Integrated and automated high-throughput purification of libraries on microscale
Carol Ginsburg‐Moraff, Jonathan E. Grob, Karl Chin, Grant Eastman, Sandra Wildhaber, Mark Bayliss, Heinrich Mues, Marco Palmieri, Jennifer Poirier, Marcel Reck, Alexandre Luneau, Stephane Rodde, John Reilly, Trixie Wagner, Cara E. Brocklehurst, R. Wyler, David W. Dunstan, Alexander N. Marziale
Abstract
We herein report the development of an automation platform for rapid purification and quantification of chemical libraries including reformatting of chemical matter to 10 mM DMSO stock solutions. This fully integrated workflow features tailored conditions for preparative reversed-phase (RP) HPLC-MS on microscale based on analytical data, online fraction QC and CAD-based quantification as well as automated reformatting to enable rapid purification of chemical libraries. This automated workflow is entirely solution-based, eliminating the need to weigh or handle solids. This increases process efficiency and creates a link between high-throughput synthesis and profiling of novel chemical matter with respect to biological and physicochemical properties in relevant assays.