Abstract: Combinatorial libraries are disclosed which are represented by Formula I:(T'--L).sub.q --S--C(O)--L'--II' Iwherein:S is a solid support; T'--L-- is an identifier residue; and --L'--II' is a ligand/linker residue. These libraries contain dihydrobenzopyrans of the formula: ##STR1## which interact (i.e., as agonists or antagonists) with .alpha. adrenergic receptors, dopamine receptors, .sigma.-opiate receptors, and K.sup.+ channels and are inhibitors of carbonic anhydrase isozymes. They are useful in the treatment of ocular diseases such as glaucoma.

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

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

Abstract: An agglutination immunoassay method and apparatus therefor in which there are conducted the steps of contacting, in a container, a test sample suspected of containing a desired analyte and a reagent comprising sensitized magnetic-material containing particles capable of reacting with and binding to a desired analyte; precipitating the particles on the bottom of the container by the application of magnetic force; allowing the container to stand at an inclination so as to cause the particles to flow along the bottom of the container to form a developed pattern of the particles; obtaining a representative length of the developed pattern of the particles by an imaging device; and detecting the presence or absence of an immune reaction from the representative length of the pattern of the particles which has flowed from the bottom of the container, thereby detecting the presence or absence of the desired analyte in the test sample.

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

Abstract: The present invention is an optical sensor apparatus for far-field viewing and imaging as well as for the optical detection and analytical measurement of at least one species of analyte in a remotely-positioned fluid sample. The apparatus employs an imaging fiber comprising a fiber optic array and a Gradient Index lens; and utilizes a remotely-positioned solid substrate having light energy absorbing indicator ligands on an external surface for reactive contact with individual species of analytes when present in a fluid sample. The optical sensor apparatus is able to view an object and provide an image of the object located at a pre-set optical distance remote from the imaging fiber. The apparatus is also able to detect and identify, qualitatively and quantitatively, one or more analytes of interest in a flowing solid, gaseous, or liquid sample at remote locations distanced from the imaging fiber itself.

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

Abstract: The invention relates to a glycosylated particle of latex or of inorganic oxide, exhibiting functional radicals at the surface. At least a proportion of said functional radicals is joined to a glycosyl residue.The particles preferably consist either of polymers obtained by polymerization of ethylenically unsaturated monomers or of silica.The invention finds an application as a detection agent in biology.

Abstract: An optical measurement apparatus includes a reaction vessel 2 which is formed in one body with a slab-type optical waveguide 1, and the apparatus adds fine-grains or water soluble dye for absorbing a fluorescent light which is radiated from fluorescent dye, and/or an exciting light so that stray light due to reagent is reduced and the S/N ratio of the optical measurement is improved.

Abstract: An assembly for use in biological assays containing an integral ceramic core and, partially abutting the core, a sheath. The ceramic core has a mean pore size of from about 1 to about 400 microns, an apparent porosity of from, about 25 to about 60 percent, a hydrophilic surface, a length of from about 10 to about 200 millimeters, and a wicking rate of at least about 20 millimeters per minute; the sheath has a wicking rate of less than 5 millimeters per minute.

Abstract: A method for detecting immunogenic responses to native macromolecules. The native macromolecule is bound to a biomaterial or pharmacologic support surface and used in an immunoassay to screen biological fluids for antibodies to the macromolecule in its bound state. The method is used to screen for immune responses to implanted biomaterials and pharmacologically administered agents where native macromolecules which have interacted with the implant are conformationally altered and elicit an immune response.

Abstract: A device and method for its use in diagnostic assays are provided. The device comprises at least one assay path, where an assay path includes a main flow path and at least one side reagent channel. The main flow path begins at a sample addition port, continues through a main reagent area into an incubation area and ends in a waste area. In fluid communication with the main flow path is at least one side reagent channel that begins at a liquid addition port, continues through a side reagent area and ends in said main channel at a region between the main reagent and waste areas, usually upstream from the incubation area. Agitation means may be included in at least one of the main and side reagent areas and/or the incubation area. At least one fluid interruption means located at various positions along the main and side reagent channels upstream from the incubation area provide for control over reagent interaction and fluid flow through the device.

Abstract: A test kit and method for the highly sensitive detection of specific analytes in a sample is provided. The presence of the analyte in the sample results in a decrease in the concentration of a growth inhibiting substance leading to proliferation of cells in the region of the analyte. The presence or absence of the analyte is determined by detecting the presence of increased numbers of cells. Assay sensitivity is accounted for by the exponential amplification of cell number that occurs during cell proliferation in the presence of analyte.

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

Abstract: Simplicity, sensitivity and versatility of optical sensors based on competitive immunoassays using antibody-antigen reactions are achieved by solid-state, single-step reactions which permit accurate sensitive qualitative and quantitative information to be obtained without human participation. All of the chemistry-biochemistry is an inherent part of the sensor. A direct reaction occurs when the sample (antigen) is brought in contact with the sensor. The sensitivity of the competitive immunoassay optical sensor is controlled and increased by selecting a tag for the antigen or altering the attachment of a tag to an antigen so that the binding of tagged antigen to an antibody is decreased relative to the binding of untagged antigen to the antibody. The user can vary size, molecular weight and geometric configuration of the tagged antigen.

Abstract: A method is provided for preparing a low density porous rigid fused-fiber matrix having a density of between about 3.5 and 5.5 pounds/cubic foot and a free volume of between about 90-98 volume percent for use as a cell-culture substrate or implant material, or in chromatographic separation of blood cells. The method is carried out by forming a slurry containing (I) silica, alumina or silica and alumina fibers having thicknesses between about 0.5 and 20 .mu.m and lengths between about 1 and 10 mm, and having a fiber:liquid weight ratio of between about 1:25 to 1:70, (ii) a thickening agent to give the slurry a viscosity between about 1,000 and 25,000 centipoise, (iii) boron nitride particles between about 2-12 percent by weight of the total fiber weight, and (iv) a dispersing agent when the slurry contains silica fibers, allowing the slurry to settle in a mold to produce a fiber block, drying the fiber block, and heating the dried fiber block to at least about 2200.degree. F.

Abstract: A method and apparatus for immunoassays utilizes an improved collection technique of fluorescence induced emissions at the solid phase/liquid phase interface from surface plasmon resonance sensing devices. In a preferred embodiment, a solid phase substrate is coated with a thin film of a conducting material on which a first specific binding partner is directly or indirectly immobilized. The coated solid phase substrate is incubated with a liquid component comprised of a biological sample containing a specific ligand or analyte and a fluorescent labeled second specific binding partner in the case of immunometric assays, or a fluorescent labeled ligand or analog thereof in the case of competitive assays.

Abstract: An optical trap is used to translate a particle through a thin film coating on an optically-flat surface. Preferably, the thin film coating is heterogeneous and the optical trap is used to move the particle through a succession of different regions of the thin film coating where different chemical, biochemical and/or biological processes take place. Examples of chemical, biochemical and/or biological processes that might be implemented in accordance with the invention include the following: oligonucleotide synthesis and sequencing, peptide synthesis and sequencing, carbohydrate synthesis and sequencing, combinatorial library synthesis and screening, conventional (i.e., Sanger or Maxam-Gilbert) DNA sequengcing, or single-molecule DNA sequencing. In one embodiment of the invention, reaction products are left behind as the particle is moved through the thin film coating. Advantageously, these products can be identified by suitable means.

Abstract: O-nitrobenzyl analogs that include a photoremovable protecting group that resists the nonspecific adsorption of biomolecules and a linking group for attaching the o-nitrobenzyl analog to a substrate are disclosed. Also disclosed are methods for using o-nitrobenzyl analogs for creating patterned arrays of anti-ligands on a substrate so that a plurality of bioassays can be conducted simultaneously. In particular, the compounds disclosed are o-nitrobenzyl-polyethylene glycol-silanes, wherein the silane group serves to attach the compound to a substrate, the polyethylene glycol group resists the nonspecific adsorption of biomolecules. The o-nitrobenzyl group provides a photoactivatable functionality that allows the polyethylene glycol group to be selectively removed upon exposure to UV radiation and be replaced by an anti-ligand.

Abstract: The present invention provides labeled synthetic libraries of random oligomers and methods and apparatus for generating labeled synthetic oligomer libraries. Each member of such a library is labeled with a unique identifier tag that specifies the structure or sequence of the oligomer. In a preferred embodiment of the present invention the identifier tag is a microchip that is pre-encoded or encodable with information that is related back to a detector when the identifier tag is pulsed with electromagnetic radiation.

Abstract: Permeable substantially spherical hollow particles of 1-5000 .mu.m in size are formed having an outer shell of a mechanically rigid porous material. Pores of the shell are through-going pores that connect the inside of the particles to surroundings and allow chemical species to traverse the outer shell. To prepare the particles, impermeable hollow particles are treated with an acid or base under reflux conditions to form pores. The outer shell is formed of anhydrous forms of silicon dioxide, metal silicates, metal borosilicates, metal oxides or boric oxide. Metals and metal alloys are not used in forming the outer shell. Particles containing a polymer are formed by immersing the permeable hollow particles in a solution of components that polymerize to form the polymer, allowing the solution to partially fill the particles via the pores and polymerizing the components.

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

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

Abstract: An analytical apparatus comprises a biosensor device (3) which forms the base of a sample chamber. A stirrer (8) extends into the sample chamber and moves within the chamber so as to homogenize a sample contained within the chamber in contact with the biosensor (3). Movement of the stirrer (8) is preferably reciprocal movement along an axis perpendicular to the surface of the biosensor (3).

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

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

Abstract: Red blood cells are removed from whole blood or a fraction thereof by agglutinating whole blood with a mixture of a free agglutinating agent and nucleating particles having agglutinating agent intimately associated therewith to form clusters of red blood cells. High molecular weight polyethylene glycol may be added further to enhance agglutination. The clusters of red blood cells are much larger than the size of individual red blood cells, so that the clusters can easily be filtered through a porous medium. The plasma, which is substantially free of red blood cells, is further passed through a filter that optionally contains an additional agglutinating agent. Flow-delay additives may be provided to retain the fluid sample in contact with a reagent for a predetermined time.

Abstract: Method and apparatus for producing combinatorial position-addressable libraries of different-sequence oligomers or different-substituent small molecule compounds are disclosed. The method employs massive parallel synthesis by stepwise subunit addition or substituent addition in a dense capillary-tube array. The libraries allow high throughput screening of library compounds in either solid phase or solution phase, and position-related identification of active library compounds.

Abstract: The invention concerns a binding matrix containing a carrier material and a solid phase reactant which is adsorbed to this via anchor groups that is capable of binding to at least one free reaction partner wherein the solid phase reactant forms a dilute and essentially laterally homogeneous binding layer on the surface of the carrier material. In addition a method for the determination of an analyte in a sample solution is claimed in which a solid phase reactant is used which is a component of a binding matrix according to the present invention. In this process the specific binding reaction is preferably determined by optical reflection techniques.

Abstract: The present invention is an assay for determining glycoprotein IIb/IIIa receptor blockade in whole blood. Agglutinization of small polymeric beads coated with a glycoprotein IIb/IIIa ligand such as fibrinogen results when the beads are contacted with whole blood containing platelets with glycoprotein IIb/IIIa receptors that are not blocked. Failure to agglutinate indicates that blockade of the GPIIb/IIIa receptors has been achieved. In a preferred embodiment, the addition of a thrombin receptor activator results in an assay that is rapid and convenient enough to be performed at bedside and that results in agglutination of the small polymeric beads within a convenient, known period of time if the glycoprotein IIb/IIIa receptors are not blocked.

Abstract: A method of determining the affinity and kinetic properties of low molecular weight ligands for their interaction with a common receptor comprises the steps of immobilizing the receptor on a sensing structure, mixing in known proportions each ligand with a ligand analogue the response of which on the sensing structure is substantially higher than that of the low molecular weight ligands, contacting each mixture with the sensing structure and measuring the response, and comparing the response of each mixture with that of the ligand analogue alone, the distortion of the ligand analogue response being representative of the affinity and kinetic properties of the ligand.

Abstract: This invention provides a device and method for preparing a plasma enriched sample for use in an immunoassay strip. All parts that contact blood or a blood fraction remain in a container and prevent contamination from used blood. In one embodiment a sampling device collects blood and enters the container. A plasma enriched sample fills a plasma receptor which in turn is transferred to an immunoassay strip. Plasma is washed out of the strip by an aqueous solution. In another embodiment the sampling device doubles as a plasma separator. The invention allows sensitive and safe immunoassays to be performed on whole blood samples outside of the normal clinical laboratory setting.

Abstract: A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

Abstract: A synthetic strategy for the creation of large scale chemical diversity. Solid-phase chemistry, photolabile protecting groups, and photolithography are used to achieve light-directed spatially-addressable parallel chemical synthesis. Binary masking techniques are utilized in one embodiment. A reactor system, photoremovable protective groups, and improved data collection and handling techniques are also disclosed. A technique for screening linker molecules is also provided.

Abstract: The invention relates to a reagent consisting of at least one enzyme and at least one other substance, which are covalently or noncovalently bound to a particle, which is smaller than or is equal to 1000 Angstrom in diameter. The invention also relates to method and use of the reagent for determination or studies of a cell or a virus or another component in a sample. According to the invention, these determinations are made with for example some ELISA-technique (competitive, sandwich, etc.), employing the reagent preferrably in the form of a suspension in buffered water, instead of and in the same way as described for soluble enzyme conjugates. The substance can be an antibody, a lectin, avidin or an antigen, the enzyme can be for example peroxidase, alkaline phosphatase, and the particle can be an inorganic or an organic polymeric compound or a combination thereof, as, for example, tresyl-activated glycerylpropyl-silica.

Abstract: An evanescent wave system and method including an optical sensor for use in assaying a reference material and at least one molecular species or analyte in a test medium or test sample for diagnostic and other applicable purposes. The sensor includes a waveguide for propagating a radiation input along its length. The radiation input causes evanescent electromagnetic waves that are capable of stimulating output emissions that are indicative of a reference material and of one or more molecular species or analytes. By comparing the emission(s) indicative of the reference material to the emission indicative of the presence of the molecular species or analyte, the presence and concentration of the molecule in the sample can be determined. The reference material provides for normalization and/or calibration of the system.

Abstract: Magnetic porous inorganic siliceous materials having a particle size of about 1 to about 200 microns useful as solid supports in various chromatography, immunoassays, synthesis and other separation and purification procedures is disclosed.

Abstract: A cover slip holder for suspension of cover slips or slides in a biochemi reactor which includes a perimeter support constructed so that the outer surface of the support will engage the interior wall of the reactor, a plurality of coiled springs secured to the perimeter support and constructed so that cover slips can be held vertically between the coils of the springs.

Abstract: A method of assay for a ligand in a sample is described in which calibration occurs within the assay. This is achieved utilizing a measurement region and one ore more calibration regions. In at least one of the calibration regions a non-zero signal results, either because of the presence of a calibration reagent or as a result of a binding reaction analogous to that which takes place in the measurement region.

Abstract: A mesoscale sample preparation device capable of providing microvolume test samples, separated into a cell-enriched fraction and a fraction of reduced cell content, for performing various analyses, such as binding assays, determinations involving polynucleotide amplification and the like. Analytical systems including such devices are also disclosed.

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

Abstract: A chemical sensor includes a thin film transistor with a gate positioned on one side. An insulating layer is positioned on the opposite side and an indicator film is positioned on the insulating layer in generally opposed relationship to the gate. Induced charge in the indicator film caused by a biological or chemical species changes the channel current in the transistor. A potential on the gate is then used to null out the resulting change in channel current. The potential used to null out the current change is an extremely sensitive measure of the induced charge.

Abstract: The present invention relates to an optical solid-phase biosensor for the detection of molecules which can be labelled with a fluorescent dye for the identification of substances in solution, for which there exists a biomolecule (receptor) which specifically recognises these and is chemically bonded to the uppermost layer of one or more layers of polyions on the surface of the sensor, by measurement of the Forster transfer between another dye molecule which is bonded in one of the uppermost layers of the sensor, and the said dye molecule.

Abstract: A chemical sensor for measuring a change in the sensor mass relating to the interaction of a surface of the sensor with a solution comprises a crystal detector oscillator capable of providing a measurement signal based upon the resonant frequency of the crystal detector oscillator. The crystal detector oscillator has a first crystal side for directly contacting the solution, and a second crystal side isolated from contacting the solution. A first electrode is integral to the first crystal side, with the first electrode having an inner and outer perimeter defining an outer portion of the first crystal side which is exterior to the outer perimeter of the first electrode and an inner portion of the first crystal side which is interior to the inner perimeter of the first electrode. A second electrode is integral to the second crystal side.

Abstract: This disclosure describes an apparatus for separation and detection of target molecules in a liquid sample containing the target molecules and non-target molecules comprising at least one absorption area, a bibulous carrier defining a first liquid transport path in fluid contact with at least one absorption area including at least one reaction area upstream of the at least one absorption area wherein the reaction area includes a capture reagent and a sample area upstream of the reaction area wherein the liquid sample when applied to sample area is transported by capillary action past the reaction area where at least a portion of the target molecules may be bound to the capture reagent to permit detection of the target molecules. The liquid sample is then transported by capillary action on to the absorption area.

Abstract: A disposable diagnostic device and method of its use are provided. The device comprises a housing containing first and second flow paths orthogonal to each other. The first flow path commences at a sample addition port and continues through a transport channel which feeds sample to an incubation area by means of capillary flow. The incubation area comprises a signal producing system and is underneath an optically-clear window. The first flow path terminates in a top waste reservoir which receives sample and wash fluid. The second flow path begins on one side of the incubation area at an inlet port over a side reagent reservoir. Liquid flows along the second flow path from the side reagent reservoir across the incubation area into the side waste reservoir. The incubation area may comprise agitation means for homogenous dispersion of reagent into liquid.

Abstract: Methods and compositions are provided for use of modified or intact phycobilisomes as extremely potent labels in sensitive monitoring kits (e.g., for blood contamination), specific binding assays (e.g., visual, photometric and fluorometric immunoassays) and optoelectronic devices (e.g., biosensors, photoelectric transducers).

Abstract: Stabilized microspherical particles having hydrophobic liquid cores prepared as oil-in-water microemulsions. The particles are stabilized by a surface layer comprising an amphiphilic compound and may be functionalized to allow covalent coupling of a ligand to the surface of the particle. When used as tracers in assays, a water insoluble dye may be incorporated in the core liquid of the microparticles.

Abstract: A "one step" device for the detection of analytein clinical assays is disclosed. A visible label comprising a visible moiety and a ligand that binds to or competes with analyte is contained in a fluid conducting membrane or prefilter; and the analyte and associated ligand are conducted by the flow of sample into a detection zone. The detection zone contains a capture reagent that binds to label or to analyte bound to label.

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