A Review of Experimental Methods for Nucleation Rate Determination in Large-Volume Batch and Microfluidic Crystallization
Cedric Devos, Tom Van Gerven, Simon Kuhn
Abstract
Determination of the experimental nucleation rate for crystallization in solution has been acknowledged as an important topic for a long time, as it improves the design and control of industrial crystallization processes and offers insights into the mechanisms of nucleation. Characterization of nucleation rates in large-volume batch crystallizers has been widely studied in the past, which has led to the development of a variety of models linking the nucleation rate to the metastable zone width and induction time. These methods remain important due to their role in industrial crystallization. More recently, the use of microfluidic platforms has resulted in the development of methods to obtain nucleation rates based on the stochastic nature of nucleation. This has opened new pathways for understanding nucleation on a molecular level. This Review presents a critical overview of nucleation rate determination methods: large-volume batch crystallizer models and microfluidic and microvial models are presented in terms of equations, advantages, and limitations. Published experimental nucleation rate values are summarized. A critical discussion of experimental nucleation rate determination is given. The objective of this Review is to be a starting point for researchers attempting to experimentally characterize nucleation behavior.