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Centrifugal Separation in Biotechnology Plenary Presentation Wallace Woon-Fong Leung Chair Professor of Innovative Products & Technologies Department of Mechanical Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong email: [email protected] Abstract: Disk-stack and tubular centrifuges have been used to separate soluble and insoluble proteins for biopharmaceutical processing. There are three common host-cell technology platforms, namely yeast, mammalian cells, and bacteria. The first two use the host cells to express extracellular protein, while the latter uses the host cell to express intracellular protein in form of submicron-sized inclusion bodies. For the yeast host-cell process, the first step is to separate yeast cells using centrifugation from dissolved protein, followed by clarification of protein solution product using centrifugation to meet the minimal turbidity requirement. The flow sheet of separating mammalian cells such as Chinese Hamster Ovaries (CHO) cells using centrifuge from the protein product is presented. The key concern is to reduce shear on the cells in the suspension (maintain high cell viability) through gentle feed acceleration to high-speed rotation to effect separation in a centrifuge. The subsequent step is to use a depth filter or microfiltration to clarify the separated liquid product removing any submicron fine solids. It is critical to ensure the centrifuge-filter work together as a system. The flow sheet of processing bacteria bearing protein is to concentrate using centrifugation the bacteria solution followed by lysing the bacteria to release the inclusion bodies. The resultant suspension is reslurried and washed, with the protein-bearing inclusion bodies separated from any impurities by centrifugation until the desired purity is reached suitable for downstream processing. Separation by centrifugation is used extensively in these three host-cell platforms, which is a major application in production of antibotics and intermediate drug substances for the biopharmaceutical market. Other important large-scale centrifugal separation in biotech processes has also been discussed. Finally, throughput and sizing of centrifuge and simulation tools are presented. Keywords: centrifugation, centrifuge, disk-stack, tubular, biopharmaceutical, biotechnology Biography of Prof. Wallace Leung Prof. Wallace Leung is Chair Professor of Innovative Products & Technologies at the Department of Mechanical Engineering at The Hong Kong Polytechnic University, Hong Kong since 2005. He was also Director of the Research Institute of Innovative Products & Technologies between 2005 and 2010 at the university during which he led a team of multidisciplinary experts to develop healthcare and medical devices. Prof. Leung started his filtration and separation career at MIT in the 70’s researching ultrafiltration of protein and lamella sedimentation of slurry containing fine particles. For 6 years, he worked on liquid flow in porous media, respectively, at Gulf Oil and Schlumberger. For 18 years, he led a research team at Bird-Baker Hughes to develop solid-liquid separation technologies including centrifugation and pressure/vacuum filters. He has covered areas including feed acceleration in a centrifuge, sedimentation, cake compaction, effluent liquid discharge. Subsequently, he found Advantech Engineering with focus on biotech separation and kaolin classification. He had researched and successfully developed over 10 technologies and held 36 US patents and many foreign patents on centrifugation. He has written two books Industrial Centrifugation Technology (1998, McGraw-Hill) and Centrifugal Separation in Biotechnology (2007, Academic Press/Elsevier). He was the Chairman of the American Filtration Society in 2000 and also the Chairman of the INDEFI 2000-2004 responsible for organizing the 9th World Filtration Congress held in New Orleans in 2004. His research interest is in centrifugal separation and classification of micron-sized particles and centrifugal separation of biosolids. Recently, he is interested in small-scale rotating devices for enhancing mixing and separation, as well as filtration of submicron aerosols. He received his BS from Cornell, and MS and ScD from MIT all in Mechanical Engineering.