Accelerating animal cell growth in perfusion mode by multivariable control: simulation studies

Area of Science:

• Biotechnology
• Chemical Engineering
• Cell Culture Technology

Background:

• Continuous hybridoma cell cultures are vital for monoclonal antibody production.
• Optimizing perfusion and bleed flow rates is crucial for efficient bioprocessing.
• Achieving fast transient start-up and disturbance rejection remains a challenge.

Purpose of the Study:

• To develop an optimal control strategy for perfusion and bleed flow rates in hybridoma cell continuous culture.
• To achieve rapid transient start-up and effective rejection of disturbances.
• To enhance the overall performance and robustness of the cell culture process.

Main Methods:

• Analysis of steady-state solutions of the nonlinear dynamic model of cell culture.
• Investigation of the relationship between key substrates: glucose and glutamine.
• Implementation of an extended prediction self-adaptive control (EPSAC) strategy.

Main Results:

• The proposed control strategy effectively manipulates perfusion and bleed flow rates.
• Simulation results show potential for fast transient start-up.
• The approach demonstrates capability in rejecting process disturbances.

Conclusions:

• Optimal manipulation of flow rates based on steady-state analysis and adaptive control is feasible.
• The developed method offers a promising approach for improving hybridoma cell culture performance.
• This strategy can lead to more robust and efficient biomanufacturing processes.