(198a) Screening of Polymorphs and Measurement of Growth Rates of L-Histidine at Controlled Supersaturation Using Continuous-Flow, Microfluidic Device

A continuous-flow, a well-mixedmicrofluidic device is presented here to measure solubility, as well as growth rates and polymorphs of L-Histidine (L-his) from ethanol-water mixtures at controlled supersaturations. While conventional tools such as microtiter plates, and droplet-based microfluidics measure polymorphs, nucleation and growth kinetics in depleting supersaturation, the continuous-flow microfluidic device can trap crystals to measure nucleation and growth kinetics while constantly feeding them with supersaturated solution. Here we use multi-inlet cyclone mixer design, similar to a mixed-suspension-mixed-product-removal (MSMPR) crystallizer, for anti-solvent crystallization using ethanol and an aqueoussolution of L-his. The supersaturation in such device is controlled by manipulating flow rates of ethanol and water solutions. Solubility data of L-his in the ethanol-watermixture is obtained by increasing the flow rate of anti-solvent until the crystals are formed and then gradually decreasing the flow rate so that crystals stop growing. At a fixed supersaturation, the evolution of crystal morphology can be processed to estimate face-specific growth rates. Since the stable and metastable forms of L-Histidine have distinct morphology, the polymorphs are directly identified using an opticalmicroscope. A multi-channel, multi-compartment microfluidic device is also shown for the continuousscreening of polymorphs of L-his.