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This study aimed to study the effect of potential large-scale bioreactor environmental heterogeneities during fed-batch culture on the performance of an industrially-relevant GS-CHO cell culture, producing an IgG antibody. Heterogeneity was created by a two-compartment scale-down model, using a well-mixed stirred tank reactor (STR) and plug flow reactor (PFR). A peristaltic pump was used to continuously circulate cell culture from the STR through the PFR. Standard culture parameters were measured and flow cytometry was used to indicate cell viability and mode of cell death. The results essentially fell into two categories: those without circulation and those with it. In all cases with recirculation, whether nutrients and alkali were added into the STR or the PFR, significantly decreased culture duration (\(\sim\)48 hours shorter) and antibody titre (\(\sim\)20% decrease) were found compared to those experiments without circulation. It was impossible to conclude anything concerning the impact of bioreactor heterogeneities. Nevertheless, damage associated with peristaltic pumping has relevance to the many aspects of cell culture processes that require transfer of cells in suspension. The 'squeezing' motion of peristaltic pumps may impose sufficient mechanical stress to have decreased cell culture performance. The high biocompatibility of the materials used suggests long-term incompatibility is less likely. |
