C. HTS Core The objective of the HTS Core is to perform accurate, cost-effective, high-throughput screening with a broad spectrum of screening modalities. While the screening capabilities that we have used during the past 10 years have been robust and productive, we have undertaken a significant modification to enhance and to expand these capabilities, including robotic screening in a BL2 and BL2+ environment. We have designed and are now validating and implementing a fully automated and integrated, modular screening and compound management system (Figure 5). This system contains five modules that include: long-term compound store;compoundmanagement module;HTS/high-content general screening module;HTS/high-content BL2+ module for virusrelated projects;HTS/high-content BL2 module for bacteria- and/or yeast-related projects. This system has been built by High Resolution Engineering, Inc. and was co-designed with our Assay Development, HTS and Informatics core groups based upon specifications from a diverse set of validated assays currently being run at the Broad Institute. The system will be fully implemented by April 2008. Long-term storage capacity is 500,000 compounds stored dry in an inert environment at -20 ?C where the inventory will be tracked using barcodes and an integrated database. Individual compounds can be selected at a rate of ~1,600 per hour. The intermediate term storage capacity in the compound management module is 500,000 compounds frozen at -20 ?C. The modularity of both the long-term store and compound-management modules enable additional inventory (when the collection is >500,000 compunds) to be rotated in from a remote store. The flexibility within each of the designated safety modules for implementing multiple assay formats and detection platforms will provide the diversity necessary to support a broad-based chemical genomic approach (see Facilities Statement for complete description of specifications and capabilities). A common informatics framework (Informatics Core, Section E) links the compound management and screening modules to provide a fully integrated robotic system within a robust LIMS environment. The existing screening facilities will continue to operate, thus leading to a substantial increase in screening capacity.
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