Biphasic culture strategy for enhancing volumetric erythropoietin productivity of Chinese hamster ovary cells

In the case of Chinese hamster ovary (CHO) cells producing erythropoietin (EPO), an optimal EPO production condition (32.5 °C and pH 7.00) was quite different from an optimal growth condition (37 °C and pH 7.20). When cells were cultivated at the two culture conditions, the EPO production at the optimal EPO production condition was approximately 3.1-fold higher than that at the optimal growth condition. However, reduced cell growth rate at the optimal EPO production condition led to only 1.2-fold increase in the volumetric productivity, compared to the optimal EPO growth condition. A biphasic culture strategy, which is composed of cell growth and EPO production phases, was applied to increase the volumetric EPO productivity. Compared with the monophasic culture at the optimal EPO production condition, a 1.4-fold increase in the volumetric productivity was achieved in the biphasic culture at a shifting time of 2 days post-inoculation. Thus, a biphasic culture strategy was found to be an efficient means to increase the volumetric EPO productivity of rCHO cells with different optimal growth and EPO production conditions.