Abstract: This invention relates to a reagent mixture, as well as to a method and apparatus, for carrying out simultaneous, automated analysis of multiple analytes in a test sample, particularly a bodily fluid. The invention is especially relevant to the field of general clinical chemistry, but may find application in other fields of use.

Abstract: A method of treating particles to be used in immunoassays reduces interference in particle agglutination assays.

Abstract: Methods for assessing immunocompetence, cellular or humoral immunity, antigen exposure, or allergic conditions in an individual by accelerating diagnostic particles into a target skin site in the individual are provided.

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: This invention relates to methods of assaying one or more analytes simultaneously. The assays of this invention are capable of providing wide dynamic range and rapid processing times. A wide dynamic working range is achieved by simultaneously incubating a sample which may contain the analyte(s) of interest with two or more independently determinable classes of particles coated with an analyte-specific binding partner. The two or more particle classes differ from each other at least in size. The analyte concentration is obtained from readings derived from these two classes by means of a combined standard curve.

Abstract: Provided are a fluorescent microsphere comprised of a plurality of fluorescent nanocrystals embedded in a polymeric microsphere; a kit prepared from the fluorescent microspheres; and a method of producing the fluorescent microspheres comprising swelling the polymeric microsphere so that into its pores can enter fluorescent nanocrystals, and then unswelling the polymeric micropsheres so that the fluorescent nanocrystals become physically entrapped in the pores of the unswelled polymeric microsphere. Also provided is a method of using the fluorescent microspheres comprising affinity ligand for determining the presence or absence of a predetermined number of analytes in a sample by contacting the sample with the fluorescent microspheres, and detecting the fluorescence signal pattern of excited fluorescent microspheres bound to one or more analytes of the predetermined number of analytes, if present in the sample.

Abstract: Described herein are assays and components for encoding and decoding microspheres. Each assay or component described utilizes at least one nanocrystal.

Abstract: A colorimetric detector for chemical and biological agents or toxins is made of a giant unilamellar vesicle (GUV) having a membrane bilayer which is polymerized to stabilize the giant unilamellar vesicle and to provide extended conjugated polymer backbone, and the GUV has at least one incorporated molecular recognition site for the chemical and biological agents or toxins. The GUVs are about 10-300 microns and preferably made of a polymerizable diacetylenic GUV where the acyl chains are crosslinked. When the agents or toxins bind to the recognition site the detector exhibits a color change. The detector can be used in a colorimetric detector apparatus where the samples can be present in air or in water.

Abstract: Methods for deceasing non-specific bindings of beads in dual bead assays and related optical bio-discs and disc drive systems. The methods include determining the suitability of a test solid phase for purposes of use in a dual bead assay. The method also includes identifying whether a target agent is present in a biological sample and involves mixing capture beads, reporter beads, and a biological sample. The mixing is performed under binding conditions to permit formation of a dual bead complex if the target agent is present in the sample. The reporter bead and capture bead are each bound to the target agent. Cleavable spacers or displacement linkers may be used in forming the dual bead complexes. The methods also include placing the capture beads and the reporter beads spatially proximally, performing a ligation reaction employing a ligase, and isolating the dual bead complex from the mixture to obtain the isolate.

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.

Abstract: A method for the multiplexed diagnostic and genetic analysis of enzymes, DNA fragments, antibodies, and other biomolecules comprises the steps of constructing an appropriately labeled beadset, exposing the beadset to a clinical sample, and analyzing the combined sample/beadset by flow cytometry. Flow cytometric measurements are used to classify, in real-time, beads within an exposed beadset and textual explanations, based on the accumulated data obtained during real-time analysis, are generated for the user. The inventive technology enables the simultaneous, and automated, detection and interpretation of multiple biomolecules or DNA sequences in real-time while also reducing the cost of performing diagnostic and genetic assays.

Abstract: The present invention provides an improved method for detection of panel reactive antibodies in serum of a subject against HLA class I antigens, which comprises the steps of adding serum from a subject to an array of microbeads, each microbead presenting HLA antigens from a cell population presenting the same HLA antigens; incubating the serum and microbeads for sufficient time for anti-HLA antibodies in the serum to bind to the HLA antigens presented on the microbeads; removing the serum components which do not specifically bind with the HLA antigens presented on the microbeads; incubating the microbeads with a labeled ligand capable of specifically binding with anti-HLA antibodies bound to said HLA antigens; removing the labeled ligand which is not bound to said HLA antigens; and detecting the presence of labeled ligand bound to said HLA antigens by flow cytometry.

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 homogeneous assay method for detection of an analyte in a sample based on the analyte-dependent aggregation or agglutination of a multivalent carrier reagent, an analyte-derivative bound or capable of binding to the carrier and an analyte-specific binding partner (R1), characterized in that the binding partner (R1) is oligomeric or is oligomerized by a reagent (R2) having at least two binding sites for (R1).

Abstract: An immunological analyzing apparatus and method using fine particles bonded with an antigen or an antibody are provided which are capable of obtaining a good analysis result with preferable reproducibility with no effect of carry-over.

Abstract: A method for the preparation of a coded chemical library, which method comprises synthesising the chemical library on a plurality of synthesis particles and writing code on the synthesis particles using high-energy radiation during library synthesis, so as to provide the chemical library on a plurality of coded synthesis particles, and wherein the identity of library compounds associated with a synthesis particle is established by reference to its code.

Abstract: Disclosed is a test cell and a method for detection of a preselected ligand in a liquid sample such as a body fluid. The test cell includes an elongate outer casing which houses an interior permeable material capable of transporting an aqueous solution and defining a sample inlet, a test volume, and a reservoir volume. The reservoir volume is disposed in a section of the test cell spaced apart from the inlet and is filled with sorbent material. The reservoir acts to receive liquid transported along a flow path defined by the permeable material and extending from the inlet and through the test volume. In the test volume is a test site which includes a first protein having a binding site specific to a first epitope of the ligand immobilized in fluid communication with the flow path. The test site can be observed through a window of the casing.

Abstract: Reagents and methods for the detection of Staphylococcus aureus are provided. The reagents contain an antibody that binds to a capsular polysaccharide of type 5 of Staphylococcus aureus, and can be used in methods for detection of oxacillin resistant Staphylococcus aureus that escapes detection by agglutination in the presence of fibrinogen and antibodies directed against protein A of Staphylococcus.

Abstract: The invention concerns a method for the immunological determination of an analyte in a sample using magnetic particles coated with the analyte to be determined or analyte-specific bonding partners and directly detectable non-magnetic particles coated with analyte-specific bonding partners or the analyte to be determined or using a non-magnetic substance which is indirectly detectable, and incubation of the reaction mixture. The method is characterized in that the magnetic particles are subsequently separated from the reaction mixture using a magnetic test strip and the analyte concentration is determined directly.

Abstract: The invention provides a particle comprising a surface, wherein a portion of the surface is capable of emitting electromagnetic radiation and another portion of the surface is capable of emitting a differential electromagnetic radiation (either different intensity, different frequency or no radiation), and wherein the arrangement of said portions of the surface defines a spatially distributed code for identifying the particle. The invention also provides method of manufacturing a particle having an identifying code comprising providing a particle with a functionalized surface which comprises functional binding moieties and selectively removing a plurality of the functional binding moieties from the surface to create a pattern of functionalized and differentially-functionalized zones on the surface. Various liquid-based assay methods employing the particle of the invention and a kit comprising the particle of the invention are also disclosed.

Abstract: Methods, compositions and systems for processing biological samples include separation reagents featuring a microparticle and a receptor for a ligand on a target species in the biological sample. The biological sample is reacted with the separation reagent to capture the target species. A covalent bond is formed between the target species and the separation reagent to form an adduct. The adduct is separated from the biological sample, and a component of the target species is separated from the target species.

Abstract: Methods and kits for simultaneously measuring both members of a binding pair are described.

Abstract: A method for analyzing blood enables one to isolate, detect, enumerate and confirm under magnification the presence or absence of target cancer cells and/or hematologic progenitor cells, or other rare events which are known to circulate in blood. The analysis is performed in a sample of centrifuged anticoagulated whole blood. The analysis involves both morphometric and epitopic examination of the blood sample while the blood sample is disposed in a centrifuged blood sampling container. The epitopic analysis of the presence or absence of cancer cells relies on the detection of epitopes which are known to be present on cancer cells and not on normal circulating blood cells; and the epitopic analysis of the presence or absence of hematologic progenitor cells relies on the detection of epitopes which are known to be present on hematologic progenitor cells and not on normal circulating blood cells.

Abstract: Rare cells are separated from a sample fluid by a positive selection or negative selection antibody by centrifuging in a tube containing a harvesting float. The harvesting float has an axial passage and a density to settle in the sample fluid and expand the layer of the target component. The antibody is preferably coupled to a particulate carrier, such as a microbead, to attach either the target component or a contaminating component to the particulate carrier. In the positive separation, the particulate carrier is recovered in the axial passage of the float.

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: Combinations, called matrices with memories, of matrix materials with remotely addressable or remotely programmable recording devices that contain at least one data storage unit are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The data storage units are preferably non-volatile antifuse memories. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.

Abstract: Provided is a technology for increasing types of color separation in accordance with density gradients by refining the mode of setting gradients in the event of two-dimensional or three-dimensional color separation. A conventional color separation is conducted in a manner that dots indicating densities are defined in intersecting points of lines parallel to the X axis and the Y axis, respectively, in the case of two-dimensional color separation. In the case of three-dimensional color separation, dots indicating densities are defined in intersecting points of lines parallel to the XY axis, the YZ axis and the ZX axis, respectively. The present invention does not define the dots in the intersecting points of those parallel lines. Instead, the dots are configured to be shifted.

Abstract: Methods and reagents for rapid purification and/or identification of particles in a liquid sample are described. The technique uses centrifugation to concentrate particles against a slanted surface having an agent specifically binding to the particles. This method is applicable for the rapid identification of viruses and other difficult or impossible to culture microorganisms without replication or amplification of the microorganism.

Abstract: A method and apparatus for urine self testing wherein the apparatus is placed directly into the toilet after urination which avoids the direct placement and retention of an apparatus in the stream of urine as is common with urine testing devices. The apparatus detects the presence of certain chemicals in dilute urine such as the presence of human chorionic gonadotropin (hCG) in the urine of a pregnant woman. An opening in the apparatus is fitted with a fluid absorption device which acts to concentrate the diluted urine on an indicator strip which contains antibodies, enzymes and antibody blockers which will provide a reactive change, usually of color, when subjected to a predetermined chemical such as hCG. The apparatus functions in dilute urine when placed in a toilet after urination and is largely constructed of biodegradable materials so that it can be flushed into the sewage system or a septic tank.

Abstract: A device and method for separating a fluid component from a non-fluid component of a sample comprises a plurality of microspheres disposed in abutting relation and forming therebetween a plurality of capillary channels, whereby when the microspheres are disposed in fluid communication with a sample the fluid component is separated from the non-fluid component by capillary flow of the fluid component through the capillary channels formed by the interstitial spacing between abutting microspheres.

Abstract: A compact assay system having a solid support has at least one capture binding agent on the support surface. By applying a combination of different binding agents on the support surface, the present invention can conduct multiple chemical reactions on the support solid support to detect analytes of interest. The specific reagents, or capture binding agents, are preferably immobilized on the solid support by means of a computer controlled, miniaturized printing system. Specifically, the reagents can be applied onto the solid support using a commercial available printhead of an ink-jet printer. In addition, the support surface also includes areas adapted to be digitally readable by laser to store information concerning binding between capture agents and analytes. The assay system is useful as a sample array holder for performing a variety of chemical analyses, such as matrix assisted laser desorption ionization mass spectrometry analyses.

Abstract: The invention relates to a method of evaluating the immunological status of a subject comprising the steps of 1) determining the content of an antibody in a liquid sample from the subject using an immunoassay, wherein the reaction between the antibody of the sample and a ligand in the form of an antigen, an antibody or a hapten, the ligand being directed to the Fab region of the sample antibody, is carried out in the presence of other constituents of the sample to obtain a measurement 1, 2) determining the content of an antibody in the liquid sample using an immunoassay, wherein the reaction between the antibody of the sample and a ligand in the form of an antigen, an antibody or a hapten, the ligand being directed to the Fab region of the sample antibody, is carried out in the absence of other constituents of the sample to obtain a measurement 2, and 3) interrelating measurements 1 and 2 to express the interference and using the interference as a parameter for evaluating the immunological status of the subje

Abstract: A method for the preparation of a chemical library, which method comprises synthesizing the library on a plurality of individually coded synthesis particles and wherein the particles are tracked during library synthesis under the control of robotic apparatus.

Abstract: Disclosed are materials and methods for detecting biomolecules in samples employing transponders associated with the bead(s) used as the solid phase in the assay, and information pertinent to the assay is encoded on the transponders memory elements. A dedicated read/write device is used remotely to encode or remotely to read the information. The invention can be used in direct or competitive ELISA-type assays, or in multiplex assays for the simultaneous assay of several analytes.

Abstract: This invention relates to encoding methods using up-converting phosphors for high-throughput screening of catalysts. In particular, the invention relates to polymerization catalysts. In one embodiment of the invention, a monomer is combined with at least one labeled catalyst particle. The labeled catalyst particle comprises an up-converting phosphor label and a catalyst. The up-converting phosphor label identifies a particular catalyst. The monomer is polymerized to form a polymer bead surrounding the labeled catalyst particle. According to the invention, it is possible to combine two or more labeled catalyst particles in a commercially relevant large scale reactor to obtain direct comparison of different catalysts, and to avoid reactor effects that may occur when performed on the microscale. After the reaction, the resulting polymer beads are sorted, based on their size and/or phosphor labels.

Abstract: Magnetic particles for separating biological mixtures consist of nacreous luster pigments with magnetic properties coated with a biological polymer.

Abstract: This invention relates to a lateral flow immunochromatographic assay device without a plastic housing. The assay includes a sample receiving region, analyte detection region and end region all made of porous material and capable of lateral flow. The analyte detection region includes labeling reagents, a capture reagent and a control reagent. The back of the porous material is laminated with a semi-rigid material with adequate mechanical strength. The top is partially covered with a thin plastic material so as to leave a portion of the sample receiving region exposed for sample application.

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: 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: 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: The invention provides a method for producing a micro-carrier, which includes patterning pluralities of bar code on a mask; exposing the bar code to a substrate coated with photoresist; etching and removing residual photoresist and electroforming to a nickel plate; placing a bead coated with biotin or poly-L-lysine between two-nickel plates, and compressing the bar code on the surface of the bead to form a microcake-like particle with bar code; and combining the particle with the corresponding bio-molecule thereof to produce a micro-carrier with a label. The invention also provides a test method for identifying a bio-molecule, which includes mixing several micro-carriers with the labeled unknown bio-molecules; and identifying the bar code on the micro-carrier via image recognition system, wherein the numbers and types of the known micro-carrier can be flexibly adjusted.

Abstract: A method for detecting the binding of a test compound to a probe molecule comprises providing a test compound, the test compound having a first fluorophore bound thereto, and providing a screening substrate. The screening substrate comprises a solid support, a probe molecule bound to the solid support, and a second fluorophore bound to the solid support adjacent the probe molecule. An advantage of the invention is that this obviates the need for binding the second fluorophore directly to the probe molecule. Preferably, the second fluorophore is bound to the solid support by a flexible linker group. This enables the second fluorophore to interogate different positions on the probe molecule, which is also bound to the solid support adjacent the linker group, enhancing the ability of the method of the invention to detect positive binding events (specific binding of the test compound to the probe molecule.

Abstract: The present invention relates to a method for at least one of detecting, quantifying or isolating at least one analyte from a liquid medium in which the analyte is distributed and comprises providing a reagent comprised of particles having a receptor for an analyte fixed to the particles distributed in the medium and a capturing means having an exposed surface defining an active zone. An intermediate reagent is formed by the complex of the reagent with the analyte. A second receptor is fixed in the active zone to capture either the analyte bound by the reagent or the receptor (capture partners). The active zone serves as a site of isolation and concentration of the capture partners.

Abstract: A compact assay system having a solid support has at least one capture binding agent on the support surface. By applying a combination of different binding agents on the support surface, the present invention can conduct multiple chemical reactions on the support solid support to detect analytes of interest. The specific reagents, or capture binding agents, are preferably immobilized on the solid support by means of a computer controlled, miniaturized printing system. Specifically, the reagents can be applied onto the solid support using a commercial available printhead of an ink-jet printer. In addition, the support surface also includes areas adapted to be digitally readable by laser to store information concerning binding between capture agents and analytes.

Abstract: Combinations, called matrices with memories, of matrix materials with remotely addressable or remotely programmable recording devices that contain at least one data storage unit are provided. The matrix materials are those that are used in as supports in solid phase chemical and biochemical syntheses, immunoassays and hybridization reactions. The data storage units are preferably non-volatile antifuse memories. By virtue of this combination, molecules and biological particles, such as phage and viral particles and cells, that are in proximity or in physical contact with the matrix combination can be labeled by programming the memory with identifying information and can be identified by retrieving the stored information. Combinations of matrix materials, memories, and linked molecules and biological materials are also provided.

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: There is used at least one probe array obtained by arraying particles having various probes, respectively, fixed thereon (probe particles) in a definite order in a holder. A plurality of capillaries or grooves packed with various kinds, respectively, of probe particles are arrayed in parallel, and one of particles contained in each capillary or groove is injected into another capillary or groove to produce a probe array in which the various kinds of probe particles are arrayed in a constant and definite order. Various fluorophore-labeled DNA's are measured at the same time by attaching various probes to particles, respectively, of different sizes. A probe array composed of various fixed DNA probes can easily be produced, and there can be provided a probe array for detecting various DNA's which is composed of various fixed arbitrary DNA probes.

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: Method for analyzing a sample using an aqueous liquid reagent to determine the concentration of HIV antibody in an individual's random urine sample in order to determine if the individual's exposure to the HIV virus, and normalizing or correcting this assay value with the sample's creatinine, cystatin C, or specific gravity concentration.

Abstract: Calibrating an immunoassay by generating two reaction rate measuring curves, from samples having higher and lower relative levels of antigen, extrapolating a combination of the curves to cover sample concentrations known to contain an excess of antigen relative to an amount of capture reagent and combining the low end linear potion of the higher reaction rate measuring curve with the higher end portion of the extrapolated reaction rate measuring curve, thereby eliminating measuring inaccuracies otherwise arising from the hook effect. For antigen concentrations higher than the assay range, a high antigen signal utilizing the two rates avoids reporting false results.