Precipitation and Crystallization

Abstract

Precipitation and crystallization are the two downstream operations wherein a biomolecule in solid phase is formed from an aqueous solution. Despite their similarity in concept, they differ in objective and procedure: precipitation occurs at the beginning of the purification train and usually results in an amorphous solid, while crystallization is a final downstream-processing operation, conducted with specific control of thermodynamic and kinetic variables. This article presents an overview of these operations, focusing on the fact that both are solid–liquid equilibrium operations. Solid–liquid diagrams, which are the basis for both operations, are presented and analyzed, showing how specific information on the solid phase can be obtained from them. The modeling of solid–liquid equilibrium may be carried out through either thermodynamic activity models or osmotic pressure equations, and both procedures are presented. While similar to precipitation, crystallization can be achieved only through specific control of supersaturation and crystal rate formation, and these are presented in a separate section.