Unified modeling framework of cell death due to bubbles in agitated and sparged bioreactors

A modeling framework is proposed to assess the detrimental effects of air sparging and other bubble phenomena (vortex entrainment, coalescence, bursting) on freely suspended cells in an aerated, agitated bioreactor. It is assumed that cells may be rendered nonviable by bubble breakup/coalescence within the medium, by bubble formation at the sparger, or by bubble bursting at the free surface. Some plausible mechanisms are argued from the energetic view point. The dominant parameters in each case are the cell-bubble encounter rate and the bubble breakup/bursting rate. These inactivation processes lead to a Michaelis-Menten expression for the specific cell death rate, which is shown to be linearly proportional to the specific bubble interfacial area (total bubble surface area per unit volume of media). By using published viable cell concentration data for retarded growth of mammalian cells due to sparging, the interfacial area correlation is demonstrated. The method is generalized to aerated bioreactor conditions. The article offers a unique, consistent perspective on how cell death can be viewed.