Chapter 12 - Alternative Separation Methods: Crystallization and Aqueous Polymer Two-Phase Extraction

Abstract

As with many other alternative separations methods, crystallization and aqueous polymer two-phase extraction (ATPE) have been well-studied academically and are amenable to predictive and process modeling. Their solution nature allows them to be optimized using high-throughput microtiter plate-based methodologies. Their liquid nature allows them to be readily scaled and, in comparison with some other separation methods, they do not require overt energy use or capital investment. Crystallization is a well-established industrial method whose application for purifying bio-macromolecules presents interesting challenges. It typically requires reasonably concentrated and quite pure target-containing solutions and its operation can require days. The resulting crystals can be very pure, and in some cases, may be suitable for use as drug product, drug storage, or even as drug-delivery colloids. ATPE can rapidly effect preliminary clarification, target concentration, and some reduction in host cell proteins, toxins, nucleic acids, and other contaminants. As noted in previous chapters, and discussed in more detail in this chapter, it is perhaps best employed upstream of other selective operations that might include chromatography or crystallization.