Partial and total cell retention in a filtration-based homogeneous perfusion reactor

Suspended mammalian cells can be cultivated in a variety of operational modes (pure chemostat, total cell retention, or partial cell retention) in a homogeneous perfusion bioreactor by varying the cell bleed rate. Hybridomas were grown in the reactor at a perfusion rate of 2.0 day-1 for over 10 weeks at different specific growth rates and viable cell densities achieved by varying the extent of cell retention. Cell metabolism in the reactor was found to vary with the extent of cell retention, which determined both cell density and specific growth rate. With partial cell retention, the nutrient consumption and metabolite production rates decreased with both increasing growth rate and increasing cell density. The specific and volumetric antibody production rates, however, increased dramatically with cell density (and to a lesser extent with decreasing growth rate). The specific MAb production rate was lower with total cell retention than with partial retention at the same growth rate. Since the reactor can be operated over a range of perfusion rates and extents of cell retention, the system can be used to culture cell lines with widely different productivity patterns.