In the past decade, automated microscopy has become an important tool for the drug discovery and development process. The establishment of imaging modalities as screening tools depended on technological breakthroughs in the domain of automated microscopy and automated image analysis. These types of assays are often referred to as high content screening or high content analysis (HCS/HCA). The driving force to adopt imaging for drug development is the quantity and quality of cellular information that can be collected and the enhanced physiological relevance of cellular screening compared to biochemical screening. Most imaging in drug development is performed on fixed cells as this allows uncoupling the preparation of the cells from the acquisition of the images. Live-cell imaging is technically challenging, but is very useful for many aspects of the drug development pipeline such as kinetic studies of compound mode of action or to analyze the motion of cellular components. Most vendors of HCS microscopy systems offer the option of environmental chambers and onboard pipetting on their platforms. This reflects the wish and desire of many customers to have the ability to perform live-cell assays on their HCS automated microscopes. This book chapter summarizes the challenges and advantages of live-cell imaging in drug discovery. Examples of applications are presented and the motivation to perform these assays in kinetic mode is discussed.

High Throughput Technology Development Studio Max Planck Institute of Molecular Cell Biology and Genetics Pfotenhauerstrasse 108 01307 Dresden Germany

High Throughput Technology Development Studio Max Planck Institute of Molecular Cell Biology and Genetics Pfotenhauerstrasse 108 01307 Dresden Germany Département de Médecine Faculté des Sciences University of Fribourg 1 Rte Albert Gockel Fribourg 1700 Switzerland

High Throughput Technology Development Studio Max Planck Institute of Molecular Cell Biology and Genetics Pfotenhauerstrasse 108 01307 Dresden Germany Department of Histology and Embryology Faculty of Medicine Masaryk University Kamenice 3 625 00 Brno Czech Republic

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