Abstract: Systems using coded particles for multiplexed analysis of biological samples or reagents, in which the codes on the particles are at least partially defined by light-polarizing materials.

Abstract: Methods of using high-density microparticles to bind and remove pathogens from biological fluids are disclosed. Pathogens include prions, viruses, bacteria and protozoa.

Abstract: A chemical and bio-chemical assay method is described which screens compounds for enzyme inhibition, or receptor or other target binding. Inhibition or binding by the library compounds causes a change in the amount of an optically detectable label that is bound to suspendable cells or solid supports. The amounts of label bound to individual cells or solid supports are microscopically determined, and compared with the amount of label that is not bound to individual cells or solid supports. The degree of inhibition or binding is determined using this data. Confocal microscopy, and subsequent data analysis, allow the assay to be carried out without any separation step, and provide for high throughput screening of very small assay volume using very small amounts of test compound.

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 recombinant protein that is a fusion protein containing a protein binding domain and a domain that is post-translationally modified to become lipid-tagged. This molecule has both a domain with highly specific binding capabilities and a domain which is very hydrophobic in nature. This type of molecule can be used to coat hydrophobic surfaces such as polystyrene easily and effectively for use in solid phase binding assays.

Abstract: Methods, compositions and kits are disclosed. The compositions are light emitting and comprise a polymeric matrix having dissolved therein a photoactive compound. The composition has the characteristic that, after activation of the photoactive compound, the rate of decrease in the intensity of light emission at any time during a 20-fold decrease in the intensity is proportional to the intensity of the light emission. In one embodiment the polymeric matrix is comprised of particles of about 20 nm to about 100 &mgr;m in diameter to which is bound a specific binding pair member. The particles generally comprise a polymeric matrix having dissolved therein about 1 to about 20% by weight of a dopant. The compositions may be used in methods for determining an analyte. A combination is provided comprising (1) a medium suspected of containing the analyte, (2) and the aforementioned composition.

Abstract: The present invention relates to the substantial elimination of errors attributable to carryover microspheres, doublets, or misclassification of microsphere subsets. The present invention is based upon passing a sufficient minimum number microspheres through the flow analyzer during an assay run.

Abstract: A process, a test kit, calibration standards, and the method of preparing such standards as useful for the qualitative and/or quantitative determination of total solid phase- or microparticle-immobilized, amine-containing reactants such as proteins is provided. The operating principle of the invention is distinct from a classical immunoassay based on antibody-antigen immune interaction or from standard calorimetric proteins assays of soluble proteins and allows the detection of as low as attogram (10−18 gm) levels of total analyte per microparticle.

Abstract: Mesoporous materials and a method for making such materials is disclosed in which the mesoporous materials are made by forming an aqueous solution having an organometallic compound; adding a solution comprising a pore forming material selected from the group consisting of monomeric polyols, polyacids, polyamines, carbohydrates, oligopeptides, oligonucleic acids, carbonyl functional organic compounds, and mixtures and derivatives of these materials to form a sol get matrix by polycondensation; drying the sot gel matrix; and removing the pore forming material from the dried sot-gel matrix to thereby form a mesoporous material. The mesoporous materials have pore diameters of from about 20 Å to about 100 Å and may be used with a biologically active agent immobilized within the pores of the mesoporous material and introduced into a biological system.

Abstract: A method of assaying for an analyte which occurs at least partially bound as a complex with its soluble receptor or binding protein, the method comprising the steps of: i) mixing a biological fluid serum sample containing the analyte to be determined with a detergent for dissociating said complex, ii) mixing the sample from step i) with reagents, including a specific binding partner of the analyte for binding to the analyte, for performing a specific binding assay for the analyte, iii) and mixing the sample from step i) with a sequestrant for the detergent, whereby the binding of step ii) is performed in the presence of the sequestrant.

Abstract: A biodegradable micro particle for tagging food is disclosed. The particle may be of irregular or regular shape and carries optically recognizable indicia on it.

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: 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: 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 method of single parameter and multiparameter characterizing of cells, particularly immunophenotyping of cells, is provided. The method preferably uses antibody-coated microspheres which are adapted to bind to specific types of cells. One or more sets of coated microspheres are contacted simultaneously or sequentially with a suspension of cells and bind the cells they are adapted to bind to form bead-cell complexes. Cells may bind to one or more microspheres. The bead-cell complexes are then separated from the suspension The complexes are preferably stained and then examined to characterize the cells, preferably the cells bound to the microspheres. A method of quantitating a specific cell type is provided. A kit and apparatus for performing the method are also provided.

Abstract: Antigens can be captured and detected from complex samples, such as food and environmental samples, in about 30 minutes using apparatus and methods that include flow of the samples through a module containing antibodies coupled to beads. The samples flow through the modified beads at about 0.2 to 1.2 liters/minute, which fluidizes the bead bed. The antigens are captured by the antibodies, and then detection of the captured antibodies is carried out with chemiluminescence, fluorescence, or spectrophotometric techniques.

Abstract: The invention provides assay methods and kits that in general measure the level of a first analyte in a sample reduced by the level of a second analyte present in the same sample. In one embodiment, where levels of a first analyte from a first source is desirably determined and first analyte in the sample released from a second source is accompanied by proportional co-release of a second analyte, the assay identifies the level of first analyte released only from the first source. For analytes within bodily fluids, the assay can differentiate between elevated levels of analyte specific to the particular physiological or pathological state and elevated levels not specific to the particular state, providing single tests with diagnostic utility.

Abstract: This method for analyzing blood enables one to isolate, detect, enumerate and confirm under magnification the presence or absence of fragments of target analyte cancer cells which are circulating in blood. The analysis is performed in a sample of centrifuged anticoagulated whole blood. The analysis of the presence or absence of fragments of cancer cells relies on the detection of external or internal binding sites which are known to be present only in or on tumorous cancer cells. Fluorophors with distinct wavelength emissions are coupled with antibodies, or other binding moieties such as complementary nucleotide sequences, which antibodies are directed against the epithelial cell fragment membrane binding sites, such as internal or external surface epitopes on the cell fragments, or internal binding sites on cell organelles; and which nucleotide sequences are complementary to portions of cell fragment RNA and/or DNA. The labled binding agents are humoric or soluble in the blood sample.

Abstract: The invention provides methods and compositions for detecting binding or unbinding of a molecule to a substrate. The molecule comprises a luminophore and the substrate comprises a semiconductor which acts as a luminescence quencher to provide distance-dependent quenching of the luminophore. Binding or unbinding of the molecule, which may be covalent or noncovalent, is detected as a decrease or increase, respectively, of the detectable luminescence of the luminophore.

Abstract: The present invention provides an improved system for detecting the presence or level of an analyte in a sample. In “competition-like” assays of the present invention, a sample including an analyte is mixed with a second ligand to which the analyte binds, and the mixture is exposed to a solid phase containing a first ligand that can compete with the analyte for binding to the second ligand. According to the present invention, the time of exposure of the mixture to the solid phase is limited so that substantially no dissociation of analyte/second ligand complex occurs. The competition-like assays of the present invention are preferably performed with a solid phase containing a substantial excess of first ligand.

Abstract: Immunoassay methods, apparatuses, and reagents are described, which are capable of measuring with out being affected by particles other than a measuring object substance in a specimen, and which do not require a labeled antibody even when such particles are included in the specimen. In addition, immunoassay methods, apparatuses, and reagents capable of simultaneously measuring multiple parameters from one sample are described.

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: This invention provides a novel fluorescent particle including a core or carrier particle having on its surface a plurality of smaller polymeric particles or nanoparticles, which are stained with different fluorescent dyes. When excited by a light source they are capable of giving off multiple fluorescent emissions simultaneously, which is useful for multiplexed analysis of a plurality of analytes in a sample. The coupled complex particles carrying on their surface fluorescent nanoparticles, methods of preparing such polymer particles, and various applications and methods of using such particles are claimed.

Abstract: The present invention discloses an electrochemical device for detecting single particles, and methods for using such a device to achieve high sensitivity for detecting particles such as bacteria, viruses, aggregates, immuno-complexes, molecules, or ionic species. The device provides for affinity-based electrochemical detection of particles with single-particle sensitivity. The disclosed device and methods are based on microelectrodes with surface-attached, affinity ligands (e.g., antibodies, combinatorial peptides, glycolipids) that bind selectively to some target particle species. The electrodes electrolyze chemical species present in the particle-containing solution, and particle interaction with a sensor element modulates its electrolytic activity. The devices may be used individually, employed as sensors, used in arrays for a single specific type of particle or for a range of particle types, or configured into arrays of sensors having both these attributes.

Abstract: A diffusion immunoassay (DIA) for determining the presence and concentration of analyte particles by detecting the diffusion front. A hydrogel containing immobilized binding particles is placed in contact with a carrier fluid containing analyte particles, which analyte particles diffuse into the hydrogel and bind with the immobilized binding particles. A detection device detects the position of the diffusion front formed in the hydrogel to determine the presence and concentration of the analyte particles which have diffused into the hydrogel.

Abstract: A solid support particle adapted for use in Combinatorial Chemistry Techniques characterised in that the particle is marked with machine readable code.

Abstract: The invention concerns a method for the purification of a target substance from a biological sample by immobilizing the target substance on a solid phase by means of a high affinity binding pair and subsequently eluting it by adding a partner of the binding pair in a free form. In addition reagent kits for carrying out the method are disclosed.

Abstract: An immunochemical method for the determination of antibodies which are specific for an antigen and are of one of the immunoglobulin classes: A, M, D or E in a fluid, with this fluid being contacted with a solid phase to which the antibodies against this immunoglobulin class, or a fragment of an antibody of this type, are bound, which results in the immunoglobulin of this class being bound to this solid phase, and this solid phase being contacted with the antigen, which carries a labeling means where appropriate, and with a labeled antibody or a labeled fragment of an antibody against the antigen if the antigen is unlabeled and determination, from the amount of labeling means which is bound to the solid phase, of the amount of these antibodies which are specific for an antigen and are one of the immunoglobulin classes, which comprises the solid phase being simultaneously in contact with the fluid containing the antibody which is to be determined and with the antigen, which is labeled where appropriate, there b

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: Particles capable of specific binding to an imprint molecule, comprises an outer shell including cavities that correspond to the imprint molecule, and an inner core substantially free of such cavities. Such particles can be used as a medium for various techniques, including separation of a target molecule.

Abstract: Apparatus and methods are disclosed which facilitate immobilization of magnetically labelled particulate entities, e.g., cells, preferably in a defined pattern, on a collection surface via binding between specific binding pair members, as an aid to particle analysis.

Abstract: Methods of determining collagen degradation in vivo, by quantitating the concentration of a peptide in a body fluid, the peptide being a C-terminal type II collagen telopeptide containing a hydroxylysyl pyridinoline cross-link or a type III collagen telopeptide containing a hydroxylysyl pyridinoline cross-link. Suitable methods include immunometric assays, fluorometric assays, and electrochemical titrations for quantitation. The structures of specific peptides having cross-links and kits for quantitating these peptides in a body fluid are described.

Abstract: The present invention relates to a robust and sensitive assay system utilizing synthetic spherical structures in place of cells for a FACS analysis. The method and system detects the affinity and neutralization activity of a biological molecule without interference from growth medium or cell supernatants. The systems associated with these methods allow high-throughput screening of assays for, in particular, neutralizing monoclonal antibodies.

Abstract: The present invention contemplates a system for rapidly isolating nucleic acids. The system comprises an insoluble silica matrix and a buffered aqueous salt solution containing salt at a concentration of at least 3 molar and a buffering agent at a concentration sufficient to provide a buffering capacity corresponding to that which either tris(hydroxymethyl)aminomethane or phosphate ion at a concentration of 0.1 to 1 molar would provide in the solution. Methods of using the system are also contemplated.

Abstract: The present application describes novel uses of ruthenium bipyridyls or palladium porphyrins as photo-activatable crosslinking agents. Crosslinking can be between any two molecules including peptides, proteins, or compounds. Crosslinking occurs in the presence of an electron donor such as ammonium persulfate, and requires only moderate intensity visible light. Crosslinking can be between peptides, polypeptides or lead candidate compounds to unknown target molecules. Reagents utilyzing ruthenium bipyridyls and palladium porphyrins crosslinkers for use in diagnostic and detection scenarios are also disclosed.

Abstract: Method for specific detection of one or more analytes in a sample. The method includes specifically associating any one or more analytes in the sample with a scattered-light detectable particle, illuminating any particle associated with the analytes with light under conditions which produce scattered light from the particle and in which light scattered from one or more particles can be detected by a human eye with less than 500 times magnification and without electronic amplification. The method also includes detecting the light scattered by any such particles under those conditions as a measure of the presence of the analytes.

Abstract: A pretreatment method for assaying a substance which comprises mixing a biological specimen with at least one pretreating agent selected from among surfactants and alkali agents, thus releasing binding proteins in the biological specimen from the substance to be assayed and, at the same time, inactivating the proteins by irreversible denaturation to thereby eliminate the effects of the binding proteins coexisting in the biological specimen.

Abstract: The present invention provides: a reagent and a kit for an insoluble carrier particle nephelometric immunoassay which stabilize the agglutination reaction by suppressing the action of blood plasma components that are involved in the agglutination reaction of insoluble carrier particles such as latex and affect the values to be determined, to provide the stable absorbances of the reaction solutions and the accurate determination results; and a method of an insoluble carrier particle nephelometric immunoassay utilizing said reagent or kit.

Abstract: A reagent for use in immunoassays reduces interference in particle agglutination assays.

Abstract: Disclosed is a fluorescent conjugate comprising a biological reagent, a fluorescent molecule, and a means for impeding phototoxic degradation of the biological reagent. The impeding means can be a cross-linking substance having a long molecular distance, whereby the cross-linking substance links the fluorescent molecule and the biological reagent; a quencher of singlet oxygen; a quencher of a free radical; or a combination thereof. Also disclosed is a solution comprising a fluorescent conjugate of a biological reagent and a fluorescent molecule together with an oxygen depleting system.

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: The invention provides improved immunoassay techniques for detecting the presence of analytes in a liquid sample. The present immunoassay methods utilize anti-allotypic monoclonal antibodies as capture reagents for primary binding proteins specific for the analytes of interest. The monoclonal antibodies are highly specific for the allotypic determinants present on the primary binding protein. The use of anti-allotypic monoclonal antibodies as capture reagents provides improved levels of specificity and accuracy of the immunoassay, in part because interference from endogenous immunoglobulins in the sample is significantly reduced. The invention further provides anti-allotypic monoclonal antibodies.

Abstract: Preparations of particles having a glass surface, wherein more than 75% by weight of these particles have a particle size between 0.5 &mgr;m and 15 &mgr;m and a glass surface which contains between 2 and 6 mole % zinc oxide, have proven to be particularly advantageous in processes for the purification of nucleic acids. This in particular results in an increased nucleic acid yield.

Abstract: A platelet/leukocyte interaction assay method and reagent therefor are provided using the presence of a solid-phase stimulus, such as magnetic or non-magnetic particles or mixtures thereof, having bound to the surface thereof one or more ligands that interact directly with platelets, leukocytes or both, for providing a fast, reliable point-of-care assessment of platelet/leukocyte interaction.

Abstract: The present invention relates to a simple immunochemical semi-quantitative assay method according to chromatography, which comprises trapping a certain amount of an analyte in a sample with a predetermined amount of a fixed antibody for the analyte before qualitative analysis of the analyte, the certain amount corresponding to the amount of the fixed antibody, and thereby decreasing a concentration of the analyte to be subjected to subsequent immunochemical qualitative determination, and an apparatus therefor.

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: This invention provides methods of retentate chromatography for resolving analytes in a sample. The methods involve adsorbing the analytes to a substrate under a plurality of different selectivity conditions, and detecting the analytes retained on the substrate by desorption spectrometry. The methods are useful in biology and medicine, including clinical diagnostics and drug discovery.

Abstract: Methods and compositions are described for the detection and quantitation of cardiac specific troponin I and troponin T in samples. Cardiac-specific troponin isoforms exist in various forms in the blood, including free and complexed forms. By selecting antibodies that are sensitive and/or insensitive to these various forms, the present invention can provide immunoassays that more accurately reflect the clinical state of an individual. These described methods and compositions can be used for providing indicators of myocardial infarction and other cardiac pathologies.

Abstract: A homogeneous immunoassay method and system for quantitative determination of total immunoglobulin E and specific antibody levels to a plurality of allergens, in which a relatively small sampling of blood is required. The method utilizes relatively small microparticles in suspension with 1-5 &mgr;L of undiluted sample. The immunoassay procedure is an immunometric sandwich procedure preferably utilizing biotin-streptavidin signal amplification techniques and R-phycoerytherin fluorescent labels.

Abstract: The present invention discloses a homogeneous fluorescent binding assay method using carrier particles.