Continuous Spherical Crystallization of Lysozyme in an Oscillatory Baffled Crystallizer Using Emulsion Solvent Diffusion in Droplets

Abstract

Continuous protein crystallization is a cost-effective alternative to traditional chromatographic purification techniques. However, proteins characteristically have slow growth rates, requiring long crystallization times to generate particles large enough for efficient isolation. In this work, spherical crystallization using an emulsion solvent diffusion (ESD) based methodology is proposed to produce large lysozyme agglomerates in an oscillatory baffled crystallizer (OBC). Process sensitivity analysis was performed to investigate the effect of the process parameters on the product’s crystal size distribution at two different scales. The concentration of ethanol in the bulk phase was found to have a significant effect on the crystallization kinetics, as its diffusivity drives supersaturation at the droplet interface. Although controlling supersaturation is important in determining product quality, maintaining droplet suspension near the injection site is critical for process longevity, as fouling is most l...