Liquid Homogenization Studies in Animal Cell Bioreactors of up to 8 m3 in Volume

Reactor Engineering in Large Scale Animal Cell Culture

“…First, the use of alkaline solutions to prevent excessively high values of pH due to pCO 2 in the latter stages of a fed-batch cultivation will be considered. Again, data from work on the 8 m 3 bioreactor using a 2/9 T Rushton turbine at a clearance off the base of 2/9 T, as discussed above, are the only ones available from a commercial scale vessel Langheinrich et al 1998) though similar results from a 2 m 3 airlift bioreactor have also been reported (Wayte et al 1997). Mixing time measurements alone were found to fit quite well with Eqs.…”

“…Po g is generally less than Po, and often significantly so for the aeration rates used in bacterial and mycelial fermentations (Nienow 1998). However, at the relatively very low air flow rates used in animal cell culture to date, Po g % Po (Langheinrich et al 1998). Nevertheless, the relationship between Po g and Po impacts on impeller selection (Nienow 1998;Nienow and Bujalski 2004) as discussed later.…”

“…Equation (10) was originally developed for multiple impellers but it has been shown also to indicate the great sensitivity of mixing time to fill height in 8 m 3 animal cell culture bioreactors Langheinrich et al 1998) of aspect ratio 1.3 with a single impeller working in the draw and fill mode. Thus, if agitation conditions are chosen, via a dO 2 process control loop, for example, to satisfy the oxygen demands of the system across the scales as discussed above, i.e., ð" e T Þ g is held constant or reduced, the degree of homogeneity as indicated by the mixing time gets significantly worse, especially at high aspect ratios.…”

“…Mixing time measurements alone were found to fit quite well with Eqs. (9) and (10), though the energy dissipation from the sparged air did have to be taken into account (Langheinrich et al 1998) in order to correlate the data.…”

“…However, recently, it has been reported that commercial bioreactors of 20,000 L or so have been commissioned at Lonza (Hoeks et al 2004) and Genentech (Meier 2005). These bioreactors and others are generally operated in the fed batch or draw and fill mode (Langheinrich et al 1998) in order to reach high cell densities. Another approach to achieving high cell densities is to use cell retention techniques, e.g., spin filters, and the use of external recycling and cell separation to achieve retention at the industrial pilot scale has been reported by Wyeth (Moran 2004).…”