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High-Content Screening: A New Approach to Easing Key Bottlenecks in the Drug Discovery Process
Kenneth A. Giuliano
BioDx, Inc., 635 William Pitt Way, Pittsburgh, PA 15238
Robbin L. DeBiasio
BioDx, Inc., 635 William Pitt Way, Pittsburgh, PA 15238
R. Terry Dunlay
BioDx, Inc., 635 William Pitt Way, Pittsburgh, PA 15238
Albert Gough
BioDx, Inc., 635 William Pitt Way, Pittsburgh, PA 15238
Joanne M. Volosky
BioDx, Inc., 635 William Pitt Way, Pittsburgh, PA 15238
Joseph Zock
BioDx, Inc., 635 William Pitt Way, Pittsburgh, PA 15238
George N. Pavlakis
ABL-Basic Research Program, National Cancer Institute-FCRDC, Frederick, MD 21702
D. Lansing Taylor
BioDx, Inc., 635 William Pitt Way, Pittsburgh, PA 15238
Recent improvements in target discovery and high throughput screening (HTS) have increased the pressure at key points along the drug discovery pipeline. High-content screening (HCS) was developed to ease bottlenecks that have formed at target validation and lead optimization points in the pipeline. HCS defines the role of targets in cell functions by combining fluorescence-based reagents with the ArrayScanTM System to automatically extract temporal and spatial information about target activities within cells. The ArrayScan System is a tabletop instrument that includes optics for subcellular resolution of fluorescence signals from many cells in a field within a well of a microtiter plate. One demonstrated application is a high-content screen designed to measure the drug-induced transport of a green fluorescent protein-human glucocorticoid receptor chimeric protein from the cytoplasm to the nucleus of human tumor cells. A high-content screen is also described for the multiparametric measurement of apoptosis. This single screen provides measurements of nuclear size and shape changes, nuclear DNA content, mitochondrial potential, and actin-cytoskeletal rearrangements during drug-induced programmed cell death. The next generation HCS system is a miniaturized screening platform, the CellChipTM System, that will increase the throughput of HCS, while integrating HCS with HTS on the same platform.
Journal of Biomolecular Screening, Vol. 2, No. 4,
249-259 (1997)
DOI: 10.1177/108705719700200410
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