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Rheology of CHO Cell Suspensions and Its Effects on High-Density Cultivation Process and Bioreactor Design
Botao Zhang1, Xinran Zhang1, Qingyuan Ran1
1State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Biotechnology Journal
|March 18, 2025
Summary
Understanding Chinese hamster ovary (CHO) cell suspension rheology is key to optimizing monoclonal antibody production. This study reveals how cell density impacts viscosity and mass transfer in bioreactors, crucial for efficient cell cultivation.
Area of Science:
- Biotechnology
- Bioprocess Engineering
- Cell Culture Technology
Background:
- Optimizing monoclonal antibody (mAb) production relies on efficient Chinese hamster ovary (CHO) cell cultivation.
- Shear stress and mass transfer are critical bioreactor parameters, yet CHO cell suspension rheology's impact is understudied.
Purpose of the Study:
- Investigate factors influencing CHO cell suspension rheology.
- Evaluate the impact of rheology on bioreactor performance, specifically shear stress and mass transfer.
- Develop correlations for optimizing high-density and ultra-high-density CHO cell cultivation.
Main Methods:
- Investigated factors affecting CHO cell suspension rheology, focusing on cell volume fraction (Φ).
- Characterized rheology using the Sisko model.
- Employed computational fluid dynamics (CFD) simulations to assess rheological impact on bioreactor performance.
Main Results:
- Cell volume fraction (Φ) significantly influences shear-thinning behavior and viscosity; higher Φ weakens shear-thinning and increases viscosity.
- Bioreactor simulations showed rheology leads to increased shear stress and a 10%-40% reduction in volumetric mass transfer coefficient (kLa).
Conclusions:
- CHO cell suspension rheology critically affects bioreactor performance and cannot be ignored in parameter design.
- Established empirical correlations (Pg/V, Vg, Φ, kLa) to guide operating parameter selection for high-density cultures.
- Provides a foundation for optimizing CHO cell cultivation, bioreactor design, and scale-up strategies.
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