Entwicklung eines neuartigen Staustrahl-Membranreaktors zur blasenfreien Begasung von Zellkulturen

Abstract

A novel ramjet membrane reactor was designed for the special requirements of cell cultures. It could demonstrate its suitability through numerous both theoretical-numerical and experimental studies. Instead of using rotating elements, mixing of the culture broth is achieved by means of a reciprocating disc-package. The discs are equipped with silicone membranes for bubble-free aeration and are connected to the air supply via the shaft. The special arrangement of through-holes in each disc, together with an up and down motion of the package leads to a periodical rebuilding of fluid jets and vortex flow within the cell suspension. Thus, bubble-free aeration and a homogeneous mixing of the reactor volume is performed by the moving membrane package at the same time. The ramjet membrane reactor can easily be scaled-up. Due to the arrangement of the discs and its periodically vertical movement instead of rotation, the reactor volume can be regarded as a parallel and serial connection of small-sized so called elementary cells. Therefore, the reactor size can be increased by just augmenting the number of elementary cells, keeping constant all parameters relevant for momentum and mass transfer. Numerical investigation of the flow field was done by means of Computational Fluid Dynamics, CFD. The results of the calculation have shown that the local turbulent energy dissipation rate — the critical quantity in animal cell cultivation — reaches a maximum value of emax = 1, 2m2/s3 at a lifting frequency of f = 0, 5 s−1, which is significantly smaller than critical values of ecrit ≈ 20 . . . 80 m2/s3 as reported to cause damage to animal cells. Even at f = 1 s−1, the maximum energy dissipation rate of emax = 7, 4 m2/s3 is very low. Therefore, damage of cells due to hydrodynamic stress is not expected in the ramjet membrane reactor. Based on the flow field, oxygen transfer was investigated by means of CFD, too. At the highest regarded lifting frequency of f = 2 s−1, the maximum oxygen transfer rate and the mass transfer coefficient was determined to OTRmax = 62 mgO2/Lh and kl = 6, 7 · 10−5 m/s, respectively. In an examplary cultivation with the insect cell line Spodoptera frugiperda SF21, the applicability of the ramjet membrane reactor was demonstrated. Cultivation was carried out in a 10-L-scale and resulted in a maximum viable cell density of 6, 1 · 106 cells/ml compared to 1, 5 · 105 cells/ml at the beginning of the experiment. The novel ramjet membrane reactor fulfills all demands of cell culture techniques. Especially concerning the scale-up properties, it promises an advantage over common bubble-free areated reactor systems.