HOMOGENIZATION AND OXYGEN-TRANSFER RATES IN LARGE AGITATED AND SPARGED ANIMAL-CELL BIOREACTORS - SOME IMPLICATIONS FOR GROWTH AND PRODUCTION

Because of concern for cell damage, very low agitation energy inputs h ave been used in industrial animal cell bioreactors, typical values be ing two orders of magnitude less than those found in bacterial ferment ations. Aeration rates are also very small. As a result, such bioreact ors might be both poorly mixed and also unable to provide the higher o xygen up-take rates demanded by more intensive operation. This paper r eports experimental studies both of k(L)a and of mixing (via pH measur ements) in bioreactors up to 8 m(3) at Wellcome and of scaled down mod els of such reactors at Birmingham. Alongside these physical measureme nts, sensitivity of certain cell lines to continuously controlled dO(2 ) has been studied and the oxygen up-take rates measured in representa tive growth conditions. An analysis of characteristic times and mixing theory, together with other recent work showing that more vigorous ag itation and aeration can be used especially in the presence of Pluroni c F-68, indicates ways of improving their performance, pH gradients of fer a special challenge.