An infrastructure for high-throughput microscopy: instrumentation, informatics, and integration.
High-throughput, image-based cell assays are rapidly emerging as valuable tools for the pharmaceutical industry and academic laboratories for use in both drug discovery and basic cell biology research. Access to commercially available assay reagents and automated microscope systems has made it relatively straightforward for a laboratory to begin running assays and collecting image-based cell assay data, but doing so on a large scale can be more challenging. Challenges include process bottlenecks with sample preparation, image acquisition, and data analysis as well as day-to-day assay consistency, managing unprecedented quantities of image data, and fully extracting useful information from the primary assay data. This chapter considers many of the decisions needed to build a robust infrastructure that addresses these challenges. Infrastructure components described include integrated laboratory automation systems for sample preparation and imaging, as well as an informatics infrastructure for multilevel image and data analysis. Throughout the chapter we describe a variety of strategies that emphasize building processes that are scaleable, highly efficient, and rigorously quality controlled.