Pilot-scale verification of a computer-based simulation for fractional protein precipitation

Abstract

The development and experimental verification at pilot scale of a suite of models for the batch precipitation by two-cut ammonium sulphate salting-out of total protein and alcohol dehydrogenase from yeast homogenate is presented. The model consists of two elements: protein and enzyme solubility prediction and precipitate phase particle property prediction. An isotherm-based approach has been used successfully to describe solubility behaviour for a range of operating conditions typical of those obtained at a process scale. Estimation of the precipitate phase particle size distributions has been achieved through a discretized population balance approach using simplified terms to account for particle breakage and aggregation. The developed model accounts for the effects of average shear rate and residence time in the precipitation vessel across a two orders of magnitude range of scale. The size-density relationship for the precipitate phase has been defined. Results of simulations are compared with pilot scale verification data to confirm the validity of the models developed.