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, coalescen ce, bursting) on freely suspended cells in an aerated, agitated biorea ctor. It is assumed that cells may be rendered nonviable by bubble bre akup/ coalescence within the medium, by bubble formation at the sparge r, or by bubble bursting at the free surface. Some plausible mechanism s are argued from the energetic view point. The dominant parameters in each case are the cell-bubble encounter rate and the bubble breakup/b ursting rate. These inactivation processes lead to a Michaelis-Menten expression for the specific cell death rate, which is shown to be line arly proportional to the specific bubble interfacial area (total bubbl e surface area per unit volume of media). By using published viable ce ll concentration data for retarded growth of mammalian cells due to sp arging, the interfacial area correlation is demonstrated. The method i s generalized to aerated bioreactor conditions. The article offers a u nique, consistent perspective on how cell death can be viewed.