Abstract: The present invention provides ligand-detection reagents, ligand analogs and methods for determining the presence of a ligand in a sample. The ligand-detection reagent comprises a ligand-binding antibody and a ligand analog to form an antibody-ligand analog complex wherein the ligand analog is covalently bonded to a reporter molecule. This complex may additionally comprise a labeling protein non-covalently bonded to the antibody to form a ternary complex wherein the labeling protein comprises a monovalent antibody fragment or a non-antibody protein that is covalently bonded to a label moiety. The reporter molecule is either quenched by the ligand-binding antibody or by the label moiety of the labeling protein, depending on the reporter molecule and the ligand-binding antibody, wherein the amount of quenching is directly related to the amount of ligand present in the sample.

Abstract: Methods and compositions for detecting and localizing light originating from a mammal are disclosed. Also disclosed are methods for targeting light emission to selected regions, as well as for tracking entities within the mammal. In addition, animal models for disease states are disclosed, as are methods for localizing and tracking the progression of disease or a pathogen within the animal, and for screening putative therapeutic compounds effective to inhibit the disease or pathogen.

Abstract: This invention provides for labeling reagents, labeled targets and processes for preparing labeling reagents. The labeling reagents can take the form of cyanine dyes, xanthene dyes, porphyrin dyes, coumarin dyes or composite dyes. These labeling reagents are useful for labeling probes or targets, including nucleic acids and proteins. These reagents can be usefully applied to protein and nucleic acid probe based assays. They are also applicable to real-time detection processes.

Abstract: The invention discloses compounds and compositions for dual phototherapy and combined therapy and diagnosis of tumors and other lesions. The compounds have a Dye that, when photoactivated, operates via Type I and/or Type II mechanisms. Other Dye or azide components may operate by the same or different mechanisms. Selection of particular components in a compound, and formulation of the compound(s) in a composition permit different activation wavelengths to be used for different therapies. A targeting moiety may be added to the compound or composition so that the Dye locates at a particular site, such as a hormone-sensitive tumor, for diagnosis and/or treatment. The compounds and compositions may be incorporated within liposomes.

Abstract: Unsymmetrical cyanine dyes that incorporate an aza-benzazolium ring moiety are described, including cyanine dyes substituted by a cationic side chain, monomeric and dimeric cyanine dyes, chemically reactive cyanine dyes, and conjugates of cyanine dyes. The subject dyes are virtually non-fluorescent when diluted in aqueous solution, but exhibit bright fluorescence when associated with nucleic acid polymers such as DNA or RNA, or when associated with detergent-complexed proteins. A variety of applications are described for detection and quantitation of nucleic acids and detergent-complexed proteins in a variety of samples, including solutions, electrophoretic gels, cells, and microorganisms.

Abstract: Method for measuring the presence or absence of chemical groups, in particular phosphate groups, attached to biological molecules in a sample in which these molecules are tagged with fluorescent markers and these fluorescent markers are activated by means of irradiating the sample with light. The method is characterized by the following steps: a) Use of a fluorescent marker, the fluorescence lifetime of which assumes a different value depending upon the presence or absence of phosphate groups attached to the biomolecule; b) Measurement of the fluorescence lifetime of the fluorescent marker attached to a biomolecule and selected in accordance with Step a); c) Classification of the biomolecules in accordance with the presence or absence of phosphate groups attached to these, based on the different lifetime of each.

Abstract: A method of inspecting a DNA chip and an apparatus therefor that allow a picture to be reconstructed in the following steps: A plurality of irradiation spots are formed on a DNA probe array mounted on a stage. Then, the stage is displaced in X, Y directions so as to execute a scanning, thereby irradiating substantially all the entire surface of the DNA probe array. Next, a plurality of emitted fluorescent lights, which are generated from the plurality of irradiation spot portions on the DNA probe array, are converged and are then detected simultaneously by multi detectors. Finally, a data processing apparatus processes the detected signals, thereby reconstructing the picture.

Abstract: A method of assaying to determine the identity and/or concentration or relative concentration in a sample solution of a particular one of a number of different target molecule types, comprise the steps of: i) adding to the sample a probe substance which binds to the or each target molecule type and which when so bound fluoresces under appropriate excitation; ii) performing a time-resolved fluorescence measurement on the sample; and iii) making said determination from analysis of the time decay data obtained from said time-resolved fluorescence measurement.

Abstract: This invention relates to a method for the determination of substances using the evanescence field method. A cuvette, a microtiter well, a solution and a kit for application in a method according to the invention are disclosed. This method can in particular be used in the field of diagnostics and in analytical procedures.

Abstract: Methods and compositions for detecting and localizing light originating from a mammal are disclosed. Also disclosed are methods for targeting light emission to selected regions, as well as for tracking entities within the mammal. In addition, animal models for disease states are disclosed, as are methods for localizing and tracking the progression of disease or a pathogen within the animal, and for screening putative therapeutic compounds effective to inhibit the disease or pathogen.

Abstract: A method of detecting target biological molecules in a target sample is provided. The method includes using spectral, temporal, and polarization characteristics of emitted light from water-stable semiconductor nanocrystal complexes to detect the presence of target biological molecules in a target sample.

Abstract: This invention relates to a biospecific assay method, in which microparticles coated with the bioaffinity reactant A binding the analyte to be assayed; the sample to be analyzed, and the labelled bioaffinity reactant B are mixed. After the binding reaction the signal strength from the labelled bioaffinity reactant B bound to the microparticles is quantitated for the determination of the concentration of the analyte in the sample. According to the invention, such an amount of sample and microparticles is used in the assay that after binding of the analyte of the sample to the said amount of microparticles, each individual microparticle will emit such a signal strength as to allow the measurement of the analyte concentration over the whole range of typical analyte concentrations, and the signal strength from each microparticle is measured separately.

Abstract: Methods are disclosed for producing electrochemiluminescence by electrochemically oxidizing an acridan compound at an electrode in the presence of a peroxide. Maintaining a sufficiently positive potential results in continuous oxidation of the acridan compound to an acridinium compound which reacts with peroxide to produce the luminescence. Light emission can be reversibly and repeatedly cycled on and off by sweeping the potential between two values. The acridan compounds can be provided with a labeling group for linking to an analyte or analyte binding partner. The present electrochemiluminescent reaction can find use in assay methods for detecting analytes by immunoassays and nucleic acid assays.

Abstract: The present invention relates generally to a method and compound for sensing the presence of anionic phospholipids, especially phosphatidylserine, on the surface of vesicles and cells.

Abstract: The present invention describes methods and cassettes for cell-based toxin detection and organ localization. The cassettes includes an array containing cells and a matrix of openings or depressions, wherein each region of the substrate enclosed by the opening or depression in the matrix forms a domain individually addressable by microfluidic channels in the device.

Abstract: A molecule with two pendant phenylarsine moieties according to the general structural Formula (I) and tautomers, acids, and salts thereof: wherein: (i) R1 or R2, are each independently O?, S?, OR3 or SR3 with the provision that if either R1 or R2 is absent, the other remaining group is ?O or ?S; or R1 and R2, together with the arsenic atom, form a ring according to one of the general structural Formulae (II), (III), (IV), or (V): wherein R3 is H, CH(OH)CH2OH, or (CH2)q—Y, with q being 1–4 and Y being H, OH, NH2, SH, COOH, OAc, CONH2 or CN, and Z represents a hydrocarbon chain comprising 2–4 singly or doubly bonded carbon atoms each of which may be further substituted with one or more of hydrogen, methyl, ethyl, 1-propyl, 2-propyl, methoxy, hydroxy, amino, carboxy, sulfo, oxo, thio, halo (fluoro, chloro, bromo, or fluoro) and (CH2)n?SO3, wherein n? is 1 or 2; (ii) R4, R5, R6 and R7 are each independently H, F, OR3, R3, OAc, NH2, N(C1–C4 alkyl)2, R1; or R4 with R5, or R6 together with R7, or both, form

Abstract: Methods and compositions are provided for detecting changes in membrane potential in membranes biological systems. In one aspect, the method comprises; a) providing a living cell with a first reagent comprising a charged hydrophobic molecule which is typically a fluorescence resonance energy transfer (FRET) acceptor or donor, or is a quencher and is capable of redistributing within the membrane of a biological membrane in response to changes in the potential across the membrane; b) providing the cell with a second reagent that can label the first face or the second face of a biological membrane within the cell; c) detecting light emission from the first reagent or the second reagent. One aspect of this method involves monitoring membrane potential changes in subcellular organelle membranes in a living cells. Another aspect of the invention is the use of certain embodiments of the method for the screening of test chemicals for activity to modulate the activity of a target ion channel.

Abstract: Methods and compositions are provided for determining the potential of a membrane. In one aspect, the method comprises: (a) introducing a first reagent comprising a hydrophobic fluorescent ion capable of redistributing from a first face of the membrane to a second face of the membrane in response to changes in the potential of the membrane, as described by the Nernst equation, (b) introducing a second reagent which labels the first face or the second face of the membrane, which second reagent comprises a chromophore capable of undergoing energy transfer by either (i) donating excited state energy to the fluorescent ion, or (ii) accepting excited state energy from the fluorescent ion, (c) exposing the membrane to radiation; (d) measuring energy transfer between the fluorescent ion and the second reagent, and (e) relating the energy transfer to the membrane potential. Energy transfer is typically measured by fluorescence resonance energy transfer.

Abstract: Water soluble hybrid phthalocyanine derivatives useful in competitive and noncompetitive assays immunoassays, nucleic acid and assays are disclosed and claimed having (1) at least one donor subunit with a desired excitation peak; and (2) at least one acceptor subunit with a desired emission peak, wherein said derivative(s) is/are capable of intramolecular energy transfer from said donor subunit to said acceptor subunit. Such derivatives also may contain an electron transfer subunit. Axial ligands may be covalently bound to the metals contained in the water soluble hybrid phthalocyanine derivatives. Ligands, ligand analogues, polypeptides, proteins and nucleic acids can be linked to the axial ligands of the dyes to form dye conjugates useful in immunoassays and nucleic acid assays.

Abstract: A method for synthesizing dyes excitable by a helium-neon laser (excitable at 633 nm) from hololepidines, e.g., 7-halolepidine, which dyes are suitable for detection and enumeration of reticulocytes in human blood samples. In another aspect, the invention provides a method for immunotyping phenocytes. The method is based on the phenomenon that when dyes of certain structure intercalate into DNA or RNA, the intensity of the dye increases. Dyes suitable for this invention can be described as having (a) a first heterocyclic moiety, (b) a second heterocyclic moiety, and (c) a linking group that connects the first and second heterocyclic moieties. Both the first and second heterocyclic moieties must contain at least two rings, preferably fused together. The dye is characterized by conjugation, whereby the first moiety is ethylenically conjugated to the second moiety.

Abstract: Methods and compositions are described for analyzing complex protein mixtures using fluorescent activity-based probes. In particular, probes that specifically react with and bind to the active form of one or more target proteins are employed. Fluorescent signals obtained from the labeled active target proteins can be related to the presence or amount of active members of the desired target protein class. The methods and compositions described herein can be used, for example, to provide diagnostic information concerning pathogenic states, in identifying proteins that may act as therapeutic targets, and in drug discovery.

Abstract: A method for the detection or quantitation of an analyte in a biological sample is disclosed. The method comprises the steps of selecting a biological sample suspected of containing a target analyte and binding the target analyte in the sample to a binding partner conjugated to an acridinium compound, wherein the acridinium compound comprises an acridinium nucleus having an electron-donating substituent directly attached to the acridinium nucleus at the C2 position. Chemiluminescent acridinium compounds useful in the method have emission maxima close to or in the near infrared (NIR) region (>590 nm). These chemiluminescent acridinium compounds when used in conjunction with short wavelength-emitting acridinium esters (with emission maxima below 450 nm) can be highly useful labels for the simultaneous detection of multiple target analytes in a single assay.

Abstract: Carriers hold remote-acting bodies which can be manipulated by a remote force, and also hold a micro-substance which is a target substance of an assay. The remote-acting bodies are manipulated in order to control the positions of the micro-substances, so as to execute assays for various target substances efficiently, at low cost, easily, and reliably. Various aspects of interest include the carriers which hold the micro-substances, a system suspending the carriers, an apparatus for manipulating the carriers, and a method of controlling the position of the carriers.

Abstract: Assays for detecting molecular modifications such as phosphate modifications and the presence and/or activity of enzymes and other agents involved in facilitating or otherwise regulating such modifications.

Abstract: The present invention provides a method for reducing undesirable light emission from a sample using at least one photon producing agent and at least one photon reducing agent (e.g. dye-based photon reducing agents). The present invention further provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one collisional quencher. The present invention also provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one quencher, such as an electronic quencher. The present invention also provides a system and method of screening test chemicals in fluorescent assays using photon reducing agents. The present invention also provides compositions, pharmaceutical compositions, and kits for practicing these methods.

Abstract: The invention relates to an optical system for determining the distribution, environment, or activity of fluorescently labeled reporter molecules in cells for the purpose of screening large numbers of compounds for specific biological activity. The invention involves providing cells containing fluorescent reporter molecules in an array of locations and scanning numerous cells in each location with a fluorescent microscope, converting the optical information into digital data, and utilizing the digital data to determine the distribution, environment or activity of the fluorescently labeled reporter molecules in the cells. The array of locations may be an industry standard 96 well or 384 well microtiter plate or a microplate which is a microplate having a cells in a micropaterned array of locations. The invention includes apparatus and computerized method for processing, displaying and storing the data.

Abstract: The present invention is directed to a method of sequencing a target nucleic acid molecule having a plurality of bases. In its principle, the temporal order of base additions during the polymerization reaction is measured on a molecule of nucleic acid, i.e. the activity of a nucleic acid polymerizing enzyme on the template nucleic acid molecule to be sequenced is followed in real time. The sequence is deduced by identifying which base is being incorporated into the growing complementary strand of the target nucleic acid by the catalytic activity of the nucleic acid polymerizing enzyme at each step in the sequence of base additions. A polymerase on the target nucleic acid molecule complex is provided in a position suitable to move along the target nucleic acid molecule and extend the oligonucleotide primer at an active site.

Abstract: The present invention provides methods, compounds, and kits useful in the analysis of reaction products and components of reaction mixtures, and in certain embodiments for the rapid and simultaneous determination of enantiomeric ratios, percent conversions, and absolute configurations.

Abstract: The invention relates to a process for quantitative detection of analytes in liquid and solid phases with the aid of binding remanence measurement, compounds that are suitable for this purpose, and their use in analytic chemistry.

Abstract: The invention relates to analytical methods in which the partition of a labeled substance between a liquid and a solid phase is determined. The assays include solid-phase reagents which can be particulate or monolithic such as, for example, a coated tube. Assays of this type are known per se to the person skilled in the art and include immunoassays and immunometric assays.

Abstract: The invention provides an apparatus and method for detection of a target molecule. The apparatus includes a probe labeled with a transition metal-ligand complex that hybridizes with the target to form an initial complex, a metal ion for doping the initial complex and forming a final complex, and a potential means for providing a potential to the final complex to produce a detectable signal indicating the presence of the target after redox reaction. The method of the invention teaches the steps of hybridizing a probe with an attached label to the target to produce an initial complex, adding a metal ion to the initial complex to form a final complex and applying a potential to the final complex to produce a measurable signal.

Abstract: The present invention relates to the use of fluorogenic or chromogenic dyes as reporter molecules for detecting cell entry by a specific molecule.

Abstract: The present invention provides luminescent lanthanide metal chelates comprising a metal ion of the lanthanide series and a complexing agent comprising at least one salicylamidyl moiety. Also provided are probes incorporating the salicylamidyl ligands of the invention and methods utilizing the ligands of the invention and probes comprising the ligands of the invention.

Abstract: The proteins in a biological sample that is sought to be analyzed for its protein composition by an electrophoretic or chromatographic procedure are coupled to a dye in an unusually efficient manner by combining the sample with a solid dry composition containing the dye, a buffering agent, and in preferred embodiments, a denaturing agent as well. The solid and dry form of the composition prevents the dye from deteriorating or decomposing, and the combination of components in the composition allows the dye to couple to the proteins in a relatively uniform manner with no overstaining of the protein when the composition and the sample are heated together and held at an elevated temperature for a short period of time.

Abstract: The present invention provides a method and apparatus for to conduct transgenic and targeted mutagenesis screening of genomic DNA. This invention also provides a system for screening DNA for a designated genetic sequence. The system includes a computer having a processor, memory and web browser, wherein the computer receives instructions concerning the designated genetic sequence and other screening parameter selection from a remote user via a form of electronic communication, and an automatic screening device that analyzes samples of genomic DNA for the designated sequence.

Abstract: The present invention relates to an immunogenic conjugate comprising a carrier molecule coupled to an autoinducer of a Gram negative bacteria. The immunogenic conjugate, when combined with a pharmaceutically acceptable carrier, forms a suitable vaccine for mammals to prevent infection by the Gram negative bacteria. The immunogenic conjugate is also used to raise and subsequently isolate antibodies or binding portions thereof which are capable of recognizing and binding to the autoinducer. The antibodies or binding portions thereof are utilized in a method of treating infections, a method of inhibiting autoinducer activity, and in diagnostic assays which detect the presence of autoinducers or autoinducer antagonists in fluid or tissue samples.

Abstract: Improved methods, reagents, and kits for quantitation of HLA-DR and/or CD11b expression on peripheral blood cells are presented. Inclusion of a lysosomotropic amine, such as chloroquine, during staining stabilizes HLA-DR and CD11b expression. Use of a novel anti-CD14 conjugate, anti-CD14-PerCP/CY5.5, permits the ready discrimination of monocytes. The improved methods, reagents, and kits may be used to assess immune competence, and to direct and monitor immunostimulatory therapies in septic patients exhibiting monocyte deactivation.

Abstract: Foreign proteins are placed into the blood of an animal so that they can be recovered at a later time and used for identification. Proteins are administered to the animal from a water bath via the animal's gills (where appropriate), gut and, through the skin. The foreign protein is detectable in small amounts using immune assays which magnify the available signals or tags in an assay.

Abstract: The invention involves identification of a mechanism of ?-amyloid peptide cytotoxicity, which enables treatment of conditions caused by ?-amyloid peptide aggregates by administration of compounds which antagonize the mechanism of cytotoxicity. The invention includes the identification and isolation of compounds which can antagonize the aggregation of ?-amyloid peptides and the neurotoxic effects of such aggregates. The compounds include isolated peptides which were selected for their ability to form a complex with a ?-amyloid peptide, or are derived from peptides so selected. Methods for treating conditions resulting from neurotoxic ?-amyloid peptide aggregates and pharmaceutical preparations are provided. Also provided are methods for selecting additional compounds which can antagonize the aggregation of ?-amyloid peptides and the neurotoxic effects of such aggregates.

Abstract: The invention includes a composition of matter and method that utilizes energy transfer between one or more donor and acceptor molecules. The composition of matter includes an encapsulation vesicle having a matrix, a surface coating of an organo-metallic complex and a transparent protection layer. The transparent protection layer is capable of modification by addition of biomolecules to the surface in order to bind other molecules. The proximity of the bound biomolecules to the protective layer allows for energy transfer from a donor molecule internal to the protection layer to an acceptor molecule outside the protection layer. The protection layer acts to diminish the effects of collisional quenching on the donor molecules caused by ubiquitous small molecules such as molecular oxygen. The application also teaches a method of making and applying the complexes to immunoassays.

Abstract: Methods and compositions for detecting and localizing light originating from a mammal are disclosed. Also disclosed are methods for targeting light emission to selected regions, as well as for tracking entities within the mammal. In addition, animal models for disease states are disclosed, as are methods for localizing and tracking the progression of disease or a pathogen within the animal, and for screening putative therapeutic compounds effective to inhibit the disease or pathogen.

Abstract: Methods and compositions for detecting and localizing light originating from a mammal are disclosed. Also disclosed are methods for targeting light emission to selected regions, as well as for tracking entities within the mammal. In addition, animal models for disease states are disclosed, as are methods for localizing and tracking the progression of disease or a pathogen within the animal, and for screening putative therapeutic compounds effective to inhibit the disease or pathogen.

Abstract: Methods and compositions for detecting and localizing light originating from a mammal are disclosed. Also disclosed are methods for targeting light emission to selected regions, as well as for tracking entities within the mammal. In addition, animal models for disease states are disclosed, as are methods for localizing and tracking the progression of disease or a pathogen within the animal, and for screening putative therapeutic compounds effective to inhibit the disease or pathogen.

Abstract: Methods and compositions for detecting and localizing light originating from a mammal are disclosed. Also disclosed are methods for targeting light emission to selected regions, as well as for tracking entities within the mammal. In addition, animal models for disease states are disclosed, as are methods for localizing and tracking the progression of disease or a pathogen within the animal, and for screening putative therapeutic compounds effective to inhibit the disease or pathogen.

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 invention relates to an optical system for determining the distribution, environment, or activity of fluorescently labeled reporter molecules in cells for the purpose of screening large numbers of compounds for specific biological activity. The invention involves providing cells containing fluorescent reporter molecules in an array of locations and scanning numerous cells in each location with a fluorescent microscope, converting the optical information into digital data, and utilizing the digital data to determine the distribution, environment or activity of the fluorescently labeled reporter molecules in the cells. The array of locations may be an industry standard 96 well or 384 well microtiter plate or a microplate which is a microplate having a cells in a micropaterned array of locations. The invention includes apparatus and computerized method for processing, displaying and storing the data.

Abstract: A method for classifying and counting leukocytes comprises the steps of: (1) adding to a hematological sample the following fluorescence-labeled antibodies labeled with fluorescent dyes which emit fluorescences distinguishable from each other; (a) a first fluorescence-labeled antibody (1st antibody) which bonds specifically to leukocytes, (b) a second fluorescence-labeled antibody (2nd antibody) which bonds to at least one kind of neutrophilic cells, and (c) a third fluorescence-labeled antibody (3rd antibody) which bonds to at least one kind of immature granulocytic cells, in order to stain leukocytic cells in the sample, and removing erythrocytes from the sample; (2) analyzing the resulting sample using a flow cytometer to measure at least one scattered light signal and three separate fluorescence signals; (3) defining a group of granulocytic cells on the basis of intensity of the scattered light and intensity of fluorescence from the 1st antibody; (4) defining neutrophilic cells in the defined group of gra

Abstract: A method for assay of an analyte by use of a material labeled with a chemiluminescent substance, which comprises adding a quencher and/or decreasing the specific activity of a chemiluminescent substance labeled probe, thereby decreasing the quantity of chemiluminescence.

Abstract: A light emitting method of an acridinium ester, comprising reacting said acridinium ester and a superoxide anion, and a method of detecting a substance to be examined, comprising detecting a light emitted by reacting a superoxide anion with an acridinium ester used as a label am described. It is possible to carry out the reaction not under strongly alkaline conditions but around the neutral point and to generate strong luminescence which is stable over a long period of time.

Abstract: The invention provides compositions electron-deficient nitrogen heterocycle-substituted fluorescein dyes and methods in which the dyes are conjugated to substrates and used as detection labels in molecular biology experiments. The electron-deficient nitrogen heterocycles include pyridine, quinoline, pyrazine, and the like. Substrates include polynucleotides, nucleosides, nucleotides, peptides, proteins, carbohydrates, and ligands.