Abstract: The present invention relates to a method for retrieving the antigenicity of a formaldehyde-fixed sample for immunological staining and to compositions used in such a method. A method of the invention comprises submerging a sample in a submersion fluid composition comprising an osmotically active compound and heating the said submerged sample under pressure. The present invention also discloses advantageous submersion fluid compositions for retrieving the antigenicity of a formaldehyde-fixed samples and their use.

Abstract: An automated system for preparing a plurality of cytological specimens from a plurality of fluid samples in vials includes an apparatus for collecting a monolayer of cells from each sample and transferring the cells to a microscope slide for fixing, staining, and inspection. The system includes a first loading station for receiving the sample vials, a second loading station for receiving consumables such as filter membranes, a slide dispenser, and an unloading area for removing completed specimen slides. To maintain one-to-one correlation between the samples and specimens produced therefrom, the system includes a subsystem for identifying each sample and permanently marking each slide with corresponding indicia prior to transferring the specimen thereto.

Abstract: Compounds disclosed which inhibit ABCB1 transporter protein are useful for treating diseases in which ABCB1 transporter protein mediates the disease state, including numerous cancers, including hematopoietic cancers, including various leukemias, especially T-lineage acute lymphoblastic leukemia, as well as cancerous tumors, especially forms which exhibit multiple drug resistance. Pharmaceutical compositions which comprise an inhibitor of ABCB1 transporter protein and at least one additional anticancer agent, optionally in combination with a pharmaceutically acceptable carrier, additive or excipient are another aspect of the present invention. A flow cytometry based, high-throughput screening (HST) assay that quantifies ABCB1 efflux is also disclosed. Methods of identifying inhibitors of ABCB1, ABCG2 and ABCC1 transporter proteins are also disclosed.

Abstract: The present invention relates to the qualitative and quantitative validation of marker indices, especially for medical diagnosis and particularly for the determination of the growth fraction in a sample with antibodies against the Ki-67 protein. Diagnostic kit for the quantification of a cell fraction labeled by a marker for in vitro diagnosis, characterized in that a pseudo-tissue is used for the intra- and inter-assay standardization of the marker index.

Abstract: Embodiments of the present invention are directed to improved methods and devices for analyzing a cell, aggregated cells, or a solid tumor. Such methods and devices are, for example, useful in the field of pathology and can provide improved cell processing and analytical results.

Abstract: Provided herein are reagents for use in an automated environment for cell conditioning of biological samples wherein the cells or tissues are predisposed for access by reagent molecules for histochemical and cytochemical staining procedures. The reagents include, but are not limited to, components optimized to facilitate molecular access to cells and cell constituents within the biological sample. Also provided herein are reagents for use in an automated environment for removing or etching embedding media by exposing a biological sample to be stained in histochemical or cytochemical procedures without the dependence on organic solvents. The reagents include, but are not limited to, components optimized to facilitate removal or etching of the embedding media from the biological sample.

Abstract: The present invention is to present a smear slide preparing apparatus capable of properly providing sample-related information on a predetermined area of a slide glass even when glass shards and dust and the like are attached to the predetermined area. A smear slide preparing apparatus comprises: a smear section for smearing a sample on a slide glass; an attached matter removing section for removing attached matter which is attached to a sample-related information area of the slide glass; and a sample-related information providing section for providing sample-related information which is related to the sample on the sample-related information area of the slide glass, the attached matter having been removed from the sample-related information area.

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

Abstract: Methods for identifying stem cells and other cells specific to embryogenesis and carcinogenesis, classifying tissue samples, diagnosing precancerous and cancerous or atherosclerotic lesions, testing the value of anticancer agents, discovering macromolecules specifically expressed in particular cell types, using stem cells in restorative tissue therapy as well as methods for preparing tissue samples so heteromorphic nuclear morphotypes remain intact are disclosed.

Abstract: The invention relates to a method for the non-invasive selection of single living cells under gentle conditions from mixtures of cells or cell cultures with respect to a specific production performance. To this end, the concentration of substances produced by the individual cells which become enriched at the cell membrane, such as reporter gene products (GFP) or specifically secreted products, such as antibodies, is determined by fluorescence-microscopic detection methods.

Abstract: The invention relates to the combination, in solution or in a kit, of a histological or cytological fixing solution and of one or more photoactivatable compounds of the family of quinones, in particular, hypericin, hypocrellin A and/or hypocrellin B. The invention also relates to a method for labeling cells or tissues by one or more photoactivatable compounds of the family of quinones, in which the cells or tissues in contact with a histological or cytological fixing solution are labeled, simultaneously or subsequently, by the photoactivatable compound(s) of the family of quinones.

Abstract: The present invention discloses methods for detecting exposure of a living subject to genotoxic agents, testing sensitivity to a genotoxic agent, and determining DNA damage caused by exposure to an agent, comprising detecting the presence of FANCD2-containing foci from a sample collected from said subject. The presence of concentrated foci is indicative of DNA damage, and the degree of foci formation is correlated with degree of exposure. Diagnostic reagents contain a ligand that binds to human FANCD2 associated with a detectable label. Kits for detecting DNA damage in a biological sample contain such diagnostic reagents and signal detection components. The invention further discloses methods for identifying agents which modulate the ability of FANCD2-containing foci to form. Among other things, such agents are potentially useful chemosensitizing agents or may confer protection against damage caused by genotoxic agents.

Abstract: The present invention provides methods and compositions for detecting bacteria of the Chlamydiaceae family in a biological sample. Methods include, for example, contacting a biological sample with an antibody that specifically binds to a chlamydial antigen displayed on the surface of a chlamydia-infected blood cell; and analyzing the sample using fluorescence microscopy or flow cytometry to detect bound antibody.

Abstract: Arrays and methods for detecting one or more biological molecules, where the methods generally comprise the steps of: providing a first support immobilized with one or more reagents; providing a second support immobilized with one or more of ligands; contacting the reagents immobilized to the first support with the ligands immobilized on the second support whereby one or more of the reagents bind to one or more of the ligands; and separating the first support from the second support so that one or more of the bound reagents remain bound to one or more ligands on the second support after separation. In one preferred method, proteins are immobilized on a support with adequate strength so that the proteins can be dissociated from the support under certain conditions, such as after binding with other proteins immobilized on another support.

Abstract: A method for preparing corneocytes specimen, which comprises stripping off corneocytes from the surface of a skin using an adhesive material, staining the corneocytes in a solution of stain in solvent containing a water-miscible organic solvent, and mounting the stained corneocytes into an oil and fat constituent and/or composition that is liquid at 1 atm, 25° C.

Abstract: The invention relates to a method for the investigation of intercellular communication and intercellular transport, wherein after singularisation cells are investigated for membrane tubes which contain F-actin and myosin, have a diameter of 50 to 400 nm, as a rule are up to 50 micrometers long or in same cases longer, and which span between the cells. The invention further relates to a method wherein the organelle transport between the cells is investigated.

Abstract: A method for identifying images of wells in an image of a well-bearing object such as multiwell plates or picowell carriers is provided. An observation component, such as a camera, is used to approach focus of a focal point of a well-bottom. An image of the focal point is acquired. The image of the well-bottom focal point is then used as a reference point or used to define a reference point from which to identify the image of the well in the image of the well-bearing component and from which to delineate the borders of the well.

Abstract: A sample acquiring device for volumetric enumeration of white blood cells in a blood sample comprises a measurement cavity for receiving a blood sample. The measurement cavity has a predetermined fixed thickness. The sample acquiring device further comprises a reagent, which is arranged in a dried form on a surface defining the measurement cavity. The reagent comprises a hemolysing agent for lysing red blood cells in the blood sample, and a staining agent for selectively staining white blood cells in the blood sample. A system comprises the sample acquiring device and a measurement apparatus. The measurement apparatus comprises a sample acquiring device holder, a light source, and an imaging system for acquiring a digital image of a magnification of the sample. The measurement apparatus further comprises an image analyser arranged to analyse the acquired digital image for determining the number of white blood cells in the blood sample.

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: Apparatuses for processing histological specimens are provided. One apparatus includes a cap that is placed on a vessel used for holding stains. The cap has a door through which a microscope slide and specimen can be inserted in order to apply stain thereon. Removal of the slide causes the door to move back into the closed position to prevent loss of stain in the vessel. An apparatus for heating the microscope slide and specimen is also provided in which the slide is received by a port of the apparatus. Heat is generated by a heater of the apparatus to affix the specimen onto the slide. An associated method is also provided.

Abstract: Apparatus, methods, and systems for high throughput, useful sampling of seed, wherein viability is optionally maintained, are disclosed. Seed from one generation in a plant advancement experiment is individually sampled by removal and collection of tissue from the seed. The tissue is then processed to derive one or more biochemical, genetic, or phenotypic characteristic of the seed before a decision is made whether to utilize that seed further in a plant advancement experiment or other plant research and development. In some embodiments of the method, the sampling is controlled to remove a useful amount of tissue for analytical purposes without significant effect on viability potential of the sampled seed. In some embodiments, the sampling is controlled to deter contamination of the sample. In some embodiments, the seed is automatically positioned and oriented to facilitate efficient and accurate sampling.

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 apparatus and method for producing tissue slides is disclosed. The apparatus includes a holding assembly for manipulating the sample block, a blade assembly for preparing a thin section from the sample block, and a transfer roller mechanism for transferring the thin section to a receiving medium. The apparatus further includes a controller that may track the sample block and thin section. The method includes the steps of first locating a sample embedded within a support medium, which may be paraffin or a similar medium. Next, the embedded sample is oriented in such a way that its working surface is presented. This orientation may entail determining the orientation of the embedded sample with respect to the blade that will produce the largest cross-sectional area. Next, a slice of the sample from said embedded sample is removed and subsequently transferred to a suitable receiving medium, which may include a microscope slide.

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

Abstract: The present invention relates generally to high-throughput assay methods that determine the proliferative status of hematopoietic stem and progenitor cells. The present invention further relates to high-throughput assays for screening compounds that modulate the growth of hematopoietic stem and progenitor cells and for identifying subpopulations thereof that are suitable for transplantation. The assay of the present invention is particularly useful for quality control and monitoring of the growth potential in the stem cell transplant setting and would provide improved control over the reconstitution phase of transplanted cells.

Abstract: The present invention relates generally to kits that provide reagent mixes and instructions for the use thereof, in performing high-throughput assay methods that determine the proliferative status of isolated target cell populations. The methods measure the luminescent output derived from the intracellular ATP content of incubated target cells, and correlate the luminescence with the proliferative status of the cells. The present invention further relates to kits that provide reagent mixes and instructions for high-throughput assays methods for screening compounds that may modulate the proliferative status of a target cell population. The kits of the present invention and methods therein described may be used for determining the proliferative status of any isolated cell line or type. The kits and methods of the present invention address the need for rapid assays that determine the proliferative status of isolated hematopoietic stem and progenitor cells and of subpopulations of differentiated cells thereof.

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

Abstract: The invention describes a method for cell analysis in which the cells to be analyzed are adhesively applied to a slide and stained with a first stain. A first digital image is then taken and stored of the cells applied to the slide and stained. After the first digital image is taken, these same cells are treated with a second stain while on the same slide in such a way that their optically measurable properties change. A second digital image is then taken of the cells applied to the slide and stored. According to the invention, a group of preparations with cells to be analyzed is first stained with a stain of a highly sensitive analysis method, and only the preparations with positive findings are further processed.

Abstract: A method for diagnosing a cell proliferative disease expressing DcR3/TR6 in a patient, which comprises the step of measuring the concentration of DcR3/TR6 in the patient's blood, plasma or serum sample, wherein a concentration of DcR3/TR6 higher than that present in the serum of a patient not suffering of a proliferative disease expressing DcR3/TR6 is indicative of that patient suffering from said disease. Methods of prognosing said diseases and compositions of matters for use in said diseases.

Abstract: A new method of evaluating the ability of drug molecules to penetrate the cornea is described. The permeation rate of the drug molecules in MDCK cells is utilized to predict the ability of the molecules to penetrate the cornea. The method is useful for in vitro screening of potential new ophthalmic drugs, as well as in the design of new drug molecules for topical ocular administration.

Abstract: Methods and kits for used as an internal or external control in rare cell analysis are disclosed. A plurality of fluorescently distinct sets of cells is used to define a range to assess the isolation of rare target cells from a sample. Thus, a known number of cells, expressing the surface and intracellular antigens present in the targeted rare cells, are stabilized and modified in such a way that they can be discriminated from the targeted rare cells. In addition, these cells are separated into at least two sets based upon the number. These sets are detectably distinct from each other and provide an upper and lower indication of the detection ability of the rare cell assay.

Abstract: A method for the identification of human foetal cell nuclei is provided wherein the method involves subjecting chromosomes of cell nuclei to exonucleolytic digestion by an enzyme so as to remove end regions of each chromosome; and detecting the presence of a DNA sequence remaining in foetal DNA but absent from maternal DNA as a result of the digestion process. Once identified, the foetal DNA can be subject to diagnosis for example to detect chromosomal abnormalities.

Abstract: A method of analyzing cells disposed in media within a vessel includes the steps of providing a vessel having an original volume of media about the cells, reducing the original volume of media about at least a portion of the cells to define a reduced volume of media, and analyzing a constituent related to the cells within the reduced volume of media. An apparatus for analyzing cells includes a stage adapted to receive a vessel holding cells and a volume of media, a plunger adapted to receive a barrier to create a reduced volume of media within the vessel including at least a portion of the cells, the barrier adapted for insertion into the vessel by relative movement of the stage and the plunger, and a sensor in sensing communication with the reduced volume of media, wherein the sensor is configured to analyze a constituent disposed within the reduced volume.

Abstract: The invention concerns an apparatus for preparing monolayers of cells. The apparatus comprises a container (6) for a cryosubstitution system and an insert (1) for the container, the insert (1) having a surface (1a) and a plurality of orifices (3). An SCS (2) together with a cellular monolayer (20) is insertable into each of the orifices (3). The SCS (2) is thus arranged perpendicular to the surface (1a) of the insert (1).

Abstract: The invention provides methods and materials for diagnosing an angina condition in a patient. Specifically, the invention provides methods and materials for classifying an angina condition as either stable or unstable. In addition, the invention provides methods and materials for determining an individual's predisposition to have a stable or unstable angina condition. The invention also provides kits for classifying an angina condition as either stable or unstable as well as kits for determining an individual's predisposition to have a stable or unstable angina condition.

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

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

Abstract: The present invention provides a method for the staining of fungi and microsporidia for observation with a light microscope based upon the presence of chitin in the composition of these organisms. With the method of the present invention a sample to be analyzed is treated with a solution of Ponceau S and Stains-all dye. The sample is then selectively decolorized and rinsed. The resulting sample is examined with a light microscope, or photographed for a permanent record, to identify the presence of a variety of microorganisms, to include fungi and microsporidia.

Abstract: The invention relates to a device and a method for carrying out in an optimized and automated manner immunological marking techniques for thin-sectioned tissue (2b). A support plate (1) which can be automatically moved by means of a computer-controlled conveying device (20) and on which several thin sections of tissue (2b) are placed on small metal screens (2) is immersed like a die into a liquid that is composed of a washing or marking solution (6) and is placed in several recesses (5) within an object support (4). The object support can also be automatically moved.

Abstract: Methods and apparatus for preparing a smear for cytopathology or other analysis. In a representative embodiment, cells of a sample are subjected to a dielectrophoretic force to segregate the cells into two or more zones of a surface. The particles are attached to the surface, thereby defining a “segregated smear.” The segregated smear is then fixed and stained for cytopathology analysis.

Abstract: A method and device are described to concentrate target organisms from a mixture of organisms. Beads (1) made of material such as nylon, polystyrene or glass are coated with antibodies of specific microorganisms. The beads (1) are contained in an enclosure (2) surrounded by grid material (4). The pore size of the grid is smaller than the size of the beads, to assure that the beads stay within the grid material and larger than the size of the microorganisms to allow the interaction of the microorganisms with the beads. A rod (5) is attached to the upper part of the enclosure (2) allowing the agitation of the device inside he growth medium containing the target organisms.

Abstract: This invention is related to novel probes, probe sets, methods and kits pertaining to the detection, identification and/or quantitation of yeasts and particularly Dekkera bruxellensis (a.k.a. Brettanomyces) an organism that spoils wine. Preferred probes for the detection of one or more species of the Dekkera/Brettanomyces genus comprise a probing nucleobase sequence, at least a portion of which is selected from the group consisting of: AGC-GGG-TCT-ATT-AGA (Seq. ID No. 1); CCA-GGT-GAG-GGT-CGC (Seq. ID No. 2); CGG-TTG-CCC-GAT-TTC (Seq. ID No. 3); TCG-CCT-TCC-TCC-TCT (Seq. ID No. 4); CGG-TCT-CCA-GCG-ATT (Seq. ID No. 5); CAC-AAG-ATG-TCC-GCG (Seq. ID No. 6); GCG-GGC-ACT-AAT-TGA (Seq. ID No. 7); CAT-CCA-CGA-GGA-ACG (Seq. ID No. 8); GTG-TAA-ACC-AGG-TGC (Seq. ID No. 9); ATG-GCT-CCC-AGA-ACC (Seq. ID No. 10) and GAC-AGA-ATC-GAA-GGG (Seq. ID No. 11).

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

Abstract: A screening method of identifying a compound for treating hepatitis. Also disclosed is a method for evaluating responsiveness of a subject having hepatitis to a drug.

Abstract: This invention provides a novel device and method for preparing cytology slides. The device comprises a book-like form including an absorbent material and filter attached to the inside surface of a front cover and a cytology slide removeably attached to an inside surface of a back cover. A sample is removed from the body of a patient, placed in a liquid-based solution, and then on the filter. When the book-like form is closed, the sample is effectively transferred to the slide. The device can be modified so that a plurality of slides are prepared at the same time.

Abstract: The present invention provides a method for determining expression levels of one or a multiplicity of target proteins in a tissue or cell sample.

Abstract: The instant invention provides for the identification, diagnosis, monitoring, and treatment of invasive cells using the laminin 5 gamma-2 chain protein or nucleic acid sequence, or antibodies thereto.

Abstract: Immunoassay methods and apparatus are provided which utilize flow cytometry, coated latex microspheres, and fluorochrome labeled antibodies, to simultaneously detect the presence and amount of one or more analytes in a sample. By combining FALS and fluorescence, it is practical to use beads of several different sizes, colors or shapes, each bead coated with a different analyte, for the simultaneous detection of one or more analytes and of cell components such as platelets in a sample.

Abstract: A correct viable cell number of a microorganism in a biological tissue is measured by cultivating a fragment of the biological tissue such as skin infected with the microorganism and administered with an antimicrobial agent, in a medium containing a phospholipid, a nonionic surfactant, or both of the phospholipid and the nonionic surfactant.

Abstract: Monoclonal antibodies, in particular 33.28 and 31.1, and chimeric antibodies, in particular mouse/humans chimeric Chi #1 specific for glycoprotein antigens of colon carcinoma-associated antigens which are immunogenic in humans, are disclosed. Such antibodies, and fragments and derivatives thereof, are useful in immunodiagnosis and immunotherapy of human colon, breast, and ovarian cancer, and for purification of antigens which can serve as immunotherapeutic agents. Methods of detecting the colon carcinoma-associated antigen in a sample, and methods for treating subjects having colon, breast, and ovarian carcinomas are disclosed.