The overall approach of the proposed work is to fundamentally understand the mechanisms of cell damage in contrast to the phenomenological/correlation type of approach which has been historically used to address this problem. The proposed approach requires the identification of the processes responsible for cell damage through initial visualization studies. Theoretical and correlational studies are then to be carried out in actual bioreactor operations to confirm that these mechanisms account for the observed cell damage. Once these mechanisms are confirmed, computer simulations of the hydrodynamic events, such as bubble rupture, will be used to determine the actual "strength" or "sensitivity" of cells to hydrodynamic forces.
