Compound Management for Quantitative High-Throughput Screening

An efficient and versatile Compound Management operation is essential for the success of all downstream processes in high-throughput screening (HTS) and small molecule lead development. Staff, equipment, and processes need to be not only reliable, but remain flexible and prepared to incorporate paradigm changes. In the present report, we describe a system and associated processes that enable handling of compounds for both screening and follow-up purposes at the NIH Chemical Genomics Center (NCGC), a recently established HTS and probe development center within the Molecular Libraries Initiative of the NIH Roadmap. Our screening process, termed quantitative HTS (qHTS), involves assaying the complete compound library, currently containing >200,000 members, at a series of dilutions to construct a full concentration–response profile. As such, Compound Management at the NCGC has been uniquely tasked to prepare, store, register, and track a vertically developed plate dilution series (i.e., inter-plate titrations) in the 384-well format. These are compressed into a series of 1536-well plates and are registered to track all subsequent plate storage. Here, we present details on the selection of equipment to enable automated, reliable, and parallel compound manipulation in 384- and 1536-well formats, protocols for preparation of inter-plate dilution series for qHTS, as well as qHTS-specific processes and issues.