Electrowetting-on-dielectric (EWOD) digital microfluidic device for in-line workup in organic reactions: A critical step in the drug discovery work cycle

As microfluidic systems play important roles to advance chemical synthesis applications in pharmaceutical and life science fields, the demand for fully-automated chemical synthesis work cycles grows. A successful automation of chemical synthesis with high yields requires not only executing sequential steps of organic chemical reactions, but also simple and adaptive purification (i.e., workup) techniques in each step. Despite recent advances in microreactor technologies, seamlessly integrating reactions and work-up toward a fully-automated chemical synthesis platform is an unmet challenge. In this study, we have demonstrated an electrowetting-ondielectric (EWOD) digital microfluidic device (DMF) as an efficient in-line work-up tool for organic chemical synthesis reactions. The model protocol performed on EWOD DMF involves an acid-base workup, liquid-liquid extraction (LLE), and in-line solvent-swap. Device operation parameters of each reactant and unit process have been optimized. This study manifests the capacity of an EWOD device to transform into a drug discovery platform, particularly by hosting synthetically important reactions that require complicated work-up sequences.