Influence of medium composition on oxygen transfer rate in animal cell culture

Abstract

Experiments were conducted in a 0.25 m diameter bubble column to investigate the effect of animal cell culture medium composition on oxygen transfer rate. Air is used as the dispersed phase. The gas superficial velocity is varied between 0.4 and 2 cm/s (aeration rate ranging between 0.05 and 0.25 vvm) and the bubble column is thus operated in the homogenous regime.Aqueous solutions the composition (electrolyte, protein concentrations) of which mimics a mammalian cell culture medium) are used as the continuous phase. In particular, the effect on oxygen transfer rate of additive such as PVP, Pluronic F-68 which are usually used to protect cells against local hydrodynamic stresses induced by bubble coalescence and bursting is addressed. For each composition, the mass transfer coefficient is measured by the "gas in -gas out" method using a fast response dissolved oxygen probe. Its increase with gas velocity is measured. The liquid viscosity and surface tension are experimentally determined as a function of culture medium composition. Bubble size distribution is measured at different scales using three experimental techniques: gas disengagement technique, two dual optical probes and photography, which lead to results in good qualitative agreement one with each other. The integrated analysis of these data allows to decouple the effects of the different additive on coefficient k L and on the interfacial area, a.

Oxygen Uptake Rate Soft-Sensing via Dynamic kLa Computation: Cell Volume and Metabolic Transition Prediction in Mammalian Bioprocesses

“…Stirred tank reactors (STRs) are currently the most widely used bioreactor type to cultivate aerobic organisms in suspension culture or on carriers. In aerobic upstream bioprocesses, the oxygen uptake rate (OUR) is crucial for cellular activity and a good indicator of changes in the metabolic state of the culture (Deshpande and Heinzle, 2004; Wahrheit et al, 2015), which can be induced by changing substrate availabilities (Toye et al, 2010; Niklas et al, 2011; Young, 2013; Zhang et al, 2016). Thus, in the context of implementing Quality by Design and Process Analytical Technology (QbD/PAT) in bioprocesses, the OUR could be an informative process indicator (Sommeregger et al, 2017).…”

Influence of pluronic F68 on oxygen mass transfer

“…In addition, some of the conclusions described in literature are contradictory regarding the effect of Pluronic F68 on mass transfer. Some authors have reported a reduction, while others reported a significant increase of mass transfer in their studies . In several cases, a mixture of media components, known to have an influence on surface tensions and viscosity, were tested, and therefore the effect of Pluronic F68 and other surface‐active components on mass transfer could not be differentiated.…”