The Effect of Controlled Mixing on ROY Polymorphism

We report the investigation of various experimental conditions and their influence on pol-ymorphism of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile, commonly known as ROY. These conditions include an in-house-developed microfluidic chip with controlled mixing of parallel flows. We observed that different ROY concentrations and different solvent to antisolvent ratios naturally favored different polymorphs. Nonetheless, identical samples prepared with different mixing methods, such as rotation and magnetic stirring, consistently led to the formation of different polymorphs. A fourth parameter, namely the confinement of the sample, was also consid-ered. Untangling all those parameters and their influences on polymorphism called for an experimental setup allowing all four to be controlled accurately. To that end, we developed a novel cus-tomized microfluidic setup allowing reproducible and controlled mixing conditions. Two parallel flows of antisolvent and ROY dissolved in solvent were infused into a transparent microchannel. Next, slow and progressive mixing could be obtained by molecular diffusion. Additionally, the mi-crofluidic chip was equipped with a piezoceramic element, allowing the implementation of various mixing rates by acoustic mixing. With this device, we demonstrated the importance of parameters other than concentration on the polymorphism of ROY.