Overview of Secondary Nucleation: From Fundamentals to Application

Secondary nucleation can bring the crystallization process into a more easily controlled state, and it is playing an important role in controlling crystal size distribution, polymorphism, and chirality of the crystal products, no matter whether in a batch or continuous crystallizer. Therefore, in this review, we revisit the research of secondary nucleation in the past 30 years to understand the fundamentals and application of secondary nucleation. First, we summarize the sources of secondary nuclei, that is, how secondary nucleation occurs. Then, we discuss the secondary nucleation threshold from the perspective of the metastable zone widths which are associated with the nucleation mechanism. Furthermore, we discuss how to employ secondary nucleation to regulate the properties of crystalline products (particle size distribution, crystal polymorphism, chirality, etc.). More importantly, we also discuss how polymorphism and chirality can act as a probe to explore the origin of secondary nucleation. Finally, we give conclusions and outlooks, mainly on the molecular nucleation mechanism and crystal growth dead zone of the current topic of secondary nucleation.