C. HTS CoreThe objective of the HTS Core is to perform accurate, cost-effective, high-throughput screening with a broadspectrum of screening modalities. While the screening capabilities that we have used during the past 10 yearshave been robust and productive, we have undertaken a significant modification to enhance and to expandthese capabilities, including robotic screening in a BL2 and BL2+ environment. We have designed and are nowvalidating and implementing a fully automated and integrated, modular screening and compound managementsystem (Figure 5). This system contains five modules that include: long-term compound store; compoundmanagementmodule; HTS/high-content general screening module; HTS/high-content BL2+ module for virusrelatedprojects; HTS/high-content BL2 module for bacteria- and/or yeast-related projects. This system hasbeen built by High Resolution Engineering, Inc. and was co-designed with our Assay Development, HTS andInformatics core groups based upon specifications from a diverse set of validated assays currently being run atthe Broad Institute. The system will be fully implemented by April 2008. Long-term storage capacity is 500,000compounds stored dry in an inert environment at -20 C where the inventory will be tracked using barcodesand an integrated database. Individual compounds can be selected at a rate of ~1,600 per hour. Theintermediate 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 additionalinventory (when the collectionis >500,000 compunds) to be rotated in from a remote store. Theflexibility within each ofthe designated safetymodules for implementingmultiple assay formatsand detection platformswill provide the diversitynecessary to support abroad-based chemical genomicapproach (see FacilitiesStatement for completedescription of specificationsand capabilities).A common informaticsframework (InformaticsCore, Section E) links thecompound managementand screening modules toprovide a fully integratedrobotic system within a robust LIMS environment. The existing screening facilities will continue to operate, thusleading to a substantial increase in screening capacity.
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