Robotic assays

Configuration of Zymate II Robotic System Flow diagram of basic robotic assay procedure Major validation elements... 

NMR line shape analysis software developed for use at Monsanto was kindly supplied by Mr. N.G. Hoffman, Research Computing Consortium, Monsanto Co., and Prof. A.J. Duben, Southeast Missouri State University. The authors would also like to thank Mr. Brad Herman of the Research Computing Consortium, Monsanto Co., for his development of the automatic sample management software. Dr. William Wise of the Physical Sciences Center (PSC), Monsanto Co., for his many valuable discussions on homonuclear 2DJ spectroscopy, and Mr. John Burquin (Monsanto PSC) for his assistance in the development of the robotic assay. Appreciation is also expressed to the many analysts who participated in the study. 

Numerous reviews cover the selection, construction, and curation of chemical libraries, debates about their size and composition, operational costs, infrastructure, and best practices of compound management of stock solutions and dry powders [2, 3, 20]. For the purposes of implementation of automated robotic assays, the practical aspects are that the entire chemical library exists as working stocks (typically 2 mM in 100 % DMSO) of individual compounds stored in heat-sealed (see also Note 4), daughter barcoded microplates of well density format matching the final screening format (96-, 384-, or 1,536-well) in a plate material consistent w/chemical inertness (cycloelefin copolymer (COC) or polypropylene) or optimized for acoustic dispensing (Echo-certified COC or diamond plates). 

The overall process and critical activities for robotic implementation of automated HTS from intake of the researcher s benchtop assay through to the identification of a validated, optimized lead series of compounds around a bona fide chemical scaffold are shown in Fig. 2. The downstream steps of hit confirmation/ validation and structure-activity relationship (SAR) elucidation and hit to lead (HTL) have been included to emphasize that the same robotic assay used for production HTS can and should be used by the HTS team to perform high-volume hit confirmation and first-line automated dose-response analysis of confirmed hits to obtain quantitative potency (IC50) rankings to elucidate the nascent SAR of emergent hit series... 

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