Effect of seed loading and cooling rate on crystal size and shape distributions in protein crystallization—A study using morphological population balance simulation

Abstract

A morphological population balance model is applied to crystallization of hen-egg white lysozyme for investigation of the effect of seed loading and cooling rate on supersaturation, and crystal size and shape distributions. Growth rates of individual faces and final crystal size and shape distributions were examined under varied seeding and cooling conditions. It was found that for growth only crystallization, desired crystal size and shape can be obtained by coordinative manipulation of the seed loading and cooling rate: low seed loading and high cooling rate lead to large crystals of low aspect ratio, but care has to be taken to avoid nucleation and major shape change such as width becoming larger than the length. The interesting results not only demonstrate the effectiveness of morphological population balance simulation for protein crystallization but also provide useful knowledge for process optimization and control.