Design of Protein Crystallization Processes Guided by Phase Diagrams

Abstract

Many proteins including pharmaceuticals and industrial enzymes, after separation and purification, are high-value-added products. In this study, a general framework based on solid liquid equilibrium (SLE) phase diagrams for the conceptual design of protein crystallization processes is proposed. First, the coordinates for phase diagrams involving proteins are defined. Second, relevant regions of the phase diagram are determined by experiments. Finally, process synthesis is performed by visualizing the process paths on the phase diagram. This approach is demonstrated with two case studies. One is the design of a lysozyme recovery process in which salt-lean lysozyme solids are recovered from a lysozyme–sodium chloride solution. The other is the design of a process for separating lysozyme and ovalbumin in the presence of ammonium sulfate. The former design is in agreement with patent literature, and the latter design was verified with experiments. Thus, the feasibility of designing protein crystallization pro...