Abstract: The invention relates to a method in the preparation of samples for microscopic examination onto which a coverslip is applied. The method is notable for the fact that the coverslipping quality is checked automatically and at least partly optically. The invention further relates to an apparatus for carrying out the method, and to an apparatus for checking the coverslipping quality of samples onto which a coverslip is applied.

Abstract: The invention is directed to methods and compositions for deparaffinizing paraffin-embedded biological samples for subsequent tissue staining. The compositions are microemulsions that may include water/oil/surfactant microemulsions, and optionally a cosurfactant. The microemulsions enable deparaffinization without the use of xylene or toluene, and also enable solvent exchange without the use of intermediary alcohol dehydration or alcohol rehydration compositions.

Abstract: The present invention relates to novel uses of the MLN 51 gene or protein. The MLN 51 gene and protein is closely related to the development of rheumatoid arthritis and serve as biomarker and therapeutic target for rheumatoid arthritis, particularly chronic synovitis.

Abstract: Compositions and methods are disclosed for substantially liquid, gel, suspension, slurry, semisolid and/or colloid storage of biological samples following admixture with the herein disclosed storage composition, permitting substantial recovery of biological activity following storage without refrigeration. In certain embodiments, unfractionated saliva samples may be stored without refrigeration for weeks, months or years in a form that permits recovery of intact DNA following the storage period.

Abstract: A microfiuidic device comprises a valve having electrically controllable wetting properties. The valve comprises a valve surface arranged in a closed valve space defined by at least the valve surface, a first liquid opening for leading a first liquid to the valve and a second liquid opening for leading a second liquid to the valve. The valve surface, in a first state, is sufficiently hydrophobic to prevent contact between the first liquid and the second liquid. The valve surface, in a second state, is sufficiently hydrophilic to allow contact between the first liquid and the second liquid. A ventilation outlet is provided for allowing gas to escape from the valve space.

Abstract: The present invention relates to a method of screening placental proteins responsible for pathophysiology of preeclampsia, and a marker for early diagnosis and prediction of preeclampsia. In accordance with one aspect of the present invention, there is provided a method of screening placental proteins responsible for pathophysiology of preeclampsia by 2D E-proteomics analysis, comprising: isolating placental proteins from a placental tissue; separating the isolated proteins two-dimensionally through 2D electrophoresis; and comparing and analyzing the separated proteins based on scanned gel images and differences in the images between normal placental proteins and preeclamptic placental proteins, wherein the comparison and analysis of the placental proteins based on the scanned gel images and differences in the images are accomplished by selecting proteins with differences of 140% or more between two placentas.

Abstract: The present invention provide for solutions of a defined composition useful in a staining protocol, such as a hematoxylin and eosin staining protocol, when used at certain points of the staining protocol. The formulations of these defined solutions are such that carry-over of the solutions will not negatively impact, or preferably, will stabilize or favorably modify staining reagent solutions coming in contact with the solutions. In certain embodiments of the invention, solutions are buffered to maintain a specific pH that when carried-over—such as carried-over into hematoxylin—will not significantly influence the pH of the next staining reagent.

Abstract: Systems and methods of sample (1) and staining processing including compression and dynamic movement of liquids (3) in a fluidically moving substantially contained liquid bridge (6) perhaps between a hydrophobic wand (4) and a hydrophilic sample support element (2). Embodiments may include low volume reagent and perhaps even low volume buffer wash in sample processing. In addition, antibodies can be conjugated with nanoparticles (64) and can be used in sample processing. Exposing a sample with or without movement to AC, DC, or even a permanent magnet field may improve staining. Staining with nanoparticle reagents could be quantified using a microscope with a magnetometer below the slide viewing area. The detection of nanoparticles attached to the chemistry may facilitate the quantification of cancerous cells stained in the tissue.

Abstract: The formulations, systems, and methods disclosed herein permit automated preparation of specimens (e.g., biological specimens) for examination. The disclosed formulations, systems, and methods provide fast, efficient, and highly uniform specimen processing using minimal quantities of fluids. The methods include at least a fixing phase for fixing a specimen to a substrate such as a microscope slide, a staining phase for staining the specimen, and a rinsing phase for rinsing the specimen. One or more of the fixing, staining, and rinsing phases include one or more agitation phases for distributing reagents evenly and uniformly across the specimen. The systems can be implemented as a standalone device or as a component in a larger system for preparing and examining specimens.

Abstract: The present invention provides compounds, compositions and methods for dedifferentiating lineage committed mammalian cells into stem cells. The present invention also provides methods of inducing dedifferentiation of lineage committed mammalian cells into stem cells, which can be further differentiated into various lineage committed cells. Methods of identifying additional compounds useful for inducing dedifferentiation of lineage committed cells into stem cells are also provided.

Abstract: The invention provides methods for production of gangliosides, e.g., GM1, from cells in culture using, for example, bone marrow cells and neuroblastoma cells. Methods include the treatment of cells with neural induction media and chloroquine, or chloroquine alone in the case of, e.g., human bone marrow cells, neuraminidase or glucosamine, to induce the production of gangliosides, e.g., GM1, in the cells. Also provided are methods of long-term, high density culturing of cells without passaging to produce gangliosides, e.g., GM1. Methods of quantifying gangliosides, e.g., GM1 in cell culture are also provided.

Abstract: The formulations, systems, and methods disclosed herein permit automated preparation of specimens (e.g., biological specimens) for examination. The disclosed formulations, systems, and methods provide fast, efficient, and highly uniform specimen processing using minimal quantities of fluids. The methods include at least a fixing phase for fixing a specimen to a substrate such as a microscope slide, a staining phase for staining the specimen, and a rinsing phase for rinsing the specimen. One or more of the fixing, staining, and rinsing phases include one or more agitation phases for distributing reagents evenly and uniformly across the specimen. The systems can be implemented as a standalone device or as a component in a larger system for preparing and examining specimens.

Abstract: Disclosed embodiments concern a composition comprising DAB chromogen, and/or derivative thereof, a stabilizer, and polymer capable of preventing or reducing DAB precipitation relative to a composition that does not comprise the polymer. Also disclosed herein is a method for using the disclosed composition and embodiments of a kit.

Abstract: Presented is a method of prognosing a patient's response to a cancer therapy wherein prior to the therapy contacting a sample of cells from the patient's tissue or organ being treated for the cancer with a solution of TCPP to permit binding of the TCPP to components of the abnormal dysplastic or carcinomic cells, if any are present; detecting TCPP fluorescence in the sample, the presence of TCPP fluorescence being indicative that the sample contains dysplastic or carcinomic cells; at intervals during the therapy and subsequent to the therapy performing steps a-c on another sample of cells from the patient's tissue or organ being treated for the cancer; and determining if the percentage of abnormal pre-cancerous cells in the samples tested during and subsequent to the therapy are reduced as compared with the sample tested prior to the therapy, the reduction being prognostic of the patients response to the cancer therapy.

Abstract: It is disclosed herein that antibodies specific for preproproteins or preproteins, which are synthesized by certain types of cells or tissues, can be used in immunohistochemistry assays to discriminate between the intracellular component of the protein (including the preproprotein, preprotein and/or proprotein forms of the protein) from the secreted component of the same protein. Accordingly, provided herein is an immunohistochemical method for specific detection of the intracellular form of a protein in a biological sample using an antibody specific for the preproprotein or preprotein form of the protein. In particular examples, the protein is albumin or an immunoglobulin light chain. Also disclosed herein are preproprotein-specific ore preprotein-specific antibodies that can be used to detect specific cell types, tissue lesions or other pathological foci and metastases by IHC. In particular, antibodies that specifically bind human preproalbumin, but do not bind the secreted form of albumin are disclosed.

Abstract: A method is disclosed for reversing fixation-induced cross-linking in tissue specimens that have been preserved for histological examination. The method involves placing the fixed tissue in a liquid under elevated temperature and pressure conditions that are sufficient to reverse the fixation-induced cross-linking, restore antigenicity to proteins, and permit improved molecular and proteomic analysis of the preserved tissue specimen. Methods are also disclosed for processing tissues for histological examination under elevated pressure conditions that enhance the perfusion of liquid reagents into the tissue and reduce overall processing times.

Abstract: The present invention provides isolated, non-viable bacterial cells comprising a plurality of nucleic acid crosslinks, methods for making said cells, and methods for using said cells to isolate DNA-protein complexes. In particular, the nucleic acids of the cells are crosslinked by contacting the cells with a furocoumarin compound and ultraviolet light.

Abstract: A tissue staining method which comprises: staining a tissue with a staining reagent wherein a biosubstance recognition site is bonded to particles carrying multiple fluorescent substances accumulated therein; in the stained tissue, counting fluorescent points or measuring fluorescent brightness; and evaluating the expression level of a biosubstance, which matches the biosubstance recognition site, in the aforesaid tissue on the basis of the number of the fluorescent points or fluorescent brightness that was measured.

Abstract: Methods are provided herein for determining antioxidant activity of a test sample in intact cells. The method includes determining the antioxidant capacity of a test sample in intact red blood cells, wherein the test sample is added to intact red blood cells and oxidative damage is measured by alteration of fluorescence intensity of an oxidation-sensitive fluorescent indicator dye.

Abstract: The present invention relates to a method for enhancing immunoreactivity of a tissue or cell sample fixed in a fixing medium, a target retrieval composition and its use. The method comprises providing a carrier in a horizontal position, said carrier having thereon a tissue or cell sample, said tissue or cell sample being on top of the carrier; contacting substantially the tissue or cell sample side of the carrier with a buffered target retrieval solution, wherein the target retrieval solution remains otherwise exposed to the environment; heating the tissue or cell sample and the target retrieval solution to a temperature above 100° C. The invention furthermore concerns the automated immunohistochemical staining of said samples, in particular the reactivation of antigens masked by fixation.

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 current invention provides a method for directly converting histopathologically processed biological samples, tissues, and cells into a multi-use biomolecule lysate. This method allows for simultaneous extraction, isolation, solubilization, and storage of all biomolecules contained within the histopathologically processed biological sample, thereby forming a representative library of said sample. This multi-use biomolecule lysate is dilutable, soluble, capable of being fractionated, and used in any number of subsequent experiments.

Abstract: Disclosed are methods and systems for automated deparaffinization and histochemical staining of tissue samples. Samples are automatically deparaffinized and stained without the use of harsh chemicals and without the use of extreme temperatures.

Abstract: The formulations, systems, and methods disclosed herein permit automated preparation of specimens (e.g., biological specimens) for examination. The formulations can include a cytological fixative solution including Azure B, a surfactant, methanol, and ethylene glycol. The disclosed formulations, systems, and methods provide fast, efficient, and highly uniform specimen processing using minimal quantities of fluids. The methods include at least a fixing phase for fixing a specimen to a substrate such as a microscope slide, a staining phase for staining the specimen, and a rinsing phase for rinsing the specimen. One or more of the fixing, staining, and rinsing phases include one or more agitation phases for distributing reagents evenly and uniformly across the specimen. The systems can be implemented as a standalone device or as a component in a larger system for preparing and examining specimens.

Abstract: A method of preparing a slide of a biological specimen, including the steps of (a) providing a slide containing a biological specimen and a cover slip, (b) placing a liquid non-evaporating sealing compound such as mineral oil at spaced locations around an area on the slide and (c) placing the cover slip over the specimen area whereby the specimen and reagent is between the slide and the cover slip and the sealing compound spreads to define a closed boundary around the specimen in the space between the slide and the cover slip. Testing of the biological specimen may then be performed automatically.

Abstract: A tissue array production method which enables even roll-shaped tissue pieces having various diameters to be steadily fixed to a substrate block is provided. In the tissue array production method in which roll-shaped tissue pieces 6 formed by rolling sheet-like tissue pieces 8 in the shape of a roll are arranged on a substrate in an array form, the tissue array is produced by placing a holding member 16 which holds a plurality of roll-shaped tissue pieces 6 so that their axis directions are vertically directed in a container 10 into which a melted embedding medium is poured for its accumulation, to hold the respective roll-shaped tissue pieces 6 in the holding member 16; by pouring the embedding medium into the container 10, to form a substrate block 40 constituted so that the plurality of roll-shaped tissue pieces 6 is arranged in the array form; and by slicing the substrate block 40 so that the roll-shaped tissue pieces 6 are ring-shaped, to place the sliced pieces on the substrate.

Abstract: A sample container (20) for receptacle devices for receiving biological objects that may be used for example as collecting devices (30) in laser microdissection systems is described, in which the sample container (20) has a coding (23) with the aid of which the sample holder in the laser microdissection system can be unambiguously identified in order subsequently to be able to allocate correctly biological objects (43) to be dissected to individual receptacle containers (31) of the identified receptacle device (30) or of the identified sample holder (20), so as to carry out a fully automated microdissection procedure.

Abstract: The various embodiments herein provide a method for detecting the cancerous cells using the carbon nanotubes. The method comprises preparing a solution of the tissue cells. The prepared solution of the tissue cells is poured on a fabricated substrate to carry out an entrapment of the tissue cells on the substrate. The substrate is dried after the entrapment in an air ambient and observed under a scanning electron microscope. The cancer cell is detected based on the biomechanical properties such as softness, deformability and an elasticity of the cancer cells. The cancer cell is detected based on the deflection of the substrate due to the entrapment of the cancer cells.

Abstract: The present invention relates to a method for determination of target cells or tissue for isolating or extracting biomolecules from fixed biological samples, the preparation of a sample in a method for extracting, isolating and/or purifying biomolecules from a fixed biological sample as well as to a kit for visualizing target cells or tissue in a fixed biological sample for extracting, isolating and/or purifying biomolecules from said target cells or tissue.

Abstract: The invention relates to antibodies that are capable to bind the extracellular domain of integrin. Another object of the invention concerns the use of said antibodies for detecting integrins in archival formalin fixed paraffin embedded (FFPE) tissue. The invention also relates to methods for preparing monoclonal rabbit antibodies, wherein the immunogen is an insect expression culture-derived recombinant extracellular integrin domain, and another method for screening anti-integrin antibodies that discriminate between closest integrin homologues and that are especially suited for immunohistochemistry in FFPE material.

Abstract: A pre-treatment method for analyzing a specified portion in a specimen composed of a biological tissue includes the steps of preparing a specimen to be analyzed, determining a specified portion in the specimen; and applying an analysis inhibitor to a portion except the specified portion of the specimen using a droplet spray method.

Abstract: Systems and methods of sample processing and temperature control are disclosed. The invention may especially relate to temperature control, and may in some embodiments be methods of temperature control of an automated sample processing system and methods of automated sample processing. Specifically, the present invention provides temperature control in relation to sample processing systems and methods of processing samples, and in some embodiments provides temperature control in relation to sample carriers and processing materials such as reagents. Corresponding systems and devices are disclosed, including sample processing systems (1), sample carrier temperature regulation systems (60), reagent temperature regulation systems, sample processing control systems, and temperature regulation devices, among other embodiments.

Abstract: The present invention demonstrates the differential sensitivity of PBLs from lung cancer patients and healthy controls to NNK-induced genetic damage. The data provide convincing evidence that the preferred CBMN assay is a robust test for detection of this sensitivity and yields results that are a good predictor of, for example, lung cancer risk. The simplicity, rapidity, and sensitivity of the CBMN test make it a valuable tool for screening and, for example, prioritizing potential cases for early detection of the disease.

Abstract: In one aspect, the invention relates to a method for fixing a short nucleic acid in a biological sample. In another aspect, the invention relates to a method for detecting a target short nucleic acid in a biological sample. The method includes contacting the biological sample with an aldehyde-containing fixative, and subsequently contacting the sample with a water-soluble carbodiimide. In a further aspect, the invention relates to a kit for fixing a short nucleic acid in a biological sample. The kit includes a support substrate for holding the sample; an aldehyde-containing fixative; and a water-soluble carbodiimide.

Abstract: This fixing solution is intended to preserve in vitro a cytological sample, comprising nucleated cells and erythrocytes and comprises alcohol for fixing the cells. It comprises physiological saline in order to avoid osmotic shocks at the wall of the cells, formalin and polyethylene glycol for retaining the size and the integrity of the nucleated cells and erythrocytes, which are fixed in said solution. The solution does not contain acetone or any compounds of the ketone or acetic acid family.

Abstract: A histologic tissue sample support device includes a tissue support formed of material that can be successfully sectioned in a microtome and is resistant to degradation from solvents and chemicals used to fix, process and stain tissue. A resilient cellular material is coupled to the tissue support and is configured to engage and retain tissue in place during processing and embedding. The resilient cellular material is also capable of successful sectioning in the microtome and porous to allow infiltration of the solvents and chemicals used to fix, process and stain tissue, and of embedding material used to embed the tissue while the tissue is retained by the resilient cellular material.

Abstract: A fixative for biological tissue made up of polymerized carbon nanotubes encapsulating osmium nanoparticles and its method of synthesis are disclosed. Carbon nanotubes are first oxidized. Next, the oxidized carbon nanotubes and monohydrated citric acid are mixed to synthesize carbon nanotubes grafted with poly(citric acid). The carbon nanotubes grafted with poly(citric acid) are then mixed with an osmium source to synthesize carbon nanotubes grafted with poly(citric acid) encapsulating osmium nanoparticles. The nano-fixative of this application has been shown to improve fixation of biological tissue relative to well-known fixatives.

Abstract: A clearing reagent according to this invention for making a biological material transparent is a solution containing, as an active component, at least one compound selected from the group consisting of urea and urea derivatives, in order to provide a novel clearing reagent for making a biological material transparent.

Abstract: A method and apparatus for measuring changes in cell volume generally includes introducing cells into a chamber having a volume between 2 and 100 times the volume of the introduced cell. A first electrically conductive extracellular fluid is introduced into the chamber and a current is applied. The voltage induced by said current flow is measured. The first fluid is exchanged with a second electrically conductive extracellular fluid and a current is applied. The voltage induced by said current flow is measured. The first induced voltage result and the second induced voltage result are used in conjunction with known voltages induced by such current flows to monitor changes in the volume corresponding to fluid flow between the cell and an extracellular fluid.

Abstract: Methods for producing an isotope-labeled mammalian, including a human, biomolecule, such as polypeptides and proteins, in a cell-free protein synthesis system. A biomolecule standard is produced having at least one isotope different in abundance than that of the naturally occurring isotopes in the biomolecule. Methods for quantifying biomolecules standards expressed using mammalian cell-free extracts are disclosed. Methods for producing such standards, kits, systems and reagents, relating to the use of isotope-labeled biomolecule as quantification standards in mass spectrometric and nuclear magnetic resonance analysis.

Abstract: A composition that includes an aldehyde, alcohol, and a ketone, the volumetric ratio of the alcohol to the ketone in the composition ranging from as low as about 0.8:1 to as high as about 4.5:1 and the volumetric ratio of the alcohol to the aldehyde in the composition ranging from as low as about 41.5:1 to as high as about 450:1.

Abstract: The invention relates to the technical field of the histological preparation of biological tissue comprising a method and means for preparing transparent biological specimens for examination under a light microscope.

Abstract: A method is disclosed for reversing fixation-induced cross-linking in tissue specimens that have been preserved for histological examination. The method involves placing the fixed tissue in a liquid under elevated temperature and pressure conditions that are sufficient to reverse the fixation-induced cross-linking, restore antigenicity to proteins, and permit improved molecular and proteomic analysis of the preserved tissue specimen. Methods are also disclosed for processing tissues for histological examination under elevated pressure conditions that enhance the perfusion of liquid reagents into the tissue and reduce overall processing times.

Abstract: The present invention relates to a method for creating two- and three-dimensional arrays. Plates of sample materials are stacked to create primary stacks. Primary stacks are sliced to form combs. Combs are stacked to form secondary stacks. Secondary stacks are sliced to form tertiary plates or two-dimensional arrays. Tertiary plates can be stacked to form three-dimensional arrays. The two- and three-dimensional arrays can be used in large-scale parallel processing of samples, pattern printing, tissue engineering, microfluidics, microelectronics, and microconstruction.

Abstract: A method of staining or pre-staining at least one cell is provided. The method comprising contacting the at least one cell with a staining agent selected from the group consisting of an extract of a Ficus elastica plant, a C23H44O4 and a proanthocyanidin, thereby staining or pre-staining the at least one cell. Also provided are methods of detecting cells of different differentiation stages and methods of diagnosing cancer and metabolic diseases.

Abstract: A method for fixing a biological sample includes delivering energy through a biological sample that has been removed from a subject, while fixing the biological sample. A change in speed of the energy traveling through the biological sample is evaluated to monitor the progress of the fixation. A system for performing the method can include a transmitter that outputs the energy and a receiver configured to detect the transmitted energy. A computing device can evaluate the speed of the energy based on signals from the receiver.

Abstract: This invention provides compositions and methods for fixing biological samples, particularly fecal samples used in the diagnosis of parasitic infection. The fixative composition of the present invention includes a zinc salt, an organic acid and water and permits staining of biological samples without use of toxic compounds, such as formaldehyde and mercury-containing compounds and without the use of additives such as polyvinyl alcohol. The fixative composition and methods are compatible with many diagnostic assays, including trichrome stains, iron hematoxlin, ELISA, fluorescent assays, and lateral flow assays.

Abstract: One aspect of the present invention relates to a method of controlling axon or dendrite development in a neuronal cell population. This method involves providing a neuronal cell population and contacting the neuronal cell population with a modulator of R-type Ca2+ channel expression or activity in controlling the neuronal cell population to induce either axon or dendrite development. Another aspect of the present invention relates to a method of treating neuronal injury in a subject. This method involves selecting a subject with neuronal injury mediated by R-type Ca2+ channel expression or activity and administering to the selected subject an inhibitor of R-type Ca2+ channel expression or activity to induce neuronal axon development under conditions effective to treat the neuronal injury in the subject. Yet another aspect of the present invention relates to a method of screening for agents that modulate R-type Ca2+ channel expression or activity.

Abstract: The formulations, systems, and methods disclosed herein permit automated preparation of specimens (e.g., biological specimens) for examination. The disclosed formulations, systems, and methods provide fast, efficient, and highly uniform specimen processing using minimal quantities of fluids. The methods include at least a fixing phase for fixing a specimen to a substrate such as a microscope slide, a staining phase for staining the specimen, and a rinsing phase for rinsing the specimen. One or more of the fixing, staining, and rinsing phases include one or more agitation phases for distributing reagents evenly and uniformly across the specimen. The systems can be implemented as a standalone device or as a component in a larger system for preparing and examining specimens.

Abstract: The invention relates to a method for detecting specific target-cells in a simple and time saving way, using paramagnetic particles, antibodies recognizing the Fc portions of target-cell associating antibodies and target-cell associating antibodies directed to specific antigen determinants in the target-cell membranes. Incubation of the cell suspension with a mild detergent and/or second set of antibodies or antibody fragments, prelabeled or not with fluorescent agents, metallocolloids, radioisotopes, biotincomplexes or certain enzymes allowing visualization, with dramatically increase the specificity of the method. The method can further be used for isolation of the target-cells by magnetic field application and kit for performing the method according to the invention is described.