Andreas Kocourek

Shaken helical track bioreactors: Providing oxygen to high-density cultures of mammalian cells at volumes up to 1000 L by surface aeration with air

A new scalable reactor was developed by applying a novel mixing principle that allows the large-scale cultivation of mammalian cells simply with surface aeration using air owing to increased liquid-gas transfer compared to standard stirred-tank bioreactors. In the cylindrical vessels (50 mL-1500 L) with a helical track attached to the inside wall, the liquid moved upward onto the track as the result of orbital shaking to increase the liquid-gas interface area significantly. This typically resulted in a 5-10-fold improvement in the volumetric mass transfer coefficient (k(L)a). In a 1500-L helical track vessel with a working volume of 1000 L, a k(L)a of 10h(-1) was obtained at a shaking speed of 39 rpm. Cultivations of CHO cells in a shaken 55-L helical track bioreactor resulted in improved cell growth profiles compared to control cultures in standard systems. These results demonstrated the possibility of using these new bioreactors at scales of 1000 L or more.

Helical Tracks in Shaken Cylindrical Bioreactors Improve Oxygen Transfer and Increase Maximum Cell Density Obtainable for Suspension Cultures of Mammalian Cells

The introduction of a helical track into a cylindrical vessel, orbitally shaken on a horizontal platform, showed a considerable improvement in the volumetric mass transfer coefficient (kLa). In helical track vessels from 50 ml to 1000 L, compared with identically dimensioned cylindrical vessels, an almost 10 fold increase of kLa was observed for some conditions. On-line dissolved oxygen (DO) measurement in a high density cell culture of CHO DG44 cells using 1 L helical track vessels demonstrated that the DO remained above 50% with the viable cell density reaching 2.0 × 107 cells ml–1. These results suggest that helical tracks within orbital shaking reactors provide significant benefits over standard cylindrical vessels and open the possibility of using this principle for large-scale shaken bioreactors of 1000 L or more.