Continuous hybridoma bioreactor: sensitivity analysis and optimal control

Area of Science:

• Biotechnology
• Biochemical Engineering
• Cell Culture Technology

Background:

• Animal cell culture is a mature technology for producing valuable products.
• Current research focuses on optimizing bioreactor design and operating conditions for increased production.
• Monoclonal antibody production is a key application area.

Purpose of the Study:

• To analyze a continuous perfectly mixed bioreactor system with cell recirculation for monoclonal antibody production.
• To evaluate bioreactor sensitivity to control parameters using entropic density.
• To determine the optimal inlet flow profile for maximizing monoclonal antibody yield.

Main Methods:

• Complex analysis involving sensitivity calculus and optimal control computation.
• Utilized a system comprising a continuous bioreactor, cell separator, mixer, and purge.
• Employed a genetic algorithms approach for optimization of the inlet flow profile.
• Introduced and applied the concept of entropic density for sensitivity analysis.

Main Results:

• Identified optimal operating conditions for monoclonal antibody production.
• Demonstrated the effectiveness of a hybrid operating sequence (fed-batch followed by continuous mode).
• Quantified bioreactor sensitivity to control parameters using entropic density.

Conclusions:

• A hybrid fed-batch and continuous operating mode is superior for high monoclonal antibody production.
• Genetic algorithms provide an effective method for optimizing bioreactor operation.
• Entropic density is a valuable metric for assessing bioreactor performance and sensitivity.