Effects of Volume Reduction on Glycine Nucleation

Crystallization in confinement is a technique used both as an approach for nanocrystal development and as way to gain access to unstable crystal polymorphs. To elucidate this, the effect of decreasing volumes in the nucleation of glycine in water was explored. Using a supersaturated aqueous solution of glycine at decreasing volumes from 1000 μL to 25 μL, induction times for primary nucleation were obtained experimentally. Analysis of probability distribution of β-glycine induction times showed that as sample volume decreases, induction time increases. Image analysis revealed that β-glycine formation serves as the primary nucleation event; however, primary nucleation shifts toward γ-glycine nucleation at volume sizes below 100 μL. These results demonstrate that feasibility of accessing metastable and unstable crystal polymorphs with the aid of confinement. However, confinement also increases induction times which relates to very low probabilities of a nucleation event.