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Review of Liquid–Liquid Phase Separation in Crystallization: From Fundamentals to Application
Crystal Growth & Design ( IF 3.2 ) Pub Date : 2021-02-24 , DOI: 10.1021/acs.cgd.0c01376
Shijie Xu 1 , Huimin Zhang 1 , Bige Qiao 1 , Yanfei Wang 1
Affiliation  

In the field of industrial crystallization, liquid–liquid phase separation (LLPS) easily makes the crystallization process into an uncontrollable state, making it extremely difficult for people to effectively control and optimize the crystallization process, which creates a big bottleneck for the precise control of the desired crystal product (polymorphism, crystal size distribution, crystal shape, etc.). In view of the significant influence of LLPS on nucleation mechanism and kinetics, which is associated with the regulation of crystalline products, we therefore review the research progress of LLPS in the crystallization process in the last 30 years and attempt to summarize the reasons for LLPS from the perspectives of thermodynamics, properties of solvent and solute, short-range attraction, and the nucleation pathway. Furthermore, we highlight the role of the dense liquid intermediate phase in nucleation by revisiting the progress of nucleation theory, especially the classical nucleation and two-step nucleation theory. Finally, we also discuss how to regulate the crystallization outcome with desired properties of crystals in the LLPS process (crystal size distribution, polymorphism, crystal habit, etc.) so as to inspire people about why and how to promote or avoid LLPS during the crystallization process.

中文翻译:

结晶中液-液相分离的回顾:从基础到应用

在工业结晶领域,液-液相分离(LLPS)容易使结晶过程进入无法控制的状态,使人们很难有效控制和优化结晶过程,这对结晶过程的精确控制造成了很大的瓶颈。所需的晶体产品(多晶型、晶体尺寸分布、晶体形状等)。鉴于 LLPS 对成核机制和动力学的显着影响,这与结晶产物的调节有关,因此我们回顾了近 30 年来 LLPS 在结晶过程中的研究进展,并尝试从热力学观点、溶剂和溶质的性质、短程引力和成核途径。此外,我们通过重新审视成核理论的进展,特别是经典成核和两步成核理论,强调了致密液体中间相在成核中的作用。最后,我们还讨论了如何通过 LLPS 过程中晶体所需的特性(晶体尺寸分布、多晶型、晶体习性等)来调节结晶结果,以启发人们为什么以及如何在结晶过程中促进或避免 LLPS过程。
更新日期:2021-02-24
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