Estimation of dissolved carbon dioxide stripping in a large bioreactor using model medium

Area of Science:

• Biotechnology
• Bioprocess Engineering
• Cell Culture Technology

Background:

• Accumulation of dissolved carbon dioxide (dCO(2)) poses a significant challenge during the scale-up of industrial cell cultures.
• Effective management of dCO(2) is crucial for maintaining optimal cell culture conditions and ensuring process efficiency.
• Predictive models are needed to understand and control dCO(2) levels across different scales and operating parameters.

Purpose of the Study:

• To develop and evaluate a model medium for estimating dissolved carbon dioxide stripping in industrial cell culture scale-up.
• To assess the influence of various operational parameters and bioreactor scales on dCO(2) stripping efficiency.
• To provide a reliable method for predicting dCO(2) behavior in real culture media.

Main Methods:

• A model medium was prepared with adjusted physicochemical properties (pH, density, viscosity, surface tension, buffer capacity) to mimic real culture media.
• Experiments were conducted across different bioreactor scales (80 L, 500 L, 2000 L) and operational parameters (sparging and agitation rates).
• Dissolved carbon dioxide stripping efficiency was quantified using the volumetric carbon dioxide transfer coefficient, k(L)a(CO2).

Main Results:

• The model medium demonstrated dCO(2) stripping behavior analogous to actual cell culture media under all tested conditions.
• The k(L)a(CO2) index effectively characterized dCO(2) stripping efficiency across various scales and operational settings.
• The model medium proved to be a reliable surrogate for real culture media in assessing dCO(2) stripping.

Conclusions:

• The developed model medium provides a valuable tool for predicting dissolved carbon dioxide stripping in industrial cell cultures.
• This approach facilitates the optimization of bioreactor design and operating conditions during scale-up.
• Utilizing this model medium can significantly aid in determining appropriate culture conditions for successful large-scale cell cultivation.