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Updated: May 28, 2026

Process Optimization using High Throughput Automated Micro-Bioreactors in Chinese Hamster Ovary Cell Cultivation
Published on: May 18, 2020
Overcoming challenges in WAVE Bioreactors without feedback controls for pH and dissolved oxygen
Inn H Yuk1, Dinesh Baskar, Philip H Duffy
1Early Stage Cell Culture, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA. inn@gene.com
This study presents a simplified method for culturing Chinese hamster ovary (CHO) cells in a WAVE Bioreactor without pH or dissolved oxygen (DO) probes. The optimized process ensures comparable cell growth and viability to traditional bioreactors, offering a cost-effective solution.
Area of Science:
- Biotechnology
- Bioprocess Engineering
- Cell Culture Technology
Background:
- The biopharmaceutical industry increasingly utilizes disposable bioreactors like the WAVE Bioreactor.
- Real-time pH and dissolved oxygen (DO) monitoring and control are common features, but add complexity and cost.
- Developing a simplified culture process without these controls is desirable.
Purpose of the Study:
- To develop a process for culturing Chinese hamster ovary (CHO) cells in a WAVE Bioreactor without relying on pH and dissolved oxygen (DO) feedback controls.
- To characterize oxygen (O2) and carbon dioxide (CO2) transfer within the WAVE Bioreactor system under varying parameters.
- To establish a cost-effective and simplified cell culture method.
Main Methods:
- Characterized O2 and CO2 transfer in the WAVE Bioreactor using cell-free studies.
- Identified key parameters influencing O2 transfer (rock rate, rock angle) and CO2 transfer/pH (incoming gas CO2 concentration, gas flow rate).
- Employed a full-factorial design to evaluate the impact of rock rate, rock angle, and gas flow rate on cell growth and pH profiles for CHO cell lines.
Main Results:
- Identified rock rate, rock angle, incoming gas CO2 concentration, and gas flow rate as critical parameters for O2 and CO2 transfer.
- Achieved comparable cell growth and pH profiles across tested ranges of these parameters for two CHO cell lines.
- Maintained desired pH (6.8-7.2) and DO (>20% air saturation) for six CHO cell lines.
- Demonstrated comparable cell growth and viability to stirred-tank bioreactors with online pH and DO control.
Conclusions:
- A simplified WAVE Bioreactor process without pH and DO probes is feasible for CHO cell culture.
- Optimized control of gas transfer parameters (rock rate, angle, flow, CO2 concentration) effectively manages pH and DO.
- This approach offers a more cost-effective and simpler alternative to traditional bioreactor setups.
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