| The removal of viruses from biotechnological and blood-related products is critical to assuring product safety and meeting regulatory guidelines. Virus filtration offers an attractive option to clear viruses from bioprocess streams on the basis of size. Virus removal membranes typically feature a multi-layer structure that is uniquely designed to provide the needed virus clearance while allowing high recovery of the desired protein product. The objective of this thesis is to develop a better fundamental understanding of how the underlying membrane structure and operating mode affect the membrane performance, including the role of membrane compaction, protein fouling, and osmotic pressure.; Experimental studies were performed using Millipore's Viresolve 180 membrane, which has an asymmetric structure with a permselective "skin" on top of a more open substructure. Significant compaction of the membrane was observed only when the membrane was used with the skin-side down. However, the membrane permeability in the skin-side up orientation is sensitive to fouling caused by even trace amounts of submicron-sized particles. This type of fouling was not seen with the skin-side down since the substructure acted as a pre-filter.; The filtrate flux and sieving characteristics of the Viresolve 180 membrane are strong functions of operating conditions and membrane orientation. The performance in the skin-side up orientation was determined primarily by protein osmotic pressure effects arising from protein retention due to a tightly packed fouling deposit on the membrane surface. In contrast, the performance in the skin-side down orientation was governed by the resistance of the protein cake that forms within the membrane substructure. These different fouling mechanisms led to large differences in capacity; the capacity in the skin-side down orientation was as much as a factor of 30 greater than that in the skin-side down orientation. A combined cake filtration/osmotic pressure model was developed to describe the performance of the Viresolve 180 membrane, capturing many of the key features observed experimentally. |
