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: Small particles of polymeric material are produced by expansion of a mixture of monomers and a propellant. The size and shape of the particles can be precisely tailored by materials selection and expansion conditions. Particles of 10 nanometers to 100 microns can be produced. If monomers exhibiting solid state reactivity are utilized, the particles thus formed can be polymerized at any time after formation. The particles produced by this method can be molecularly imprinted by incorporating a template into the particle prior to fully curing the particle, in a manner which allows selective extraction of the template from the cured particle after formation without deformation of the imprint site. A two step polymerization process allows the particles to be deposited on and adhered to a wide variety of substrates without additional agents.

Abstract: Conjugates of a biodegradable aliphatic polyester-based polymer with Tat49-57 peptide or a peptide chain containing the Tat49-57 peptide, and nanoparticles manufactured using the same. Intracellular permeability of the Tat49-57 peptide can be enhanced by exposing Tat peptide moieties to the surface of the nanoparticles.

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: A combinatorial library comprises a plurality of ligand-bearing support units, where the ligand-bearing support units comprise (a) a solid carrier, (b) one or more ligands covalently bound to the solid carrier, and (c) one or more encoding metal salts impregnated on the support unit, where the distribution of the cations of the encoding metal salts provides a code for identifying the ligand or ligands that are attached to the support units, and the cations have been stabilized against dissolution by treatment with one or more anions that form insoluble or poorly soluble salts of the cations.

Abstract: A system for the rapid characterization of multi-analyte fluids, in one embodiment, includes a light source, a sensor array, and a detector. The sensor array is formed from a supporting member into which a plurality of cavities may be formed. A series of chemically sensitive particles are, in one embodiment positioned within the cavities. The particles may be configured to produce a signal when a receptor coupled to the particle interacts with the analyte. Using pattern recognition techniques, the analytes within a multi-analyte fluid may be characterized.

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: New protein coated surfaces, which have a high capacity for capturing target molecules, thus yielding assays with enhanced sensitivity, are disclosed. Surfaces prepared according to the present invention contain a coating consisting essentially of streptavidin, avidin or “NeutrAvidin” in polymeric form, wherein polymerization has been controlled to an extent such that the polymer is predominantly dimers, trimers and tetramers of the native molecule.

Abstract: A hapten-polymer carrier complex was found to be useful for immunoassay purposes, specifically ELISAs, for the detection of pesticides and their degradation products in hydrosoil and ground water. The degradation products of Casoron G® (also known as dichlorobenzonitrile and dichlorbenil) and Prefix® (also known as chlorthiamid and dichlorobenzthiamide) are analytes detected with high specificity and sensitivity, particularly the degradation product BAM (2,6-dichlorobenzamide). The polymer carrier complex is bound to the hapten via a linker unit, strategically positioned meta to the amide or amide derivative of BAM.

Abstract: A covalent conjugate of a 4′-hydroxyazobenzene-2-carboxylic acid derivative (HABA) and an avidin-type molecule, of the formula: wherein A is (CH2)n or —CH═CH—, wherein n is an integer from 0-10; B is (CH2)n wherein n is an integer from 2 to 10; m is zero or 1; and Av is the residue of an avidin-type molecule selected from the group comprising native egg-white avidin, recombinant avidin, deglycosylated avidins, bacterial streptavidin, recombinant streptavidin, truncated streptavidin and other derivatives of said avidin-type molecules. These HABAylated avidins are red colored in the quinone configuration and can be used in many applications in the avidin-biotin technology.

Abstract: Arrays of flowable or fixed particle sets are used in microfluidic systems for performing assays and modifying hydrodynamic flow. Also provided are assays utilizing flowable or fixed particle sets within a microfluidic system, as well as kits, apparatus and integrated systems comprising arrays and array members.

Abstract: An improved method of making a series of bead or microsphere or particle populations characterized by subtle variation in a proportion or ratio of at least two fluorescent dyes distributed within a single bead of each population is provided. These beads, when excited by a single excitation light source are capable of giving off several fluorescent signals simultaneously. A set containing as many as 64 distinct populations of multicolored, fluorescent beads is provided and when combined with analytical reagents bound to the surface of such beads is extremely useful for multiplexed analysis of a plurality of analytes in a single sample. Thus, methods of staining polymeric particles, the particles themselves, and methods of using such particles are claimed.

Abstract: Protein arrays for the parallel, in vitro screening of biomolecular activity are provided. Methods of using the protein arrays are also disclosed. On the arrays, a plurality of different proteins, such as different members of a single protein family, are immobilized on one or more organic thinfilms on the substrate surface. The protein arrays are particularly useful in drug development, proteomics, and clinical diagnostics.

Abstract: A process of producing particles for diagnostic reagent, including a step of polymerizing a polymerizable monomer in the presence of a matrix particle having a magnetic substance layer containing at least one of Fe2O3 and Fe3O4 on the surface thereof and having a mean particle size of 0.4-200 &mgr;m to form a polymer layer on the magnetic substance layer.

Abstract: An assay element for analyzing a charged analyte employs an immobilized receptor and a material having a net charge which is the same as that of the analyte. In a preferred embodiment, the analyte is an aminoglycoside and the material is a polymer having a net positive charge.

Abstract: Polymeric hollow particles for delivery of an agent are provided that change permeability in response to a change in an external stimulus such as pH, temperature, light, ionic strength, electric field, magnetic field and/or solvent composition. The particles can have a shell formed of an amphiphilic triblock ABA or BAB copolymer, where A is a hydrophilic block and B is a hydrophobic block. Low permeability particles with a reversibly permeable shell expand and increase permeability in response to a stimulus so that an active agent such as a therapeutic, prophylactic or diagnostic agent can be introduced. Removing the stimulus allows the particles to return to a low permeability state to form particles loaded with the active agent. Surfaces of the particles can be modified with specific ligands that allow the particles to be directed to a specific target via molecular recognition.

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: Electrokinetic devices having a computer for correcting for electrokinetic effects are provided. Methods of correcting for electrokinetic effects by establishing the velocity of reactants and products in a reaction in electrokinetic microfluidic devices are also provided. These microfluidic devices can have substrates with channels, depressions, and/or wells for moving, mixing and monitoring precise amounts of analyte fluids.

Abstract: A biosensor based on complexes between biomolecule receptors and colloidal Au nanoparticles, and more specifically, colloid layers of receptor/Au complexes that can be used to detect biomolecule analytes through measuring of binding-induced changes in electrical resistance or surface plasmon resonance. Also disclosed is a method for detecting and analysing carrier-borne chemical compounds with Raman spectroscopy using an improved SERS substrate. Further disclosed is an improved method for detecting compounds in solvents using capillary electrophoresis in conjunction with Raman spectroscopy.

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: Compositions and methods are disclosed for detecting multiple target analytes in a sample using microparticles having molecular tags attached by cleavable linkages. Generally, an assay mixture is formed comprising a sample and a reagent comprising multiple such microparticles under conditions that permit stable complexes to form between binding moieties on the surfaces of the microparticles and the analytes. In one aspect of the invention, the a second binding composition is added so that complexes form among the microparticle-bound binding moieties, the analytes, and second binding moieties of the second binding composition. Such second binding moieties have cleavage-inducing moieties attached that upon activation cause the cleavage of the cleavable linkages and the release of molecular tags. Released molecular tags are separated and the presence and/or amount of the target analytes are determined based on the analysis of the released and separated molecular tags.

Abstract: The invention relates to methods, kits and systems for determining an analyte in a liquid sample as well as the use thereof for concentration analysis and screening purposes. In one method, a specific binding partner to the analyte is permitted to compete with a conjugate containing the analyte or an analyte analogue for the binding to free analyte. The conjugate also contains a component that specifically binds to a solid support so that reacted and unreacted conjugate are bound thereto when the reaction solution is contacted with the solid support. The amount of analyte is then determined by measuring by a label-free mass-detection technique, such as surface plasmon resonance, the amount of binding partner immobilized on the solid support via the reacted conjugate. This is made possible by the binding partner having a considerably greater mass than the conjugate. Variants of this method are also disclosed.

Abstract: A method for producing a derivatized aldehydic support matrix material includes activating surface hydroxyl groups on the support matrix material and reacting the activated hydroxyl groups with an aldehydic alkoxy silane. The derivatized aldehydic support matrix material produced is useful for immobilizing bio-molecules in biological applications.

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: Methods for the parallel, in vitro screening of biomolecular activity using miniaturized microfabricated devices are provided. The biomolecules that can be immobilized on the surface of the devices of the present invention include proteins, polypeptides, nucleic acids, polysaccharides, phospholipids, and related unnatural plyomers of biological relevance. These devices are useful in high-throughput drug screening and clinical diagnostics and are preferably used for the parallel screening of families of related proteins.

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: A particle-enhanced assay for determining an analyte in a test sample in which an additive for reducing non-specific particle aggregation is added in an amount to substantially reduce non-specific aggregation.

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

Abstract: A combinatorial chemistry system allows for the dual processing of different molecules coated on a library of beads. The system includes beads coated with different molecules on each bead, a bead holder, screening equipment and characterization equipment. Molecules on the beads are both screened and characterized simultaneously.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.

Abstract: This invention relates methods for conditioning affinity chromatography resins to decrease leaching of the ligand during purification. The methods involve incubating the resin in a buffered solution of a hydroxyalkylamine compound (e.g., ethanolamine) prior to use of the resin for an affinity purification. The treatment removes unstably bound ligand from the resin.

Abstract: Disclosed are novel protein and peptide compositions comprising soluble and bound forms of immunologically-active blood group antigens including mammalian Rh antigens. In preferred embodiments methods for the isolation and purification of serologically-active human Rh antigens such as D, c, C, E, and e are disclosed. Also disclosed are methods for the adsorption of immunologically-active Rh antigens to solid supports. Diagnostic kits, methods, and devices for the detection of Rh antibodies in clinical and non-clinical samples are also disclosed. Devices, compositions and methods for the isolation, purification and quantitation of anti-Rh antibodies from solution are also provided.

Abstract: Disclosed are devices for detecting the presence of a preselected analyte in a fluid sample. The devices comprise a substrate microfabricated to define a sample inlet port, and a mesoscale flow system that includes a sample flow channel extending from the inlet port. The mesoscale flow system further includes an analyte detection region in fluid communication with the flow channel comprised of a binding moiety for specifically binding the analyte. The detection region is constructed with a mesoscale dimension sufficiently small to enhance binding of the binding moiety and the analyte. The binding moiety may be immobilized in the detection region. The mesoscale detection systems of the invention may be used in a wide range of applications, including the detection of cells or macromolecules, or for monitoring reactions or cell culture growth.

Abstract: A particle for a diagnostic agent, which comprises a polymer particle comprising (A) from 20 to 100% by weight of a structural unit derived from at least one of acrylate having an aliphatic hydrocarbon group and methacrylate having an aliphatic hydrocarbon group, (B) from 0 to 10% by weight of a structural unit derived from unsaturated carboxylic acid, and (C) from 0 to 80% by weight of a structural unit derived from a vinyl monomer copolymerizable with the acrylate, methacrylate and unsaturated carboxylic acid, and a turbidmetric immunoassay using the same.

Abstract: A novel HIV type O immunodeficiency virus is disclosed which has the designation MVP-2901/94 and which has been deposited with the European Collection of Animal Cell Cultures (ECACC) under No. V 950121601. The characteristic antigens which can be obtained from the virus and which can be employed for detecting antibodies against retroviruses which are associated with immunodeficiency diseases are also disclosed, as are the partial DNA and amino acid sequences of the virus.

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: Described herein is an ELISA based assay for the detection of HCV infection. This new assay can detect HCV infection earlier than the currently used assays for the screening of blood for HCV infection by using a combination of HCV antigens and anti-core antibodies to capture HCV.

Abstract: A selective adsorption material, especially suitable for adsorption of biological macromolecules, is described. The, adsorption material comprises a matrix with immobilised ligands, localised to selectively adsorb a predetermined molecule. A process for preparing a selective adsorption material, especially suitable for adsorption of biological macromolecules, is also described. The process is characterised in that a print molecule having at least two separate binding sites is bonded to the corresponding, at least two immobilisable ligands, the ligands are immobilised, and subsequently the print molecule is removed. The selective adsorption material can be used for purification or analysis, especially of biological macromolecules.

Abstract: Compositions and methods of use thereof for capture and detection of selected molecules are described. In one embodiment, a first composition includes a ligand component, such as an antibody coupled to a nucleic acid component. An a preferred embodiment, the nucleic acid is labeled with a fluorescent marker to facilitate detection. Another aspect of the invention is the ligand component bound to a solid support via a complementary nucleic acid component and a linker moiety. The method involves binding the target with the first composition in free solution, then binding the target to the solid support by means of both DNA hybridization and antibody-antigen affinity binding. Unbound molecules are washed away, and then the bound targets are detected by fluorescence detection. Vital stains can also be used to detect viable cells.

Abstract: A method is provided for preparing an active slide, including introducing a monomer containing an aldehyde group, or a mixture of a monomer containing an aldehyde group and an acidic functional group provider into a plasma chamber; and depositing the aldehyde group and acidic functional group onto the surface of an organic or inorganic matrix using plasma deposition to form a slide comprising a layer of polymerized actively functional groups thereon. The aldehyde groups and negatively charged groups are deposited on the surface of the active slide, such that the bio-molecules bound thereto possess the properties of an inducible orientation and thus form a mono-layer.

Abstract: A chromatographic assay device according to the present invention provides a unidirectional immunoassay for an analyte in a whole blood sample with improved sensitivity and freedom from interference.

Abstract: A rapid, simple, and inexpensive sandwich enzyme-linked receptor based immunodot assay detects pathogens or pathogenic products in test samples using receptors for a characteristic component of the pathogen. This assay is widely applicable because it is highly specific, it does not require special equipment, and the results can be obtained within a few hours with the naked eye. Since the lipid-based receptors have a long-shelf life, they can be easily stored and used for a long time.

Abstract: Electrokinetic devices having a computer for correcting for electrokinetic effects are provided. Methods of correcting for electrokinetic effects by establishing the velocity of reactants and products in a reaction in electrokinetic microfluidic devices are also provided. These microfluidic devices can have substrates with channels, depressions, and/or wells for moving, mixing and monitoring precise amounts of analyte fluids.

Abstract: A method and apparatus for the manipulation of colloidal particulates 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.

Abstract: A polybifunctional reagent is provided having a polymeric backbone, one or more pendent latent reactive (preferably 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: Biological materials in a mixture of substances are separated, detected or quantified using magnetic spherically shaped cross-linked polyvinyl alcohol (PVAL) polymer particles ranging in size from 1 to 10 &mgr;m. The particles containing a coupled ligand are used to bind a biological material in a mixture of substances, and the particles containing bound biological material are isolated from the mixture. 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.

Abstract: An improved method for detecting antibodies is disclosed. The method employs a recombinant denatured bacterial enzyme. The invention also relates to a test kit useful for performing an immunoassay which comprises a container containing a denatured recombinant bacterial enzyme.

Abstract: Disclosed is a method for fabricating biosensors, using hydrophilic polyurethane. Bio-active reagents, including enzymes, antibodies, antigens, cells and receptors, are mixed with hydrophilic polyurethane and the mixture is directly coated over a signal transducer to form a sensing film which serves as a signal detector. The method using hydrophilic polyurethane allows the simplification of the fabrication of biosensors without conducting complicated chemical reactions and washing steps, such as crosslinking. The bio-active reagent entrapped within the hydrophilic polyurethane film can retains its high activity for an extended period of time and the intrinsic potentiometric response of the underlying ion-selective polymeric membrane is not affected by the bio-active reagent immobilized polyurethane film coated on its sensing surface. Therefore, the biosensors are superior in specificity, selectivity, and stability.

Abstract: A combinatorial chemistry bead that includes an electromagnetic spectral emitter that radiates a distinct electromagnetic code for each bead that uniquely identifies each bead, a terminal apparatus for receiving the electromagnetic code from each bead, and a method for performing combinatorial synthesis using a bead that transmits a distinct electromagnetic code. The invention includes a large number of spectrally narrowed light emitting mechanisms for generating distinct optical codes.

Abstract: A system and method for removing contaminants from a surface. The system is designed to use particles having means thereon which are capable of selectively binding to a contaminant or contaminants of interest. The particles are applied to the surface whereupon the contaminants bind to the particle. When the particle is removed, the desired contaminants are also removed. Preferably, the present invention utilizes magnetic particles having iron therein. The particles may then be readily removed using magnets. The means for binding the contaminant to the particle preferably comprise a ligand or a charge specifically designed to remove the contaminant of interest. The particles may be included in a carrier to facilitate their application to the surface. The invention is especially useful for the removal of contaminants from skin.