Membrane-based crystallization of biomolecules

Crystallization of biomolecules is a cost-effective technique that can potentially play a crucial role in downstream processing of pharmaceutical active ingredients (API), including proteins. In this field, membrane-based crystallization is today recognized as a promising method for the production of API with controlled shape, size distribution and polymorphic form. Extension to monoclonal antibodies (mAbs) purification as substitute for a chromatographic (Protein A) process step is today under investigation [1]. According to this innovative technology, membranes are used: (i) to promote mass transfer for a better control of supersaturation (the driving force for crystallization); (ii) to activate heterogeneous nucleation by decreasing the Gibbs free energy barrier to the formation of critical nuclei [2,3]. The impact of physico-chemical properties of microporous hydrophobic polymeric membranes on the nucleation rate of HEW Lysozyme and other protein models, the evidence of polymorphic selection of amino acids and biological molecules as a function of process parameters, and the ability to promote specific intermolecular interactions inducing preferred spatial orientations of solute molecules in proximity of polymeric films are presented.