Abstract: An automatic analyzer that dispenses a sample and a reagent in a reaction cuvette and measures the mixed solution, including a dispensing probe configured to suction the sample from the sample container and to discharge the sample into the reaction cuvette; a detecting unit configured to detect the sample in the sample container by the end part of the dispensing probe contacting the sample; and a washing unit configured to wash a wide range of the external surface containing a broad end part, rather than the end part of the dispensing probe, which keeps the suctioned sample in the sample container in a second downward suction position, rather than a first suction position detected by the detection unit, wherein the washing unit is configured to have a washing tube, wherein the dispensing probe enters into an upper part of the washing tube, and a pump that supplies the washing tube with cleaning liquid and makes the cleaning liquid flow up through the inside of the washing tube.

Abstract: The invention relates to a reaction vessel, a device and a method for detecting specific interactions between molecular target and probe molecules. The present invention especially relates to a reaction vessel which has a shape and size typical of a laboratory reaction vessel and in which a supporting element with probe molecules immobilized thereon on predetermined regions is arranged on its base surfaces.

Abstract: The invention relates to an analytical measuring and evaluation method for determining the interaction parameters between an analyte and a ligand, preferably in a biosensor. According to the inventive method, the concentration of the analyte is gradually changed at defined intervals ti and the initial association or dissociation rates or association and dissociation rate constants are determined. The invention further relates to a device for carrying out the inventive method.

Abstract: The instant invention provides for methods for detecting the internalization of a transmembrane protein of interest expressed at the surface of a cell. More specifically, the methods involve (a) labelling the protein of interest with a fluorescent metal complex, the lifetime of which is greater than 0.1 ms, (b) adding to the reaction medium a composition capable of causing the internalization of the protein of interest, (c) adding to the reaction medium (1) a modulating agent which is a fluorescent FRET acceptor compound compatible with the fluorescent metal complex, the final concentration of which in the reaction medium is greater than 10?7M; or (2) a reducing agent, the redox potential of which is less than +0.1 V and preferably between 0.25 and 0.

Abstract: The present invention relates to methods and kits for the prediction of risk for heart failure using post-translation modified forms of cardiac troponin T as a biomarker.

Abstract: The invention provides methods and compositions for simultaneously detecting the activation state of a plurality of proteins in single cells using flow cytometry. The invention further provides methods and compositions of screening for bioactive agents capable of coordinately modulating the activity of a plurality of proteins in single cells. The methods and compositions can be used to determine the protein activation profile of a cell for predicting or diagnosing a disease state, and for monitoring treatment of a disease state.

Abstract: An anti-antibody reagent for use in a competitive or sandwich simplex or multiplex assay, said reagent comprising one or more labeled anti-antibodies for the primary antibodies to be determined in the assay, the reagent further comprising a corresponding unlabeled anti-antibody in an excess or near excess concentration with respect to their binding partners.

Abstract: The present invention provides for methods and materials for diagnosing and treating neuromyelitis optica (NMO).

Abstract: A method for the enumeration of micronucleated erythrocyte populations while distinguishing platelet and platelet-associated aggregates involves the use of a first fluorescent labeled antibody having binding specificity for a surface marker for reticulocytes, a second fluorescent labeled antibody having binding specificity for a surface marker for platelets, and a nucleic acid staining dye that stains DNA (micronuclei) in erythrocyte populations. Because the fluorescent emission spectra of the first and second fluorescent labeled antibodies do not substantially overlap with one another or with the emission spectra of the nucleic acid staining dye, upon excitation of the labels and dye it is possible to detect the fluorescent emission and light scatter produced by the erythrocyte populations and platelets, and count the number of cells from one or more erythrocyte populations in said sample.

Abstract: The present invention comprises methods and systems that use acoustic radiation pressure.

Abstract: A system and method for determining the dissociation constant for a particular ligand is disclosed. In accordance with certain embodiments, the method creates a chemical denaturation curve of a protein in the absence of the ligand. A particular point is selected from this curve, such as the point at which 90% of the protein is unfolded. The molarity of chemical denaturant is determined for this selected point. A one point test is then performed for the protein with a predetermined concentration of the particular ligand. The fraction of protein which is unfolded at this point is then used to determine the dissociation constant for the ligand. This constant is used to quickly determine whether a particular ligard is well suited to be considered a potential drug candidate against that protein target.

Abstract: Whole cell, simultaneous target and drug-target assay using differentially labeled antibodies and flow cytometry. First antibody binds to total target and second antibody binds to the drug binding site of the target, thus drug binding will competitively inhibit the second antibody allowing for a competitive inhibition assay of drug-target binding. The assay allows for whole cell analysis and even analysis of mixed populations of cells, yet provides detailed kinetic assessment of drug activity.

Abstract: An instrument and a method for the automated thermal treatment of liquid samples are disclosed. An inter-distance between a temperature-controlled receptacle for loading with a plurality of vessels for containing the samples and end portions of optical fibers can be varied, wherein the receptacle is configured to form a thermal communication with the loaded vessels and wherein the optical fibers have first and second end portions. The first end portion and the second end portion of each optical fiber is fixed with respect to each other for transmitting light, wherein the variation of the inter-distance allows the vessels to be loaded to or unloaded from the receptacle and to enable detection of light from the samples contained in the one or more receptacle-loaded vessels.

Abstract: A method for determining an appropriate treatment option for a patient who has been diagnosed with disseminated intravascular coagulation (DIC) but who may have thrombotic thrombocytopenic purpura (TTP), by analyzing the amount and/or enzyme activity of a von Willebrand factor (vWF)-cleaving protease (ADAMTS13) and the amount of vWF in a patient that has been diagnosed with DIC is disclosed. Using the method of the present invention, a differential diagnosis of patients with thrombotic thrombocytopenic purpura (TTP) can be made from among patients diagnosed with DIC, which could not previously be distinguished on the basis of only clinical findings or known markers. Also disclosed is a kit for determining an appropriate treatment option, the kit comprising an antibody or a fragment thereof which specifically binds to ADAMTS13.

Abstract: An assay device for performing an assay on a liquid sample using a detection conjugate capable of binding to an antigen and containing a label. The device includes a substrate surface having a sample addition zone, a reaction zone and an absorbing zone, the zones being connected by at least one fluid passage, wherein the device has a first functionality verifying feature located between the sample addition zone and the reaction zone, and a second functionality verifying feature located within the absorbing zone. Both functionality verifying features are capable of undergoing a detectable change when contacted by the sample, in which the assay device further includes at least one alignment verification zone. There is further provided a kit of parts and a method of conducting an assay.

Abstract: Disclosed are antibodies that selectively bind to blood coagulation factor FVIII, and highly sensitive immunological assays comprising these antibodies. Preferred assays can detect FVIII at about 3500-fold below the normal physiological levels, and have a wide array of applications including accurate monitoring of FVIII concentration in pharmaceutical products for treatment of blood coagulation disorders, and determination of FVIII levels in plasma of human patients, including those with blood coagulation disorders such as hemophilia.

Abstract: Nanosubstrates as biosensors, methods of making such nanosubstrates, and methods of using such nanosubstrates to detect biomarkers are described.

Abstract: An anchoring/capturing system for selecting or analyzing a CHO cell according to a product secreted by the CHO cell is described. The anchoring/capturing system comprises a first antibody or a first antigen-binding fragment for anchoring to the extracellular surface of the CHO cell, and a second antibody or a second antigen-binding fragment for binding the secreted product. Uses and methods involving the anchoring/capturing system are provided.

Abstract: A method for obtaining the binding kinetic rate constants using fiber optic particle plasmon resonance (FOPPR) sensor, suitable for a test solution with two or more concentrations, which employs the following major steps: providing one FOPPR sensor instrument system, obtaining optical time-resolved signal intensities starting at the initial time to the steady state of the two or more regions, substituting the measured signal intensity values into the formula which is derived by using the pseudo-first order rate equation model. In addition, this method measures the temporal signal intensity evolution under static conditions as the samples are quickly loaded. As a result, unlike the conventional device where the sample is continuously infused, the method is able to measure the association and dissociation rate constants of which the upper bounds are not limited by the sample flow rate.

Abstract: The current invention is directed to the velocity factor. Based on the velocity factor antibodies can be classified, i.e. antibodies can be characterized on their binding properties as e.g. entropic or enthalpic antigen binder. A velocity factor based classification does not require detailed thermodynamic determinations and/or calculations. The velocity factor is the ratio of the antigen-antibody complex association rate constants ka determined at 37° C. and 13° C. As only two experimental determinations are required to calculate the velocity factor this is a fast and high-throughput suited method.

Abstract: The present invention relates to antigen binding molecules (ABMs). In particular embodiments, the present invention relates to recombinant monoclonal antibodies, including chimeric, primatized or humanized antibodies specific for human EGFR. In addition, the present invention relates to nucleic acid molecules encoding such ABMs, and vectors and host cells comprising such nucleic acid molecules. The invention further relates to methods for producing the ABMs of the invention, and to methods of using these ABMs in treatment of disease. In addition, the present invention relates to ABMs with modified glycosylation having improved therapeutic properties, including antibodies with increased Fc receptor binding and increased effector function.

Abstract: A method for the enumeration of micronucleated erythrocyte populations while distinguishing platelet and platelet-associated aggregates involves the use of a first fluorescent labeled antibody having binding specificity for a surface marker for reticulocytes, a second fluorescent labeled antibody having binding specificity for a surface marker for platelets, and a nucleic acid staining dye that stains DNA (micronuclei) in erythrocyte populations. Because the fluorescent emission spectra of the first and second fluorescent labeled antibodies do not substantially overlap with one another or with the emission spectra of the nucleic acid staining dye, upon excitation of the labels and dye it is possible to detect the fluorescent emission and light scatter produced by the erythrocyte populations and platelets, and count the number of cells from one or more erythrocyte populations in said sample.

Abstract: The present invention generally provides methods and systems for performing in vivo flow cytometry by using blood vessels as flow chambers through which flowing cells can be monitored in a live subject in vivo without the need for withdrawing a blood sample. In some embodiments, one or more blood vessels are illuminated with radiation so as to cause a multi-photon excitation of an exogenous fluorophore that was previously introduced into the subject to label one or more cell types of interest. In some other embodiments, rather than utilizing an exogenous fluorophore, endogenous (intrinsic) cellular fluorescence can be employed for in vivo flow cytometry. The emission of fluorescence radiation from such fluorophores in response to the excitation can be detected and analyzed to obtain information regarding a cell type of interest.

Abstract: An embodiment relates to a method of detecting a drug resistance in a patient comprising adding nanoparticles to sample platelets to form activated platelets containing the nanoparticles and comparing a difference in activation of the activated platelets and the sample platelets. Another embodiment relates to a method of monitoring a thrombotic risk factor in a subject in a general population comprising adding nanoparticles to sample platelets to form activated platelets containing the nanoparticles and comparing a difference in activation of the activated platelets and the sample platelets. Yet another embodiment relates to a kit comprising nanoparticles, a fluorescence dye tagged antibody and optionally a buffer, wherein the kit is configured to detect a drug resistance in a patient or a likelihood of the thrombotic risk factor in a subject in general population.

Abstract: A method for determining the amount of NT-proBNP in blood samples from felines. The method includes detecting degradation products of feline NT-proBNP by various methods, including using antibodies, kits and devices.

Abstract: The present disclosure relates to novel bis-maleic anhydrides and to the surprising discovery that bis-maleic anhydride cross-linking agents can be used for preservation/fixation of a cell or tissue sample. Various bis-maleic anhydride cross-linking agent scan be used in methods requiring fixation of a cell or tissue sample. These reagents and methods are especially useful in procedures that require that the fixation agent be removed in order to facilitate analysis with other reagents. The inventive reagents and methods make it easier to reliably assay for various proteins, a nucleic acid and the like using analytical methods such as like immunohistochemistry, fluorescence in situ hybridization, RT-PCR, and the like.

Abstract: A method for estimating binding kinetic rate constants by using a fiber optic particle plasmon resonance (FOPPR) sensor mainly employs the steps of: providing a FOPPR sensor instrument system, obtaining optical signal intensities at an initial time and steady state signal intensities of first and second regions in an intensity versus time graph separately, substituting the measured signal intensity values into a formula derived by using a pseudo-first order rate equation model. According to this method, no fluorophore labeling is required. In addition, this method measures a temporal signal intensity evolution under static conditions as the samples are quickly loaded. As a result, unlike the conventional device where the sample is continuously infused, the method is able to measure binding and decomposition rate constants whose upper limit is not limited by a sample flow rate.

Abstract: A microfluidic test module for detecting target nucleic acid sequences in a fluid, the test module having an outer casing configured for hand-held portability, the outer casing having an inlet for receiving the fluid containing the target nucleic acid sequences, a hybridization chamber mounted in the casing, the hybridization chamber containing electrochemiluminescent (ECL) probes for detecting the target nucleic acid sequences, each of the ECL probes having an ECL luminophore for emitting photons when in an excited state and a functional moiety for quenching photon emission from the ECL luminophore by resonant energy transfer, and electrodes for receiving an electrical pulse to excite the ECL luminophores, wherein, the hybridization chamber has a volume less than 900,000 cubic microns.

Abstract: A test module for excitation of electrochemiluminescent probes configured to detect target nucleic acid sequences, the test module having an outer casing having a receptacle for receiving a fluid containing the target nucleic acid sequences, electrochemiluminescent (ECL) probes having an ECL luminophore for emitting photons when in an excited state and a functional moiety for quenching photon emission from the ECL luminophore by resonant energy transfer, electrodes for receiving an electrical pulse to excite the ECL luminophores, a detection photosensor for exposure to the photons emitted by the ECL luminophores, control circuitry providing the electrical pulse to the electrodes, and, a universal serial bus (USB) connection such that the outer casing is configured as a USB drive for transmitting data regarding detection of the targets in the fluid to an external device, wherein during use, the ECL probes that have detected one of the target nucleic acid sequences reconfigure such that the functional moiety do

Abstract: A microfluidic test module for detecting target nucleic acid sequences in a fluid, the test module having an outer casing having an inlet for receiving the fluid containing the target nucleic acid sequences, electrode pairs for receiving an electrical pulse, electrochemiluminescent (ECL) probe spots in contact with each of the electrode pairs respectively, the ECL probe spots containing ECL probes having an ECL luminophore for emitting photons when in an excited state and a functional moiety for quenching photon emission from the ECL luminophore by resonant energy transfer, such that the electrical pulse to the electrode pair excites the ECL luminophores, wherein, the mass of the ECL probes in each of the probe spots is less than 270 picograms.

Abstract: Whole cell, simultaneous target and drug-target assay using differentially labeled antibodies and flow cytometry. First antibody binds to total target and second antibody binds to the drug binding site of the target, thus drug binding will competitively inhibit the second antibody allowing for a competitive inhibition assay of drug-target binding. The assay allows for whole cell analysis and even analysis of mixed populations of cells, yet provides detailed kinetic assessment of drug activity.

Abstract: A combined detector capable of simultaneously detecting both a value indicating a physical/chemical phenomenon such as a pH value and the intensity of an energy beam such as light. The combined detector comprises a physical/chemical phenomenon detecting system (10) and an energy beam detecting system. The physical/chemical phenomenon detecting system (10) has a sensing section (21) whose potential varies with a physical/chemical phenomenon, a charge supply section (22) for supplying first charge to the sensing section, a charge supply control section (23) provided between the sensing section (21) and the charge supply section (22), a first charge storage section (26) for storing the first charge transferred from the sensing section (21), and a charge transfer control section (27) provided between the sensing section (21) and the first charge storage section (26).

Abstract: A portable test module for excitation of electrochemiluminescent probes configured to detect target nucleic acid sequences, the test module having an outer casing configured for hand-held portability, the outer casing having a receptacle for receiving a fluid containing the target nucleic acid sequences, electrochemiluminescent (ECL) probes having an ECL luminophore for emitting photons when in an excited state and a functional moiety for quenching photon emission from the ECL luminophore by resonant energy transfer, and, electrodes for receiving an electrical pulse to excite the ECL luminophores, wherein during use, the ECL probes that have detected one of the target nucleic acid sequences reconfigure such that the functional moiety does not quench the photon emission from the ECL luminophore when excited by the electrodes.

Abstract: A test module for detecting target nucleic acid sequences in a fluid, the test module having an outer casing having a receptacle for receiving the fluid containing the target nucleic acid sequences, electrochemiluminescent (ECL) probes having an ECL luminophore for emitting photons when in an excited state and a functional moiety for quenching photon emission from the ECL luminophore by resonant energy transfer, electrodes for receiving an electrical pulse to excite the ECL luminophores, and, a detection photosensor for exposure to the photons emitted by the ECL luminophores.

Abstract: A test module for concentrating pathogens in a biological sample, the test module having an outer casing with a receptacle for receiving the sample, a dialysis device in fluid communication with the receptacle and configured to separate the pathogens from other constituents in the sample, and, a lab-on-a-chip (LOC) device being in fluid communication with the dialysis device and configured to analyze the pathogens.

Abstract: Disclosed are methods for conducting assays of samples, such as whole blood, that may contain cells or other particulate matter. Also disclosed are systems, devices, equipment, kits and reagents for use in such methods. One advantage of certain disclosed methods and systems is the ability to rapidly measure the concentration of an analyte of interest in blood plasma from a whole blood sample without blood separation and hematocrit correction.

Abstract: Methods and reagents are disclosed for pretreating a sample suspected of containing a hydrophobic drug for conducting an assay method for detecting the hydrophobic drug. A combination is provided in a medium that includes the sample, a releasing agent for releasing the hydrophobic drug and the metabolites from endogenous binding moieties, and a selective solubility agent that provides for substantially equal solubility of the hydrophobic drug and the metabolites in the medium. The selective solubility agent includes a water miscible, non-volatile organic solvent and is present in the medium in a concentration sufficient to provide for substantially equal solubility of the hydrophobic drug and the metabolites in the medium. The medium, which may further include a hemolytic agent, is incubated under conditions for releasing the hydrophobic drug and the metabolites from endogenous binding moieties. The pretreated sample may be subjected to an assay for determining the hydrophobic drug.

Abstract: The present invention provides an approach for the simultaneous determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of potentiators of cellular activation allows for characterization of such pathways and cell populations.

Abstract: Pax3, a member of the paired class homeodomain family of transcription factors and an essential protein for early skeletal muscle development, was shown to be phosphorylated in proliferating mouse primary myoblasts. Furthermore, Ser205, Ser201 and Ser209 were identified as the only sites of phosphorylation on Pax3 in proliferating mouse primary myoblasts. Phosphorylation of Ser205 was shown to be required for the efficient phosphorylation of Ser201 and/or Ser209. Site-specific antibodies were made to each of these three sites when phosphorylated. These three sites are also present and phosphorylated in the Pax3-FOXO1 fusion protein, and phosphorylation of these sites may play a role in ARMS. Thus, these new antibodies may be used in studying the regulation of nerve and muscle development and differentiation and in finding therapeutic solutions for certain disorders, including Waardenburg syndrome and childhood solid muscle tumor alveolar rhabdomyosarcoma (ARMS).

Abstract: The present invention identifies biomarkers that are diagnostic of nerve cell injury, organ injury, and/or neuronal disorders. Detection of different biomarkers of the invention are also diagnostic of the degree of severity of nerve injury, the cell(s) involved in the injury, and the subcellular localization of the injury.

Abstract: Human PGD genes are identified as modulators of the PTEN pathway, and thus are therapeutic targets for disorders associated with defective PTEN function. Methods for identifying modulators of PTEN, comprising screening for agents that modulate the activity of PGD are provided.

Abstract: The present invention aims to provide a convenient and low-cost method for detection of a wide variety of compounds interacting with a target molecule located on a cell membrane, using a living cell without need of separating the cell membrane or the like from the cell. The present invention also aims to provide a kit for carrying out the method of the present invention. The method for detection of the compound interacting with the molecule located on the cell membrane in the present invention comprises steps of, allowing a compound having a moiety capable of binding selectively to the molecule located on the cell membrane and a radicalization-promoting moiety, to act on the cell; further allowing a compound having a group capable of being radicalized by the radicalization-promoting moiety and a labeling group, to act on the cell; and identifying the interacting compound bound by the compound radicalized by the radicalization-promoting moiety.

Abstract: Disclosed are methods for conducting assays of samples, such as whole blood, that may contain cells or other particulate matter. Also disclosed are systems, devices, equipment, kits and reagents for use in such methods. One advantage of certain disclosed methods and systems is the ability to rapidly measure the concentration of an analyte of interest in blood plasma from a whole blood sample without blood separation and hematocrit correction.

Abstract: The present invention provides novel microfluidic devices and methods for performing pulsed field mobility shift assays in microfluidic devices. In particular the devices and methods of the invention utilize differences between electrophoretic mobilities (e.g., as between reactants and products, especially in non-fluorogenic reactions) in order to separate the species and thus analyze the reaction.

Abstract: The application relates to a method of diagnosing neuropsychiatric diseases, eating disorders and/or metabolic diseases, which comprises: (i) measuring the affinity and/or the avidity of antibodies, derived from a biological sample, directed against a biological molecule involved in homeostatic regulation and/or in motivational behavior and/or in emotion; (ii) comparing the affinity value obtained with a control value.

Abstract: The present invention provides methods and systems for performing in vivo flow cytometry. In one embodiments, selected circulating cells of interest of a subject are labeled with fluorescent probe molecules. The labeled cells are irradiated in-vivo so as to excite the fluorescent probes, and the radiation emitted by the excited probes is detected, preferably confocally. The detected radiation is then analyzed to derive desired information, such as relative cell count, of the cells of interest. In some embodiments, the circulating cells comprise apoptotic cells whose detection can allow, e.g., non-invasive monitoring of the efficacy of a cancer treatment, such as an anti-tumor or an anti-angiogenic therapy.

Abstract: The present invention provides an approach for the simultaneous determination of the activation states of a plurality of proteins in single cells. This approach permits the rapid detection of heterogeneity in a complex cell population based on activation states, and the identification of cellular subsets that exhibit correlated changes in activation within the cell population. Moreover, this approach allows the correlation of cellular activities or properties. In addition, the use of potentiators of cellular activation allows for characterization of such pathways and cell populations.

Abstract: The current invention is directed to the velocity factor. Based on the velocity factor antibodies can be classified, i.e. antibodies can be characterized on their binding properties as e.g. entropic or enthalpic antigen binder. A velocity factor based classification does not require detailed thermodynamic determinations and/or calculations. The velocity factor is the ratio of the antigen-antibody complex association rate constants ka determined at 37° C. and 13° C. As only two experimental determinations are required to calculate the velocity factor this is a fast and high-throughput suited method.

Abstract: The invention provides methods and compositions for simultaneously detecting the activation state of a plurality of proteins in single cells using flow cytometry. The invention further provides methods and compositions of screening for bioactive agents capable of coordinately modulating the activity of a plurality of proteins in single cells. The methods and compositions can be used to determine the protein activation profile of a cell for predicting or diagnosing a disease state, and for monitoring treatment of a disease state.

Abstract: The present invention provides methods and systems for performing in vivo flow cytometry. In one embodiments, selected circulating cells of interest of a subject are labeled with fluorescent probe molecules. The labeled cells are irradiated in vivo so as to excite the fluorescent probes, and the radiation emitted by the excited probes is detected, preferably confocally. The detected radiation is then analyzed to derive desired information, such as relative cell count, of the cells of interest.