Fluid shear driven secondary nucleation using α-and γ-glycine seeds confirmed with rigorous control experiments.

The effect of fluid shear on secondary nucleation has long been debated in the crystallization literature. In this work, we investigated the influence of seed polymorphism on secondary nucleation under flow conditions in the absence of mechanical impact, using a "seed-on-a-stick" technique to isolate the effect of fluid shear on secondary nucleation induced by a single glycine seed crystal in aqueous solutions. In situ imaging and particle count analysis were used to assess the impact of seed polymorphism on secondary nucleation kinetics. The presence of glycine seeds induced earlier nucleation under all conditions investigated here, as evidenced by shorter delay times compared to those for control and unseeded experiments. By seeding with either α- or γ-glycine, we found that the solid form of the seed had no significant impact on secondary nucleation rates or delay times and α-glycine consistently nucleated irrespective of the seed solid form. This indicates that cross-nucleation of metastable α-glycine can occur with γ-glycine seeds under flow conditions. We propose that fluid shear driven secondary nucleation may operate similarly to primary nucleation near a solution-solid interface, where enhancement of nucleation is due to stabilisation and aggregation of solute clusters in the interfacial solution region.