Crystal Breakage of Mechanically Labile Protein Crystals in the Field of Mechanical Solid-Liquid Separation

The market demands for proteins to catalyze reactions is increasing worldwide. A common advantage in using proteins to catalyze chemical reactions is their ability to convert substances in an enantiomerically pure form. The purification of proteins requires several methods from the field of solid-liquid separation and thermal process engineering like the selective crystallization of the target protein. A successful preparative protein crystallization step does not only increase the purity but also serves as a formulation step. The further processing of the protein crystals with mechanical solid-liquid separation requires special care. Protein crystals are built up by large molecules and have a high crystal water content. Therefore, these crystals have less mechanical strength compared to conventional organic or inorganic crystals. For solid-liquid separation, this means that filtration and centrifugation of the crystallizate may lead to crystal breakage. In the early development stages, the available amount of protein crystal suspension is limited. To allow an early characterization of the filtration behavior, a downscaled filtration setup is presented in this chapter and used to characterize four different protein crystal systems. Furthermore, the ability to apply the small scale results to a larger filtration device is shown. Finally, the breakage behavior of the protein crystals has to be considered carefully. Many devices induce normal and shear stress on the crystal suspension. The results show, that especially the combination of normal and shear stress leads to a strong comminution, even at low pressures and shear velocities.