Other

Vala Sciences, Inc.

University of California

Sanford-burnham Medical Research Institute

Q3dm, LLC

The Rockefeller University

Burnham Institute for Medical Research

The Rockfeller University

Vala Science, Inc.

Jeffrey H Price

Patrick M McDonough

David Arthur Gough

Fabio Cerignoli

Brian Kloss

Justin Blau

Michael W Young

Albert L Kellner

Ross J Whittaker

Miguel Bravo-Zanoguera

Piyush Gehalot

David Jean Charlot

Derek Fuller

Randall S Ingermanson

Mark Mercola

Edward Hunter

Lam Khanh Nguyen

Joseph S Takahashi

Behrad Azimi

Martin Weinigel

Patrick M Mc Donough

Ivana Mikic

Miguel Bravo-Zanoquera

Phillip L Lowrey

Video recordings from two or more optical channels are produced, processed, and analyzed simultaneously in order to provide quantitative analysis of action potentials, calcium transients and ionic flux in excitable cells loaded with voltage or ion sensitive dyes with distinct excitation and emission wavelengths. The specific wavelengths of fluorescent light emitted from each dye are separated and recorded. The recordings are mutually registered and cytometric analysis is performed to provide a quantitative analysis of the action potentials, calcium transient, and/or ionic flux on a cell-by-cell and well-by-well basis in microtiter plates. The cells are then fixed, labeled for other biomarkers, and scanned again. The resulting fixed cell images are registered with the live cell recordings and analyzed; missing cells that were washed off are detected relative to the live recordings, and cytometry data from live and fixed cell scans is collated cell-by-cell.

Analysis of action potentials, transients, and ion flux in excitable cells

The present invention provides a method, system and composition for screening drug candidates for cardiotoxicity and for novel drugs that effect cardiomyocyte contractility and function. The invention provides an efficient and reliable screening assay to detect the effect of new and potential drug candidates on cardiomyocyte calcium flux, membrane depolarization, and/or the propagation of action potentials.

Method, system and composition for optically inducing cardiomyocyte contraction

Multifunction autofocus for automated microscopy includes automatic coarse focusing of an automated microscope by reflective positioning, followed by automatic image-based autofocusing of the automated microscope performed in reference to a coarse focus position. In some aspects, the image-based autofocusing utilizes astigmatism in microscope optics for multi-planar image acquisition along a Z axis direction of a microscope. In some other aspects, the image-based autofocusing utilizes astigmatism in microscope optics in combination with chromatic aberration for multi-planar image acquisition along the Z axis direction.

Multifunction autofocus system and method for automated microscopy

Video recordings from two or more optical channels are produced, processed, and analyzed simultaneously in order to provide quantitative analysis of action potentials, calcium transients and ionic flux in excitable cells loaded with voltage or ion sensitive dyes with distinct excitation and emission wavelengths, The specific wavelengths of fluorescent light emitted from each dye are separated and recorded. The recordings are mutually registered and cytometric analysis is performed to provide a quantitative analysis of the action potentials calcium transient, and/or ionic flux on a cell-by-cell and well-by-well basis in microtiter plates. The cells are then fixed, labeled for other biomarkers, and scanned again. The resulting fixed cell images are registered with the live cell recordings and analyzed; missing cells that were washed off are detected relative to the live recordings, and cytometry data from live and fixed cell scans is collated cell-by-cell.

A method, system, and instrument for automatically measuring transient activity in cells uses image time sequences to identify transients in cells. Preferably, the transient activity is stimulated or provoked in synchronism with acquisition of the image time sequences. A cell mask is applied to each image of an image time sequence in order to localize the transient activity with respect to each cell. Localization enables cell-by-cell analysis of properties of the transient activity.

Automated transient image cytometry

In an automated scanning cytometry system, chromatic aberration is used for multiplanar image acquisition.

Automated scanning cytometry using chromatic aberration for multiplanar image acquisition

A system, method and kit for processing an original image of biological material to identify certain components of a biological object by locating the biological object in the image, enhancing the image by sharpening components of interest in the object, and applying a contour-finding function to the enhanced image to create a contour mask. The contour mask may be processed to yield a segmented image divided by structural units of the biological material.

System, method, and kit for processing a magnified image of biological material to identify components of a biological object

Methods and apparatus are described for enhancing operator independent image cytometry. Aspects of the invention include enhanced tissue surface tracking which can detect both tissue surfaces. The surface detection can aid cytometry, such as by reducing the amount of image data to be stored. Segmentation is described for 3D images in which 3D least squares filtering is applied to increase contrast for simplifying the delineation of objects from backgrounds. A method of creating 3D FIR image filters based on ideal objects is also described. A data structure is defined by which 3D object data may be organized for image representations if samples. Methods of performing remote segmentation processing are also described toward centralizing the necessary processor power and applications and reducing the burden on researchers and clinicians.

Fast 3D cytometry for information in tissue engineering

An analog circuit for an autofocus microscope system measures a degree of focus of an object directly from the video signal of a microscope CCD camera. The circuit then returns an index to a host computer for the purpose of adjusting the position of the microscope's objective lens to bring the object in focus. Best focus is found by comparing indices at several different vertical positions. The criterion adopted for determining the degree of focus is derived from the energy distribution of the video signal spectrum. The high frequency energy of the video spectrum is a maximum at best focus and as the optics defocus, the distribution shifts to lower frequencies. Low cost, real time autofocus is achieved with the analog circuitry of this invention, replacing more expensive dedicated, real time image processing hardware.

Analog circuit for an autofocus microscope system

A system for imaging of a sample is disclosed. The system includes a plurality of detectors which are each focussed at a respective focal plane in a sample volume. The system also includes light selection optics positioned between the plurality of detectors and the sample volume. The light selection optics transmit to the detectors a portion of light originating at the respective focal planes while screening out light which originates from outside of the respective focal planes.

Multiparallel three dimensional optical microscopy system

Volume imaging is supported in an optical apparatus that simultaneously acquires multiple images from multiple focal planes in an image object. A plurality of image detectors is arranged with respect to an objective lense. A plurality of reflective devices are disposed between the objective lense and the plurality of detectors to divide the light travelling through the objective lense to the detectors into channels such that each channel is registered with a respective detector.

The invention provides an apparatus, and related method, for continuous volume imaging a specimen using imaging a plurality of image planes at predetermined focal depths. The focal depth for each image plane is adjustable in accordance with a variety of desired spatial configurations. The images generated at the image planes are processing in parallel and the image corresponding the an optimal focal depth at an specimen location is selected for imaging the specimen at that location. The volume imaging apparatus of the invention allows for rapid scanning of an entire microscope slide at high image resolution.

Automatic on-the-fly focusing for continuous image acquisition in high-resolution microscopy

The present invention discloses the identity of the first enzyme that has been demonstrated to be involved in maintaining circadian rhythms. This enzyme, the Drosophila DOUBLETIME protein is also shown to be an ortholog of human casein kinase-1&egr;. In addition, a variant of this enzyme is shown to be cause of the hamster tau mutant phenotype. Thus the present invention also relates to variants of DOUBLETIME, and their nucleic acid and amino acid sequences. The present invention further provides methods of using these variants in drug assays and diagnostics.

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San Diego, CA, United States of America

Jeffrey H Price