Abstract: The invention generally relates to assemblies for displacing droplets from a vessel that facilitate the collection and transfer of the droplets while minimizing sample loss. In certain aspects, the assembly includes at least one droplet formation module, in which the module is configured to form droplets surrounded by an immiscible fluid. The assembly also includes at least one chamber including an outlet, in which the chamber is configured to receive droplets and an immiscible fluid, and in which the outlet is configured to receive substantially only droplets. The assembly further includes a channel, configured such that the droplet formation module and the chamber are in fluid communication with each other via the channel. In other aspects, the assembly includes a plurality of hollow members, in which the hollow members are channels and in which the members are configured to interact with a vessel.

Abstract: A method for rendering biological tissue sufficiently optically transparent for three-dimensional light microscopy imaging, comprising incubating biological tissue with an optical clearing solution, wherein the optical clearing solution comprises: (i) 20-50 wt % formamide, (ii) 10-90 wt % glycerol, and (iii) water as remainder. Also described herein is a method for ridding tissue of blood to make them amenable for optical clearing, comprising incubating biological tissue in a decolorizing solution, wherein the decolorizing solution comprises: (i) 0.5-3 wt % hydrogen peroxide, (ii) 0.05-1 wt % sodium azide, (iii) 5-20 wt % DMSO, and (iv) phosphate buffered saline as a remained.

Abstract: The present disclosure relates to foam beads of an elastomeric composition comprising a propylene-based elastomer. The foam bead has a density of less than 0.5 g/cm3. The foam beads can be made from pellets of elastomeric compositions by expanding with supercritical fluid blowing agent. The foamed bead has reduced lightness while maintaining elasticity.

Abstract: A method and a machine for drying blood smears and an automatic smearing device are provided. In the method, a dry gas is used as a drying medium to dry a blood film on a blood smear in drying the blood smear, thus reducing drying time and the number of blood smears which are dried together. The dry gas is obtained by: first, removing a liquid from a pressurized gas, second, filtering a vapor, and finally, decompressing the dried pressurized gas to be a non-pressurized gas having lower humidity. In addition, the dry gas is further heated for further reducing the humidity of the dry gas. In order to prevent cell distortion from occurring, the heated dry gas is caused to gently flow over the blood smear in a direction which the blood film is spread.

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 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: A method of identifying or evaluating skin-care actives that improve the metabolism of a skin cell. The method includes contacting cells with a stressor and a test agent and determining a response of the cells to the stressor and test agent, based on the change in metabolic indicators associated with glycolysis and/or oxidative phosphylation. The test agent may be identified as a skin-care active when the oxidative phosphorylation and/or glycolysis response corresponds to an improvement in cellular metabolism.

Abstract: A method for determining a mean cell volume for a blood sample includes: illuminating the sample with incident light at a plurality of illumination wavelengths and obtaining a two-dimensional image of the sample at each of the plurality of illumination wavelengths; identifying a plurality of cells that appear in each of the images; for each one of the plurality of cells, determining an integrated optical density corresponding to each of the plurality of illumination wavelengths; for each one of the plurality of cells, determining a cell volume based on the integrated optical densities corresponding to each of the plurality of illumination wavelengths; and determining the mean cell volume for the blood sample from the cell volumes for each one of the plurality of cells.

Abstract: The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNF, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNF, and low immunogenicity. Said antibodies are designed for the diagnosis and/or treatment of TNF-mediated disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of said antibodies in medicine are also disclosed.

Abstract: Assays, methods and kits for predicting a subject's (e.g., human) risk of primary glomerulopathy, secondary glomerulopathy or recurrence (e.g., post-transplant recurrence) of any glomerular disease include examining cells for the presence or absence of cytoskeletal disruptions or rearrangements and examining cells for modulation of expression and/or activity of markers such as SMPDL-3b. Assays for predicting if a diabetic subject will develop kidney disease or a patient with FSGS will develop recurrent disease after transplant also include examining cells for the presence or absence of cytoskeletal disruptions or rearrangements and examining cells for modulation of expression and/or activity of markers such as SMPDL-3b. Also described herein are compositions and methods for treating and preventing the afore-mentioned disorders.

Abstract: The present disclosure relates to immobilization of a cell using a carboxylated surface by contacting the carboxylated surface with a sample comprising the cell for a sufficient time to permit the cell to bind to the carboxylated surface. The immobilized cell may then be separated from the remainder of the sample and further manipulated to isolate, concentrate, and/or analyze the cell or a component thereof.

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: Provided herein are methods for treating a cancer treatable by inhibition of phosphorylation of PRAS40, GSK3? or p70S6K1, comprising administering an effective amount of a TOR kinase inhibitor to a patient having a cancer treatable by inhibition of phosphorylation of PRAS40, GSK3? or p70S6K1.

Abstract: A method for rapidly collecting cells from a surface, such as a surface bearing fingerprints, for subsequent macromolecular analysis involves dispensing a predetermined amount of an aqueous solution onto the surface, and subjecting the aqueous solution to ultrasound waves to promote a detachment of the cells from the surface. Extraction of macromolecules such as DNA from the cells can be effected directly in the solution containing the collected cells by further subjecting the solution to ultrasound waves for a prescribed period of time to lyse the cells, and then extracting the DNA.

Abstract: Provided herein are methods of staining biological material for the purpose of detecting, and in some examples also identifying, microorganisms. Methods of Gram staining bacteria using a slow-acting decolorizing formulation, such as one that includes 1,2-propandiol or ethylene glycol, can be used to extend the time of the decolorizing step, and thus permit automation of the Gram staining method. Also provided are compositions and kits for performing automated Gram staining on microscope slides.

Abstract: The present invention is directed towards methods of culturing non-keratinocyte epithelial cells, with the methods comprising culturing non-keratinocyte epithelial cells in the presence of feeder cells and a calcium-containing medium while inhibiting the activity of Rho kinase (ROCK) in the feeder cell, the non-keratinocyte epithelial cells or both during culturing.

Abstract: Provided is an activatable probe that undergoes intramolecular cyclization and subsequent aggregation in apoptotic tumor cells upon peptidase-initiated, and most advantageously caspase-3, activation. These caspase-sensitive nano-aggregation probes (C-SNAFs) are generally biocompatible, possess NIR spectral properties or may serve as PET or MRI imaging agents, and have a mechanism of target-mediated nanostructure self-assembly amenable to in vivo use. The probes encompass biocompatible condensation chemistry products that comprise D-cysteine and 2-cyano-6-hydroxyquinoline (CHQ) moieties linked to an amino-luciferin scaffold, and which can be activated by a two-step reaction requiring caspase-3/7-mediated cleavage of an aspartate-glutamate-valine-aspartate (L-DEVD) capping peptide and the free intracellular thiol-mediated reduction of the disulfide bond.

Abstract: The present invention relates to methods and devices for observing eukaryotic cells devoid of cell wall, in particular for observing the cytokinetic ring, the device comprising a plurality of wells suitable for containing only one single eukaryotic cell and characterized in that the dimensions of the wells constrain the cells into an oblong shape with a long axis parallel to the depth of the wells.

Abstract: Stromal stem cells are prospectively isolated from human bone marrow then expanded into clonal populations and cultured and used, the isolation being on the basis of expression of a cell surface marker, wherein the cell surface marker binds an antibody and wherein said antibody cross reacts with a cell surface marker found on mouse stromal stem cells or rat stromal stem cells, and optionally also on a cell of at least one other mammalian species selected from mouse, rat, horse, rabbit and pig cells. Useful stromal stem cell populations are positive for SDC2.

Abstract: The present invention relates to an in vitro method for diagnosing the infectious state of an individual on the basis of a sample of white corpuscles arising from a biological specimen taken from an organ potentially infected by a pathogenic micro-organism of said individual, comprising at least the following two steps: i) measuring the mean cellular intensity of the autofluorescence of said sample, and ii) comparing the intensity measured in step i) with a control value, so as to determine the infectious state of said individual. The diagnostic method of the invention uses a routine optical material making it possible to work in wavelength regions which are compatible with the cellular autofluorescence, and thus constitutes a rapid, reliable and inexpensive aid for the diagnosis or monitoring of an infection in an individual.

Abstract: Methods and devices for cutting and collecting dissected specimens are described herein.

Abstract: A method for the homogeneous distribution of cell components suspended in a liquid on a surface and a device for the implementation thereof.

Abstract: A system is disclosed that enables the automated measurement of cellular mechanical parameters at high throughputs. The microfluidic device uses intersecting flows to create an extensional flow region where the cells undergo controlled stretching. Cells are focused into streamlines prior to entering the extensional flow region. In the extensional region, each cell's deformation is measured with an imaging device. Automated image analysis extracts a range of independent biomechanical parameters from the images. These may include cell size, deformability, and circularity. The single cell data that is obtained may then be used to in a variety of ways. Scatter density plots of deformability and circularity may be developed and displayed for the user. Mechanical parameters such as deformability and circularity may be gated or thresholded to identify certain cells of interest or sub-populations of interest. Similarly, the mechanical data obtained using the device may be used as cell signatures.

Abstract: The present invention refers to a fixative composition for cytology, comprised by an alcoholic base and toluidine blue, preferably mucous cells, like cells from the oral cavity and cells from exo and endocervix. The present invention also describes a method for cytology fixation, and the application and method of this composition for medical use, namely, in neoplasic detection, preferably, cervix and oral cavity cancers.

Abstract: A method for accurately counting desired cells or microorganisms (viable bacteria) in a sample fluid in which contaminants are included is provided. One or plural types of membrane-permeable fluorochromes whose fluorescence amount is amplified by binding to a nucleic acid and glycerin are added to a sample fluid containing cells or microorganisms to be counted and allowed to stand for a certain time. Glycerin is added before or after or simultaneously with the mixing of the sample fluid and the fluorochrome(s). The cells or microorganisms to be counted are counted by staining the cells or microorganisms to be counted, followed by irradiating with light having a specific wavelength to detect the fluorescence emitted from the cells or microorganisms.

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: The present invention generally relates to systems and methods for counting biomolecules or cells. In certain embodiments, the invention provides a cell counting or biomolecule counting system including: a covered chamber having a known height and configured to hold a suspension of biomolecules or cells in a sample; at least one fluorescent light source connected to at least one fluorescent light beam narrowing device; a bright-field light source connected to a bright-field light beam narrowing device; a microscope objective; a detection device; a fluorescent filter assembly to allow only excitation light to illuminate the sample and allow only emission light from the sample to be imaged by the detection device; and a movable light shutter to block bright-field light during fluorescent detection.

Abstract: A chromatographic optical detection system includes an optical detector disposed to receive light scattered from a stream of particles and configured to convert the received light to an electrical signal; a signal-processing unit in signal communication with the optical detector to receive the electrical signal, and configured to convert the electrical signal to digital pulses and count the digital pulses to output a first signal corresponding to a number of particles detected in a time interval, and configured to integrate and digitize the electrical signal to output a second signal corresponding to the number of particles detected in the time interval; and a data station in signal communication with the signal-processing unit, and configured to select the first signal, if the number of particles detected in the time interval is less than a threshold criterion, and to select the second signal if the number of particles detected in the time interval exceeds the threshold criterion.

Abstract: An endscopic imaging device is described that achieves longitudinal axis (z-axis) scanning into a tissue or sample, using a piezoelectric microactuator. In some configurations, additional lateral (xy-plane) scanning is also achieved, to allow for the creation of full three-dimensional imaging, ex vivo or in vivo. The techniques may be used to image and diagnosis allergic rhinitis and eosinophilic esophagitis in tissue.

Abstract: Methods and devices for cutting and collecting dissected specimens are described herein.

Abstract: Disclosed herein are methods and devices for sectioning cell colonies. Also disclosed are methods of purifying cell colonies. A method of sectioning cell colonies can include providing a cell colony on a culture plate comprising a known thickness; positioning a bottom of the culture plate using automated focus technology; and sectioning the cell colony into one or more pieces using a pattern of laser cutting lines. Devices for performing the method are also disclosed.

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: 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: Various embodiments of the present invention provide methods and systems for optimally staining biological samples for analysis. In one embodiment, images of a sample are recorded before and after the application of a staining reagent and a decolorization reagent. A difference image is then generated based at least in part on a comparison of the images of the sample recorded before and after the application of the staining and decolorization reagents. Application parameters of the staining and decolorization reagents are then corrected based at least in part on the difference image such that the reagents may be optimally reapplied to generate a final image of the sample that may enable a user to better differentiate at least one target of interest in the sample. In one example, embodiments of the present invention allow for the generation of images that show only Gram-positive bacteria or only Gram-negative bacteria.

Abstract: The present invention relates to detection of cancer, or assessment of risk of development thereof. In particular, the present invention provides compositions and methods detection of field carcinogenesis by identification of ultrastructural and molecular markers in a subject.

Abstract: The invention relates to a method for preparing specimens from tissue samples for cytology microscopic examination, and includes inventive compositions and a device used in said method. The invention also includes a diagnostic kit comprising the inventive compositions and device.

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: 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: 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: The invention relates to an assembly of a cooperating capillary and cap for containing an aqueous solution in an inner volume of the capillary. The assembly is used in a high pressure freezer in which the aqueous solution is frozen at a high pressure to form an amorphous frozen sample at a cryogenic temperature. The cap forms a closure at one end of the capillary, and the part of the cap that is in contact with the inner volume of the capillary has an indent; as a result of which the cap, after freezing the aqueous solution, can be removed from the capillary and a free standing pillar of frozen aqueous material extends from the capillary.

Abstract: A method for quantitatively evaluating chromatin structural changes using pixel imaging of the nucleus is provided. Pixel imaging of the nucleus can include capturing one or more images of a nucleus of one or more nucleic acid stain treated cells. The stain intensity can be measured by quantitating the intensity. The mean and/or standard deviation of stain intensity per pixel can be used to determine chromatin condensation levels or chromatin structural change.

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: The present invention provides a method for the staining of fungi and microsporidia for observation with a light microscope based upon the presence of chitin in the composition of these organisms. With the method of the present invention a sample to be analyzed is treated with a solution of Ponceau S and Stains-all dye. The sample is then selectively decolorized and rinsed. The resulting sample is examined with a light microscope, or photographed for a permanent record, to identify the presence of a variety of microorganisms, to include fungi and microsporidia.

Abstract: The present invention is directed to a method for inactivation and/or extraction of fungus samples (e.g., mold or yeast samples), the method comprising the following sequential steps: (a) acquiring a test sample known to contain or that may contain fungus and suspending the test sample in a container containing water and/or suspension medium; (b) adding ethanol to the suspension; (c) centrifuging the container to pellet the fungus and removing and discarding the supernatant; (d) resuspending the fungus in formic acid; (e) adding acetonitrile to the sample; (f) centrifuging the sample; and (g) recovering the supernatant. In accordance with the present invention, the recovered supernatant can be subjected to mass spectrometry analysis for characterization and/or identification of the unknown fungus.

Abstract: The present invention relates to processes for staining biological samples, and in particular to automated processes for staining biological sample with hematoxylin stains. In the processes and systems of the invention, separate hematein and mordant solutions are provided which may be premixed prior to application to a biological sample. This method prevents precipitation common in hematein staining solutions and which fouls automated slide/sample processing equipment.

Abstract: The invention provides compositions (e.g., kits) and methods for determine the number of bacteria and other microbes in samples having low concentrations of microbes, for use, e.g., in biological warfare defense, microbe detection and agricultural and environmental sciences.

Abstract: This disclosure relates to methods of inducing a natural killer (NK) cell-mediated immune response and increasing NK activity in a mammal for the treatment of tumors and virus infections, comprising isolating peripheral blood mononuclear cells (PBMCs) from a subject, exposing them in vitro to a protein conjugate comprising granulocyte macrophage colony stimulating factor (GM-CSF) covalently linked to a soluble peptide antigen to activate the PBMCs, and administering the activated PBMCs to the subject. The method also relates to assessing NK cell activity of activated PBMCs to determine whether the subject has had a therapeutically effective response to the protein conjugate.

Abstract: The present invention discloses methods for detecting exposure of a living subject to genotoxic agents, testing sensitivity to a genotoxic agent, and determining DNA damage caused by exposure to an agent, comprising detecting the presence of FANCD2-containing foci from a sample collected from said subject. The presence of concentrated foci is indicative of DNA damage, and the degree of foci formation is correlated with degree of exposure. Diagnostic reagents contain a ligand that binds to human FANCD2 associated with a detectable label. Kits for detecting DNA damage in a biological sample contain such diagnostic reagents and signal detection components. The invention further discloses methods for identifying agents which modulate the ability of FANCD2-containing foci to form. Among other things, such agents are potentially useful chemosensitizing agents or may confer protection against damage caused by genotoxic agents.

Abstract: Devices for the microencapsulation of cells include a first chamber for containing a cell-solution suspension. A plate covers one end of the first chamber. The plate has a plurality of apertures. A second chamber is provided for receiving encapsulated cells. The second chamber is separated from the first chamber by the plate. Cells from the first chamber are encapsulated by passing through the apertures in the plate and into the second chamber when pressure is applied to the cell-solution suspension.

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.