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We report the investigation of various experimental conditions and their influence on polymorphism 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 considered. 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 customized 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 microfluidic 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.

In this work, we report the investigation of various experimental conditions and their influence on the polymorphism of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophen carbonitrile, commonly known as ROY. These conditions include an in-house-developed microfluidic chip with controlled mixing of parallel flows. ROY is known for its ability to form a large variety of polymorphs, including at least ten forming under standard conditions. Nucleation is triggered by adding water as an antisolvent to ROY dissolved in acetone. We observe that different ROY concentrations and different solvent-to-antisolvent ratios naturally favor different polymorphs. Nevertheless, identical samples prepared with different mixing methods, such as shaking and magnetic stirring, consistently lead to the formation of different polymorphs. In addition, different mixing rates that can be linked to shear stress strongly influence the crystallization. A fourth parameter, namely confinement of the sample, is also found to be critical. Untangling all of these parameters and their influences on polymorphism calls for an experimental setup allowing all four to be controlled accurately. To that end, we developed a novel customized microfluidic setup allowing reproducible and controlled mixing conditions. Two parallel flows of antisolvent and ROY dissolved in solvent are injected into a transparent microchannel. Next, slow and progressive mixing can be achieved through molecular diffusion. Additionally, the microfluidic chip is equipped with a piezoceramic element, allowing the implementation of various mixing rates through acoustic mixing. With this device, we demonstrate the importance of parameters other than concentration that are involved in the polymorphism of ROY.

We examine the effect of rough surfaces on crystal nucleation by means of kinetic Monte Carlo simulations. Our work makes use of three-dimensional kMC models, explicit representation of transport in solution and rough surfaces modeled as randomly varying height fluctuations (roughness) with exponentially decaying correlation length (topology). We use Forward-Flux Sampling to determine the nucleation rate for crystallization for surfaces of different roughness and topology and show that the effect on crystallization is a complex interplay between the two. For surfaces with low roughness, small clusters form on the surface but as clusters become larger they are increasingly likely to be found in the bulk solution while rougher surfaces eventually favor heterogeneous nucleation on the surface. In both cases, the rough surface raises the local supersaturation in the solution thus leading to another mechanism of enhanced nucleation rate.