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

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 obtained crystals. In this work, we introduce a novel approach for controlling polymorphic crystallization by using quasi-double-emulsions (QDEs) as programmable microcrystallizers. The QDEs utilize a thin oil layer to separate aqueous droplets trapped in a high-density 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 semi-permeability of its middle oil film, the QDEs platform can facilely and flexibly vary the supersaturation rate and solvent composition of its inner aqueous phase (IAP) via changing its outer aqueous phase (OAP). 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 QDEs platform provides more controllability and flexibility in polymorphic crystallization, being a powerful tool for solid form screening in pharmaceutical, fine chemicals, and food industries.