Effective bioreactor pH control using only sparging gases

Area of Science:

• Biotechnology
• Biochemical Engineering
• Cell Culture Technology

Background:

• pH control is crucial for bioreactor performance, often relying on CO2 sparging and base addition.
• Base addition can negatively impact cell culture by increasing osmolality and causing pH excursions, especially in large-scale operations.

Purpose of the Study:

• To assess the feasibility of using sparge gas composition control for pH regulation in Chinese hamster ovary (CHO) fed-batch cultures.
• To evaluate fine pH control strategies in small-scale bioreactors and demonstrate scalability.

Main Methods:

• Implemented a feedback control loop adjusting air sparge composition for pH regulation.
• Conducted experiments in ambr®250 bioreactors with Chinese hamster ovary (CHO) cells at various pH setpoints.
• Validated the control strategy's effectiveness and scalability from benchtop (ambr®250) to pilot scale (200 L).

Main Results:

• Successfully maintained desired culture pH setpoints using air sparge feedback control.
• Demonstrated that increased air sparging effectively removes CO2, thereby increasing culture pH, and vice versa.
• Confirmed the seamless transferability and scalability of the air sparge control method.

Conclusions:

• Controlling sparge gas composition is a viable alternative to base addition for pH control in bioreactors.
• This air sparge strategy offers precise pH management and is scalable for industrial bioprocessing, potentially improving culture performance.