Abstract: Disclosed is a fluorescent semiconductor microparticle assembly comprising at least three kinds of fluorescent semiconductor microparticles with an average particle size of from 1 to 10 nm, having the same chemical composition, a different average particle size and a different emission maximum wavelength in the emission spectra, wherein a standard deviation of emission intensity in each of the at least three kinds of fluorescent semiconductor microparticles is not more than 15%.

Abstract: A reagent for measuring a basophil and/or a nucleated red blood cell is described. The reagent comprises (a) an alcohol having 4 to 8 total carbon atoms, and (b) one or more fluorescent dyes selected from the group consisting of a compound of the general formula (I) and a compound of the general formula (II).

Abstract: A subject of the invention is a method for discriminating between and counting at least two populations of biological elements carrying specific characteristics, optionally present in a sample. The invention allows the clear and unambiguous detection of at least three populations of biological elements by the use of only two detection means, which means that at least two populations of biological elements are detected by one and the same detection means. The invention can be carried out if three different probes are used, each recognizing and becoming fixed to one of the populations of biological elements to be detected, each of the probes being itself rendered detectable by a different marker, two of said markers having two emission spectra having at least one common part (overlapping emission spectra) and the third having an emission spectrum having essentially no part in common with the other two (non-overlapping spectrum).

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: Control and calibration solutions are described that provide control and calibration data that is recognized by a test meter allowing the meter to segregate the control and calibration data from regular test data. Recognition and segregation of the control and calibration data can occur automatically with no additional input from the meter's user. Methods for use of the solutions are also provided.

Abstract: The present invention relates a method for the enumeration of in vivo gene mutation. The method utilizes differential staining of GPI-anchor deficient erythrocyte populations to distinguish between wild-type and pig-a gene mutants. Quantitative analyses can be conducted on erythrocytes and/or reticulocytes, and is based upon fluorescent emission and light scatter following exposure to an excitatory light source. Counting of mutant erythrocytes or reticulocytes relative to the number of total erythrocytes or reticulocytes can be used to assess the DNA-damaging potential of an exogenous chemical agent, the DNA-damaging potential of an exogenous physical agent, the effects of an exogenous agent which can modify endogenously-induced DNA damage, and the effects of an exogenous agent which can modify exogenously-induced DNA damage. Kits for practicing the invention are also disclosed.

Abstract: The present invention relates to a processing method for long-term stabilization of biological red blood cell volume. The red blood cells can be further used in reference materials and calibrators of a hematology analyzer. The method of the present invention comprises contacting the sample with a solution comprising a membrane-fixation reagent and an aldehyde for a processing period to terminate or slow down the red blood cell metabolism. It is provided by experiments that such process enables the volume of the red blood cells to be stable in a period over 120 days.

Abstract: A microsphere-based analytic chemistry system is disclosed in which self-encoding microspheres having distinct characteristic optical response signatures to specific target analytes may be mixed together while the ability is retained to identify the sensor type and location of each sensor in a random dispersion of large numbers of such sensors in a sensor array using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which individual microsphere sensors are disposed in microwells at a distal end of the fiber bundle and are optically coupled to discrete fibers or groups of fibers within the bundle. The identities of the individual sensors in the array are self-encoded by exposing the array to a reference analyte while illuminating the array with excitation light energy.

Abstract: Method of enriching specific cells from cellular samples are disclosed, comprising contacting in solution a cellular sample with affinity-tagged ligands (ATLs) each comprising a first ligand linked to an affinity tag, wherein the ligand selectively binds a cellular marker of the rare cells and the affinity tag can be selectively captured by a capture moiety, wherein the affinity tags do not comprise a magnetic particle; and flowing the sample through a microfluidic device comprising the capture moiety to selectively retain ATL-bound cells. Methods for enriching circulating tumor cells, and devices for enriching specific cells from cellular samples are also disclosed.

Abstract: The invention concerns a method for differentiating and counting cellular components present in a biological fluid sample comprising a primary cytological analysis step typically implemented by a flow cytometry equipment (1) to obtain a set of primary results enabling the set of cellular components of the sample to be differentiated and counted in different populations; and a complementary step of cytological analysis of a particular type of cellular components, based on an identified cellular peculiarity, to obtain complementary results enabling at least one cell population or subpopulation of the sample to be differentiated and counted for identification of said cellular peculiarity. The invention is applicable in particular to hematological analyses.

Abstract: A system for checking measurement results is provided with a urine qualitative analyzer for measuring the specific gravity of a urine, urinary particle analyzer for measuring urine conductivity, and a computer. The urine specific gravity measured by the urine qualitative analyzer, and the urine conductivity measured by the urinary particle analyzer are respectively transmitted to the computer. The correlative relationship between urine specific gravity and urine conductivity is stored in the memory of the computer, and the computer determines whether or not the received urine specific gravity and conductivity match the correlative relationship, and this determination result is output.

Abstract: The present invention describes diagnostic calibration methods and related compositions for flow cytometry instruments using synthetic control particles as an internal reference standard. The invention provides synthetic control beads which substantially reduce the drawbacks of conventional control beads. Synthetic beads coated with C3, C4 or CR1 and a non-specific spacer protein such as ovalbumin provide a control bead without the positive reactivity seen in conventional BSA controls. The present invention further provides a buffer system containing non-specific blockers and assay performance enhancers that do not interfere with analyte detection. The invention provides advantageous improvements over prior instrument calibration procedures, and provides control beads that enable consistent, reproducible data for diagnostic assays using flow cytometry.

Abstract: High resolution particle differentiation process and separation system that provides enhanced resolution of particles based upon selected particle characteristics. In particular, the system may include an enhanced resolution flow cytometer. In an embodiment, the invention can include at least one fluid source conduit (24) that introduces 0 fluid source stream (24) into an enhanced resolution nozzle (25) at an angle that enhances particle resolution by the cell sensing system (13).

Abstract: Method for the automatic analysis of a blood sample in which: an analysis solution containing the blood sample, a diluent, and at least one compound to lyze the erythrocytes; at least one compound to stabilize the haemoglobin in the form of a chromogenic complex, is formed in a single dilution and analysis tank, the haemoglobin level is measured in this analysis solution by spectrophotometry in the tank after the lysis of the erythrocytes; and an appropriate quantity of this analysis solution is taken from the tank on which a leucocytic differentiation is carried out by an optical elements characterized in that the analysis solution also contains at least one compound to protect the leucocytes, allowing the distinguishing of at least four main leucocyte sub-populations. A haematological analysis apparatus for the implementation of such a method is disclosed.

Abstract: A reference control for cell by cell analysis on flow cytometric analyzers contains cellular analogs made of permeated blood cells containing therein aggregated intracellular proteins and preserved antigenic sites thereof, having cellular membrane permeable to antibodies and a suspension medium. The reference control is frozen after being prepared and thawed prior to use. The cellular analogs further contain a fluorescence marker therein. Further disclosed are a method of making the reference control and a method using the reference control, as an internal or stand-alone control, for measurements of cellular hemoglobin and cellular hemoglobin variant of a blood sample.

Abstract: Bodily fluid is analyzed for the presence of drugs of a selected panel of drugs in a simultaneous assay in which sample of the fluid is incubated with additional amounts of all drugs of the panel, antibodies specific to each of the drugs of the panel, and microparticles, the microparticles being divided into subsets, one subset for each drug in the panel and each subset distinguishable from the others. The incubation is performed in a liquid medium in which competitive binding occurs, the drugs in the sample competing with those added to the assay medium for binding to the antibodies. In one procedure, the added drugs are pre-coupled to the microparticles while the antibodies are not, and the incubation is followed by further incubating the microparticles with labeled ligands that have affinity for the antibodies.

Abstract: A blood analyzer configured to prevent an abnormal number of white blood cells caused by lipid particles or red blood cells of poor hemolysis from being output. The blood analyzer includes a system for obtaining a first white blood cell number and a system for obtaining a second white blood cell number. The analyzer also includes an output device for outputting the second white blood cell number, and a system for determining whether the second white blood cell number is abnormal. The output device is configured to output the first white blood cell number when the second white blood cell number has been determined to be abnormal.

Abstract: The enumeration of cells in fluids by flow cytometry is widely used across many disciplines such as assessment of leukocyte subsets in different bodily fluids or of bacterial contamination in environmental samples, food products and bodily fluids. For many applications the cost, size and complexity of the instruments prevents wider use, for example, CD4 analysis in HIV monitoring in resource-poor countries. The novel device, methods and algorithms disclosed herein largely overcome these limitations. Briefly, all cells in a biological sample are fluorescently labeled, but only the target cells are also magnetically labeled. The labeled sample, in a chamber or cuvet, is placed between two wedge-shaped magnets to selectively move the magnetically labeled cells to the observation surface of the cuvet. An LED illuminates the cells and a CCD camera captures the images of the fluorescent light emitted by the target cells.

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: 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: Apparatus and method for determining concentration of one or more target compounds in a sample solution containing one or more nontarget compounds that uses an affinity column to immobilize the target compounds. The target compounds are eluted and passed through a separation/detection system to determine quantitative measure of concentration for each of the target compound.

Abstract: Elevated number of Circulating Endothelial Cells (CEC) have been implicated in disease conditions associated with the formation or destruction of blood vessels such as acute coronary syndrome, thrombocytopenic purpura, sickle cell disease, sepsis, lupus, nephrotic syndromes, rejection of organ transplants, surgical trauma and cancer. This invention provides a method for assessing the levels of CEC which vary between different studies using a sensitive enrichment, imaging, and enumberation analysis. CD146 is one of the most specific endothelium-associated cell-surface antigens which can be used in image cytometry. CEC analysis provides an essential tool in prognostic/diagnostic evaluation in the clinic.

Abstract: The present invention provides compositions and methods for treating or preventing antibody mediated graft rejection and blood typing.

Abstract: A measuring method and a measuring apparatus which can classify and count myeloblast more precisely without influence of other component in a sample including platelet aggregation in measurement of a blood sample with a flowcytometry, wherein damage is given to a cell membrane of erythrocyte and mature leukocyte contained in a hematological sample, a hemocyte in which a cell membrane is damaged is constricted, and this is dyeing-treated with a fluorescent dye which can stain a nucleic acid to obtain a sample, the sample is measured with a flowcytometer, and a cell contained in a first cell group containing myeloblast, which is specified based on forward scattered light information and side scattered light information, and contained in a second cell group containing myeloblast, which is specified based on forward scattered light information and fluorescent information, is counted as myeloblast.

Abstract: The present invention relates to methods and kits for diagnosing, ascertaining the clinical course a of myelodysplastic syndrome(MDS) and ascertaining response to a therapy regimen of myelodysplastic syndrome. Specifically the invention provides method and kits useful in the diagnosis and determination of clinical parameters associated with MDS based on surface markers unique to MDS.

Abstract: The invention relates to methods of isolating white blood cells (WBCs) from a sample, e.g., whole blood, using magnetic particles that specifically bind to WBCs and a series of specific steps and conditions. The methods can include one or more of decreasing the viscosity of the sample prior to WBC isolation, agitating the sample at specified frequencies, and/or using a sample container arranged such that all of the sample is placed in close proximity (e.g., within 5, 2, 1, or 0.5 mm) to the source of the magnetic field. The new methods provide for isolation of WBC preparations with high yield, purity, and viability. The methods are designed for compatibility with automation protocols for rapid processing of multiple samples.

Abstract: The methods and reagents described in this invention are used to analyze circulating tumor cells, clusters, fragments, and debris. Analysis is performed with a number of platforms, including flow cytometry and the CellSpotter® fluorescent microscopy imaging system. Analyzing damaged cells has shown to be important. However, there are two sources of damage: in vivo and in vitro. Damage in vivo occurs by apoptosis, necrosis, or immune response. Damage in vitro occurs during sample acquisition, handling, transport, processing, or analysis. It is therefore desirable to confine, reduce, eliminate, or at least qualify in vitro damage to prevent it from interfering in analysis. Described herein are methods to diagnose, monitor, and screen disease based on circulating rare cells, including malignancy as determined by CTC, clusters, fragments, and debris. Also provided are kits for assaying biological specimens using these methods.

Abstract: High resolution particle differentiation process and separation system that provides enhanced resolution of particles based upon selected particle characteristics. In particular, the system may include an enhanced resolution flow cytometer. In an embodiment, the invention can include at least one fluid source conduit (24) that introduces 0 fluid source stream (24) into an enhanced resolution nozzle (25) at an angle that enhances particle resolution by the cell sensing system (13).

Abstract: An apparatus for analyzing biologic fluid is provided that includes a first planar member, a second planar member, and at least three separators. At least one of planar members is transparent. The separators are disposed between the members, and separate the members to form a chamber having a height. At least one of the members or separators is sufficiently flexible to permit the chamber height to approximate the mean size of the separators. During use, the biologic fluid to be analyzed is disposed within the chamber.

Abstract: A sample holder holds various sizes of capillaries or cuvettes for use in dynamic light scattering (DLS) or quasi-elastic light scattering (QELS), such as in DLS of fluid samples such as platelet solutions, whole blood, colloids or the like. The sample holder has a base with a stationary backing member and a sliding, rail-mounted clamping member that is magnetically biased toward the backing member. The sample holder has Peltier-type thermoelectric heating/cooling elements that extend the full height of the clamping and backing members to optimize heat transfer efficiency. The sample holder further includes horizontal slots that enable collection of scattered light from various angles around the device. Finned heat sinks are mounted above and below the horizontal slots on the outwardly facing surfaces of the backing and clamping members to stabilize the temperature of the fluid sample in the sample holder without interfering with incident or scattered light.

Abstract: The present invention provides an apparatus and method for measuring the properties of blood using ultrasound. The present invention is particularly suitable for measuring HCT, HGB, MCV, RBC, MCHC, MCH or TPC of blood.

Abstract: Fluorescently labeled microsphere calibration and quality control particles for use in establishing standardized fluorescence detector setup, monitoring daily QC of flow cytometers and quantitative calibration of the fluorescence detectors in traceable units of measure (molecules equivalent soluble fluorescence; MESF).

Abstract: A sheath liquid for a particle analyzer used to analyze particles contained in a sample is described. The sheath liquid includes water and a refractive-index adjustment agent with glycerols and/or sulfate. A method for producing the sheath liquid and a method for analyzing particles using the sheath liquid are also described.

Abstract: The present invention relates a method for the enumeration of in vivo gene mutation. The method utilizes differential staining of GPI-anchor deficient erythrocyte populations to distinguish between wild-type and pig-a gene mutants. Quantitative analyses can be conducted on erythrocytes and/or reticulocytes, and is based upon fluorescent emission and light scatter following exposure to an excitatory light source. Counting of mutant erythrocytes or reticulcoytes relative to the number of total erythrocytes or reticulocytes can be used to assess the DNA-damaging potential of an exogenous chemical agent, the DNA-damaging potential of an exogenous physical agent, the effects of an exogenous agent which can modify endogenously-induced DNA damage, and the effects of an exogenous agent which can modify exogenously-induced DNA damage. Kits for practicing the invention are also disclosed.

Abstract: Method to quantitate peptides in a sample by mass spectroscopy wherein the improvement comprises providing internal standard peptides isobarically tagged at the N and C terminus.

Abstract: Disclosed are compositions and methods related to joint inflammation diseases. Disclosed is the relationship between osteoclasts and inflammatory joint diseases and osteoclast precursor cells.

Abstract: An automated method for classifying a cytological sample is provided. The method comprises interrogating the sample with one or more wavelengths of light to obtain a result, and then attaching one or more designators to the sample based on whether the result meets a given criterion. The method allows for rapid feedback on the characteristics of the sample, permitting automated designation of the sample as positive for a given characteristic, and allowing for immediate remedial actions if the sample fails to meet the criterion.

Abstract: Mass cytometry method. In one aspect, the method includes providing a sample having at least one cell type and mixing the sample with material such as nanoparticles functionalized with affinity molecules for the at least one cell type. The sample is transported through a suspended microchannel resonator to record a mass histogram and a cell count for the at least one cell type is determined from the histogram.

Abstract: The present invention provides methods for identifying and/or enriching fetal cells from maternal blood, using as fetal cell markers the antibodies that the mother produces against paternally inherited fetal antigens. The fetal cell-maternal antibody complexes are identified and isolated using labelled agents that bind to the maternal antibodies. The present invention also provides fetal cells, isolated by use of said maternal antibodies, as a source of fetal DNA for prenatal genetic diagnosis of the fetus.

Abstract: Arrays of microparticle populations, each population labeled with a single fluorescent dye, are provided for use in multiplex assays. The populations form a virtual multidimensional array wherein each microparticle is identified by fluorescence intensity in two different fluorescence detection channels. The arrays are useful in a variety of assays, including multiplex, multi-analyte assays for the simultaneous detection of two or more analytes by, for example, flow cytometry, and a labeling reagents in, for example, microscopy. The use of singly-dyed microparticles to form multidimensional arrays greatly simplifies the creation of multiplex assays.

Abstract: The invention provides among other things methods and kits based on assaying for cardiac troponin autoantibodies, either in conjunction with an assay for cardiac troponin and/or as an independent indicator of cardiac pathology, such as myocarditis, cardiomyopathy, and/or ischemic heart disease. Assay methods of the invention can be employed among other things to identify cardiac pathology, or risk thereof, in subjects who have an autoimmune disease or who are related to an individual with an autoimmune disease. In particular embodiments, the invention also provides a method of determining whether a subject having, or at risk for, a cardiac pathology is a candidate for immunosuppressive therapy or immunoabsorption therapy. The invention also provides kits and kit components that are useful for performing the methods of the invention.

Abstract: The present invention is directed to a novel method for quantifying antigen, such as the amount expressed on a cell. The method comprises formulating an equation of correlation between the amount expressed of expressed antigen and the intensity of fluorescence from fluorescent labelled antibody.

Abstract: A microsphere-based analytic chemistry system is disclosed in which self-encoding microspheres having distinct characteristic optical response signatures to specific target analytes may be mixed together while the ability is retained to identify the sensor type and location of each sensor in a random dispersion of large numbers of such sensors in a sensor array using an optically interrogatable encoding scheme. An optical fiber bundle sensor is also disclosed in which individual microsphere sensors are disposed in microwells at a distal end of the fiber bundle and are optically coupled to discrete fibers or groups of fibers within the bundle. The identities of the individual sensors in the array are self-encoded by exposing the array to a reference analyte while illuminating the array with excitation light energy.

Abstract: A linearity control system includes a series of linearity control compositions, each thereof includes white blood cell analogs and stabilized red blood cells in a suspension medium. The concentration of the white blood cell analogs in the series of control compositions increases from 0.2×103 to 800×103 analogs per microliter, and the concentration of the white blood cell analogs in at least one control composition is greater than 120×103 analogs per microliter. The stabilized red blood cells facilitate mono-dispersion of the white blood cell analogs in the suspension medium by gently mixing. The control compositions further include platelet analogs, or additionally include reticulocyte and/or nucleated red blood cell analogs. The linearity control system allows the verification of the reportable measurement range and linearity of the measurements of hematology analyzers for white blood cells, red blood cells and platelets in extended concentration ranges.

Abstract: The enumeration and analysis of residual white blood cells in a sample of leukocyte-reduced blood products is conducted by forming a suspension of the leukocyte-reduced blood products with a sufficient amount of a lysing reagent. The lysing reagent comprises a buffer with a low molar concentration, and a non-ionic surfactant. The suspension of leukocyte-reduced blood products and the lysing reagent is incubated for a sufficient time at a temperature sufficient to selectively lyse the platelets and red blood cells without damaging the white blood cells. The white blood cells of the lysed blood products are then contacted with a suitable dye to stain the white blood cells and the number of stained white blood cells is measured. The lysing reagent is free of harsh organic solvents which can damage the plastic components of automated clinical analyzers.

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: A method and an apparatus for enumerating one or more specific elements within a biologic fluid sample are provided. An embodiment of the method includes the steps of: a) providing a chamber formed between a first planar member that is transparent and a second planar member, which members are separated from one another by a substantially uniform height; b) introducing the biologic fluid sample into the chamber, wherein the chamber height is sized such that the sample extends between the first and second members, and sized relative to the specific elements within the sample such that the specific elements non-uniformly distribute within the sample upon introduction into the chamber; c) examining substantially all of the sample within the chamber and enumerating all of at least one of the specific elements; d) determining the volume of sample contained within the chamber; and e) determining the number of the at least one of the specific elements per unit volume.

Abstract: A urine analysis system includes a urinary particle analyzer and a computer. The urinary particle analyzer has a measuring unit that measures a cast concentration from the urine and an electric conductivity sensor that measures the electric conductivity of the urine. The computer has a function of correcting the cast concentration measured by the measuring unit on the basis of the electric conductivity of the urine measured by the electric conductivity sensor and a function of outputting the corrected cast concentration.

Abstract: A packaging system in accordance with the principles of the present invention includes a sterilization pouch. The pouch includes a posterior portion attached to an anterior portion along three edges. The two portions define the pouch. The top part of the pouch is inverted so that the inside part of the pouch is facing outward and forms a cuff around the pouch. An integral internal sterilization indicator is further provided. The integral indicator comprises a sterilizing agent sensitive substance. The sterilizing agent sensitive substance can be an indicator ink printed as an ink line on the interior of the sterilization pouch below the cuff. Thus, the indicator becomes visible during aseptic delivery of the packaged article to provide a clear indication as to whether or not adequate conditions for sterilization have been achieved. In a further embodiment, the indicator ink line repeats as a pattern throughout the interior of the sterilization pouch.

Abstract: The invention provides compositions and methods for cell separation. These reagents and techniques specifically agglutinate cells via surface antigen recognition and can be used to recover even rare cell types in high yield.