Abstract: A method is disclosed for producing a soluble conjugate vaccine, and preferably protein/polysaccharide conjugates. In this process, the polysaccharide is reacted with a reagent so as to provide a functional group on the polysaccharide molecule. Once the functional group is in place, the polysaccharide is reacted with a homobifunctional or heterobifunctional vinylsulfone to produce a vinylsulfone derivatized polysaccharide. Thereafter, the vinylsulfone derivatized polysaccharide is reacted with a protein to produce the conjugate. If desired, the protein may be derivatized with a functional group prior to the conjugation reaction step. In an alternative embodiment, the protein may be functionalized with a reactive group and then derivatized with the vinylsulfone group to produce a vinylsulfone derivatized protein. This protein may then be reacted with a polysaccharide to produce the conjugate. Optionally, the polysaccharide may be functionalized with a reactive group prior to the conjugation reaction.

Abstract: Microporous solid phase materials that are suitable for lateral flow and other assays for detecting the presence of analytes in test samples, that are stable under variations in humidity and, even after storage for extended periods of time, can form stable covalent bonds with molecules containing a free primary or secondary amine group or sulfhydryl group are described. The invention further concerns chemically derivatized solid phase materials, and conjugates comprising such materials. Examples of lateral flow devices for the quantitative or semi-quantitative determination of an analyte in a biological sample are described.

Abstract: The rate of degradation in vivo of a body protein is determined by measuring the amount of a D-amino acid containing fragment of the protein in a body fluid using an antibody capable of discriminating between the D-amino acid containing fragment and its L-amino acid containing analogue.

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: The present invention relates to a system (80) for determining analyte concentration. The system (80) includes an optical detection system (92) that detects fluorescence from fluorescent binding assays in a biosensor (88). A processing system (96) may be used to determine analyte concentration from the fluorescence detected by the optical detection system (92). The optical detection system (92) may include photodetectors with or without in series lenses. Alternatively, a CCD camera (146) may be used.

Abstract: The present invention is directed to a composition and method for regulating the adhesion of cells and biomolecules to hydrophobic surfaces and hydrophobic coated surfaces. The composition is a biomolecule conjugated end-group activated polymer (FGAP). The biomolecule conjugated EGAP can be put to numerous uses including cell adhesion, cell growth, cell sorting, and other biological assays.

Abstract: The invention describes quality control devices for assays that measure analytes in cells and tissue samples, and methods of use thereof. In particular, the quality control device comprises a matrix affixed with synthetic controls in different concentrations, or different synthetic controls. The quality control device can be adhered to a microscope slide and processed simultaneously with a tissue sample.

Abstract: The invention relates to surfaces coated with streptavidin and avidin for use in immunoassays, wherein the surfaces comprise a layer of streptavidin and avidin which are bonded on a surface of a solid supporting material through a biotinylated adhering agent.

Abstract: The present invention relates to processes for the direct detection of biochemically functional retroviruses in biological samples. The processes of the invention are characterized by the structure-specific extraction of retrovirus particles and a subsequent analysis and detection of retrovirus-specific enzymatic reactions. The processes of the invention have broad application in the diagnosis of retroviral infection and virological research.

Abstract: A magnetic focusing immunosensor for the detection of pathogens comprising a laser, an exciting fiber and a collecting fiber, a fiber optic magnetic probe in communication with the collecting and exciting fibers and means for detecting, collecting and measuring fluorescent signals in communication with the collecting fiber. The probe and the collecting and exciting fibers are configured to focus paramagnetic microspheres attached to antigen/antibody/optically labeled complexes in a predetermined pattern in the field of view of the collecting fiber while blocking background interference.

Abstract: The invention provides a human cyclic GMP phosphodiesterase (PDE9A) and polynucleotides which identify and encode PDE9A. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for treating or preventing disorders associated with expression of PDE9A.

Abstract: A method for isolating an active catalyst from a library of compounds that are potential catalysts is disclosed. The method involves providing a library which comprises a plurality of discrete solid supports, each solid support having a different organic compound bound thereto; and providing a reaction solution in a reaction vessel, the reaction solution containing the reactant or reactants necessary for a chemical reaction to occur in the presence of a catalyst for that reaction. The library and the reaction solution are then combined in the reaction vessel, and then one of the discrete solid supports is detected that is characterized by a temperature change in said solution greater than the temperature change of a plurality of other of said discrete solid supports in said solution. The detected solid support carries an active catalyst for the chemical reaction. Continuous flow apparatus for carrying out the method is also disclosed.

Abstract: This invention relates to a fluorescence-based immunoassay method for the detection of an analyte, or for the measurement of its concentration in a biological sample. The method is based on the ability of a multivalent analyte to induce aggregation of receptor molecules labeled with a fluorophore, which molecules are anchored to and are freely mobile on a lipid membrane, and thereby cause changes in the fluorescence.

Abstract: An extended fibre point (1) is coated with photbiotin and irradiated with U.V. light, causing the photobiotin to bind with the fibre pint. The fibre point is then brounght into contact with streptavidin and submerged in a solution containing dyed copies of the DNA molecule to be sequenced. Biotin is also bonded to the 5′ end of the dyed DNA molecules (4A). the biotin coupled to individual DNA molecules binds with the streptavidin at the fibre point. Light is coupled into the fibre to detect the thus obtained bonds. The evanescent field of said light excites a dyed DNA molecule to emit fluorescent light as soon as it binds with the fibre point. When a bond is deteccted, the fibre is immediately remvoded from the solution, and the fibre point is inserted into a microcapillary (5). The microcapillary is filled with a buffer solution containing exonucleases which decompose the DNA colecule base after base.

Abstract: The present invention relates to a method of detecting specific antibodies directed against HPV proteins in body fluids, comprising the following steps: (I) incubating a native carrier material-bound HPV protein with body fluids, and (II) reacting specific antibodies (a) bound to the HPV protein with labeled antibodies (b) directed against antibodies (a) or with unlabeled antibodies (b) and the latter with labeled antibodies (c) directed against antibodies (b). Furthermore, this invention concerns a kit usable for this purpose.

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

Abstract: The fragmentation pattern of collagen, especially of type 1, as reflected in breakdown products of collagen in a body fluid such as serum or urine is estimated by measuring the levels of such breakdown products using two or more distinct immunoassays. The results may be combined into a numerical index diagnostic of one or more pathological conditions or patient types.

Abstract: This invention is thus related to a biospecific multiparameter assay employing single molecule detection. In particular, this invention is related to a new method for determination of several different biomolecules simultaneously in the same reaction solution. The method uses a fluorescent label for labelling biospecific primary probes and a combination of other labels, bound to secondary probes. Complexes are formed comprising primary probes, analyte molecules and secondary probes in the biospecific reaction. These single molecule complexes are counted selectively while discriminating the signals from other fluorescent molecules using confocal fluorometry or two-photon excitation fluorometry including an auto- and cross-correlator for the signals obtained from said fluorescent labels.

Abstract: Spherically shaped polyvinyl alcohol (PVAL) polymer particles are prepared encapsulating a magnetic colloid that provides the particles with magnetic properties for use in binding biomolecules. The particles have a size of 1-10 &mgr;m that makes them particularly suitable for use in cell separation/sorting, cleaning biosubstances in suspension and diagnostic assays. The particles are prepared by dispersing a magnetic colloid containing a magnetic material such as a ferromagnetic or superparamagnetic substance in an aqueous solution of polyvinyl alcohol containing reactive hydroxyl groups, adding the resultant mixture to an organic phase containing a mixture of at least two emulsifiers, and adding a water-soluble cross-linking agent such as a dialdehyde that reacts with the hydroxyl groups of polyvinyl alcohol to form the polymer particles. The emulsifiers are miscible in the polyvinyl alcohol solution, and at least one emulsifier is semi-hydrophilic and at least one emulsifier is lipophilic.

Abstract: The invention pertains to an electrically conductive copolymer of the general formula I: wherein A is a first polymerizable monomer which produces an electrically conductive polymer when polymerized, and represents a polymerized unit of said monomer A in the electrically conductive polymer; B is a second polymerizable monomer which when copolymerized with monomer A produces an electrically conductive polymer, and represents a polymerized unit of said monomer B in the electrically conductive polymer; w is an integer greater than or equal to 0; x is an integer greater than or equal to 1; y is an integer greater than or equal to 0; z is an integer greater than or equal to I; 11, and 12 are each independently covalent linkers or spacer arms; 13 is substituent group having a desired chemical functionality; and Bt′ is selected from the group consisting of biotin and complexes of biotin with a molecule selected from the group consisting of avidin, streptavidin, derivatives of avidin

Abstract: An immunochromatography-assisted device is disclosed which facilitates accurate and rapid detection of an antigen contained in a fluid sample and from which background coloring and blank coloring possibly causing a malfunction at detection are successfully eliminated. The immunochromatography-assisted device comprises a porous carrier having an additive-impregnated part between a sample introducing part and a determining part, the additive-impregnated part carrying at least one selected from the group consisting of a surfactant, a water-soluble ammonium salt and a pH buffer such that it dissolves in a sample introduced into the carrier in order to move with the movement of the sample through the carrier. The porous carrier also has a labelled part segmented into plural zones.

Abstract: The invention relates to a method for detecting specific target-cells in a simple and time saving way, using paramagnetic particles, antibodies recognizing the Fc portions of target-cell associating antibodies and target-cell associating antibodies directed to specific antigen determinants in the target-cell membranes. Incubation of the cell suspension with a mild detergent and/or second set of antibodies or antibody fragments, prelabeled or not with fluorescent agents, metallocolloids, radioisotopes, biotincomplexes or certain enzymes allowing visualization, with dramatically increase the specificity of the method. The method can further be used for isolation of the target-cells by magnetic field application and kit for performing the method according to the invention is described.

Abstract: The invention relates to an immunoassays, binding assays, solid phase substrates (12) and other devices with an antigen or antibody or ligand or receptor (11) embedded into a solid phase substrate (12). The antigen or antibody is mixed with a molten thermoplastic and formed into the solid phase substrate (12).

Abstract: Oligonucleotides and other biomolecules are immobilized in high density on solid substrates through covalent forces using either a permanent thioether bond, or a chemoselectively reversible disulfide bond to a surface thiol. Substrates which have hydroxyl groups on their surfaces can be first silanized with a trichlorosilane containing 2-20 carbon atoms in its hydrocarbon backbone, terminating in a protected thiol group. The oligonucleotides or other biomolecules are first connected to a tether consisting of a hydrocarbon or polyether chain of 2-20 units in length which terminates in a thiol group. This thiol may be further modified with a halobenzylic-bifunctional water soluble reagent which allows the conjugate to be immobilized onto the surface thiol group by a permanent thioether bond. Alternatively, the oligonucleotide-tether-thiol group can be converted to a pyridyldisulfide functionality which attaches to the surface thiol by a chemoselectively reversible disulfide bond.

Abstract: Solid phase immunoassay for detecting specific inhibitors of proteolytic enzymes in biological fluids, which comprises: a) contacting a tubulin peptide covalently linked to a support with a solution containing a proteolytic activity together with a protease inhibitor, b) detecting the inhibitor activity against the selected proteases by contacting the support with a solution containing a labelled monoclonal antibody which specifically recognises the free end of the tubulin peptide linked to the support.

Abstract: A system and method are disclosed for separating particles having different sedimentation velocities. The system includes a container containing a binding substance including first particles and ligands attached to the first particles. When the binding substance is mixed with a liquid carrying at least second and third particles, the ligands bind the first and second particles together to form groups of bound particles. The groups of bound particles are separated from the third particles in a fluid chamber configured to be mounted on a centrifuge rotor. One of the disclosed methods includes forming a saturated fluidized bed of particles to retain the particles groups in the fluid chamber. Another of the disclosed methods includes removing at least some of the first particles after the binding substance is mixed with the liquid carrying second and third particles.

Abstract: The present invention relates to compounds that are bis-biotins. These compounds comprise two biotinyl radicals connected by a chain of atoms, usually at least 16 atoms in length. The bis-biotin is conjugated to a member of a specific binding pair ("sbp member") wherein the chain is not part of the sbp member. Also disclosed are compositions comprising a complex of avidin and a bis-biotin as described above. The compounds and compositions of the invention find use in an assay for an analyte wherein there is employed a reagent system comprising an avidin reagent and a biotin reagent. The improvement of the present invention comprises using as the biotin reagent a bis-biotin as described above. Also disclosed are kits comprising the present bis-biotins and methods of preparing a bis-biotinylated conjugate of a member of a specific binding pair ("sbp member") for use in a specific binding assay.

Abstract: Devices, processes and compositions are provided for effective separation of cells from a mixture of cells, where depletion or positive selection may be employed to provide a cellular population of interest. Of particular utility is the separation of cells from peripheral blood mononuclear cells, where members of the lymphoid or myeloid lineages may be isolated and used for research, diagnosis or therapy. Also of interest are cellular separation from bone marrow, tumor suspensions or lymphoid tissue suspensions, where cells can be isolated and used for a variety of purposes. The separated cells may be homogeneous, free of exogenous biologicals, viable, capable of replication and exhibit their full complement of biological activities. Multiple phenotypes can be captured simultaneously. Captured cells can be specifically activated with cytokines and antigens to provide cells which are MHC restricted and have antigen-specific effector functions.

Abstract: Disclosed is a high throughput compatible assay that is useful for the identification of specific antagonists of TRAF-receptor interactions. The modular flexibility of the assay makes it possible to introduce simple modifications in order to measure the interaction of any TNF receptor cytoplasmic domain (or TRAF-binding protein) with any of the six TRAF proteins, TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 and TRAF6.

Abstract: An assay for the identification of neutralizing botulinum antibodies in sera is provided which includes the steps of separating non-sodium dodecyl sulfate, non-trypsinized complex botulinum toxin in an arylamide gel by electrophoresis, the separation occurring on a basis of botulinum toxin protein size and charge. Thereafter, the separated protein is electrophoretically transferred onto a solid support, the transferred separated protein being bound to the solid support at spaced apart sites. Remaining sites on the solid support not occupied by bound protein are blocked and the solid support and bound protein are contacted with a sera sample containing an antibody directed against botulinum toxin. The contacted solid support is then exposed to a second antibody capable of reacting to produce an insoluble colored substrate of intensity relative to a quantity of antibodies present. Finally, the second antibody is reacted to produce the insoluble colored substrate which is visually identified.

Abstract: A highly specific surface for biological reactions, which includes a support with at least one essentially compact layer of an organic compound. On the outside of the organic compound layer is an exposed group containing an ethylenic double bond, which has affinity for a molecule with biological activity under certain reaction conditions. The other elements of the organic compound layer are essentially inaccessible to the molecule with biological activity under the reaction conditions.

Abstract: An arrangement for the investigation of hydrophilic macromolecules (1) in an aqueous solution having a solid carrier surface (5) onto which a lipid film (24) is disposed, wherein the molecules (1) to be investigated are bound, by means of a molecular coupling system (20), to the lipid film (24) and thus are immobilized, is characterized in that the molecular coupling system (20) comprises at least two, preferably three molecular or nuclear components (21, 22, 23), which can be coupled to each other, of which a first component (21) is bound to the lipid film (24) and a second component (22) is bound to a hydrophilic macromolecule (1) to be investigated. In this way, it is rendered possible to immobilize and investigate any hydrophilic macromolecules, wherein the coating of the solid carrier surface should be able to be carried out in an as easy as possible and reversible manner.

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 polybifunctional reagent is provided having a polymeric backbone, one or more pendent photoreactive moieties, and two or more pendent bioactive groups. The reagent can be activated to form a bulk material or can be brought into contact with the surface of a previously formed biomaterial and activated to form a coating. The pendent bioactive groups function by promoting the attachment of specific molecules or cells to the bulk material or coated surface. Bioactive groups can include proteins, peptides, carbohydrates, nucleic acids and other molecules that are capable of binding noncovalently to specific and complimentary portions of molecules or cells.

Abstract: Type I collagen degradation products are assayed in a body fluid by conducting a competition immunoassay in which sample molecules compete with a peptide or isomerized peptide in binding to an immunological binding partner for the peptide or isomerized peptide respectively, wherein the peptide or isomerized peptide comprises the amino acids AHDGGR optionally extended at the N-terminal end with one or more amino acids that do not form a contiguous sequence with AHDGGR in type 1 collagen, and wherein D represents aspartic acid or .beta.-aspartic acid. The peptide C(X).sub.n AHDGGR, where X is any amino acid and n is preferably from 4 to 6 is provided for use in such assays and in diagnostic assay kits.

Abstract: Degradation of body proteins such as bone collagen is studied by detecting in body fluids isomerized peptide fragments of said proteins in which peptide bonding to the .alpha.-carboxylic acid group of aspartic acid or asparagine has become isomerized to an amide bond to the side chain carboxylic acid group of aspartic acid. Antibodies specific for the isomerized peptide sequences are used in assays.

Abstract: There are electrically conductive, electroactive functionalized conjugated polymers having formula (I): ##STR1## These electrically conducive, electroactive conjugated polymers may be covalently bonded to a first biological molecule or antiligand. Polymers bonded to a first biological molecule or antiligand may be used to form an electrode and may be used to assay for, detect and/or extract a second biological molecule or ligand.

Abstract: A method of assaying for a ligand in a sample which includes incubating, simultaneously or in any desired sequence,a) the sampleb) a reagent X andc) a reagent Y immobilised on the surface of an optical structure capable of exhibiting surface plasmon resonance,one of reagents X and Y is a specific binding partner to said ligand and the other of reagents X and Y is either a ligand analogue or a specific binding partner to said ligand, reagent X being such, that any formation of a direct or indirect complex between reagents X and Y results in an optical surface having an appreciably enhanced optical thickness as compared to the optical thickness of the optical surface which would prevail in the absence of reagent X,which method includes the step of determining whether and, if desired, the extent to which and/or rate at which the surface plasmon resonance effect exhibited by the optical structure is altered by said complex formation.

Abstract: The invention provides a method for isolating nucleic acid from a sample, said method comprising boiling said sample and allowing it to cool, and condensing the nucleic acid onto a high-surface area solid support, and in particular the use of such a method in the preparation of nucleic acid samples for subsequent amplification. The method has particular utility in the isolation of nucleic acid from aged, fixed or otherwise distressed samples.

Abstract: A method of detecting an antibody in a sample using a labelling compound and comprising the steps of mixing a ligand antigen, antibody or hapten bound to biotin with the sample; an antibody directed against the antibody to be detected bound to paramagnetic particles; and a chemiluminescent acridinium compound bound to avidin or streptavidin to form a solid phase complex; separating the solid phase from the liquid phase; and analyzing the separated solid phase for the presence of chemiluminescent complex.

Abstract: A chemical linking agent is formed of a di- or higher functional photoactivatable compound having at least one group that is charged to improve water solubility, and two or more photoreactive groups (preferably comprising an aryl ketone such as benzophenone) that allow use of the agent in aqueous systems. Charged groups include salts of organic acids such as sulfonate, phosphonate and carboxylate groups, onium groups such as quaternary ammonium, sulfonium and phosphonium groups, and protonated amines. A surface can be coated with a substance such as a synthetic polymer, carbohydrate, protein, lipid, nucleic acid, drug, vitamin, cofactor or dye by forming an aqueous solution of the linking agent and the substance, placing the solution in contact with the surface and activating the photoreactive groups of the linking agent to cross-link the substance to the surface.

Abstract: Methods of detecting antibody to GM1 ganglioside in a sample, comprising covalent linkage of GM1 ganglioside to a solid-phase reactant, are disclosed. The methods of detecting antibody to GM1 ganglioside can be used in methods of diagnosing motor neuropathies, such as multifocal motor neuropathy or immune-mediated motor neuropathy, in an individual. The amount of antibody specific to GM1 ganglioside in a test sample from a individual is measured; a titer of antibody to GM1 ganglioside that is greater than 1,800 is indicative of disease.

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

Abstract: Antibodies against Ins(1,4,5)P.sub.3 were raised by immunizing rabbits with two types of IP.sub.3 -BSA conjugates which were synthesized by covalently coupling Ins(1,4,5)P.sub.3 to the carrier protein via alkyl linkages. The anti-Ins(1,4,5)P.sub.3 antibodies were detected by an ELISA where Ins(1,4,5)P.sub.3 was covalently attached to a microplate well surface. Both antiserum preparations showed specific binding with Ins(1,4,5)P.sub.3. The specificity of these antibodies was enhanced by affinity purification for the antiserum through Ins(1,4,5)P.sub.3 -agarose chromatography. The affinity-purified antibodies have IC.sub.50 values of 12 nM and 73O nM for Ins(1,4,5)P.sub.3 and Ins(1,3,4,5)P.sub.4, respectively. These antibodies showed many properties similar to those of biologically relevant receptors for Ins(1,4,5)P.sub.3.

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

Abstract: A self-addressable, self-assembling microelectronic device is designed and fabricated to actively carry out and control multi-step and multiplex molecular biological reactions in microscopic formats. These reactions include nucleic acid hybridizations, antibody/antigen reactions, diagnostics, and biopolymer synthesis. The device can be fabricated using both microlithographic and micro-machining techniques. The device can electronically control the transport and attachment of specific binding entities to specific micro-locations. The specific binding entities include molecular biological molecules such as nucleic acids and polypeptides. The device can subsequently control the transport and reaction of analytes or reactants at the addressed specific micro-locations. The device is able to concentrate analytes and reactants, remove non-specifically bound molecules, provide stringency control for DNA hybridization reactions, and improve the detection of analytes. The device can be electronically replicated.

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. Conversely, the biomolecule can contain the amine moiety and the 2-aminoalcohol moiety can be 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, and the 2-aminoalcohol moiety is oxidized with a periodate to an aldehyde moiety which reacts with the amine moiety to crosslink the coating.

Abstract: A material is provided for immobilization of biologically active substances which are reactive with a carbodiimide group. The material contains a carbodiimide group-containing polymer supported on a carrier such as a plastic, an inorganic polymer, a metal, a natural polymer or a ceramic. The carbodiimide group-containing polymer has 2 to 100 carbodiimide groups per molecule and a molecular weight of 1,000 to 100,000, and is prepared by carbodiimidization of an organic polyisocyanate in the presence of a catalyst. The polymer may be supported as a film on part or the whole area of the carrier. Biologically active substances that may be immobilized include enzymes, hormones, antibodies, antigens, heptenes, peptides, DNAs and RNAs.

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

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