Abstract: The invention generally relates to mass spectral analysis. In certain embodiments, methods of the invention involve analyzing a lipid containing sample using a mass spectrometry technique, in which the technique utilizes a liquid phase that does not destroy native tissue morphology during analysis.

Abstract: In a wide variety of human solid tumors, an aggressive, metastatic phenotype and poor clinical prognosis are associated with expression of the receptor tyrosine kinase Met. Disclosed herein are (a) a monoclonal antibody named Met4, which antibody is specific for Met, and (b) a hybridoma cell line that produces Met4. The Met4 antibody is particularly useful for detecting Met in formalin-fixed tissue. Methods of using the Met4 antibody for detection, diagnosis, prognosis, and evaluating therapeutic efficacy are provided.

Abstract: A stabilized hematoxylin composition is disclosed that includes one or both of a host compound and an antioxidant. The disclosed composition exhibits sufficient stability to be utilized in an automated staining process without undue degradation prior to use of the composition to stain a biological sample. Methods of using and making the stabilized composition also are disclosed.

Abstract: A method for processing frozen slices of tissue of biospecimens mounted on or adhered to glass slides, i.e. forming a frozen section (2), and arranged on a carrier (1), has the following steps: a.) immersing the frozen tissue slices in a fixative, b.) staining the tissue slice, c.) dehydrating the tissue slice, and d.) optionally clearing the tissue slice. Steps a.) to d.) are performed by automatically transferring the frozen sections (2) on the carrier (1) between and into and out of at least a container (C1) holding a fixative, at least one or optionally more, preferably two containers (C3, C5) holding a staining solution, a container (C6, C7) holding a dehydrating solution, and optionally a container (C8) holding a clearing solution. The transfer and the time duration during which the tissue slices are in said containers (C) are controlled by a control unit controlling an actuator (10).

Abstract: In a microdissection method and a microdissection system, first and second objects are transported from a preparation to first and second collection devices, respectively, so that a position of the second collection device relative to the first collection device substantially corresponds to a position of the second object relative to the first object in the preparation.

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 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: A method for operating a tissue processor and a respective tissue processor for performing this method are described for the processing tissue samples. The tissue processor comprises at least one retort for receiving the tissue samples and at least one container for receiving a process medium. The process medium is transferred at least one of from the container into the retort and from the retort into the container. A value is automatically measured in the course of transferring the process medium, the value representing a characteristic property of the process medium. The process medium is identified based on the value.

Abstract: A cassette for fixing, embedding and slicing biological tissues includes a base sheet and a lid sheet formed of an elongated plastic sheet which is sliceable and has not less than predetermined strength. The base sheet has grooves as biological tissue receiving portions. The base plate and the lid sheet are formed by folding the plastic sheet along a fold line so that the lid sheet can be selectively opened and closed. Biological tissues are pressed against the bottoms of the grooves with pressing/retaining sponge members secured to the lid sheet at its portions corresponding to the respective grooves. In this state, the biological tissues are fixed by a fixing agent, and the cassette is dehydrated, infiltrated with paraffin as an embedding agent to embed the cassette, thereby forming a block including an embedding frame. The block is then sliced with a microtome to provide good biological tissue specimens.

Abstract: The invention discloses new substituted anthraquinone dyes that may be useful as cellular stains. In some aspect of the invention, the nuclear stains are useful for staining the nuclei of dead or fixed cells. Another aspect of the invention relates to substituted anthraquinone dyes comprising an enzyme substrate moiety that is transformable or cleavable by an enzyme such that the transformation or cleavage of the substrate moiety causes a detectable change in the functionality or spectral properties of the dye.

Abstract: A stabilized hematoxylin composition is disclosed that includes one or both of a host compound and an antioxidant. The disclosed composition exhibits sufficient stability to be utilized in an automated staining process without undue degradation prior to use of the composition to stain a biological sample. Methods of using and making the stabilized composition also are disclosed.

Abstract: The disclosure includes a method of screening for, diagnosing or detecting non-small cell lung carcinoma or an increased likelihood of developing non-small cell lung carcinoma in a subject. The method comprises: (a) determining the level of at least one biomarker in a test sample from the subject wherein the at least one biomarker is selected from the biomarkers set out in Table 2, 4A, 4B, 6 and/or 7; and (b) comparing the level of the at least one biomarker in the test sample with a control; wherein detecting a difference in the level of the at least one biomarker in the test sample compared to the control is indicative of whether the subject has or does not have non-small cell lung carcinoma or an increased likelihood of developing non-small cell lung carcinoma.

Abstract: The invention encompasses micelle assemblies, compositions having micelle assemblies, and methods for preparing micelle assemblies and compositions thereof. The invention also encompasses a prolamine protein conjugated to a polymer, such as a polyethylene glycol (PEG) chain, which conjugates can be used to prepare micelle assemblies. The invention further encompasses methods of encapsulating molecules using the conjugates of the invention. The micelle assemblies can be used for a variety of applications, such as treating cancer, targeting tumors, reducing the toxicity of a drug in vivo, increasing the efficacy of an encapsulated agent in vivo, protecting an encapsulated agent against degradation, and enhancing the water solubility of a drug or other agent.

Abstract: The present invention provides a method for detecting or diagnosing in vitro Alzheimer's disease, or memory and/or cognitive disorders, using a human biological sample and the inactivation of STAT3 protein as an indication, and a method for screening for a therapeutic drug for Alzheimer's disease or memory and/or cognitive disorders, using the activation of STAT3 protein as an indication.

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: An aldehyde fixative solution at a first temperature is caused to contact a tissue sample for a first time period, additionally an aldehyde fixative solution is caused to contact the tissue sample at a second temperature higher than the first temperature for a second time period. The first time period typically ranges from about 15 minutes up to about 4 hours, and the first temperature typically is from greater than 0° C. to at least 15° C. The second temperature typically is from greater than about 22° C. to about 55° C., and the second time period ranges from about 1 hour to about 4 hours. Using this process, improved tissue morphology and IHC staining as well as superior preservation of post-translation modification signals have been accomplished in approximately 4 hours compared to 24 hours for room temperature protocols, and more even morphology and antigen preservation are observed.

Abstract: The disclosed invention relates to monoclonal antibodies (MAbs) which recognize human fatty acid synthase (hFAS) and are distinct from previously known anti-hFAS antibodies. Compositions, devices and kits comprising the MAbs are provided along with methods of using the MAbs in a variety of applications.

Abstract: Method and apparatus for processing tissue specimens against decomposition, putrefaction and autolysis which use a simple three step procedure in a single vessel or container. First, the specimens are saturated with a solvent mixture of a ketone and a hydrocarbon, e.g., an Acetone/Hexane or an Acetone/Xylene mixture, to dissolve lipids and other cellular solutes. The container is then flooded with melted Paraffin. In a last step, the solvent mixture is vaporized and evacuated from the container, allowing the melted Paraffin to replace the vaporized solvent and impregnate the specimens. Raw, i.e., non-processed and non-burred specimens up to 5 mm thick can be processed in about 60 minutes. A solvent regenerator distills the evacuated solvent; and converts vent waste gases into carbon dioxide and water through a thermocatalytic oxidizer.

Abstract: Claimed is an imaging and diagnostic system and method for focal scanning of a specimen using optical projection tomographic microscopy and computer generation of three-dimensional images. One embodiment comprises a light source and an imaging system having an adjustable focal position which acquires a plurality of digital 2D projection images of biological tissue placed within a specimen tube that translates and rotates past an optical lens in a helical pattern. A computer captures the images and generates a 3D composite image. Also claimed is a system and method for preparing a specimen for optical microscopy. One embodiment comprises fixing, staining, and/or optically clearing biological tissue within a microfluidic specimen chamber prior to placement in a specimen tube.

Abstract: The present invention relates to the field of endothelial haematopoietic transition (EHT) and epithelial-mesenchymal transition (EMT) and more particularly relates to the use of fish embryo or larva as a model for the study of EHT and EMT.

Abstract: Systems and methods for accelerating tissue processing by treating tissue samples and one or more tissue processing agents with infrasonic vibrations are discussed. Some non-limiting examples of tissue processing agents include a tissue fixative, dehydrating agent, clearing agent, impregnating agent, embedding agent, tissue stain, enzyme, or another chemical that diffuses into the tissue sample when the sample is being preserved or prepared for microscopic examination. The infrasonic vibrations can have a frequency from about 10 to about 600 Hz. The infrasonic vibrations can have an amplitude that is sufficiently high, when combined with the frequency, to induce turbulent mixing of the processing agent and accelerate tissue processing. The tissue sample may optionally be vibrated with ultrasonic vibrations. The ultrasonic vibrations can have a frequency and amplitude that are sufficiently high to induce turbulent mixing of the processing agent and to accelerate tissue processing.

Abstract: A tissue processing system includes a plurality of processing stations. Each processing station includes a plurality of tissue receiving areas that are each configured to accommodate a tissue sample as well as physically isolate that tissue sample from other tissue samples at other receiving areas of the same processing station. Each processing station is configured to separately and individually process the tissue sample at each receiving area to either reduce or eliminate any potential for cross-contamination between the tissue samples undergoing processing at the same processing station. For each receiving area of each processing station, the system is configured to immerse a tissue sample at a particular receiving area in processing fluid for a pre-determined time according to a pre-defined protocol that is based upon parameters of that tissue sample.

Abstract: Human neutrophil peptide (HNP) 1-3, used as diagnostic and therapeutic molecular probes, are found in clinical tissues of gastric cancer patients. In the analytical process according to the present disclosure, pairs of gastric cancer tissues are used to seek the putative biomarkers by proteomic strategy based on matrix assisted laser desorption ionization-imaging mass spectrometry (MALDI-IMS). Then, three differential biomarkers, including HNP-1, -2 and -3, are identified (P<0.001) and overexpressed in gastric cancer. At last, western blotting and immunohistochemistry are used to validate the protein expression in gastric cancer tissues. In conclusion, the use of the up-regulated proteins, HNP1-3, helps diagnosis and therapy in clinical for gastric cancer after validating the sensitivity and specificity.

Abstract: Methods that combine processing and staining of tissue samples such that the processed tissue is stained and ready for histological evaluation prior to embedding and sectioning, and separate staining of the sectioned tissue is not required. The method may be used with chemical and/or mechanical/thermal tissue penetrant enhancers in an automated tissue processing system.

Abstract: A first permeable mesh membrane may be configured to be tautly stretched over a tissue sample and overlaid over a surface. A first permeable mesh membrane may sandwich and secure a tissue sample in between a first permeable mesh membrane and a surface. A first permeable mesh membrane may have a sieve size of approximately 10 ?m to approximately 100 ?m.

Abstract: The present invention provides mouse models for Pompe disease and methods of using the same to test agents that may be effective in the treatment of Pompe disease.

Abstract: This invention is an apparatus and method for affixing frozen tissue sections to microscope slides. It has three elements; teasing implements, an affixing block and a heating element. The elements are used inside a cryostat prior to processing for molecular biology procedures such as immunohistochemistry or laser micro dissection. The tissue sections are collected onto an affixing block which has indentations that decrease the contact surface area while providing structural support. The tissue sections are then transferred onto a slide via transient application of a heating element to the back of slide. The invention decreases folding of tissue sections, increases morphological consistency, enables the placement of many sections on one slide and enables the adherence of tissue sections with greater thickness.

Abstract: Methods and apparatus for bonding block of paraffin having cellular material embedded at one end thereof with an additional amount of paraffin are disclosed, including a method comprising placing the paraffin block in a well of a mold with the paraffin-embedded cellular material positioned on a support structure that elevates the cellular matter from a bottom surface of the well; heating the mold to thereby soften and at least partially melt and blend together the embedding paraffin and additional paraffin located in the well, the support structure sized such that some of the additional paraffin flows on the bottom surface of the well at least partially surrounding the support structure; and cooling the mold to thereby bond the additional paraffin to the embedding paraffin and re-solidify the paraffin block, wherein the retained cellular matter is spaced apart from an end of the re-solidified paraffin block defined by the bottom surface of the well.

Abstract: To simplify the process of preparing tissue specimens on slides, an advanced automated slide processing device is disclosed. The automated slide processing device comprises a robotic arm that both senses input and delivers output. The input sensing may include sensing radio frequency identifiers (RFIDs). The output includes arm movements, the acquisition and delivery of reagents. A control program runs on a computer system for controlling the robotic arm. The robotic arm delivers reagents to individual slide modules that each feature a controllable heating element and a controllable chamber unit that can form a small chamber on the top of a slide for retaining chemical reagents.

Abstract: A method of in situ immunohistochemical analysis of a biological sample is provided. The method allows for the multiplex and simultaneous detection of multiple antigens, including multiple nuclear antigens, in a tissue sample.

Abstract: The present invention relates to a method for providing molecules that are capable of inhibiting angiogenesis, comprising the steps of providing a range of molecules; testing whether these molecules can prevent interaction between JAM-B and JAM-C; testing the positive molecules for their ability to block angiogenesis in vivo; and selecting molecules that are positive in the angiogenesis test as angiogenesis inhibiting molecules. The method may further comprise the step of isolating or producing the angiogenesis inhibiting molecules. The invention further relates to the angiogenesis inhibiting molecules thus provided and produced, to their use in the treatment of cancer, to therapeutical compositions comprising them. In a particular embodiment the invention relates to monoclonal antibodies, in particular Mab H33, to soluble JAM-C and JAM-B and to small molecules.

Abstract: Antibody compositions and methods for treatment of neoplastic disease in a mammalian subject are provided. Methods of diagnosing cancer in a mammalian subject are also provided.

Abstract: To preprocess a tissue sample, a first permeable mesh membrane is tautly stretched out over the tissue sample and overlaid on top of a flat surface. This covering sandwiches and secures the tissue sample in between the first permeable mesh membrane and the flat surface. If it is desired to reinforce the mechanical strength of the first permeable mesh membrane, a second permeable mesh membrane can be tautly stretched out and overlaid on top of the sandwich. Alternatively, the second permeable mesh membrane can be attached onto a third component, such as a disposable solvent resistant frame, to create a framed mesh. Thereafter, the first permeable mesh membrane may be attached to the framed mesh to create a compound framed mesh. The tissue sample may then be sandwiched and secured in between the compound framed mesh and the flat surface. To retain and flatten the tissue sample, gentle pressure may be uniformly applied.

Abstract: A device is operable to measure the size of tissue particles. The device includes a reservoir for receiving tissue particles and an ultrasonic transducer. The ultrasonic transducer is operable to emit ultrasonic energy toward tissue particles in the reservoir. Control circuitry is operable to process ultrasonic energy received from the ultrasonic transducer to determine the size of tissue particles in the reservoir. If the tissue particles are larger than a predetermined size range, the particles may be minced to reduce their size. If the tissue particles are smaller than a predetermined size range, the particles may be disposed of. It the tissue particles have a size within a predetermined range, they may be processed further, such as by stimulating the tissue particles and dewatering the tissue particles. The tissue particles may then be incorporated in a medical fluid and be therapeutically administered to a patient.

Abstract: Disclosed are methods for detecting protein complexes of sigma factors and interacting proteins in a sample containing Mycobacterium tuberculosis. Such methods are useful for the diagnosis and/or monitoring of tuberculosis in a subject. Also disclosed are methods for screening compounds that affect the interaction of one or more sigma factors with one or more interacting proteins.

Abstract: Provide is a method for evaluating test agents as candidates for treating prostatic diseases, including benign prostatic hyperplasia (BPH) and androgen dependent and androgen independent prostate cancer. The method comprises providing a mouse comprising a human prostate primary xenograft, where the xenograft contains blood vessels that include human endothelial cells, initiating androgen deprivation in the mouse, administering to the mouse a test agent within a period of 1-7 days after initiating the androgen deprivation, and determining a reduction in human epithelial cells in the xenografts and/or a reduction in number of the endothelial cells or blood vessels in the xenograft. Also provided is a method for treating an individual for human prostate cancer or benign prostatic hyperplasia.

Abstract: A method for controlling a tissue processor and a tissue processor for processing tissue samples is described. A retort is provided including a cover that can be opened and closed by an operator. The retort cover is closed prior to tissue processing. The actuation state of a first and a second operating element can be determined. An operator is prompted to confirm unlocking of the closed retort cover by actuating a second operating element. The tissue processing is interrupted when an actuation of the second operating element is determined and the closed retort cover is unlocked and is continued after the retort cover is once again locked. After having completed tissue processing the retort cover is unlocked. By means of the described method and tissue processor improper intervention during ongoing tissue processing is prevented.

Abstract: The present invention dedicates to detect nephritis in early stage of either primary or secondary nephritis using an anti NC1 monoclonal antibody. The present invention dedicates to provide useful information for diagnosis of renal function to detect NC1 by immunofluorescent stain method in renal biopsy section obtained at early stage where immunoglobulins do not deposit yet in renal GBM etc, or by antigen-antibody reaction in urine or serum specimens. Furthermore, the present invention comprises to utilize for therapeutic use.

Abstract: A pathology sample processing workstation. The samples are positioned on containers having RFID tags and processed at stations having RFID transceivers coupled to a computer. Information regarding the samples can stored on the RFID tags and retrieved using the transceivers.

Abstract: A carrier strip having a plurality of areas for retaining anatomical pathology specimens may have a backing, a cover coupled to the backing along side regions located along opposite longitudinal edges of the carrier strip and along lateral intermediate regions positioned between each of the plurality of areas for retaining anatomical pathology specimens. The carrier strip may be configured to individually retain each of the anatomical pathology specimens in one of the plurality of areas for retaining anatomical pathology specimens between the backing and the cover. Diagnostic studies of anatomical pathology specimens may be facilitated by distributing a digital copy of an image of the specimen may be to a pathologist. A diagnosis may be received from the pathologist based on the digital image of the specimen.

Abstract: Systems, devices, and methods for removing areas of tissue are described. A programmable laser may remove precise areas of tissue while the tissue remains substantially frozen. The laser is programmed in part by analyzing a reference image of a representative tissue section. A software program may receive digital images of test slices. Areas of interest in the image may be selected by a user. The software program can then create and send cut instructions to the programmable laser. The laser may be configured to make perforated cuts to remove the area of interest without melting the removed section.

Abstract: Described are methods of visualizing biological samples using histological staining and invisible light (e.g., infrared or near-infrared) fluorescence.

Abstract: A system combining a clonogenic differentiation assay with an instrument-based ATP bioluminescence proliferation assay to produce a standardized colony-forming stem and progenitor cell potency assay is provided.

Abstract: A method of analyzing cellular samples that include a chemically crosslinked analyte is provided. The analysis typically involves the use of mass spectrometry.

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: A container for use in processing a biopsy sample. Biopsy sample and materials are received within a sample processing area of the container. A semi-permeable barrier is positioned at a downstream portion of the sample processing area and prevents the prevent passage of the biopsy sample. A cap is positioned at the downstream side of the barrier, and holds fluids within the container.

Abstract: An automated machine for handling and embedding tissue samples contained on microtome sectionable supports. The machine includes an input member configured to hold a plurality of the microtome sectionable supports prior to a tissue embedding operation. An output member is configured to hold a plurality of the microtome sectionable supports after the tissue embedding operation. A cooling unit is configured to hold at least one of the microtome sectionable supports during the tissue embedding operation. A motorized carrier assembly is mounted for movement and configured to hold at least one of the microtome sectionable supports. The carrier assembly moves the support from the input member to the cooling unit and, finally, to the output member. A dispensing device dispenses an embedding material onto the microtome sectionable support and at least one tissue sample carried by the microtome sectionable support during the embedding operation.

Abstract: Thin-section slide samples are manufactured from respective embedding blocks containing a biological sample and held in an embedding cassette having imprinted thereon individual data. The embedding cassette is transported to a cutting position where an embedding block is cut into sheet-like thin sections, and the individual data is read out. Each of thin sections is flattened and transferred onto a substrate to form a thin-section slide sample. A memory part stores the individual data read out and a condition table into which is input manufacturing conditions for manufacturing the thin sections. Thereafter, it is evaluated whether or not each of the thin sections is prepared in accordance with the manufacturing conditions input into the condition table.

Abstract: The invention provides biomarkers that can discriminate between prostate cancer and normal tissue as well as identification of associated metastatic disease. One biomarker was identified as a peptide fragment of MEKK2. Methods of diagnosing prostate cancer, including metastatic cancer, by detecting the differential expression of one or more biomarkers are also provided.

Abstract: The current invention provides a method for discovering protein biomarkers of disease for use in diagnostic assays of bodily fluids by determining differential expression patterns of proteins secreted or released directly by normal and diseased epithelial cells into glandular lumens. Determining those secreted or released proteins directly from the glandular lumen of diseased and normal solid tissue would lead to a catalogue of proteins that have a high degree of probability to be present in various bodily fluids in persons with specific diseases. This would prove useful as a means to diagnose specific conditions and diseases by simply assaying easily acquired bodily fluids. Past efforts to discover such diagnostic/screening markers in bodily fluids have proven difficult at best due to overriding complexity of the proteins within bodily fluids.