Wave bioreactor is a very useful choice for quicker monoclonal antibody production in small institutes. I have a feeling that some clones like “wave”, but some clones did not, espceially when the clone secrets IgG3. The cells either showed low viability, low growth rate or low antibody concentration. We also had bad luck when using wave bioreactor for CHO K1 cells. Can you tell us what physiodynamic mechanisms may influence cell growth of certain cells? Is there any way to control this?

Answer

There are certainly clonal differences in e.g. shear sensitivity or general robustness. The type of recombinant protein should not have a major impact except when expressing receptors or other surface proteins. As with other bioreactors, cells may need adaptation to the agitated environment in a WAVE Bioreactor. Taking special care about equilibrating the bioreactor before inoculum transfer, use of relatively high inoculum concentrations e.g. 4E+05 c/mL and the addition of shear protectants like Pluronic F-68 may help during this phase. Hydrodynamic conditions in the WAVE Bioreactor have been characterized and information is available in the product literature. When transferring from a characterized stirred tank, it is possible to select agitation conditions in the WAVE Bioreactor that result in comparable mixing time and gas transfer rates. This should also be indicative for the shear that cells are exposed to.
When scaling up from a static or shake flask culture and the shear sensitivity of the cell line is not well understood, it is also an option to investigate it in a WAVE Bioreactor by starting at low agitation and increasing it periodically e.g. every two days while cell growth and viability is closely monitored.