Abstract: Genetic modification or selection of avians requires that large numbers of birds be genetically analyzed for sequences of interest. Typically, DNA is extracted on an individual basis from samples taken from the birds. Current methods of DNA extraction extract the DNA from blood or other tissues using tedious and time-consuming procedures. The present invention provides a high throughput screening assay for detecting a genetic sequence in multiple samples. The assay further provides a DNA extraction method that allows DNA to be extracted rapidly from multiple avian samples, such as red blood cells. The extraction method is extremely reliable and does not require that each sample be quantitated post-extraction. The extracted DNA can be used for a variety of genetic assays, including a high throughput screening assay to identify insertion of a transgene. The present invention is particularly useful for extracting DNA from nucleated RBCs.

Abstract: A method and kit of diagnosing endometriosis in a female patient suspected of having endometriosis. The method includes obtaining a sample from the patient. The sample is analyzed to detect the presence of a purified and isolated endometriotic haptoglobin designated ENDO-I and functional analogs thereof. A therapeutic for treating endometriosis by modulating the expression of a purified and isolated endometriotic haptoglobin designated ENDO-I and functional analogs thereof and a pharmaceutically acceptable carrier.

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: The present patent describes a biocompatible composite made of a first fibrous layer attached to a three-dimensional inter-connected open cell porous foams that have a gradient in composition and/or microstructure through one or more directions. These composites can be made from blends of absorbable and biocompatible polymers. These biocompatible composites are particularly well suited to tissue engineering applications and can be designed to mimic tissue transition or interface zones.

Abstract: The invention relates to a method for the examination of cells (20, 38) in a culture medium, in particular for in-situ microscopy in a bio-reactor, whereby cells in a sample volume, the depth (d) of which is defined by windows (14, 16) in the direction of the optical axis of the microscope (18), are microscopically imaged and are automatically recorded and processed by means of an image processing system (30). Said method is characterized in that the depth (d) of the sample volume (12) is adjusted to the size of the cells (20, 38) by successively reducing the separation (d) of the windows while the image size (G) of the cells is simultaneously verified by the image processing system (30) such that a separation value (D) is determined at which the image size (G) of the cells begins to grow, thus corresponding to flattening caused by the contact pressure of the windows (14, 16), and that the separation (d) of the windows (14, 16) is set to said separation value (D) for the examination.

Abstract: Methods of fixing and processing tissue and samples on a membrane by using ultrasound radiation as a part of the method are presented. Ultrasound of a frequency in the range of 0.1–50 MHz is used and the sample or tissue receives 0.1–200 W/cm2 of ultrasound intensity. The use of ultrasound allows much shorter times in the methods. Also presented are apparati comprising transducers of one or of multiple heads for producing the ultrasound radiation and further comprising a central processing unit and optionally comprising one or more sensors. Sensors can include those to measure and monitor ultrasound and temperature. This monitoring system allows one to achieve accurate and optimum tissue fixation and processing without overfixation and tissue damage. The system also allows the performance of antigen-antibody reactions or nucleic acid hybridizations to be completed in a very short time while being highly specific and with a very low or no background.

Abstract: Improved techniques for performing assays using nematode worms, such as nematode worms from the genus Caenorhabditis. The assays generally comprise exposing nematodes to at least one compound which paralyzes or kills the nematodes.

Abstract: An isolated nucleic acid comprising the nucleotide sequence of SEQ ID NO:1, or the full complementary sequence thereof. Presence of said nucleic acid in a subject predisposes the subject to an adenocarcinoma. Also disclosed are a method of diagnosing an adenocarcinoma.

Abstract: The present invention provides nucleic acid molecules unique to M. paratuberculosis. The invention also provides the polypeptides encoded by the M. paratuberculosis-specific nucleic acid molecules of the invention, and antibodies having specific binding affinity for the polypeptides encoded by the M. paratuberculosis-specific nucleic acid molecules. The invention further provides for methods of detecting M. paratuberculosis in a sample using nucleic acid molecules, polypeptides, and antibodies of the invention. The invention additionally provides methods of preventing a M. paratuberculosis infection in an animal.

Abstract: Compositions and methods are provided for dewaxing wax-embedded biological specimens prior to histochemical analysis. The compositions and methods provided can effectively remove wax or improved wax-based embedding materials, particularly paraffin-based, from specimens during preparation for histochemical or other diagnostic analyses, while minimizing danger to users, achieving compatibility with automated use, and maintaining compatibility with downstream histochemical analyses, particularly immunostaining. Compositions of the invention comprise a paraffin-solubilizing organic solvent, a polar organic solvent, and a surfactant. Compositions can further comprise water. The method involves contacting a wax-embedded specimen with the dewaxing composition to solubilize the wax impregnating the specimen prior to histochemical analysis.

Abstract: Disclosed is a recipient block for arraying a certain tissue sample into a desired position on a tissue microarray slide, comprising(a) an additive and (b) a wax. The present invention also discloses a method of preparing a recipient block, including (1) preparing an aqueous solution of an additive; (2) pouring the aqueous solution of the additive into a mold and cooling the mold to gelate the aqueous solution of the additive; (3) dehydrating the resulting additive gel in alcohol; (4) immersing the dehydrated additive gel in an organic solvent to make the dehydrated additive gel transparent; (5) penetrating a wax into the transparent additive gel to provide a block; and (6) providing a plurality of cylindrical holes in the block.

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

Abstract: The present invention provides 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 comprise components optimized to facilitate removal or etching of the embedding media from the biological sample. The present invention also provides reagents for use in an automated environment for cell conditioning biological samples wherein the cells are predisposed for access by reagent molecules for histochemical and cytochemical staining procedures. The reagents comprise components optimized to facilitate molecular access to cells and cell constituents within the biological sample.

Abstract: Disclosed is an apparatus for measuring a micro area in a specimen in which a reagent necessary for observation and examination of a cell smear specimen or a tissue specimen is dropped to cause a reaction for a measurement and an analysis by way of an image. The apparatus includes: a micro reaction unit that is able to select a specific micro area in the specimen and to subject the specific micro area to a reaction-operation; a unit that measures; records and displays an image of the micro area; and a control unit that controls the measuring, recording, and displaying unit. Reactions can be effected quickly on such specimens as smear cell specimens and tissue slice specimens. The application of the reagent solution can be saved. A comparison between local presence of a gene or anti-body and a cell image can be made quickly and easily.

Abstract: A method and apparatus for preparing tissue specimens for histological study utilizing two connectable sections each with hollowed cylinders for receiving first and second buttons, each button including planar disc and cylindrical stem portions, such that the stem portions can be slideably mounted in hollowed cylinders. The planar disc portions of the buttons are capable of receiving tissue specimens.

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: The present invention relates to a method for monitoring the effect of in vivo administration of Cathepsin S inhibitors by measuring accumulation of an intermediate degradation product of invariant chain (Ii), in particular the p10 Ii fragment, in blood of dosed subjects.

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: Peptide sequence tags are identified and used to produce a class of global antibodies, which recognize all members of a particular protein family with uniform specificity, regardless of the species of origin. The tags are used to create antibodies to the major proteins of photosynthesis, and carbon and nitrogen metabolism. The antibodies have a range of applications as diagnostic detection reagents for major environmental processes.

Abstract: This invention provides methods to the determination of the viability of the cell by a first reagent and the phenotype of a cell by use of one or more second reagent. The first reagent is one that is detectable in viable, or living, cells even after they have been fixed such that they are no longer viable. The one or more second reagent is compatible for use in fluorescence activated cell sorting (FACS) including intracellular FACS. The invention thus provides methods of simultaneously identifying a cell as both viable and having a phenotype of interest. The invention also provides compositions for use in the disclosed methods.

Abstract: A method of staining an ocular structure, the structure being a human or other mammalian eye or portion thereof, the method comprising staining the ocular structure with either indigotindisulfonate, Patent Blue V, Sulphan Blue, tolonium chloride, or Evans Blue. Ocular structures of particular interest are the anterior lens capsule and the vitreo-retinal interface.

Abstract: Screens that directly or indirectly measure or qualitatively observe CTLA-4 expression or function by animals or cell cultures, or that indirectly measure dependence of an agent on CTLA-4 by comparison to animals or cell cultures that lack CTLA-4, identify agents that are useful in immunosuppression and the generation of immunologic tolerance for the prevention and treatment of transplant rejection, autoimmune and inflammatory diseases.

Abstract: The present disclosure describes novel methods for localized and controlled staining of intact corneal tissue surfaces to provide therapeutic benefits in ophthalmic applications, such as for example, the correction of iris defects, the correction of corneal tissue scarring, and the creation of a pupil in aniridia. A first method for staining tissue surfaces is directed to covalently bonding sulfonic acid dyes to deprotonated proteins in tissue. Another disclosed method is directed to staining corneal tissue surfaces with black sulfonic acid dye compositions, particularly for forming black rings on the corneal surface.

Abstract: The present invention provides a more efficient and faster way to prepare tissue samples for sectioning. More particularly, in accordance with the present invention, a tissue sample is embedded in a porous embedding media in a desired orientation, processed, and sectioned all while being held in the porous embedding media. The post-tissue processing step of manual embedding in paraffin is eliminated from the process.

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: An automated staining system and a reagent container designed for use with the automated staining apparatus. The reagent container includes a reagent containment section capable of containing a volume of a reagent. The reagent containment section includes an upper wall and a base wall that are spaced apart along an axis. The base wall includes a well having a nadir that is aligned axially with an access opening in the upper wall so that a reagent probe entering the opening parallel to said axis will travel toward the nadir. In another aspect of the invention, the reagent container may include a two-dimensional data element containing reagent information. The staining apparatus may include one removable drawer for holding reagent containers and another removable drawer holding slides.

Abstract: The invention relates to a novel polymethine dyes containing at least one acylsulfonamido group of the formula (I) in which n, Y, A and R have the meaning given in the claims, and at least one compound of the formulae (a) to (n) given in the claims. The polymethine dyes according to the invention are suitable for use as dyes and/or labels, in particular for staining or labeling biomolecules.

Abstract: The invention provides methods for the detection of prion diseases, such as scrapie of sheep, bovine spongiform encephalopathy of cattle, Creutzfeld-Jacob disease of man, whereby aberrant proteins or prion proteins are detected in tissues which can be sampled from line animals.

Abstract: This invention provides a novel universal collection medium for cell collection. The medium allows for the first time the ability to perform cytology and direct molecular analysis on cells preserved in a single sample. This invention also provides novel methods for analyzing cells to assess human conditions.

Abstract: The present invention describes devices and methods for performing protein analysis on laser capture microdissected cells, which permits proteomic analysis on cells of different populations. Particular disclosed examples are analysis of normal versus malignant cells, or a comparison of differential protein expression in cells that are progressing from normal to malignant. The protein content of the microdissected cells may be analyzed using techniques such as immunoassays, 1D and 2D gel electrophoresis characterization, Western blotting, liquid chromatography quadrapole ion trap electrospray (LCQ-MS), Matrix Assisted Laser Desorption Ionization/Time of Flight (MALDI/TOF), and Surface Enhanced Laser Desorption Ionization Spectroscopy (SELDI).

Abstract: Novel fluorescent derivitization reagents are described that are suitable for coupling to biomolecules that contain aldehyde or ketone functional groups. In one embodiment is provided reagents that have the following formula: wherein Q is carbonyl, thiocarbonyl, or sulfonyl, and R5 is -L-Z; L is arylene, or a C1-6 perfluoroalkylene, or a single covalent bond; Z is a carbonyl hydrazide, hydrazide, sulfonyl hydrazide, or a thiocarbonyl hydrazide; R11-R14 are independently H, C1-6 alkyl, C1-6 alkoxy, C1-6 perfluoroalkyl, C1-6 alklyamino, di(C2-12alkyl)amino, amino, carboxy, cyano, halogen, hydroxy, nitro, phenyl, or sulfo; and R21-R24 are independently H, C1-6 alkyl, C1-6 alkoxy, C1-6 perfluoroalkyl, C1-6 alklyamino, di(C2-12-alkyl)amino, amino, carboxy, cyano, halogen, hydroxy, nitro, phenyl, sulfo, or -L-Z. The method of treating a sample with the derivativization reagents is described.

Abstract: The present invention relates to the identification and characterization of classes and subclasses of circulating cancer cells, including microtumors from body fluid samples using molecular, cytological, and morphological analyses, and methods for staging patients and measuring the efficacy of medical treatments.

Abstract: An object of the present invention is to provide a reagent for activating and unmasking antigens in a immuno-tissue-chemical staining. A slice of tissue cells on a slide glass is heated or heated under pressurization by an electric pot, autoclave, microwave oven, scalder, or constant-temperature bath for a sufficient time period in CCA aqueous solution of suitable pH and CCA concentration, thereby activating and unmasking antigenicity of antigen masked by aldehyde fixation.

Abstract: This disclosure relates to CryoArrays, which permit the analysis of samples (such as protein, nucleic acid, virus, or cell samples) in arrays that are prepared at low temperatures. Because CryoArrays are constructed as a block of substantially columnar samples, the block can be sliced to provide a plurality of identical or substantially identical individual arrays. The individual arrays can be used for parallel analysis of the same array feature set, for instance with different probes or under different conditions. Also provided are methods of making CryoArrays, devices for making CryoArrays, and kits.

Abstract: This invention provides methods by which test substances can be screened for their ability to inhibit, enhance or eliminate double minute (DM) or extrachromosomal DNA by micronucleation in cells. This invention also provides a method for inducing maturation or death of a cell having the capacity to generate micronuclei. It also provides a method of treating a disease in a subject, the cells correlated with the disease having DM and extrachromosomal DNA as well as the capacity to generate micronuclei to capture them. Further provided is a method of detecting chromosomal and extrachromosomal DNA in a cell.

Abstract: The present invention provides a device and method for determining the adequacy of squamous (ectocervical) cells, columnar (endocervical) cells, neutrophils, and noncellular material in a liquid based cytology specimen. The invention first analyzes a liquid based cytology specimen using light scatter to create a light scatter characteristic representing a predetermined cell. Next the invention determines the presence of squamous (ectocervical) cells versus columnar (endocervical) cells versus neutrophils versus noncellular material using the results of the light scatter. The light scatter characteristic that may be used may be forward light scatter, side light scatter, or both side and forward light scatter.

Abstract: The present invention relates to methods of screening for target polypeptides that bind to RNA, using affinity purification methods, and the use of such target polypeptide for drug discovery and in methods of treating and preventing disease, e.g., HCV infection.

Abstract: The present invention relates to a method and composition for stabilizing clinical specimens (i.e., cells in biological samples) for transport and subsequent testing for diagnosis. The composition is specifically capable of maintaining nucleic acid in the cells intact for hybridization with oligonucleotide capture and detector probes.

Abstract: The invention relates to a mounting medium that can be used in the preparation of slides for investigation by microscopy techniques. More in particular the mounting medium comprises a solution, in at least one organic solvent selected from the group consisting of saturated hydrocarbons optionally mixed with one or more alcohols, of at least one (meth)acrylate resin based on one or more monomers having formula I: Formula I: wherein R is hydrogen or a methyl group and n has a value of 0-19. The mounting medium of the invention is particularly suited for use in histochemistry, immunochemistry and/or cytochemistry, i.e. to provide slides of samples of blood, cells tissue or other biological fluids or materials, including but not limited to samples/materials which have been stained to facilitate microscopic examination, e.g. for scientific and/or diagnostic purposes.

Abstract: Methods of detecting bioactive compounds include exposing compounds to one or more classes of chromatophores and measuring or sensing associated changes in one or more of the chromatophores. Representative methods permit identification and quantification of neurotransmitters, toxins, hormones, and chemical warfare agents with or without prior knowledge of the content of a sample. In some examples, chromatophores based on Betta fish are used. Cytosensor apparatus using such chromatophores include means for exposing chromatophores to a sample and optical detection systems for assessing changes in chromatophore optical properties. Compounds can be identified or quantified based on a red-green-blue or hue saturation-value representations of transmitted or reflected light or based on other characterizations of transmitted or reflected light.

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 provides a method for creating a frozen tissue array. An oil in a liquid form is added into a recipient block containing frozen tissue cores where the oil has a freezing point lower than the freezing point of the tissue cores; and the recipient block containing the oil is cooled to a temperature about equal to or below the freezing point of the oil; the subsequently frozen oil locks the frozen cores in the recipient block. The oil may also be added to the recipient block prior to inserting the frozen tissue cores. The recipient block may be formed using a cryoarray device comprising a mold plate, an ejector plate, mold alignment pins, ejector pins, and cryoarray pins. Such method may be used for preparing frozen sections with multiple tissue specimens for assays such as in-situ hybridization and immunohistochemistry.

Abstract: The present invention includes a method and apparatus for the detection of a target material. The method and apparatus includes providing a substrate with a surface and forming a domains of deposited materials thereon. The deposited material can be placed on the surface and bound directly and non-specifically to the surface, or it may be specifically or non-specifically bound to the surface. The deposited material has an affinity for a specific target material. The domains thus created are termed affinity domains or deposition domains. Multiple affinity domains of deposited materials can be deposited on a single surface, creating a plurality of specific binding affinity domains for a plurality of target materials. Target materials may include, for example, pathogens or pathogenic markers such as viruses, bacteria, bacterial spores, parasites, prions, fungi, mold or pollen spores.

Abstract: Laser capture microdissection occurs where the transfer polymer film is placed on a substrate overlying visualized and selected cellular material from a sample for extraction. The transfer polymer film is focally activated (melted) with a pulse brief enough to allow the melted volume to be confined to that polymer directly irradiated. This invention uses brief pulses to reduce the thermal diffusion into surrounding non-irradiated polymer, preventing it from being heated hot enough to melt while providing sufficient heat by direct absorption in the small focal volume directly irradiated by the focused laser beam. This method can be used both in previously disclosed contact LCM, non contact LCM, using either condenser-side (or beam passes through polymer before tissue) or epi-irradiation (or laser passes through tissue before polymer). It can be used in configuration in which laser passes through tissue before polymer with and without an additional rigid substrate.

Abstract: The invention disclosed herein improves upon existing tissue microarray technology by using frozen tissues embedded in tissue embedding compound as donor samples and arraying the specimens into a recipient block comprising tissue embedding compound. Tissue is not fixed prior to embedding, and sections from the array are evaluated without fixation or post-fixed according to the appropriate methodology used to analyze a specific gene at the DNA, RNA, and/or protein levels. Unlike paraffin tissue arrays which can be problematic for immunohistochemistry and for RNA in situ hybridization analyses, the disclosed methods allow optimal evaluation by each technique and uniform fixation across the array panel. The disclosed arrays work well for DNA, RNA, and protein analyses, and have significant qualitative and quantitative advantages over existing methods.

Abstract: Methods and apparatuses for the separation a predetermined cellular component from a bodily fluid or tissue by centrifugation are provided. More specifically, this invention provides a method for the separation and isolation of one or more components, such as stem cells, buffy coat, bone marrow cells, erythrocytes, leukocytes, thrombocytes, serum, fluorescently labeled cells, and magnetically labeled cells, from whole blood, bone marrow, buffy coat, fat tissue, muscle tissue, and nerve tissue by centrifugation, wherein the components are isolated while the centrifuge is rotating.

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.

Abstract: A rapid method of microwave-assisted formalin fixation of tissue that is described as: (a) a two-step process; (b) applicable to large (>5 mm thick) and small (<5 mm thick) tissues; (c) exposure of fresh tissue (i.e. a surgical biopsy) in a formalin solution to continuous microwave irradiation; (d) formalin circulated and cooled to maintain a constant temperature; (e) microwave-assisted formalin fixation performed at a temperature between 4° C. and 40° C.; (f) a temperature probe used to monitor fixative temperature in the cavity (g) after processing via microwave-assisted formalin fixation, the tissue can be processed by microwave methods or in an automatic tissue processor into paraffin for diagnostic evaluation. The two step process consists of a first low power microwave run followed by a second high power microwave run.

Abstract: A method is provided for the labeling of individual cells. Labeling is accomplished by coating a particle with at least one dye or nucleic acid sequence encoding a marker protein. The particle is then propelled toward the cell resulting in the particle contacting the cell for a time sufficient for the dye or nucleic acid to leave the particle and enter the cell. The present method allows for the differential labeling of individual cells within dense populations of cells.