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Hydrodynamic Stress and Heterogeneities in Animal Cell Culture

L. A. Palomares,O. Ramírez

Published 2019 in Comprehensive Biotechnology

ABSTRACT

Abstract The importance of hydrodynamic stress for animal cell culture has shifted from the most important factor in the 1970s and 1980s, to an additional parameter that should be considered during scale up. While in the beginning the most significant concern was cell death, now the importance of sublethal effects has been recognized. Sublethal effects influence productivity and product quality. Sensitivity of animal cells to the energy dissipation rate originating mostly from bubble bursting, has limited mass transfer in the bioreactor, causing the accumulation of carbon dioxide with several effects on the culture. As scale increases, both by increasing culture volume and by increasing cell concentration to several tens of millions per mL, mixing becomes challenging and heterogeneities can arise. As a consequence, cells are exposed to transient environmental conditions that influence their physiology and performance. A solution is the addition of shear protectants, that have allowed to increase mass transfer rates and mixing efficiency without damaging cells. Here, recent advances and the current point of view on hydrodynamic stress and mixing in animal cell culture bioreactors are presented and discussed.

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