44 results about "High-content screening" patented technology

The present invention provides protein fragment complementation assays for drug discovery, in particular to identify compounds that activate or inhibit cellular pathways. Based on the selection of an interacting protein pair combined with an appropriate PCA reporter, the assays may be run in high-throughput or high-content mode and may be used in automated screening of libraries of compounds. The interacting pair may be selected by cDNA library screening; by gene-by-gene interaction mapping; or by prior knowledge of a pathway. Fluorescent and luminescent assays can be constructed using the methods provided herein. The selection of suitable PCA reporters for high-throughput or high-content (high-context) assay formats is described for a diversity of reporters, with particular detail provided for examples of monomeric enzymes and fluorescent proteins. Methods are described for constructing such assays for one or more steps in a biochemical pathway; testing the effects of compounds from combinatorial, natural product, peptide, antibody, nucleic acid or other diverse libraries on the protein or pathway(s) of interest; and using the results of the screening to identify specific compounds that activate or inhibit the protein or pathway(s) of interest. Single-color and multi-color assays are disclosed. Further disclosed are universal expression vectors with cassettes that allow the rapid construction of assays for a large and diverse number of gene / reporter combinations. The development of such assays is shown to be straightforward, providing for a broad, flexible and biologically relevant platform for drug discovery.

Disclosed herein are systems methods for high content screening for microscope imaging. In some embodiments, the system comprises: a microscope; and a processor configured to implement: a slide loader module; a reference imager module; a slide imager module; a region of interest (ROI) finder module; a compare imager module; a calibrator module; and an image stitcher module.

A method and system for setting image analysis parameters to control image analysis operations. The method and system include collecting set of digital training images including a set of states for the set of digital training images. An objective function is defined to determine a relative quality of plural different parameter sets used for digital image analysis. Values for the plural different parameter sets that maximize (or minimize) the objective function are determined. The method and system increases a usability of high content screening technologies by reducing a required level of expertise required to configure digital image processing.

The present invention involves the pooling of multiple high content cell-based screening assays, and carrying out a primary screen in a one or more channels of a fluorescence detection device, which drastically increases the number of simultaneous high content cell-based screening events that can be carried out. Subsequent deconvolution of primary screen “hits” (ie: those wells or locations on an array of locations in which the one or more test compounds caused a change in the fluorescence signal(s) from the fluorescent reporter molecules in the cells) enables much more rapid generation of high content cell screening data than was previously possible, and at significantly reduced costs.

The present invention is directed to Protein-fragment Complementation Assays (PCAs) and assay compositions based on fluorescent proteins. The invention provides methods for fragmenting fluorescent proteins and generating mutant fragments with desired spectral characteristics for PCA. The invention encompasses assays and compositions based on fluorescent proteins from the species Aequorea, Anemonia and Anthozoa. In particular, the invention is directed to fragments of mutant fluorescent proteins having improved spectral properties over the wild-type proteins. The invention encompasses fragments of mutant versions of A. Victoria green fluorescent protein (GFP), in particular yellow fluorescent proteins (EYFP and super-EYFP), ‘Venus’, cyan, ‘citrine’, blue, cyan-green, and photoactivatable variants of GFP The invention also encompasses red fluorescent PCAs based on Discosoma red fluorescent protein (RFP PCA)and a kindling fluorescent protein PCA (KFP1 PCA) derived from Anemonia sulcata. Any useful mutation of a fluorescent protein can be engineered into a fragment, generating a wide range of assays useful for drug discovery, target validation, high-throughput screening, high-content screening, pathway mapping, drug mechanism-of-action studies, biosensors, and diagnostics.

In one aspect, the present invention relates to a method 200 for identifying one or more phenotypes from a multi-parameter data set. The method 200 comprises measuring 202 correlation between pairs of parameters within the multi-parameter data set, modifying 204 correlated parameter values within a predetermined multi-parameter data analysis set to form an analysis parameter set, and analyzing 206 the multi-parameter data set using the analysis parameter set to identify one or more phenotypes from the multi-parameter data set. Various embodiments of the present invention may, for example, be used in an automated high-content screening (HCS) apparatus 100 for biological cellular analysis.

Described herein is a three-dimensional cell culture scaffold composition comprising an absorbent rigid (AR) component, and in some embodiments, further comprises a gel component. The absorbent rigid component preferably comprises a glass fiber material. It is a surprising finding of the present invention that an AR component having a void volume of between approximately 70% and 95% results in a three-dimensional cell culture composition that allows for robust, high-throughput screening and high-content screening accessible tissue models with preserved cell morphology, heterogeneity of cell types and cell populations, extracellular matrix constituents, functional cell-cell and cell-extracellular matrix interactions and signaling with sufficient specificities to tissue physiology and pathology.

The invention relates to an establishing method and application of a dilated cardiomyopathy and zebrafish disease model. A disease model simulating human congenital dilated cardiomyopathy (CDCM) is firstly established; and the disease model can be used as a drug screening model to be applied to screening of drugs capable of relieving symptoms of heart failure caused by CDCM. The method provided by the invention is an economic and rapid high-content screening method; and the obtained compound has relatively high specificity and druggability.