Fluctuations in continuous mammalian cell bioreactors with retention

Area of Science:

• Biotechnology
• Biochemical Engineering
• Cell Culture Technology

Background:

• Continuous flow bioreactors with cell retention are increasingly utilized for mammalian cell cultivation.
• These systems offer potential for high cell concentrations and volumetric productivities.
• Observed fluctuations in cell concentrations present challenges in system operation and analysis.

Purpose of the Study:

• To analyze the dynamics of cell concentration fluctuations in continuous flow bioreactors with cell retention.
• To identify operational parameters influencing biomass variability.
• To provide insights for stabilizing these bioreactor systems.

Main Methods:

• A model-based approach was employed to simulate bioreactor dynamics.
• Simulations investigated the impact of retention ratio fluctuations at high dilution rates.
• Cross-correlation statistical analysis was performed on experimental data to assess parameter dependence.

Main Results:

• High dilution rates and high cell retention amplify biomass fluctuations in response to retention ratio variations.
• Cell concentration fluctuations are significantly dependent on dilution rate and retention ratio.
• Continuous culture without retention exhibits slower dynamics and is less prone to fluctuations.

Conclusions:

• Continuous culture with cell retention can be stabilized by precise control of both retention ratio and dilution rate.
• Understanding fluctuation dynamics is crucial for optimizing mammalian cell cultivation in bioreactors.
• The findings suggest that continuous culture without retention may be more suitable for kinetic studies.