Stratified high-throughput screening sets enable flexible screening strategies from a single plated collection.

Customized compound picking and plating of very large corporate screening decks (many 100,000s) for high-throughput screening is generally restricted, both from a time and cost perspective. Here we present a stratified screening deck with accompanying plating design for use with very large corporate compound collections. The deck is plated as a whole, but copies for screening can be downsized flexibly and quickly on the fly, without the need for repicking of physical samples. We show that such downsized sets maximize returns and yield results superior to randomly picked subsets of the same size. For the proposed stratified plating design, structurally diverse subsets that cover the full collection in terms of compound diversity and favorable compound properties can be produced economically and quickly from the full set of master plates. The design was implemented globally at AstraZeneca in 2009 and has enabled substantial cost-saving in screening campaigns, as set size requirements can be met on a per-screen basis, using a single, preplated master deck.