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    Screening Technology
     
    bullet point  High Content Screening
     
     

    High Content Screening (HCS) is an extension of a revolution in cell analysis that began about 3 decades ago when fluorescence labeling technologies were combined with electronic imaging technologies and used to study individual cells on a light microscope. The innovation that drove the development of HCS, and what distinguishes HCS systems from the many confocal and wide field microscopes, is the integration and automation of the entire analytical process. The first HCS platforms were introduced to the drug discovery market by Cellomics, Inc. (Pittsburgh, PA) starting in 1997. There are now more than ten models of HCS imagers established in the market. HCS platforms automate the capture and analysis of fluorescent images of millions of individual cells in tens of thousands of samples on a daily basis, and have made fluorescence microscopy and image analysis compatible with the needs of drug discovery and systems cell biology. Through selection of appropriate probes, antibodies, fluorescent protein fusion partners, biosensors, environmentally sensitive probes and stains, fluorescence microscopy can be applied to many drug target classes, may be configured for simultaneous multiple target readouts (multiplexing), and can provide information on distributions and cell morphology in addition to simple intensities. Image based assays therefore provide multi-parameter quantitative and qualitative information beyond the single parameter target data typical of most other assay formats, and thus are referred to as high “content” assays. In recent years there has been a growing trend in drug discovery towards the implementation of cell based assays where the target is screened in a more physiological context than in biochemical assays of isolated targets. Fluorescence microscopy, whether confocal or wide field, is one of the most powerful tools that cell biologists can use to interrogate bio-molecules and investigate the molecular mechanisms of the cell. Automated imaging platforms are therefore being deployed throughout the drug discovery process; target identification/target validation, primary screening and lead generation, hit characterization, lead optimization, toxicology, bio-marker development and diagnostic histopathology. Furthermore, these platforms are now spreading into the research markets for application in high throughput biology.

     
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