ANIMAL-CELL CULTURE IN STIRRED BIOREACTORS - OBSERVATIONS ON SCALE-UP

The scale-up of stirred tank bioreactors from 0.02 m3 to a 0.3 M3 comm ercial plant is discussed for hybridoma suspension cultures. Schemes f or dissolved oxygen control with sparged air in serum containing media are described, as well as mechanical breakage of foam in small and la rge bioreactors. Porous metal spargers (180-200 x 10(-6) m) were found to produce foams which were hard to control. Aeration with larger (gr eater-than-or-equal-to 0.001 m) multihole spargers is recommended Comb ined cell damage due to foam formation and control, and possible damag e at mechanical seals or submerged bearings, were found to have no mea surable effect on cell growth relative to roller bottle production. Hy bridomas are shown to withstand significant impeller tip speed (> 1 m s-1) and fluid turbulence as evidenced by impeller Reynolds numbers in excess of 10(5). The size of the energy-dissipating terminal eddies w as calculated to be greater than ten-fold that of the hybridoma cells. The specific fluid turnover rate was employed as the scale-up criteri on.