Abstract: A method, composition, and kit for isolating biomolecules from a biological sample wherein the sample is mixed with a soluble, linear polymer, such as polyvinylpyrrolidone, to form a precipitate. The biomolecule of interest is found in the precipitate or is isolated from the supernatant.

Abstract: A method for protecting leukocytes in a blood sample, comprising contacting the blood sample with a preparation comprising an aliphatic aldehyde, a salt of an alkali metal or an alkaline earth metal, and optionally an agent to adjust isotonicity and hypotonically lysing erythrocytes in the blood sample.

Abstract: An aqueous wash solution is buffered to a pH of from about 5 to about 9 and contains at least about 1.5 weight percent of a compound comprising a lower alcohol sulfate anion having from 6 to 10 carbon atoms and an alkali metal or ammonium cation, such as sodium decyl sulfate. This wash solution is useful in a method for the determination of an immunological ligand, and is not prone to crystallization at lower temperatures. Particularly, it is useful for washing the immunological complex formed between the ligand and a receptor molecule therefor. Unreacted materials can be readily separated from the complex by the washing, particularly if the separation is carried out using a filtration membrane in a test device. A test kit for ligand determination comprises the wash solution as well as one or more receptors for the ligand, at least one of which is labeled for detection. This kit is particularly useful for measuring human chorionic gonadotropin (hCG) as an early indicator of pregnancy.

Abstract: A method of separating a first class of lipoprotein in a sample from a second class of lipoprotein in the sample including: precipitating the second class of lipoprotein; contacting the sample with a magnetically responsive particle; and placing the sample in a magnetic field until the magnetically responsive particle has sedimented, thereby causing the precipitated second class of lipoproteins to sediment, leaving the first class of lipoproteins in the supernatant of the sample.

Abstract: A method and a kit for separating double-stranded nucleic acid molecules from a mixture containing both single-stranded and double-stranded nucleic acid molecules. The method is particularly suitable for separating hybridized from unhybridized probe nucleic acid.

Abstract: Dyeing agents which are excellent in visual recognition of discernible or tangible components in a sample cause no coagulation of proteins, sugars or glycoproteins dissolved in the sample. An apparatus for image analysis of flow type stain particles uses the dyeing agents, and particles of discernible components suspended in a flowing sample can be detected so that images of the particles can be efficiently photographed and the discernible components can thus be analyzed by image processing of the thus-obtained image.

Abstract: An assay and sample mixture for the enumeration of fluorescently stained target components of a whole blood sample by an imaging instrument. The sample preparation method ensures that the amount of target components per unit of volume of the whole blood sample is preserved by elimination of certain non-quantitative preparation steps while producing an even hematocrit layer within a scan capillary. Typical target components include white blood cells that express certain surface antigens, such as CD-4 and CD-8 proteins. To inhibit aggregation of the red blood cells, a reagent is added to an aliquot of whole blood sample. The aliquot of whole blood is mixed and with a preselected amount of a fluorescent dye and ligand complex which tags the target components.

Abstract: The present invention is directed to the assay and purification of proteins, and particularly to the non-radioactive assay and purification of protein kinases, phosphatases and protease by incubating the enzyme with a substrate modified peptide to form a product modified peptide under conditions where the enzyme is active. The product modified peptide and substrate modified peptide are then separated, and the product modified peptide is measured. The present invention is also directed to kits and bioreagents for performing the assays.

Abstract: A reagent semi-sphere is disclosed comprising at least one biological reagent and a glass forming filler material in a concentration sufficient to facilitate formation of a glassy, porous composition, wherein the reagent semi-sphere is room temperature stable, water soluble, and has a T.sub.g above room temperature.

Abstract: A method and a device for the simultaneous and quantitative, flow cytometric analysis of nucleated red blood cells (NRBC) and white blood cells (WBC) in a whole blood sample.

Abstract: A method of preparing an extract of an intracellular component, wherein cells are contacted with an extractant to generate an extract solution, which comprises contacting the solution with a cyclodextrin to neutralize the extractant. preferred extractants are cationic or other kinds of surfactants. The cyclodextrin is preferably used in solution. Preferred intracellular components are ATP which can, after neutralization of the extractant, be assayed by a firefly luciferase assay; and DNA or RNA which can, after neutralization of the surfactant, be amplified or further processed in other ways.

Abstract: A reagent for analyzing leukocytes having at least one nonionic surfactant having an addition polymerization molar number of polyoxyethylene of 3 to 9, at least one cationic surfactant, and a buffer adjusting a pH value to 2.5 to 4.0, which can determine a cell size of and the morphological features of leukocytes contained in the blood sample.

Abstract: In a process for mixing two initial solutions to produce a working solution with an accurately defined mixing ratio, the two initial solutions are coarsely mixed in a first step, having a mixing ratio lying within a given range, and the value of an internal parameter of the working solution is determined in a second step. The values of this internal parameter are known and differ significantly for the two initial solutions. Then the accurate mixing ratio of the working solution is determined from the measured value of the internal parameter in a third step.

Abstract: A method and composition for isolating biomolecules from a biological sample wherein the sample is mixed with a soluble, linear polymer, such as polyvinylpyrrolidone, to form a precipitate. The biomolecule of interest is found in the precipitate or is isolated from the supernatant.

Abstract: A method is disclosed for differentiating white blood cells. The method uses at least one surfactant and at least one dilute acid which together selectively strip the cytoplasm from certain classes of white blood cells and not others. More particularly, the method causes lysis of lymphocytes, monocytes, eosinophils and neutrophils, but not basophils. Thus, basophils are differentiated from other PMN sub-classes by their appearance as intact cells. The method totally avoids the need for dye preparation and the vagaries of staining techniques and can be used either manually or with instrumentation.

Abstract: A multipurpose reagent system for rapid analysis of a whole blood sample allowing the determination of at least five classes of peripheral white blood cells, nucleated red blood cells, and lymphocyte immunophenotyping on automated hematology instrumentation. The multipurpose reagent system lyses red cells rapidly, while it concurrently fixes white cells and preserves surface antigens on lymphocytes. The multipurpose reagent system comprises from about 3 to 7 grams per liter of a non-quaternary ammonium salt, from about 0.04 to about 0.10 percent by volume of an aliphatic aldehyde with one to four carbons, from about 10 mM to about 20 mM of a non-phosphate buffer which is inert to the aliphatic aldehyde, and a sufficient amount of water to give a pH between 5.5 and 7.5 and an osmolality of between about 160 to about 310 mOsm per liter.

Abstract: A method that provides techniques for determination of urinary constituents (Blood (Red Blood Cells/Hemoglobin), Leukocytes, pH, Specific Gravity, Bacterial Reductase/Nitrite/Indole activity, Total Ketone Bodies, Protein, and Glucose) at low chemically significant levels with a carrier independent reagent system that can be placed on a high throughput autoanalyzers. Thus, giving the analyst the ability to run multiple urinary assays on a single sample of urine simultaneously with the ability to compare to reference standards on the same run. This system is designed to neutralize urinary interfering substances. This method is fast, efficient, an adaptable to many of the currently available discrete and continuous flow automated analyzers, effective at sample to reagent ratios of 1 to 13 or more. This method is applicable to samples with high turbidity, high ionic strength, high color content, wide pH extremes, and buffer strengths, among other interfering substances.

Abstract: A hematology control product comprising leukocyte analogs is described. The analogs comprise red blood cells which simulate at least two physical properties of human leukocytes. A method for making leukocyte analogs from blood cells having desired physical properties is also described. The process comprises expanding the cell volume, changing the hemoglobin content of the cell and fixing the cell. Generally, the monocyte and lymphocyte analogs leak hemoglobin from the cell while the eosinophil analog has the hemoglobin precipitated in the cell. A further method is described to use the control product to determine whether an automatic instrument is operating within manufacturer's specification.

Abstract: This invention provides methods and compositions for the analysis of parasites in fecal samples. A parasitological fixative is provided which contains glyceraldehyde, a salt of an organic acid, organic solvent and water. The parasitological fixative does not contain formaldehyde, formalin or other harmful chemicals commonly associated with fixative compositions. The invention further describes a slide fixative composition comprising a protein solution, glycerin and an adhesion enhancing agent which improves the adhesion of sample components to a microscope slide.

Abstract: The present invention is a method for blood analysis which provides a rapid treatment of a blood sample so that it can be analysed for counting and classification of leukocytes. Leukocytes are permeablized by treatment with a surfactant solution and labeled, preferably with a fluorescent dye. The method provides labeled leukocytes that can be counted and classified by optical means, including flow cytometry by analysis of a fluorescence signal.

Abstract: The present invention provides a novel lytic reagent composition highly selective in its interactions with the cell membranes of blood cells and also provides a method of using the reagent composition in a semi-automated or an automated system to effect a significantly improved white blood cell differential determination. The lytic reagent composition is characterized by an ability to selectively shrink the white blood cells into the increasing size order of lymphocytes, a midregion consisting mainly of monocytes, other mononuclear cells, some basophils and eosinophils, and neutrophils and can readily be optimized to effect a significantly improved three component separation on the histogram of commercially available semi-automated and automated blood analyzers when compared to the reagents conventionally employed on such instruments.

Abstract: A method and composition for fixing and stabilizing tissues, cells, and cell components such that the antigenic sites are preserved for a useful period of time. The fixative employs a formaldehyde donor that is non-toxic, non-flammable, and that stabilizes the cell with minimal damage to and alteration of the cell morphology. In particular, the cell antigenic sites are left intact so that studies with monoclonal antibodies may be conducted. The invention also discloses a method for developing a positive control for test reagents and for test instrumentation.

Abstract: A method for isolating nucleated fetal erythrocytes (NFEs) from a maternal blood sample by separating erythrocytes in the maternal blood sample from all other nucleated cells therein using a leukocyte depletion device; and isolating NFEs from nonnucleated maternal erythrocytes. Preferably the maternal blood is peripheral maternal blood. The isolated NFEs can then be analyzed for genetic disorders and the like, such as by in situ hybridization.

Abstract: This invention provides methods and compositions for the analysis of parasites in fecal samples. A parasitological fixative is provided which contains glyceraldehyde, a salt of an organic acid, organic solvent and water. The parasitological fixative does not contain formaldehyde, formalin or other harmful chemicals commonly associated with fixative compositions. The invention further describes a slide fixative composition comprising a protein solution, glycerin and an adhesion enhancing agent which improves the adhesion of sample components to a microscope slide.

Abstract: An eliminating agent used for the measurement of the amount of glycosylated hemoglobins in a blood sample is provided. The eliminating agent comprises condensed phosphoric acids and/or the salts thereof as the main ingredient, wherein the agent eliminates labile glycosylated hemoglobin A.sub.1c into non-glycosylated hemoglobin and glucose. There is also provided a reagent comprising the eliminating agent and a hemolysis agent, which is used for the measurement of the amount of glycosylated hemoglobins; and an eluent comprising the eliminating agent, which is used for the separation of glycosylated hemoglobins in blood samples by ion-exchange chromatography to measure the amount of the glycosylated hemoglobins. A method for measuring the amount of glycosylated hemoglobin A.sub.1c in a blood sample involves the use of the eliminating agent, the reagent comprising the eliminating agent and the hemolysis agent, and/or the eluent.

Abstract: A serum separating sealant having a specific gravity at 20.degree. C. of 1.035 to 1.065, a viscosity of 100 to 400 Pa.S and a yield stress of 100 to 400 dyne/cm.sup.2 and comprising:(A) 100 parts by weight of a polymer having specific gravity at 20.degree. C. of 0.94 to 1.06 and a viscosity of 10 to 140 Pa.S, derived from an alkyl acrylate or alkyl methacrylate monomer having the formula (I): ##STR1## wherein R.sup.1 denotes H or CH.sub.3, R.sup.2 denotes an alkyl group having 1 to 18 carbon atoms;(B) 0.5 to 10 parts by weight of at least one component selected from silica and bentonite; and(C) 0.01 to 2 parts by weight of at least one surfactant selected from the group consisting of:(C-1) fluorocarbon-based surfactants;(C-2) polyester modified alkylpolysiloxane based surfactants.

Abstract: A method for leukocyte classification by flow cytometry that uses a first fluid that is hypotonic acidic fluorescent dye solution and a second fluid that is a solution that changes the osmolarity and pH of the first fluid is disclosed. The first fluid to be used in the method incorporates not only the first and second dyes but also the third dye and this insures that even leukocytes with damaged cell membrane can be distributed as entities distinct from other leukocyte types on a two-dimensional plot. And, hence, high precision of leukocyte classification is assured even in the case of assaying blood that contains damaged cells as a result of prolonged standing at room temperature after sampling.

Abstract: A method of separating a first class of lipoprotein in a sample from a second class of lipoprotein in the sample including: precipitating the second class of lipoprotein; contacting the sample with a magnetically responsive particle; and placing the sample in a magnetic field until the magnetically responsive particle has sedimented, thereby causing the precipitated second class of lipoproteins to sediment, leaving the first class of lipoproteins in the supernatant of the sample.

Abstract: A system for identifying and tracking samples of biological material during the preparation of that tissue for microscopic evaluation. The system includes a plurality of colored aqueous embedding media, microscope slides marked to correspond to the colored embedding media, and, optionally, color-coded containers for the embedding media. A process for preparing samples of biological material using the identification system is also provided, as well as compositions for several embedding media including one or more coloring agents.

Abstract: Reagents for enabling leukocytes to be classified and counted lyse erythrocytes and act on leukocytes to stabilize them are disclosed. The reagents contain polyoxyethylene-based surfactants, and may contain hyperosmotic or hypoosmotic agents and solubilizing agents. One embodiment of the invention contains surfactants selected from the anionic and nonionic polyoxyethylene-based surfactants having 18-30 repeating oxyethylene units per molecule. A second embodiment of the invention contains nonionic polyoxyethylene surfactants only, having 20-100 repeating oxyethylene units per molecule, does not employ either saponin or quaternary ammonium compounds, and provides for adjustment of the pH of the resulting solutions. The invention allows leukocytes to be classified into as many as five types, each type to be quantified, and enables the detection of abnormal cells, when used in conjunction with particulate analysis flow cytometers employing the RF method and the DC method.

Abstract: An antithrombin III is described comprising a lyophilized powder of antithrombin III and a polyoxyethylene glycol sorbitan alkyl ester as well as a kit composed of a container wherein a lyophilized powder of antithrombin III is placed and a solvent for the powder, characterized in that a polyoxyethylene glycol sorbitan alkyl ester is added to either or both of the powder and the solvent. The preparation has a high solubility in water by retaining its activity.

Abstract: This invention primarily is directed to a hematology reference control solution, the three separate white cell control portions thereof consisting of three types of fixed red cells of determined size distribution for checking the operation of a particle analyzing instrument, including its predetermined lower and upper threshold settings for each class or subclass of leukocytes.For preparing a human granulocyte analogue, nurse shark erythrocytes are altered and fixed in a chilled solution to simulate in number, size and distribution the granulocytes in human whole blood.

Abstract: A method for identifying, characterizing, categorizing and enumerating cells within a cell population. The survivorship characteristics of the different cell populations is used to obtain quantitative and qualitative information about the cell populations initially present in the sample solution before conditions were imposed on the sample solution to elicit a response. The monitored cell survivorship response may be either direct disappearance of intact cells or the appearance of cell structures, carcasses, ghosts or residuum. In a preferred embodiment, a leukocyte cell decay rate in the presence of an erythrolytic agent is determined by monitoring leukocyte counts at several time intervals after the addition of the erythrolytic agent to the sample solution. The leukocyte decay rate is then used to indicate the presence of a fragile leukocyte population, and to accurately estimate the number of leukocytes initially present in the whole blood sample.

Abstract: An aqueous wash composition has been found useful in methods for determination of specific binding ligands. The composition is buffered to a pH of less than or equal to 6 or greater than or equal to 9. It also includes as its essential component at least about 0.1 weight percent of an anionic surfactant which is represented by the formula:[A-SO.sub.3+y ].sup.-(1+y) [X.sup.+m ].sub.nwherein A is a hydrocarbon having a molecular weight of at least about 180, X.sup.+m is hydrogen or a monovalent or divalent cation, m is 1 or 2, is 0 or 1, and n is 1 or 2 provided that m and n are not both 2. Optionally and preferably, the wash composition also includes a nonimmunoreactive protein. This wash composition is particularly useful in methods for determination of microorganisms associated with periodontal diseases. Such methods can be of a variety of formats, but immunometric assays are particularly useful. The wash composition can be included as part of a diagnostic test kit.

Abstract: A method for rapidly lysing liposomes having transition temperatures in the range of 35.degree. to 65.degree. C. is provided. Such liposomes are treated with a surfactant including ##STR1## wherein x represents an average of 9 or 12. The method is applicable to fluorescence immunoassay procedures.

Abstract: Methods for characterizing and distinguishing reticulocytes and mature red blood cells use reagent compositions which include organic cationic dyes for staining the reticulocytes in the blood sample and buffer solutions for maintaining a pH of about 6 to about 9. The dyes may be the blue absorption dyes Oxazine 750 or New Methylene Blue.

Abstract: A stabilized, aqueous composition containing FK506. FK506 degrades rapidly in most aqueous matrices. The rate of degradation is decreased in the presence of unfixed blood cells or fragments of blood cells from human or animal sources. A number of matrices using blood components are possible. Blood can be used directly or the blood cells can be lysed. The blood is diluted with a solution of an alkali halide.

Abstract: A hematology control product comprising leukocyte analogs is described. The analogs comprise red blood cells which simulate at least two physical properties of human leukocytes. A method for making leukocyte analogs from blood cells having desired physical properties is also described. The process comprises expanding the cell volume, changing the hemoglobin content of the cell and fixing the cell. Generally, the monocyte and lymphocyte analogs leak hemoglobin from the cell while the eosinophil analog has the hemoglobin precipitated in the cell. A further method is described to use the control product to determine whether an automatic instrument is operating within manufacturer's specification.

Abstract: A lytic reagent composition highly selective in its interactions with the cell membranes of white blood cells and also provides a method of using the reagent composition in a particle analyzing system to effect a significantly improved white blood cell differential determination. The lytic reagent composition is characterized by an ability to selectively shrink the white blood cells into the increasing size order of lymphocytes, basophils, monocytes, eosinophils and neutrophils, and effect a five component separation of these major subpopulations of white blood cells on the histogram of an automated blood analyzer when used in conjunction with a suitable blood diluent.

Abstract: A composition which reduces the turbidity of samples of artificial or naturally occurring biological fluids comprising:a buffering agent;a nonionic surfactant;a lipolytic enzyme; and water.The composition provides a catalyst for and agents which hydrolyze triglycerides present in the sample to glycerol and free fatty acids. Also present in the composition is a fatty acid scavenging agent or agents to render the catalyzed fatty acids water-soluble. The fatty acid scavenging agent may be cyclodextrin, albumin or mixtures thereof.

Abstract: A blood serum sample useful as a calibration baseline comprising a natural blood matrix is disclosed. This serum sample contains less than an HPLC-detectable amount of cortisol. Also disclosed is a serum sample containing less than HPLC-detectable amounts of cortisone and corticosterone and less than RIA-detectable amounts of testosterone, androstenedione, progesterone, DHEA sulfate and 17-OH progesterone. A method of preparing such a serum sample is also disclosed.

Abstract: A hematological specimen for classifying and counting leukocytes with a flow cytometer is prepared. A sample to be assayed is prepared by eliminating influences of erythrocytes from a hematological sample without changing leukocytes morphologically; adjusting the pH value to a level suitable for staining; and staining the leukocytes with at least two dyes including Astrazon Yellow 3G capable of specifically staining at least basophils and immature granulocytes and Neutral Red capable of specifically staining at least eosinophils. Thus leukocytes contained in the hematological sample can be classified at least three or six groups including immature granulocytes by measuring a single specimen with a flow cytometer.

Abstract: An eliminating agent used for the measurement of the amount of glycosylated hemoglobins in a blood sample is provided. The eliminating agent comprises condensed phosphoric acids and/or the salts thereof as the main ingredient, wherein the agent eliminates labile glycosylated hemoglobin A.sub.1c into non-glycosylated hemoglobin and glucose. There is also provided a reagent comprising the eliminating agent and a hemolysis agent, which is used for the measurement of the amount of glycosylated hemoglobins; and an eluent comprising the eliminating agent, which is used for the separation of glycosylated hemoglobins in blood samples by ion-exchange chromatography to measure the amount of the glycosylated hemoglobins. A method for measuring the amount of glycosylated hemoglobin A.sub.1c in a blood sample involves the use of the eliminating agent, the reagent comprising the eliminating agent and the hemolysis agent, and/or the eluent.

Abstract: Methods for blood sample preparation using reagent compositions which include a zwitterionic surfactant for sphering of cells to eliminate orientational noise. When the reagent composition including a for staining a subset of cells is reacted with an anticoagulated blood sample, and the reaction mixture is passed through the sensing region of a flow cytometer, the light scattered and absorbed by each cell is measured, the stained cells can be distinguished from the unstained cells, and when the cells are reticulocytes and mature erythrocytes, respectively, the volume and hemoglobin concentration of each reticulocyte or erythrocyte, and the hemoglobin content, mean cell volume, mean corpuscular hemoglobin concentration, and mean cell hemoglobin of the reticulocytes or erythrocytes are calculated from the measured cell-by-cell volume and hemoglobin concentration.

Abstract: A method and kit for the isolation and quantitation of glycated hemoglobin and other glycated proteins, specifically albumin, from a single sample of whole blood. Glycated hemoglobin is calculated from an eluate resulting from the contact of the whole blood hemolysate with a boronated resin. Glycated albumin and other plasma proteins are calculated using immunoturbidimetry, resulting from reaction between a buffered antibody solution and the albumin or other protein in the previous eluate.

Abstract: An aqueous coenzyme reagent composition contains NADH, a carbonate/bicarbonate buffer (with a pH of about 9.5-11) and water. Both NADH and the buffer are at low concentrations, e.g., about 2-5 mM for NADH and about 2-15 mM for carbonate/bicarbonate. When this coenzyme reagent is mixed with an enzyme reagent, the mixture achieves a neutral pH. The combination of high pH, low NADH concentration and low buffer concentration permit the aqueous reagent to be stored for extended periods at low temperatures without NADH degrading to form impurities which interfere with or inhibit enzyme activity, such as the activity of lactate dehydrogenase or malate dehydrogenase in an assay for ALT or AST.

Abstract: Reference controls comprised of aldehyde-fixed white blood cells stabilized red blood cells and simulated blood platelets exhibiting a white blood cell histogram profile that is substantially that of whole blood are obtained by the addition of a lipoprotein to the control and an antioxidant to inhibit lysis of stabilized red blood cells by said lipoprotein.

Abstract: A hematological specimen for classifying and counting leukocytes with a flow cytometer is prepared. A sample to be assayed is prepared by eliminating influences of erythrocytes from a hematological sample without changing leukocytes morphologically by adding a first aqueous solution of a low osmotic pressure including a buffer for adjusting the pH value within an acidic region and a second aqueous solution including an osmolarity compensating agent and a buffer for giving pH value suitable for staining, optionally further adding a salt, which dissociates into ions in aqueous solutions so as to control the electrical conductivity of the aqueous solution at a preferable level, while damaging the cell membranes of erythroblasts contained in said sample; and staining the leukocytes with at least four dyes including Astrazon Yellow 3G and Neutral Red.

Abstract: A non-toxic composition, and method, for the clarification of raw sugar-containing juices, especially sugar cane juice, and related products, for analysis. A composition constituted of A) aluminum chloride hydroxide, B) lime and C) activated bentonite, bentonite containing calcium aluminum silicate, and preferably also a polymeric flocculating agent, has been found highly effective as a reagent for the clarification of sugar-containing juices, notably sugar cane juice, and related products.

Abstract: A lytic reagent composition highly selective in its interactions with the cell membranes of blood cells and also provides a method of using the reagent composition in a semi-automated or an automated system to effect a significantly improved white blood cell differential determination. The lytic reagent composition is characterized by an ability to selectively shrink the white blood cells into the increasing size order of lymphocytes, a midregion consisting mainly of monocytes, other mononuclear cells, some basophils and eosinophils, and neutrophils and can readily be optimized to effect a significantly improved three component separation on the histogram of commercially available semi-automated and automated blood analyzers when compared to the reagents conventionally employed on such instruments.