Abstract: Chemically reactive carbocyanine dyes incorporating an indolium ring moiety that is substituted at the 3-position by a reactive group or by a conjugated substance, and their uses, are described. Conjugation through this position results in spectral properties that are uniformly superior to those of conjugates of spectrally similar dyes wherein attachment is at a different position. The invention includes derivative compounds having one or more benzo nitrogens.

Abstract: Methods of identifying specific target molecules for design of anti-angiogenic and vascular targeting approaches are disclosed. Transcriptional profiles of tumor endothelial cells were compared with that of normal resting endothelial cells, normal but angiogenically activated placental endothelial cells, and cultured endothelial cells. Although the majority of transcripts were classified as general angiogenesis markers, 17 genes were identified that show specific overexpression in tumor endothelium. Antibody targeting of four cell-surface expressed or secreted products (vimentin, CD59, HMGB1 and IGFBP7) inhibited angiogenesis in vitro and in vivo. Finally, targeting endothelial vimentin in a mouse tumor model significantly inhibited tumor growth and reduced microvessel density. The results demonstrate the utility of the identification and subsequent targeting of specific tumor endothelial markers for anticancer therapy.

Abstract: Chemically reactive carbocyanine dyes incorporating an indolium ring moiety that is substituted at the 3-position by a reactive group or by a conjugated substance, and their uses, are described. Conjugation through this position results in spectral properties that are uniformly superior to those of conjugates of spectrally similar dyes wherein attachment is at a different position. The invention includes derivative compounds having one or more benzo nitrogens.

Abstract: Provided is a disease diagnosis apparatus and method for detecting a specific disease. The disease diagnosis chip, includes: a light sensing layer; a probe molecule fixed on the light sensing layer; and an electrode connected to the light sensing layer to detect an electric signal corresponding to photoelectric charges of the light sensing layer.

Abstract: An apparatus and method are described that achieve independent and simultaneous processing of a plurality of substrate-supported biological samples. In one embodiment, substrate holders arranged in a minor arc are independently moveable between a processing position and an access position, and reagents are delivered to substrates held in the substrate holders through a nozzle plate that moves along the arc of substrate holders. The disclosed apparatus and method are particularly suited for implementation of lean processing of biological samples.

Abstract: A large part of cytostatics, among them paclitaxel (Taxol®) and other recently discovered substances that mimic its antitumour effects, have cellular microtubules as their target. The present invention is a high-efficiency homogeneous test based on the use of stabilised microtubules and fluorescent taxoids for detecting any substances that can substitute paclitaxel in its binding site in microtubules, and constituting potentially anticancerous agents.

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

Abstract: The 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, solublization, 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: A sample processing system that may be configured to achieve rapid sample processing such as rapid histochemical processing may involve a wave element that can use angular microscopic slide movements to cause repeated elimination and reapplication of a fluidic substance perhaps through the action of capillary motion in order to refresh a microenvironment adjacent to a sample such as a biopsy or other such sample. Through such refreshing of a microenvironment, depletion of the microenvironment is avoided and the time necessary for slide processing may be dramatically shortened from a more common 60 to 120 minute to perhaps less than 15 minutes so as to permit use of such a system in an intraoperative or surgical environment such as recommended by the College of American Pathologists intraoperative guidelines or the like. Patients may thus avoid a need to be subjected to an additional surgical procedure when lab results become available to see if tumors or the like were fully removed in a prior procedure.

Abstract: The present invention provides new and useful features and mechanisms for the localization and transport of biopsy specimens. The invention having a specimen board, an absorbent material in operative engagement and in coplanar alignment with the specimen board, a compression sheet, radio opaque indicia located within the specimen board, and a flexible connection between the compression sheet and the specimen board, and an attachment device which provides for removable engagement of the specimen board and compression sheet. The apparatus further provides for a clear visualization window and operating instructions. The absorbent material is capable of adjustable movement between a first and second position, providing orthogonal positioning relative to the specimen board. As a result, the apparatus may be used to create three dimensional radiographic images allowing tissue analysis resulting in orthogonal views while maintaining original positional reference points.

Abstract: Systems and methods for automated laser microdissection are disclosed. A sample of biological material is located between a polymer membrane and 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. An infrared laser activates at least a portion of the transfer film such that the transfer film in the vicinity of targeted portion of biological material adheres onto the polymer membrane. The infrared laser is directed in a closed or substantially closed curve around the targeted portions or directly at the targeted portions. The transfer film is then separated removing the targeted portions of biological material which are adhered along with the membrane from the remaining portion of the tissue sample.

Abstract: The present invention relates to an automatable method for the improved diagnosis of pathologically altered cells by simultaneously staining at least two different molecular markers, which exhibit a change in gene expression which is disease-associated, in a cell or constituent regions of a tissue sample by means of using combinations of antibodies and accrediting signal intensities.

Abstract: An improved method and apparatus for staining samples of biological material for accurate analysis of the sample. Biological material is applied to a substrate, such as a microscope slide. The biological specimen is then stained with a selected staining composition, which may be gentian violet for a Gram's Stain analysis. The stained biological material is at least partially decolorized and the level of decolorization is analyzed optically. If necessary, the decolorizing step and the optical analysis steps are repeated until a selected level of decolorization is obtained.

Abstract: Apparatus and methods for detecting molecules in a fluidic environment are provided, including nanodevices and methods for fabricating, functionalizing, and operating such nanodevices. At least one of the methods includes selective heating of nanodevices in an array.

Abstract: A method for obtaining a response of a tissue model system to an activator includes contacting a bio-artificial tissue model system with an activator and measuring cellular mechanical response thereto of at least one of contractile force and tissue stiffness. A method for obtaining a response of a tissue model system to an activator includes contacting a bio-artificial tissue model system with an activator and measuring cellular mechanical response thereto of at least one of contractile force and hysteresis.

Abstract: The invention relates to methods and devices that use focused radiation to handle and/or monitor pathogenic fluids. In particular, a method is provided for dispensing one or more droplets of a fluid containing a pathogen. The method involves providing the pathogen-containing fluid in a reservoir and applying focused radiation to the pathogen-containing fluid in the reservoir in a manner effective to eject a droplet of the fluid therefrom. Often, a pathogen-impermeable enclosure is used.

Abstract: Provided are compositions relating to novel MDR1 polymorphisms, including nucleic acids, polypeptides, and recombinant cells, as well as methods for detection of MDR1 polymorphisms in biological samples and elucidation of the influence of MDR1 polymorphisms on MDR1 protein function. Also provided are a rat MRP1 cDNA and protein, stable cell lines expressing the rat MRP1 protein, and methods of assessing drug penetration or disposition in a cell line expressing a recombinant mammalian MRP1 or MDR1 protein, or a homolog thereof.

Abstract: The present invention relates a method for the enumeration of mammalian cell micronuclei, while distinguishing micronuclei from the chromatin of dead and dying cells. The method utilizes differential staining of chromatin from dead and dying cells, to distinguish the chromatin from micronuclei and nuclei that can be detected based upon fluorescent emission and light scatter following exposure to an excitatory light source. Counting of micronuclei events relative to the number of nuclei can be used to assess the DNA-damaging potential of a chemical agent, the DNA-damaging potential of a physical agent, the effects of an agent which can modify endogenously-induced DNA damage, and the effects of an agent which can modify exogenously-induced DNA damage. Kits for practicing the invention are also disclosed.

Abstract: Methods and devices for preparing a biological sample for analysis are described. The biological sample from an organism has at least macromolecule having a primary structure that naturally degrades after the sample is removed from the organism. The method includes causing the biological sample to adopt a shape to permit rapid and uniform heating. The shaped sample is then rapidly and uniformly heated, thereby altering a secondary structure of the macromolecule while preserving its primary structure.

Abstract: Composition based on alkyl C5-C20 and at least one aliphatic alcohol used for the preparation of histological, autoptic and cytological samples for examination, said composition being suitable for use in place of the various reagents employed up to s now according to rigidly fixed sequences.

Abstract: Embodiments of the present disclosure provide for RGD compounds that include a multimeric RGD (arginine-glycine-aspartic acid (Arg-Gly-Asp)) peptide, methods of making the RGD compound, pharmaceutical compositions including RGD compound, methods of using the RGD compositions or the pharmaceutical compositions including RGD compositions, methods of diagnosing and/or targeting angiogenesis related disease and related biological events, kits for diagnosing and/or targeting angiogenesis related disease and related biological events, and the like. In addition, the present disclosure includes compositions used in and methods relating to non-invasive imaging (e.g., positron emission tomography (PET) imaging) of the RGD compounds in vivo.

Abstract: The invention aims to efficiently collect microorganisms from a test sample and accurately detect and quantify the collected microorganisms. A microorganism-collecting chip of the invention basically comprises a filter for removing contaminants and a filter for trapping microorganisms. A microorganism-collecting kit comprises the foregoing microorganism-collecting chip and a suction filtration unit. The suction filtration unit is, for example, a negative pressure tube provided at an opening with a rubber stopper. The microorganism-collecting chip has a liquid specimen injection container for injecting a liquid specimen and a hollow needle capable of penetrating the rubber stopper mounted at the opening of the negative pressure tube. The liquid specimen injected into the liquid specimen injection container is suction-filtered with a pressure of the negative pressure tube.

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 the 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 for holding slides.

Abstract: A sample processing system that may be automated and methods are disclosed where samples are arranged on a carrier element and a process operation control system automatically processes the samples perhaps robotically with an operationally-influential exteriorly-consequential information monitor or a data capture element. Significant process details as well as operationally-influential exteriorly-consequential information may be monitored and an automatic notice element may cause notification of a person at some display that may be remote. Various people may be notified, such as an administrator, a supplier, or a manufacturer of an opportunity for some action such as reagent reordering or the like. A simulated motion display may be included to “watch” simulated operation in real time or long after completion of the actual processing.

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

Abstract: The present invention concerns a process for analyzing an analyte in a hydrogel contact lens following its wear on the eye, comprising the steps of (a) physically or chemically inducing a volume reduction of the hydrogel contact lens and thereby squeezing the analyte out of the polymer material making up the contact lens and (b) feeding the analyte obtained according to step (a) into an analyzer. The process of the invention provides a new concept for noninvasively measuring various analytes occurring in the tear fluid that is comfortable to the user.

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

Abstract: A microorganism detecting kit according to the present invention includes a self-adhesive layer 102 containing the following compounds incorporated therein: 4?,6-diamidino-2-phenylindole dihydrochloride 2 for staining living and dead cells, propidium iodide 3 for staining dead cells, 6-carboxyfluorescein diacetate 4 for staining living cells and 4-methylumbelliferyl-?-D-galactoside 5 reacting with a substance derived particular microorganisms, a support 103 and a grip portion 6. Microorganisms deposited to a specimen are deposited to the self-adhesive layer 102, and then, the compounds react with the microorganisms and are bonded individually to the microorganisms to color them. The microorganism detecting kit, a microorganism counting apparatus and a microorganism counting process according to the present invention are used to confirm of the presence of living and dead cells, dead cells and living cells by counting the colored cells in an adding manner.

Abstract: A method for diagnosing the presence in an animal of an infection due to a microorganism in which a test sample obtained from the animal is exposed to a population of the microorganism and the presence of binding of the microorganism by an antibody in the test sample is determined.

Abstract: Improvements in FISH staining employing an aqueous acetonitrile/dimethylsulfoxide mixture in a fluorophore coupling reaction.

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

Abstract: An isolated polypeptide comprising an amino acid sequence having at least 80% sequence identity to the sequence SEQ ID NOS:2, 4, 6 or 8, polynucleotides encoding these peptides, and antibodies to the polypeptides are useful in treating cancers.

Abstract: A process for the production of paraffin sections of biological tissue, especially for molecular pathology studies is disclosed. In the process, the tissue sample is simultaneously fixed, dehydrated and cleared in a first step, subsequently dehydrated and cleared in a second step and infiltrated with an inert specimen matrix in a third step. The specimen can then be further embedded in a casting supporting matrix according to the standard procedures followed by any local pathology or research laboratory. A kit and a processing station for automating paraffin embedding of a tissue sample suitable for histopathological and molecular analysis is also described. A bio-indicator system is described for measuring the degree of crosslinking. A tissue sample holding means or a vial which includes a tissue sample holding means provided with a data logging device capable of registering and transmitting data regarding the sample and conditions where the sample was processed is also disclosed.

Abstract: The invention relates to a device for preparing specimens for a cryo-electron microscope, comprising an environmental chamber, a holder for a sample or a carrier, and at least one blotting element to which a medium for absorbing liquid is or can be attached, both disposed in the environmental chamber, and a cooling medium for cooling down said sample. The said blotting element can be moved towards the sample or carrier in a controlled manner.

Abstract: A method of determining the status of a disease or healthful condition by correlating such condition to amounts of one or more heterodimers of ErbB, or Her, cell surface membrane receptors measured directly in a patient sample is described. The invention includes a method of determining a status of a cancer in a specimen from an individual by correlating measurements of amounts of one or more heterodimers of ErbB cell surface membrane receptors in cells of the specimen to such status, including presence or absence of a pre-cancerous state, presence or absence of a cancerous state, prognosis of a cancer, or responsiveness to treatment. Preferably, methods of the invention are implemented by using sets of binding compounds having releasable molecular tags that are specific for multiple components of one or more types of receptor dimers. After binding, molecular tags are released and separated from the assay mixture for analysis.

Abstract: The invention relates to methods and devices that use focused radiation to handle and/or monitor pathogenic fluids. In particular, a method is provided for dispensing one or more droplets of a fluid containing a pathogen. The method involves providing the pathogen-containing fluid in a reservoir and applying focused radiation to the pathogen-containing fluid in the reservoir in a manner effective to eject a droplet of the fluid therefrom. Often, a pathogen-impermeable enclosure is used.

Abstract: A workstation that provides an efficient method to collect biological tissues in a column tissue array format from blocks of embedded, frozen tissues, or fresh tissues. The workstation has a control unit for directing operations of the workstation and the operation unit for performing the production of the tissue column array. The operation unit comprises an array of vertical tubes in a platform, an arbor which engages and presses down the designated tube in the array, the embedded tissue block which is mounted directly below the designated tube, assemblies of motors responsive to the control unit for driving the platform and the tissue block, a light source block for generating an alignment signal, and a light detector block which measures the signal from the light source to determine the degree of alignment between the arbor, punch tubes, and the specimen block.

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

Abstract: A cell observation apparatus includes a cell recognition unit that recognizes a cellular region representing a cell from cell image data acquired by imaging the cell at a plurality of time points; and a cell parameter measurement unit that measures cell parameters characteristic of the cellular region recognized by the cell recognition unit. The apparatus also includes a cell viability determination unit that determines cell viability by comparing the cell parameters measured by the cell parameter measurement unit with thresholds.

Abstract: In various aspects, the invention provides Brassica juncea plants, seeds, cells, nucleic acid sequences and oils. Edible oil derived from plants of the invention may have significantly higher oleic acid content than other B. juncea plants. In one embodiment, the B. juncea line MJ02-357-3 contains a mutant allele MJ02-313-1/BjFAD2-a at the BjFAD2-a gene locus, having a single base-pair change (a G to A substitution in the ORF at position 281 in reference to the first ATG start codon) relative to the wild type sequence. The change is predicted to encode a Glycine-94 Aspartic acid mutation in the sequence of the predicted BjFAD2-a protein. In another embodiment, the B. juncea line MJ02-357-3 contains a mutant allele MJ02-357-3/BjFAD2-a at the BjFAD2-a gene locus, having a single base-pair change (a C to T substitution in the ORF at position 647 in reference to the first ATG start codon) relative to the wild type sequence.

Abstract: In accordance with the present invention, there are provided methods for determining a prognosis of disease free or overall survival in a patient suffering from cancer. Also provided are methods for predicting the risk of tumor recurrence or spread in an individual having a cancer tumor. Methods for screening a cancer patient to determine the risk of tumor metastasis; methods for determining the proper course of treatment for a patient suffering from cancer; and kits for use in practicing the invention methods.

Abstract: Method and compositions relate diagnostic tools to determine invasive potential of tumor cells. Therapeutic patches include a component from the extracellular matrix seeded with tumor cells from an individual and a fibrin backing. Extracellular matrix-based constriction assays are useful to screen for anti-tumor compounds.

Abstract: A method of identifying a compound with efficacy in the treatment of chronic inflammatory disease by testing the compound for an ability to selectively inhibit the ability of Tck cells to induce pro-inflammatory cytokine release from a monocyte is disclosed. The method includes pre-incubatin Tck cells with a compound to be tested, optionally resuspending the Tck cells in the absence of the test compound, co-culturing the Tck cells with monocytes, and assaying for the production of pro-inflammatory cytokines by the monocytes. The Tck cells are produced by incubating a population of T cells with one or more cytokines or the Tck cells are isolated from synovial tissue. The Tck cells have not been contacted with an anti-CD3 antibody. The ability to selectively inhibit cytokine release indicates that the compound has efficacy in the treatment of chronic inflammatory disease.

Abstract: A method of identifying the elements of a blood sample including placing an aliquot of blood on a transparent substrate such as a coverslip. The blood is allowed to stand and the cells to settle to form a layer or matrix. Inverted microscopy is used to identify the elements in the sample. Various forms of illumination may be used alone or in multiple combinations. The method improves the accuracy due to homogenous distribution of formed elements in the wet drop or aliquot, simplifies the method, lowers the cost of the test and results in a shortened analytical cycle time.

Abstract: Disclosed is an evaluating method for the properties of a corneocyte in a horny layer sample originating in the skin. In the above method, detected and evaluated are selective staining of a cornified envelope in a corneocyte, selective staining of a nuclear component and the antigenicity.

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; removing unbound TCPP from the sample; c 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's response to the cancer therapy.

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: Markers for TSE that are present prior to formation of detectable pathological prion protein are useful to detect this infection prior to clinical signs. Additional markers are useful to detect the stage of TSE infection and distinguish it from other conditions which have similar clinical symptoms. Determinations on isolated cell preparations are particularly useful, especially those derived from peripheral (non-brain) sources.