Purifying the masses: integrating prepurification quality control, high-throughput LC/MS purification, and compound plating to feed high-throughput screening |
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| Authors: | Isbell John J Zhou Yingyao Guintu Christina Rynd Matthew Jiang Shumei Petrov Dimitri Micklash Ken Mainquist Jim Ek Jared Chang Jim Weselak Mark Backes Bradley J Brailsford Andrew Shave Darcy |
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| Affiliation: | Genomics Institute of the Novartis Research Foundation (GNF), 10675 John Jay Hopkins Drive, San Diego, California 92121, USA. |
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| Abstract: | In this paper we report using a parallel, four-channel HPLC/MUX/MS purification system, the Purification Factory, to purify thousands of compounds destined for high-throughput screening in a single month. The maximum sample throughput during this 20-workday month was 704 samples/day. Since this purification throughput exceeded the postpurification sample and data handling capabilities provided by commercial solutions, a custom-integrated solution was designed to address these shortcomings. In this paper we detail the key improvements in automation, solvent handling, and sample handling logistics implemented to sustain a mean throughput of 528 samples/day over a multimonth time period. |
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