosed.

Abstract: Surfaced-enhanced, analytical procedures wherein a surfaced article includes a substrate surface, metal islands, a spacing/coupling agent layer, and binding partner molecules which bond with work piece molecules to be detected. A population of spaced apart metal islands are formed on the substrate and have at least some interconnections formed between them. A continuous layer coats the islands and all surfaces between the islands. The continuous layer includes a coupling agent which immobilizes first binding partner molecules. The first partner molecules bond to the coupling agent and the second binding partner molecules bind to the first binding partner molecules to allow detection of presence or concentration of the work piece binding partner molecules.

Abstract: Adjuvant compositions for modulating an immune response to an antigen administered to a host comprise a mineral salt adjuvant and at least one other adjuvant. The compositions provide an adjuvanting effect on an antigen which is greater than the adjuvanting effect attainable by one of the adjuvants alone. An antigen is covalently bonded to a glycolipid analog to provide a discrete molecule which exhibits an enhanced adjuvanting effect on the antigen which is greater than the adjuvanting effect attainable in the absence of such covalent bonding.

Abstract: An efficient method for the microfabrication of electronic devices which have been adapted for the analyses of biologically significant analyte species is described. The techniques of the present invention allow for close control over he dimensional features of the various components and layers established on a suitable substrate. Such control extends to those parts of the devices which incorporate the biological components which enable these devices to function as biological sensors. The materials and methods disclosed herein thus provide an effective means for the mass production of uniform wholly microfabricated biosensors. Various embodiments of the devices themselves are described herein which are especially suited for real time analyses of biological samples in a clinical setting. In particular, the present invention describes assays which can be performed using certain ligand/ligand receptor-based biosensor embodiments.

Abstract: Ligands that interact with a target can be more easily identified if false positive interactions (either specific or non-specific) from the detecting system are differentiated from the target-specific interaction. An improved method of identifying peptides which bind with a target protein is presented. The steps are: binding a random library of peptides to a support material, allowing detection reagents to contact the peptides and the support material then identifying these interactions, then allowing the target protein to selectively bind to the peptides, allowing detection reagents to contact the bound target protein, and characterizing the peptide bound to the identified support material. Interaction of a ligand or the support material with the detection reagents will cause a distinct color change which distinguishes those ligands which selectively bind to target protein. The characterized peptide can then be used in affinity purification of the target protein.

Abstract: A method is provided for immobilizing a biomolecule coating on the surface of a medical device to obtain improved biocompatibility characteristics for contacting with tissue or body fluids such as blood. The method includes oxidizing a 2-aminoalcohol moiety of a material disposed on the surface with a periodate to form an aldehyde moiety, combining the aldehyde moiety with an amine moiety of a material to bond the aldehyde moiety to the amine moiety through an imine moiety and reacting the imine moiety with a reducing agent to form the coating immobilized on the surface by an amine linkage.

Abstract: Process for the identification or assay of a particular polypeptide antigen X in which an immunological determination of the presence of said polypeptide antigen X is carried out in a sample, characterized in that the sample is treated in vitro using at least one chemical reagent reactingon an epsilon -NH.sub.2 function of a lysine residue oron a terminal alpha -NH.sub.2 function of a peptidein order to carry out the linking of said reagent to said polypeptide antigen X and in this way to obtain a modified polypeptide antigen X, (polypeptide antigen Xm), the immunological determination of the presence of said polypeptide antigen X in said sample is then carried out using at least one antibody produced by immunization against a polypeptide antigen Y identical to the polypeptide antigen Xm or to an antigenic fragment of this antigen Xm.

Abstract: A piezoelectric biosensor substrate useful for immobilizing biomolecules in an oriented manner on the surface of a piezoelectric sensor has a ladder polymer of polyacrylonitrile. To make the substrate, a solution of an organic polymer, preferably polyacrylonitrile, is applied to the surface of a piezoelectric sensor. The organic polymer is modifying by heating the polymer in a controlled fashion in air such that a ladder polymer is produced which, in turn, forms the attachment point for the biomolecules comprising the piezoelectric biosensor.

Abstract: The invention relates to a process for immobilization onto the surface of enzyme linked immunosorbent assay (ELISA) plates of a compound or for immunization with a compound, wherein said compound is in the form of a compound carrier complex which is either an avidin-biotinyl compound complex or a streptavidin-biotinyl compound complex.

Abstract: The invention is directed to monoclonal antibodies, their fragments, single chains and polypeptide mimics of their hypervariable regions which immunoreact with bare small moieties such as metallic cations and small organic molecules, the hybridomas for production of the monoclonal antibodies, immunogen compounds for developing the hybridomas, and methods for use of the monoclonal antibodies.

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: The present invention provides crosslinking, conjugating and reducing agents which are functional with at least one phosphorothioate monoester group (--SPO.sub.3.sup.-2). Crosslinking and conjugation methods as well as solid phase reagents and conjugates which are useful in immunoassays are also provided.Crosslinking and conjugating agents of the invention generally comprise a compound corresponding to the formula (I), shown below, wherein n at least 1 and Q is a straight or branched monomer, polymer or oligomer having an average molecular weight between about 200 and about 1,000,000. Additionally, when n is 1, Q comprises at least 1 additional reactive functionality.Q--(S--PO.sub.3 .sup.-2)n (I)The reducing agents that are provided conform to a compound of the formula (Y), shown below, wherein (A) and (Z) can be independently selected from C.sub.1 -C.sub.5 alkyl and CONH(CH.sub.2)p wherein p is an integer between 1 and 5.

Abstract: A device for detecting the presence of substances, particularly biological materials, contained in a liquid sample is formed of a series of layers of film materials. A first film has a cut-out which forms an upper reservoir for receiving the liquid sample. A first reagent is provided in the upper reservoir capable of reacting with a substance possibly contained in the liquid sample. A first membrane is situated at the base of the upper reservoir and is made of a material which is temporarily impermeable so that the liquid sample is temporarily retained in the upper reservoir in contact with the first reagent, but after awhile the membrane becomes permeable and allows the liquid to pass. A second film has a cut-out which forms a median reservoir positioned for receiving the liquid passing through the first membrane. A second reagent is provided in the median reservoir capable of reacting with a predetermined substance.

Abstract: For the determination of an immunologically detectable substance based on a heterogeneous immunoassay by use of a solid phase on which one of the immunologically active reaction components is bound, a reaction vessel is used as the solid phase on the inner surface of which streptavidin or avidin is bound in such an amount that 0.1 to 2.5 .mu.g are present per ml reaction volume.A suitable reaction vessel for this has optically transparent wall areas which face one another and has avidin or streptavidin coated walls which are at least partially within the inner wall region intended as a receptacle for liquid, wherein the inner space of the container intended as a receptacle for liquid and the respective streptavidin or avidin content of the coating are so matched that 0.1 to 2.5 .mu.g streptavidin or avidin are present per ml reaction volume.

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: Perfluorocarbon polymer-based matrices are coated with a hydrophilic polymer for use in bioaffinity separations. Coating is carried out by dispersing porous particles of inert perfluorocarbon polymer in a water-miscible organic solvent such as acetone or tetrafydrofuran to wet surfaces of the particles, forming a dispersion of the wetted particles in an aqueous solution of hydrophilic polymer such as poly(vinyl alcohol) containing a plurality of hydroxyl groups, at least one being at an end of a polymer chain, to adsorb the hydrophilic polymer onto the wetted surfaces of the particles, admixing a homobifunctional cross-linking agent such as glutaraldehyde with the particles to cross-link the hydrophilic polymer, activating hydroxyl groups on the surface of the cross-linked hydrophilic polymer and covalently bonding a ligand or ligand binder to the activated hydroxyl groups.

Abstract: What is described are methods and apparatus for performing a binding assay for an analyte of interest present in a sample. The methods include the steps of: forming a composition containing said sample, an assay-performance-substance which contains a component linked to a label compound capable of chemiluminescing when triggered, and a plurality of coated magnetic particles capable of specifically binding with the analyte and/or said assay-performance-substance; incubating said composition to form a complex which includes a particle and said labeled component; magnetically collecting said complex at the surface of an electrode; inducing said label to luminesce by contacting it with a trigger, said trigger being formed in-situ by conversion of a precursor molecule upon introduction of electrochemical energy; and measuring the emitted luminescence to measure the presence of the analyte of interest in the sample.

Abstract: A particularly efficient design for a nonbibulous lateral flow one step assay for an analyte in a biological sample is disclosed. In the improved device of the invention, three zones which are in nonbibulous lateral flow contact are employed: a sample receiving zone, a labeling zone, and a capture zone. The sample containing analyte is carried through the labeling zone and interacts with an assay label comprising visible moieties, preferably particles, which are coupled to specific binding reagent for analyte or to a competitor with analyte for a capture reagent. The flow continues into the capture zone where the visible moieties to which analyte or competitor are coupled are captured. Excess fluid is absorbed into an absorbent zone in contact with the capture zone. A positive result is obtained by visualizing the visible moieties in the capture zone.

Abstract: A particularly efficient design for a nonbibulous lateral flow one step assay for an analyte in a biological sample is disclosed. In the improved device of the invention, three zones which are in nonbibulous lateral flow contact are employed: a sample receiving zone, a labeling zone, and a capture zone. The sample containing analyte is carried through the labeling zone and interacts with an assay label comprising visible moieties, preferably particles, which are coupled to specific binding reagent for analyte or to a competitor with analyte for a capture reagent. The flow continues into the capture zone where the visible moieties to which analyte or competitor are coupled are captured. Excess fluid is absorbed into an absorbent zone in contact with the capture zone. A positive result is obtained by visualizing the visible moieties in the capture zone.

Abstract: A membrane comprising a closely packed array of self-assembling amphiphilic molecules, and is characterized in that it incorporates a plurality of ion channels, and/or at least a proportion of the self-assembling molecules comprise a receptor molecule conjugated with a supporting entity. The ion channel is selected from the group consisting of peptides capable of forming helices and aggregates thereof, corronands, cryptands, podands and combinations thereof. In the amphiphilic molecules comprising a receptor molecule conjugated with a supporting entity, the receptor molecule has a receptor site and is selected from the group consisting of immunoglobulins, antibodies, antibody fragments, dyes enzymes and lectins. "The supporting entity is selected from the group consisting of a lipid head group, a hydrocarbon chain(s), a cross-linkable molecule and a membrane protein. The supporting entity is attached to the receptor molecule at tan end remote from the receptor site.

Abstract: An affinity support is provided containing a high flux semipermeable hydrogel membrane surface-modified with an affinity ligand, such as a protein which may be an antibody or enzyme, or a cell receptor complement, useful for affinity separation of biological macromolecules, including insoluble proteins, cells, and cell fragments, from solution. The exclusion limit (molecular weight cut-off) of the matrix is selected to substantially restrict immobilized protein or other ligand to the surface thereof for maximization of available ligand binding capacity. The exclusion limit is also selected to permit reagent(s) used for the matrix/ligand linkage to penetrate into and form covalent bonds with the membrane on the interior surfaces of the membrane for optimizing packing densities of the affinity ligand exterior to the membrane.

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: A method is provided for preparing a labeled protein, immobilized protein or protein-bioactive agent composition by attaching a label, support or bioactive agent to a protein by exopeptidase catalysis at a site that is remote from the active site of the protein. More specifically, an amine or alcohol group of an amino acid, amine or alcohol nucleophile is reacted by exopeptidase catalysis with a C-terminus carboxylic acid group of a protein such as an antibody, enzyme or hormone to couple the nucleophile to the protein to form an adduct, and the adduct is bound to an auxiliary substance such as a support, label or bioactive agent or its combination with a linker arm by reacting a reactive substituent of the nucleophile with a reactive group of the auxiliary substance. Alternatively, the nucleophile is bound to the auxiliary substance or its combination with a linker arm to form an intermediate, and the intermediate is coupled by exopeptidase catalysis to the protein.

Abstract: There are disclosed a magnetic particle for an immunoassay method, which comprises a core and a coating layer formed on the surface of the core wherein said core comprises an organic polymer matrix and said coating layer comprises a mixed crystal ferrite represented by the formula:M.sub.x Fe.sub.(3-x) O.sub.4wherein M represents at least one metal selected from the group consisting of Mn, Ni, Zn, Co, Cu, Mg, Sn, Ca and Cd, and x is a number satisfying the relation: 0<x<3,and an antigen or an antibody is bound onto the surface of the coating layer and wherein said particle has a particle size of 0.03 to 10 .mu.m, and an immunoassay method using the same.

Abstract: A method is disclosed for preparing water soluble protein polymer conjugates which stabilize the protein so as to retain functional properties in a hostile environment. The method comprises covalently bonding the polymer to the protein through at least three linkers which linkers have three or more hydroxyl groups. The protein is conjugated at lysines or arginines.