(477d) Comparative Screening of Polymorphs of o-Aminobenzoic Acid Using Microtiter Plates and Novel Continuous-Flow, Microfluidic Devices
Screening of polymorphs, morphologies, and crystallization kinetics is crucial for the development of crystallization processes for the synthesis of materials such as pharmaceuticals, agrochemicals, catalysts, semiconductors, and metal-organic frameworks. The existing screening techniques use either microtiter plates or droplet-based microfluidic devices consisting of small compartments in which the crystals nucleate and grow while supersaturation depletes continuously affecting polymorphs and morphologies. Setbacks are often encountered during the scale-up of crystallization process due to the effect of varying supersaturation in screening evaluations. Therefore, a screening technique where supersaturation can be controlled is much needed for the effective design of crystallization processes. Additionally, such constant-supersaturation screening technique is an indispensable tool to boost innovation in continuous manufacturing, also supported by the U.S. Food & Drug Administration. Here we analyze five different types of continuous-flow microfluidic devices including conventional T-junction, cross-flow, and cell sorter devices; and novel H-shaped, and cyclone mixer designs for their ability to trap crystals that are nucleating and growing in a constant supersaturation. These continuous-flow microfluidic devices have three connected sections- thermalizer, mixer, and diffuse, whose optimal dimensions and operating conditions are determined using Multiphysics simulations. A facile technique is also shown to fabricate such microfluidic devices using a stereolithographic3D printer. Although T-junction, cross-flow, and cell sorter devices are able to operate at constant supersaturation near stagnation point, the crystals are constantly dragged away from the trap zone and hence such devices cannot be used for screening. The H-shaped design relies on countercurrent diffusion of solvents to create stable supersaturation gradient along the mixer, which can be used to screen proteins or metal-organic framework with longer induction time and slower growth kinetics. The cyclone mixer design with multiple inlets is demonstrated to not only operate at constant supersaturation but also trap crystals for in situanalysis of polymorphs and morphologies. The polymorphs and morphologies of o-aminobenzoic acid (o-ABA) at two different supersaturations are analyzed using cyclone mixer design and a traditionalmicrotiter plate. While the polymorphs and morphologies of o-ABA are affected by depleting supersaturation in a microtiterplate, the cyclone mixer design shows consistently stable and metastable forms of o-ABA. We expect the H-shaped and cyclone mixer designs will advance innovations in crystalline materials research in various applications.