Static and Surfactant-Free Quasi-Double Emulsions as Programmable Microcrystallizers for Controllable Polymorphic Crystallization

Abstract

Controlling crystal polymorphism is critical in many fields such as pharmaceuticals, biomineralization, and catalysis. However, it is challenging for conventional batch crystallization approaches to effectively control the polymorphism of the obtained crystals. In this work, we introduce a novel approach for controlling polymorphic crystallization by using quasidouble emulsions (QDEs) as programmable microcrystallizers. The QDEs utilize a thin oil layer to separate the aqueous droplets trapped in a highdensity microwell array from the continuous aqueous phase, forming a large number of water−oil−water (W/O/W) structures similar to double emulsions. Benefitting from the semipermeability of its middle oil film, the QDE platform can facilely and flexibly vary the supersaturation rate and solvent composition of its inner aqueous phase (IAP) via changing its outer aqueous phase. Such variations can tune the kinetics of crystallization in the IAP, thus achieving highly controlled polymorphic crystallization and obtaining desired crystal polymorphs. In a proof-of-concept application, we demonstrated the convenience and versatility of the QDE platform by applying it for regulating the polymorph of glycine. Compared to traditional crystallizers, the QDE platform provides more controllability and flexibility in polymorphic crystallization, being a powerful tool for solid form screening in pharmaceutical, fine chemical, and food industries.