Cell Damage of Microcarrier Cultures as a Function of Local Energy Dissipation Created by a Rapid Extensional Flow

Microcarrier cultures of Chinese hamster ovary cells were subjected to a range of energy dissipations created by an abrupt contraction. These flow conditions can be characterized as a rapidly transient, extensional, and shear flow. Cell damage was measured using a lac- tate dehydrogenase assay. The laminar flow in the de- vice was modeled using two commercial, computation fluid-dynamic codes: POLYFLOW and FLUENT. Cell dam- age was correlated to numerical values of energy dissi- pation. The magnitude of energy dissipation at which cell damage began to be detected, 10 4 ergs cm ˛3 s ˛1 (10 4 cm 2 s ˛3 ), is consistent with values of energy dissipation esti- mated in bioreactors operated under conditions which result in cell damage. This magnitude of energy dissipa- tion is orders of magnitude lower than those values re- ported to cause damage to suspended animals cells which is also consistent with generally accepted experi- mental observations. Finally, an analysis and discus- sion of the presence and relative importance with re- spect to cell damage of shear vs. extensional flow is in- cluded. © 2000 John Wiley & Sons, Inc. Biotechnol Bioeng 69: 171-182, 2000.