Abstract: The invention relates to a method with which proteins from formalin-fixed biological samples can be dissolved and subsequently quantified. The method makes it possible to extract intact full-length proteins from the samples and to conduct a subsequent analysis thereof.

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: 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: Improved methods and systems for processing of solid tissue are described. The method may be performed manually or automatically. The system may have modules such as (i) a grossing module where a fresh tissue is sliced to prepare a tissue specimen, (ii) a hardening module that hardens the tissue specimen, (iii) an impregnating module that impregnates the tissue specimen that was hardened, and (iv) an embedding module that embeds a tissue specimen that was hardened and impregnated. Fresh (i.e., not fixed or frozen) tissue, which was excised to diagnose disease or to assess surgical treatment, is grossed to about 0.6 mm Preferably, the hardening of fresh tissue is initiated, but not completed, during grossing by contact with a chemical admixture. Preferably, dry ice, a thermoelectric device, or a gas condenser cools a metal mold containing the embedded specimen.

Abstract: The present invention relates to a method for measuring a biological value Vb in a liver wherein said method comprises the steps of: a/ applying an infrared radiation having at least a first wave number range between 2800 cm?1 and 3000 cm?1 to one or more portions, pi, of a sample of said liver, b/ detecting the intensity of the radiation after it has passed through each of one or more portions, p;, and generating a signal related to the detected intensity, c/ processing the generated signal(s) to calculate an average value va; d/ comparing said average value Va to a standard to obtain the biological value Vb.

Abstract: The present disclosure relates to an Extra Cellular Matrix composition specific for cancer type and a tumor microenvironment platform for long term culturing of tumor tissue, wherein said culturing provides human ligands and tumor tissue micro-environment to mimic physiologically relevant signalling systems. The present disclosure further relates to the development of a Clinical Response Predictor and its application in the prognostic field (selection of treatment option for the patient) and translational biology field (development of anticancer drugs). The disclosure further relates to a method of predicting clinical response of a tumor patient to drug(s). The disclosure further relates to a method for screening tumor cells for the presence of specific markers for determining the viability of said cells for indication of tumor status.

Abstract: A protein retrieval treatment system used for activating proteins contained in a deparaffinized tissue section obtained by removing paraffin from a formalin-fixed paraffin-embedded tissue section. The protein retrieval treatment system includes: a dispensing unit for dispensing a retrieval treatment solution over a dispensing area including a measurement area on the deparaffinized tissue section; and a moist-heat treatment unit for heating, in a saturated water vapor, the deparaffinized tissue section with the dispensing area covered with the retrieval treatment solution.

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: Feature analysis on consecutive tissue sections (FACTS) includes obtaining a plurality of consecutive tissue sections from a tissue sample, staining the sections with at least one biomarker, obtaining a digital image thereof, and identifying one or more regions of interest within a middle of the consecutive tissue sections. The digital images of the consecutive tissue sections are registered for alignment and the one or more regions of interest are transferred from the image of the middle section to the images of the adjacent sections. Each image of the consecutive tissue sections is then analyzed and scored as appropriate. Using FACTS methods, pathologist time for annotation is reduced to a single slide. Optionally, multiple middle sections may be annotated for regions of interest and transferred accordingly.

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: In accordance with preferred embodiments of the present invention, a method for imaging tissue, for example, includes the steps of mounting the tissue on a computer controlled stage of a microscope, determining volumetric imaging parameters, directing at least two photons into a region of interest, scanning the region of interest across a portion of the tissue, imaging layers of the tissue, sectioning a portion of the tissue, capturing the sectioned tissue, and imaging additional layers of the tissue in a second volume of the tissue, and capturing each portion of sectioned tissue, and processing three-dimensional data that is collected to create a three-dimensional image of the region of interest. Further, captured tissue sections can be processed, re-imaged, and indexed to their original location in the three dimensional image.

Abstract: The disclosure relates to a processor for processing histological samples. The processor comprises an inlet for insertion of a closed fixing container having the samples present therein.

Abstract: The disclosure relates to a method for fixing a histological sample, in which a target fixing time for the sample is defined and the sample is exposed to the action of a fixative, the exposure start time being stored in a memory associated with the sample. The sample is no longer exposed to the fixative when an action time of the fixative on the sample is equal to or greater than the target fixing time.

Abstract: Automated sample processing systems may include onboard efficient high-speed mixing of at least two components with an automatic vertical force fluidic turbulent component mixer of which a mixed component may be aspirated and high-speed dispensed in a mixing vial. Other aspects may include single sweep applying a multi-treatment cleaning cycle to at least one slide. A multi-treatment cleaning cycle may include a washing treatment and a drying treatment. In yet other aspects the present invention may include an automated recovery sample processing system with the capability of detecting at least one immediate condition of a fortuitously terminated automatic sample processing run and perhaps even an automatic terminated sample processing run reconstruction calculator.

Abstract: A method and apparatus for producing histological sections by means of a microtome are suggested. A histological section of predefined thickness is produced with a microtome from a block comprising a tissue sample. A carrier material is applied with an application apparatus onto the block prior to before production of the histological section. To ensure that the histological sections do not roll up, and to enable improved downline processing of the histological sections as compared with a carrier material embodied in the form of an endless strip and that the carrier material is cut out prior to application to a size and/or a shape that corresponds substantially to the cross-sectional area of the block; and that the cut-out carrier material is then applied onto the block. The suggested apparatus is designed to apply the carrier material onto a histological section to be prepared by a microtome.

Abstract: Squamous carcinoma stem cells (SCSC) are identified. The cells can be prospectively isolated or identified from primary tumor samples, and are shown to possess the unique properties of cancer stem cells in functional assays for cancer stem cell self-renewal and differentiation, and to form unique histological microdomains useful in cancer diagnosis.

Abstract: Disclosed embodiments concern histochemical process compositions comprising at least one nanoparticle in an amount effective to reduce or substantially eliminate the average number of spots per slide that result from a sample staining protocol. The nanoparticle can be any of various nanoparticles, or combinations thereof, including metals, metal alloys, metal oxides, ceramics, functionalized metals or metalloids, and other miscellaneous nanoparticles, such as carbon nanoparticles and diamond nanoparticles. Typically, the nanoparticle concentration is from greater than zero to at least about 25 parts per million, more typically from about 2 parts per million to about 20 parts per million. Embodiments of a method for using process nanosolutions also are disclosed. One embodiment concerns applying a histochemical process composition to a sample, followed by performing a staining protocol on the sample.

Abstract: Dewaxing buffers containing a water-soluble organic solvent, methods for use thereof, and kits incorporating dewaxing buffers. The dewaxing buffers contain a water soluble organic solvent that has a boiling point of at least 80° C. The dewaxing buffers described herein can be used to quickly and efficiently remove embedding paraffin from slide-mounted tissue sections in an aqueous buffer solution at elevated temperature without fear of paraffin redeposition of the slides. In addition, the dewaxing buffers described herein can be used to perform dewaxing and HIER in a single step, which can substantially reduce protocol time and lower the risk of sample loss or damage.

Abstract: There is provided a cell chip, a cell slice sample, and a manufacturing method thereof. The cell chip includes a plate member; biomaterials attached to one surface of the plate member; and a solidifiable material formed on one surface of the plate member to form a layer including the biomaterials.

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: A laser microdissection device includes a microscope stage for carrying a specimen to be cut, a laser light source for generating a laser beam and a microscope objective for focusing the laser beam onto the specimen. An optical laser scanning device is configured to deflect the laser beam so as to move the laser beam focus in an X-Y direction perpendicular to a main axis of the microscope objective. The laser microdissection device also includes at least one of a Z displacement device configured to move the microscope stage in a Z direction, or an optical focus shifting device configured to move the focus of the laser beam in the Z direction. The Z displacement device and/or optical focus shifting device are controllable, together with the optical laser scanning device, so as to move the laser beam focus in the specimen along a three-dimensional cut line in an X-Y-Z direction.

Abstract: An apparatus and a method for isolating histological sections produced with a microtome and a microtome are suggested. A previously and currently produced histological section are connected to form a section strip. In order to simplify isolating the previously and currently produced histological sections from each other a nozzle device is provided by means of which the histological sections when positioned on a blade holder are subjected to an air stream of adjusted direction and intensity so that the previously produced histological section of the section strip is separated from the currently produced histological section that is positioned on the blade holder and is removed from the blade holder.

Abstract: Systems and methods for automated laser microdissection are disclosed including automatic slide detection, position detection of cutting and capture lasers, focus optimization for cutting and capture lasers, energy and duration optimization for cutting and capture lasers, inspection and second phase capture and/or ablation in a quality control station and tracking information for linking substrate carrier or output microdissected regions with input sample or slide.

Abstract: Improved specimen containers, methods and materials for use in connection with excised tissues are described.

Abstract: Systems and methods for automated laser microdissection are disclosed. In one variation, targeted biological material is manually or automatically selected and a transfer film is placed in juxtaposition to the location of an interior of a cut path. In another variation, a sample of biological material is mounted onto a polymer membrane which is then placed onto a substrate. Targeted biological material is manually or automatically selected and a transfer film is placed in juxtaposition with the targeted biological material on the side of the biological material. In yet another variation, a sample of biological material is mounted onto a polymer membrane which is then inverted onto a substrate. Targeted biological material is manually or automatically selected and a transfer film is placed in juxtaposition with the targeted biological material on the side of the polymer membrane.

Abstract: The present invention relates to the use of TFF3 in the diagnosis and detection of Barrett's esophagus using non-invasive, non-endoscopic methods.

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: Histochemical process compositions comprising at least one nanoparticle in an amount effective to reduce or substantially eliminate the average number of spots per slide that result from a sample staining protocol are disclosed. Various nanoparticles, or combinations thereof, including metals, metal alloys, metal oxides, ceramics, functionalized metals or metalloids, and other miscellaneous nanoparticles, such as carbon nanoparticles and diamond nanoparticles, can be used. The nanoparticle concentration typically is from about 2 parts per million to about 20 parts per million. One embodiment of a disclosed method concerns applying a histochemical process composition to a sample, followed by performing a staining protocol on the sample. Particular embodiments concern dispensing a nanosolution onto a sample using an automated system, heating the sample, and performing a sample staining process.

Abstract: A film (14) with a tissue section (10) is placed with the tissue section (10) downward on a microscope slide (18) and the microscope slide (18) positioned in the object plane of an inverse microscope; where an adhesive tape (20) is arranged, with a bonding agent (22) downward, above the film (14) and therefore above the tissue section (10); wherein the next step, tissue (36) to be isolated is excised by a focused laser beam, which also divides the film (14); whereupon removal of the adhesive tape (20) from the microscope, the excised tissue pieces (36) adhere to the adhesive tape (20), and the remnant of the film (14) and of the tissue section (10) remains adhering to the microscope slide (18).

Abstract: A method and a device for producing thin sections of a sample by means of a microtome is described, in which a camera acquires at least one image of a surface generated by sectioning of the sample. With the aid of an evaluation device, the image of the surface is evaluated in terms of predefined characteristic values of a section quality. As a function of the characteristic values that are identified, a decision is then made as to whether the section of the sample is accepted or not.

Abstract: This invention provides antibodies immunologically specific for human ARL-1 (also referred to AKR1B10), a species of the aldo-keto reductase superfamily of proteins. The invention also provides methods of making and methods of using said antibodies.

Abstract: A group of small pieces of divided base substrate is arrayed on a sheet without gaps therebetween by means of a simple method. Provided is a substrate-sheet fabricating method including cutting into a group of small pieces a base substrate whose first-side surface is attached to a first sheet member; transferring the group of small pieces to a second sheet member by attaching the second sheet member, which can be contracted in the direction along a surface thereof, to second-side surfaces of the group of small pieces and by peeling off the first sheet member from the first-side surfaces of the group of small pieces; and making the second sheet member contract in the direction along the surface thereof.

Abstract: The present invention relates to a composition and method for handling tissue samples for analysis. In particular the present invention relates to a composition and method for orientating tissue for histological and/or pathological laboratory analysis.

Abstract: A sectionable tissue sample support structure including a gel compound formed into a self supporting geometric shape for retention and orientation of at least one tissue sample during a histopathology process including processing, embedding and microtome slicing of the tissue sample. A method of orienting, processing, embedding and microtome slicing a tissue sample using a gel compound preformed into a self supporting geometric shape. A combination including the sectionable tissue sample support structure and a package containing the sectionable tissue sample support structure.

Abstract: A method of collecting target regions from a target object is described. The method in one embodiment comprises mounting a negatively-charged membrane on a first side of a substrate, mounting a target object on the membrane, positioning a collection material adjacent to the target object, and passing a laser beam from a second side of the substrate, through the substrate, the membrane, and the target object, to dissect target regions from the prepared tissue section, whereby the dissected target regions adhere to the collection material. In another embodiment, the present invention is a system for collecting target regions from a target object. In one embodiment, the system comprises a substrate having a first side and a second side, a negatively-charged membrane adhered to the first side of the substrate, and a collection material mountable adjacent to the membrane.

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 invention relates to a method and device for the cross-referencing of identification (1) of tissue slice supports (2), for microtomised analytical samples still to be mounted thereon, with identification information (3) of a tissue sample holder (4) of a tissue sample (5) which is not yet microtomised. The conventional problem of cross-referencing is improved in a simple manner, whereby the identification information (3) for the tissue sample holder (4) is automatically detected when positioned in the microtome (6) and an identification (1) corresponding thereto is automatically transferred to at least one tissue slice support (2) and that tissue slice support (2), provided with the identification (1), is dispensed for application of the tissue sample slice at the moment when a tissue sample slice must be applied to a tissue slice support (2).

Abstract: Disclosed are methods for determining the risk of tumor cells undergoing metastasis, for assessing the prognosis of a subject undergoing treatment for a localized tumor, and for determining a course of treatment for a localized tumor comprising detecting the presence of an endothelial cell, a macrophage, and an invasive tumor cell in direct apposition in a tumor sample from a subject.

Abstract: Systems and methods for providing guided slicing of histological samples. The samples are acquired, spacially labeled with a fiducial marker, and imaged with a scanning system. The images are analyzed, either manually, semi-automatically or automatically, and likely locations of pathologies are identified. A slicing program is then generated and the sample sliced according to the slicing program, thereby ensuring that likely locations of pathologies are analyzed.

Abstract: The invention relates to a method for optimizing the automatic fluorescence pattern recognition in immunodiagnosis. In this method, in addition to or together with the fluorescence dye, one or more other indicator dyes for the identification of relevant structures are incubated before an image is taken with a camera.

Abstract: The invention relates to methods and compositions of detecting a biological marker in a sample. In certain embodiments, the methods and compositions comprise a first binding agent that specifically binds to a biological marker in a sample; a second binding agent linked to a first polymer, wherein the second binding agent specifically binds to the first binding agent; a third binding agent linked to a second polymer, wherein the third binding agent specifically binds to the second binding agent; and a detectable substance. In certain embodiments the biological markers are detected immunologically.

Abstract: Provided is a method of identifying Hsp90 inhibitors with substantially less ocular toxicity or with substantially improved ocular toxicity profile. The method comprises measuring the respective concentrations of an Hsp90 inhibitor in the retina and plasma at certain time points following the administration of the Hsp90 inhibitor in a subject, and determining the concentration ratio of the Hsp90 inhibitor between retina and plasma, where a certain ratio is indicative that the Hsp90 inhibitor has substantially less ocular toxicity. The method also includes identifying an Hsp90 inhibitor with substantially less ocular toxicity, or with a substantially improved ocular toxicity profile, by determining the elimination rate of the Hsp90 inhibitor from the retina following administration of the Hsp90 inhibitor, where a certain elimination rate is indicative that the Hsp90 inhibitor will induce substantially less ocular toxicity.

Abstract: This invention relates, e.g., to a method for predicting a subject's response to a chemotherapeutic agent and/or the subject's prognosis, comprising measuring the phosphorylation state of at least one member of the mTOR pathway, and/or of at least one member of an interconnected polypeptide pathway (e.g. a member of the Akt pathway or a member of the IRS pathway), compared to a baseline value, in a cancer tissue or cancer cell sample from the subject, wherein an elevated level of the phosphorylation state compared to the baseline value indicates that the subject is a non-responder to the chemotherapeutic agent and/or has a poor prognosis. Also described is a method for treating a cancer in a subject in need thereof, wherein the subject exhibits an elevated level of the phosphorylation state, comprising administering one or more inhibitors of the mTOR and/or an interconnected pathway.

Abstract: In order to pick up a sufficient amount of cells for a genetic test from a section of a biological tissue with a simple structure and a simple operation, provided is a cell collection apparatus comprising: a substrate which is provided to be dividable into a plurality of small pieces along a predetermined dividing line, and which has a flat surface to which a section of a biological tissue can be pasted; a sheet-shaped expandable member to which the substrate can be adhered in a detachable manner, and which is expandable in a direction along the surface; a expansion unit for expanding the expandable member in at least a region adhered with the substrate, in a direction along the surface; and a pickup unit for detaching and picking up the divided small pieces from the expandable member.

Abstract: This invention describes the use of a laser scanning device, for example a laser scanning CYTOMETRY (LSC), with a double-fluorescent labeling technique as a quantitative method that can be used to objectively and accurately measure endothelial cell death, endothelial tumor cell death and blood vessel density of tumor tissue. These parameters can be used as markers of efficacy in tumors treated with anti-angiogenic or traditional therapies and can distinguish patients who respond to these drugs from those who do not.

Abstract: A method of tissue analysis integrates a pathology diagnostic step (subjective human inspection of a stained tissue section or image of it) with one or more gene/biomarker tests to enable perform of both procedures side-by-side on the same instrument.

Abstract: The present invention relates to a method of determining the presence of a retinoblastoma protein (Rb)-mediated cancerous or pre-cancerous condition in a sample of fixed cells that involves exposing the sample to an antibody that recognizes phosphorylation of serine on the retinoblastoma protein (pS-Rb), and identifying cells in the sample that are recognized by the antibody to pS-Rb, where the recognition of pS-Rb in the sample determines the presence of an Rb-mediated cancerous or pre-cancerous condition. The method also involves identifying the presence of specific cell cycle markers and positive and negative cell cycle regulators to assess the stage of disease progression in a cancer patient having an (Rb)-mediated cancer. The present invention also relates to methods of assessing the efficacy of cancer therapy for an Rb-mediated cancer, determining the mechanism of cell cycle progression in an Rb-mediated cancer, and identifying cells predisposed to developing an Rb-mediated cancerous condition.

Abstract: The present invention provide reagents and methods of using the reagents, for example, on automated staining devices, that facilitate detection of two or more antigens in a sample simply and efficiently.

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 of cutting at least one thin section from a sample block that is arranged in a cassette and tagging at least one specimen slide such that it can be allocated to the specific sample block from which the thin section has been cut. The method includes removing a cassette from a cassette magazine; reading the machine-readable coded information of the cassette identifier; generating by at least one tagging unit a specimen slide identifier that interrelates to the cassette identifier read by the reading unit; inserting the cassette into a microtome; transferring data from the microtome to a tagging unit via a data transfer path while the cassette is inserted into the microtome; enabling tagging of the specimen slide; tagging the specimen slide by the tagging unit; and cutting the thin section and transferring it onto the specimen slide that was tagged by the tagging unit.