Control of pH in large-scale, free suspension animal cell bioreactors: alkali addition and pH excursions.

It is likely that, in the future, animal cell cultures of a higher cell density and/or cell lines with higher specific oxygen demands will be available. Such developments will lead to the need for improved homogeneity in the bioreactor and a greater supply of nutrients. The accompanying significant increase in CO(2) production and accumulation and the resulting reduction in pH are also important implications for process engineering. Such pH reduction is typically controlled by the addition of sodium carbonate. Previous studies using flow visualization mimicking the operating conditions in a typical plant-scale reactor showed potentially cell-damaging regions within it due to pH excursions. This paper confirms the existence of these excursions by pH measurements in the alkali addition zone. It also identifies the accumulation of alkali in a region of poor local liquid homogenization as a serious scale-up problem and shows how a change in the addition point significantly reduces it. Copyright 1999 John Wiley & Sons, Inc.