High-Throughput Droplet Microfluidics for Chemical Reaction Discovery and Development
In the search for breakthrough medicines and therapeutics, the rapid preparation of new, complex molecules for biological evaluation is of paramount importance to the medicinal chemistry community. The use of high-throughput experimentation (HTE) techniques represents a streamlined approach for enabling the exploration of a myriad of catalysts and reaction conditions in a time and resource-efficient manner. It is in this context that we aim to access novel HTE technology, with the goal of expanding upon the robust capabilities and impact of photoredox catalysis in drug discovery and development. In particular, we have identified droplet microfluidics as an optimal platform for reaction discovery and optimization for flow-based synthesis. Microfluidic technology allows for the generation of 10^9 droplets per millimolar amount of material consumed for screening. Furthermore, sample throughput rates exceeding one droplet per second (3600 per hour) are achievable by electrospray ionization mass spectrometry (ESI-MS), enabling the rapid analysis of this wealth of information. We envision this platform to enable the direct optimization of flow reaction parameters (i.e. flow rate, residence time) and in turn, expedite the translation of discovery scale flow conditions to pilot scale continuous flow operations.