Abstract: Separation apparatus and method for separating magnetic and/or magnetically-labeled particles from a test medium in a reaction chamber which incorporates baffles, a spinner, a stirrer, or a plunger operable to be displaced along a collection surface to define a narrow flow path through which the particle-laden test medium must flow. The collection surface is a thin-walled non-magnetic material having a plurality of magnetic pole faces positioned therearound. Test medium within a reaction chamber is caused to flow past a collecting surface, and a high-gradient magnetic field is applied to the surface to capture magnetically responsive particles in the test medium. The particles are deflected toward the collection surface in the flow path for the test medium. The narrow flow path assures that substantially all of the particles pass within the high-gradient magnetic field along the collection surface.

Abstract: Methods for solid phase and combinatorial synthesis using a resin activation/capture approach are provided. In particular, methods for the production of dihydropyridones, N-acyidihydropyridones, tetrahydropyridones, pyridines, aminopyridines, N-acyltetrahydropyridines and tetrahydropyridines compounds and libraries containing such compounds are provided. Methods for screening the libraries and compounds and pharmaceutical compositions containing compounds prepared by the methods are provided.

Abstract: Solid substrates and methods for their preparation are provided, where enhanced functionalization of solid substrates is achieved, so that higher levels of binding of a wide variety of moieties can be obtained. The surface is nitrated with a nitronium agent, where the nitro groups may be modified in a variety of ways to serve as sites for linking. The resulting solid substrates find use in therapy, diagnosis and processing.

Abstract: The invention relates to a microfluidic device with microchannels that have separated regions which have a member of a specific binding pair member such as DNA or RNA bound to porous polymer, beads or structures fabricated into the microchannel. The microchannels of the invention are fabricated from plastic and are operatively associated with a fluid propelling component and detector.

Abstract: The present invention relates to a method for binding antibody or antigen molecules to solid phase. The reactive compound comprising an antibody or antigen molecule and a solide phase are formed by coupling a specific antibody or antigen molecule to a solid phase using a two-step reaction. The coupling is covalent, between the active groups of the solid phase and the antibody, a fragment thereof or the antigen molecule, in the presence of an anionic surfactant, after adding an alkaline/solution to raise the pH to the basic region.

Abstract: A method of assaying collagen fragments in body fluids, including bringing a sample of body fluid in contact with at least one immunological binding partner for the collagen fragments, said binding partner being immunoreactive with synthetic peptides, the sequences of which are essentially derived from collagen and containing potential sites for cross-linking. The immunological binding partners are incorporated, either as whole antibodies or as immunologically active fragments thereof, in an assay for quantitative determination of collagen fragments in the sample. In addition to being contacted with the immunological binding partner(s), the sample may be brought into direct contact with the corresponding synthetic peptide. The invention further comprises a test kit and specific means for carrying out the method. The structure of specific peptides is also described.

Abstract: A process for the preparation of polymers having nucleobases as side groups by means of multicomponent reactions, especially the Ugi reaction, is described. Because of the multicomponent nature of preparation, the properties of the polymers can be varied substantially better than has hitherto been possible and can be adapted to requirements for use as an antisense or antigen therapeutic agent or as a diagnostic agent.

Abstract: The present invention relates to a process of coding and identifying individual members of a chemical combinatorial library synthesized on a plurality of solid supports which undergo mix and split synthesis. The process provides for tagging the solid supports with a coding identifier that is attached to the solid support and which can be decoded by infrared or raman spectroscopy when directly attached to the support.

Abstract: An assay device and method are provided which allow the determination of the presence or absence of at least one analyte in a test sample, while providing specific identification of the test subject. The assay device includes a reaction medium having at least one reaction zone and at least one control zone, which is capable of providing a pattern suitable for identifying the test subject. The pattern suitable for identifying the test subject is preferably a fingerprint. In a preferred embodiment of the invention, the reaction zone and the control zone include at least one member of a ligand/receptor pair.

Abstract: A method for isolating molecules, cells and other particles which are specifically bound to a large particle. It includes: 1) incubation of the sample with one or more sets of large particles which are able to specifically bind/capture a large number of molecules, cells or other particles, 2) analysis of each individual large-capturing particle mixed with the sample, and 3) sorting the large particles containing specifically-bound molecules, cells or other particles.

Abstract: A method of allophycocyanin inhibition of enterovirus and influenza virus reproduction resulting in cytopathic effect, with the ingredients utilized including allophycocyanin, wherein a virus and cell culture is first cultivated in an incubator containing a culture medium solution and following cell preparation, the virus suspension of the preparation is quantitatively determined and an antiviral pharmaceutical inhibition concentration determination procedure is utilized for pharmaceutical neutralization experiments, the results indicating that allophycocyanin possesses enterovirus neutralization capability; furthermore, utilizing ingredients including allophycocyanin as the primary ingredient, virus and cells are first cultivated in an incubator containing a culture medium solution and following a virus plaque inhibition assay, the results indicate that allophycocyanin possesses influenza virus reproduction inhibition capability.

Abstract: The invention relates to an immunochemical method for detecting deposit of Bacillus thuringiensis delta-endotoxin or pesticidally-active fragment thereof on a plant or tree. The invention further relates to kits for using such a method.

Abstract: A method of assaying type II collagen fragments in body fluids, including bringing a sample of body fluid in contact with at least one immunological binding partner for the collagen fragments, said binding partner being immunoreactive with synthetic peptides, the sequences of which are essentially derived from collagen and containing potential sites for cross-linking. The immunological binding partners are incorporated, either as whole antibodies or as immunologically active fragments thereof, in an assay for quantitative determination of collagen fragments in the sample. In addition to being contacted with the immunological binding partner(s), the sample may be brought into direct contact with the corresponding synthetic peptide. The invention further comprises a test kit and specific means for carrying out the method. The structure of specific peptides is also described.

Abstract: Mixtures of chemical compounds are provided having antibacterial and other utility. The mixtures are formed, preferably in solution phase, from the reaction of a purine or pyrimiding heterocyclic scaffold with a set of related chemical substituients, optionally through employment of a tether moiety. Libraries formed in accordance with the invention have utility per se and are articles of commerce. They can be used to screen for pesticides, drugs and other biologically active compounds.

Abstract: A method for the detection of substances contained on textile fibers or other natural or synthetic polymers is disclosed. The contained substances are identified with immunochemical methods, where the immunochemical reaction can occur on the fiber or polymer. The method is especially suitable for the determination of substances that can act as allergens.

Abstract: Methods and devices are provided for controlling a fluid flow over a sensing surface within a flow cell The methods employ laminar flow techniques to position a fluid flow over one or more discrete sensing areas on the sensing surface of the flow cell. Such methods permit selective sensitization of the discrete sensing areas, and provide selective contact of the discrete sensing areas with a sample fluid flow. Immobilization of a ligand upon the discrete sensing area, followed by selective contact with an analyte contained within the sample fluid flow, allows analysis by a wide variety of techniques. Sensitized sensing surfaces, and sensor devices and systems are also provided.

Abstract: Disclosed is a sensor for sensing the presence of an analyte component without relying on redox mediators. This sensor includes (a) a plurality of conductive polymer strands each having at least a first end and a second end and each aligned in a substantially common orientation; (b) a plurality of molecular recognition headgroups having an affinity for the analyte component and being attached to the first ends of the conductive polymer strands; and (c) an electrode substrate attached to the conductive polymer strands at the second ends. The electrode substrate is capable of reporting to an electronic circuit reception of mobile charge carriers (electrons or holes) from the conductive polymer strands. The electrode substrate may be a photovoltaic diode. Also disclosed is method of forming a sensor capable of sensing the presence of an analyte component. This method includes (a) contacting a sensor substrate (e.g.

Abstract: Conjugate probes are prepared in a one step process by incubating a macromolecule and a labeling group with an unsaturated polyaldehyde as the conjugating agent. The conjugating agent is capable of bonding virtually any labeling group to a macromolecule. Conjugate probes have been shown to have a high degree of specificity and exhibit a strong signal with minimal background.

Abstract: Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide with an integral semi-cylindrical lens, and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor and assay method have patches of capture molecules each specific for a different analyte disposed adjacent within a single reservoir. The capture molecules are immobilized to the patches on the waveguide surface by site-specific coupling of thiol groups on the capture molecules to photo-affinity crosslinkers which in turn are coupled to the waveguide surface or to a non-specific-binding-resistant coating on the surface. The patches of different antibodies are produced by selectively irradiating a portion of the waveguide surface during the process of coupling the photo-affinity crosslinkers the selective irradiation involving a mask, a laser light source, or the like.

Abstract: Polymer particles are formed containing molecular memory recognition sites and magnetically susceptible components. The particles are prepared by co-polymerizing one or more monomers and a cross-linking agent in the presence of at least one imprint molecule and at least one magnetically susceptible component such as iron oxide or nickel oxide, and removing the imprint molecule to form molecular memory recognition sites. The particles are also prepared by co-polymerizing the monomer and cross-linking agent in the presence of the imprint molecule to produce particles, removing the imprint molecule and associating magnetically susceptible components with the particles. The particles may also be prepared containing selective adsorbents such as cells or antibodies. The particles are used for selective adsorption of a product such as separating and resolving two different enantiomeric forms due to one of the forms adsorbing to a memory recognition site created by using the form as an imprint molecule.

Abstract: Combinations of HCV antigens that have a broader range of immunological reactivity than any single HCV antigen. The combinations consist of an antigen from the C domain of the HCV polyprotein, and at least one additional HCV antigen from either the NS3 domain, the NS4 domain, the S domain, or the NS5 domain, and are in the form of a fusion protein, a simple physical mixture, or the individual antigens commonly bound to a solid matrix.

Abstract: The invention provides methods for preparing a reaction substrate for use as assay devices comprising parallel printing of arrays of biosites on reaction substrates, wherein each biosite comprises a single type of capture probe bound to the reaction substrate and the array of biosites is deposited on the reaction substrate by a capillary bundle printer device.

Abstract: A method of making a molecularly imprinted porous structure makes use of a surfactant analog of the molecule to be imprinted that has the imprint molecule portion serving as the surfactant headgroup. The surfactant analog is allowed to self-assemble in a mixture to create at least one supramolecular structure having exposed imprint groups. The imprinted porous structure is formed by adding reactive monomers to the mixture and allowing the monomers to polymerize, with the supramolecular structure serving as a template. The resulting solid structure has a shape that is complementary to the shape of the supramolecular structure and has cavities that are the mirror image of the imprint group. Similarly, molecularly imprinted particles may be made by using the surfactant to create a water-in-oil microemulsion wherein the imprint groups are exposed to the water phase.

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 the 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: The invention relates to an assay system for the improved detection of analytes, and the ability to distinguish them from cross-reacting substances. Samples giving a positive reaction in a direct assay test are treated with a neutralizing antibody that inhibits reactivity of the true analyte, but not the interfering substance. In adsorption type confirmatory assays, the neutralizing antibody is provided in an amount sufficient to adsorb the analyte but not all of the interfering substance. When retested in an immunoassay, the neutralized sample gives a negative result if it originally contained the true analyte. Samples giving a positive reaction in both the direct and confirmatory tests are marked as containing an interfering substance. The confirmatory assay easily distinguishes the true analyte and reduces the rate of false positives, even when the interfering substance is unknown and present at high concentration.

Abstract: A method for assaying bone resorption rates which consists of quantitating the concentration of peptide fragments derived from bone collagen, found in a body fluid is disclosed. The method includes immunometric assay, fluorometric assay and electrochemical titration. The structure of specific peptide fragments having 3-hydroxypyridinium cross-links found in urine of Paget's disease patients and procedures for making monoclonal antibodies is described.

Abstract: A slide having a portion thereof provided with transparent adhesive which adheres to a test sample. The slide and adhesive may be transparent. Specific types of infection and particularly fungal infections can be detected in the test sample using immunotest-methods. In a special embodiment the adhesive slide is fashioned with a peripheral lip or well to contain a test sample and a reagent.

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: The present invention relates to methods and compositions for the direct detection of analytes using observable spectral changes in biopolymeric systems. In particular, the present invention allows for the direct colorimetric detection of analytes using color changes that occur in glycopolythiophene polymer systems in response to selective binding of analytes.

Abstract: The present invention concerns a method for separating at least one species of biological entities from a sample solution, by contacting the sample with a matrix of magnetic particles formed on a substrate such as a sheet a gel, etc. The particles in the matrix are coupled to entities capable of specifically binding to the species of biological entities to be separated. The separation is carried out either for detection purposes for obtaining separately each species of biological entities or for synthesis purposes. The invention further concerns matrices of magnetic particles formed on various substrates and kits for use in the method.

Abstract: The present invention relates to a method for detecting a substance having an activity to inhibit HIV infection rapidly, economically and safely. The present invention uses the characteristics that if a function of transmembrane protein gp41 of HIV is inhibited, HIV infection is also inhibited, and therefore the function of gp41 depends on the interaction between two helical structures of gp41. The method of the present invention is to detect a substance to inhibit HIV infection by an immunoassay using the interaction between the variant protein Trx-N, which is prepared by binding the N-terminal helical domain of gp41 to Trx (thioredoxin) and the variant protein GST-C, which is prepared by binding the C-terminal helical domain of gp41 with GST-C (Glutathione S-transferase). This immunoassay can be used for automatic detection of the substance to inhibit the activity of gp41 can be carried out by the method.

Abstract: The present invention provides internally calibrated competitive assays for use on a solid support. Additionally, the invention provides a method of using such assays.

Abstract: Non-invasive methods are provided for obtaining biological samples of mammary fluid or mammary fluid components by administering oxytocin to a patient to stimulate expression of mammary fluid. During or after mammary fluid expression, a biological sample is collected in the form of whole mammary fluid, whole cells or cellular components, other selected liquid or solid fractions of the mammary fluid, purified or bulk proteins, glycoproteins, peptides, nucleotides or other desired Constituents of mammary fluid. Methods and kits are also provided for determining the presence or amount of a breast disease marker in biological samples of mammary fluid or mammary fluid components obtained according to the above sample collection methods. Also provided within the invention are novel breast pump and breast pump adapter devices which incorporate a solid phase sample collection medium integrated within the breast pump or adapter or otherwise fluidly connected therewith.

Abstract: The present invention involves an optical assay device and method of use for the detection of an analyte of interest in a sample that conveniently allows control of the flow characteristics of the sample through the device without significant user intervention. The optical assay device includes a base having an absorbent material, and a member having an optically active test stack that is rotatably coupled to the base for rotation between a lowered position and a raised position. In the lowered position, the optically active test stack contacts the absorbent material for drawing the sample through the surface. In the raised position, the optically active test stack does not contact the absorbent material.

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: An improved multi-layered diagnostic sanitary test strip for receiving a heterogenous fluid, such as whole blood, to test for presence and/or amount of a suspected analyte in the fluid by facilitating a color change in the strip corresponding to the amount of the analyte in the fluid, wherein the test strip includes fluid volume control dams to prevent spillage of the fluid from the strip and a chemical reagent solution that facilitates end-point testing. The improved test strip comprises (a) an upper support strip having a fluid receiving port and (b) a lower support strip having a color change viewing port and securely sandwiched therebetween (c) a spreading mesh screen for uniformly distributing the fluid, (d) a chemically treated separating layer for removing an undesirable element, e.g.

Abstract: The invention relates to methods and test kits for diagnosis of periodontal disease activity in mammals, especially in human. The methods of the invention provide for rapid chair-side diagnosis of periodontitis, peri-implantitis and HIV (+)-infection/AIDS-disease related periodontal diseases. Especially, the methods of the invention provide for rapid chair-side diagnosis of the loss of bone density associated with periodontal diseases.

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: An electrochemical affinity assay system for detection of ligand—ligand receptor binding.

Abstract: An optical assaying method and system having a movable sensor is described. In one aspect, the present invention is a sensing system having a rotating sensor disk coated with indicator dyes sensitized to a variety of substances. In this configuration the sensing system further includes a detector for sensing spectral changes in light received from one or more of the indicator dyes. In another aspect, the present invention is a sensing system having a surface plasmon resonance sensor disk having grooves extending radially from a center of the disk. In yet another aspect, the present invention is a sensing system including a diffraction anomaly sensor disk having a dielectric layer that varies in thickness. The present invention allows for construction of an inexpensive sensing system that is capable of easily detecting a variety of substances either in a sample or a surrounding environment.

Abstract: The present invention relates to a process of coding and identifying individual members of a chemical combinatorial library synthesized on a plurality of solid supports which undergo mix and split synthesis. The process provides for tagging the solid supports with a coding identifier that is attached to the solid support and which can be decoded by infrared or raman spectroscopy when directly attached to the support.

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: The present invention refers to a method that allows the use of filamentous bacteriophages to detect the presence of molecules of interest in biological samples. It consists of a series of combined operations, which are drawn up and defined according to the characteristics of the phages employed. These have, exposed on the surfaces of the capsid, at least one molecule, generally but not exclusively of proteic nature, capable of binding at least one molecule of interest present in the biological sample. Detection of the presence of the molecule takes place, according to the method of the invention, using the association between the molecule exposed on the surfaces of the phage and the genome of the phage itself. The ability to form specific complexes typical of the molecule exposed on the capsid enables formation of phage-molecule of interest complexes, which can be detected by means of amplification of known sequences in the phage DNA.

Abstract: Analytical test kits and assay procedure employs test cards or strips of an inert plastic carrier having a flat, non-absorbent surface, containing thereon spots of insolubilized reagent for the determination of an analyte, such as an antigen or an antibody, in a liquid medium such as serum or other body fluids in a solid phase enzyme immunoassay of the sandwich type. Different binding partners can be placed as separate spots on the same card for the assay of a group of related or unrelated analytes in the same test sample. An insoluble colored product on a spot, qualitatively and quantitatively, is indicative of a positive result.

Abstract: A hand held, self-contained, automatic, low power and rapid sensor platform for detecting and quantifying a plurality of analytes. A sample solution potentially containing an unknown amount of an analyte is passed through an affinity column which contains antibodies to which the analyte binds thereby extracting the analyte. The affinity column is then rinsed to remove any other chemicals that may fluoresce. The rinsed affinity column is then eluted with a known volume of elution fluid causing the analyte to release from the antibody and dissolve in the fluid (eluant). The eluant is then placed in the quartz cuvette of a fluorometer. The analyte suspended in the eluant fluoresces at a waveband which is different than that of the light source that excites it. The amount of fluorescence is measured and the level of analyte determined.

Abstract: An indirect agglutination immunoassay includes the steps of providing, in a container, an immunoassay system comprising a test sample containing a desired analyte, and a reagent composed of magnetic particles or magnetic-material containing particles containing iron therein, wherein the magnetic particles or magnetic-material containing particles have been sensitized to allow specific binding to the desired analyte, and have a particle size in the range of 1 to 5 &mgr;m, with the content of the iron being in the range of 8 to 20 wt. %, precipitating the magnetic particles or magnetic-material containing particles by the application of magnetic force, allowing the container to stand at an inclination, and detecting the presence or absence of an immune reaction from the absence or presence of slippage observed of the precipitated magnetic particles or magnetic-material containing particles on the bottom of the container.

Abstract: The present invention relates to a method of carrying out an immunoassay in a multiphase system. A sample containing an analyte is brought into contact with a receptor A and a tracer. The analyte can either form a complex with the tracer, or counteract the formation of a complex of receptor A and tracer by competing with the tracer for binding to receptor A, or counteract the formation of a complex of receptor A and tracer by competing with receptor A. Receptor B is added and the signal is determined. In this method, receptor A and receptor B are suitably immobilized, ensuring that the tracer either cannot enter into any binding involving the simultaneous participation of receptors A and B or can enter into such a binding to only such a slight extent that it is nevertheless possible to detect and differentiate differing analyte concentrations.

Abstract: An assay plate for detecting the presence of a mobile reactant that binds to a immobilized reactant and the methods of making and using the same. An assay plate according to the present invention includes a substrate and at least one dried aliquot of the immobilized reactant, the immobilized reactant being bound to the surface of the substrate. The immobilized reactant binds the mobile reactant when a solution containing the mobile reactant is brought into contact with the immobilized reactant. The mobile and immobilized reactants may be any pair of biological compounds that have a specific affinity for one another For example the reactants may be nucleic acids or antibody-antigen pairs.

Abstract: The invention describes the 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: A method and apparatus for the manipulation of colloidal particles and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations.