(737d) Miniaturized Purification Platform for Automated Screening of Flow Synthesis Using Extraction and Crystallization

R&D for continuous flow chemistry (e.g. end-to-end continuous manufacturing and automated synthesis lab) necessitates a modular and reconfigurable chemical synthesis platform capable of screening of a variety of chemical pathways. Flow microreactors are now commercially available, and more recently, drop-on-demand formulation device, such as ink- and droplet-based pharmaceutical printers, have made it to market. While these devices can be naturally combined to construct a modular end-to-end continuous flow platform, the platform cannot be fully realized without its purification counterpart. Nevertheless, microscale purification platform is not yet well established; Although a number of innovative separation techniques have been reported in the microfluidics literature, including evaporation, extraction, crystallization, filtration and chromatography, most of these processes have been designed as a standalone for lab-on-a-chip applications. An automated and reconfigurable purification device which can seamlessly integrate with other parts of the flow synthesis platform in a flexible and scalable manner is therefore desirable. In this work, a microscale purification platform which can virtually be constructed using off-the-shelf parts is described. Specifically, our device consists of a combination of commercially available parts, such as capillaries, chips, mixers, fittings, etc. as well as custom parts, including tubing heaters and zero-dead volume Y-junctions. In addition, the device support multiple reservoirs for use with aqueous and organic solvents, a Peltier-based heating and cooling system, a couple of process analytical tools, including UV and non-contact Raman spectroscopy and an auto-sampler for sample collection of offline analysis using techniques such as MS and UPLC. The device operation is controlled using a LabView software which integrates, controls and monitors electronic actuators, including syringe pumps, valves, pressure sensors, etc., and executes a sequence of instructions to perform priming, loading and cleaning. The capability of the device is demonstrated via automated screening of continuous and segmented (air and liquid) flow extraction and crystallization under various favorable and unfavorable conditions for the purification of model APIs including diphenhydramine and atropine.