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

Scale-up of stirred tank bioreactors from 0.02 m3 to 0.3 m3 commercial plant is discussed for hybridoma suspension culture. Schemes for dissolved oxygen control with sparged air in serum containing media are described as well as mechanical breakage of foam in small and large bioreactors. Porous metal spargers (180-200 x 10(-6) m) are found to produce foams which are hard to control. Aeration with larger (greater-than-or-equal-to 0.001 m) multihole spargers is recommended. Combined cell damage due to foam formation and control, and possible damage at mechanical seals or submerged bearings, are found to have no measurable effect on cell growth relative to roller bottle production. Hybridomas are shown to withstand significant impeller tip speed ( > 1 ms-1) and fluid turbulence as evidenced by impeller Reynolds numbers in excess of 10(5). The size of the energy dissipating terminal eddies is calculated to be > 10-fold that of the hybridoma cells. Specific fluid turnover rate is employed as the scale-up criterion.