Euler-Lagrangian Simulations: A Proper Tool for Predicting Cellular Performance in Industrial Scale Bioreactors

Area of Science:

• Bioprocess Engineering
• Computational Fluid Dynamics
• Cellular Biology

Background:

• The Eulerian-Lagrangian approach has gained prominence in bioprocesses over the last decade.
• It is recognized as a potent tool for addressing bioprocess scale-up and scale-down challenges.
• This method offers a way to track individual cell histories and their microenvironments within bioreactors.

Purpose of the Study:

• To introduce the fundamental principles of the Eulerian-Lagrangian method for investigating cellular responses in bioreactors.
• To illustrate practical aspects of the particle tracking technique within this framework.
• To discuss the advantages and challenges of employing this approach in bioprocess analysis.

Main Methods:

• Eulerian-Lagrangian approach for simulating multiphase flow.
• Particle tracking techniques to represent individual cells or cell groups.
• Digital twin technology for bioreactor simulation.
• Analysis of substrate and product gradients, and high-shear regions.

Main Results:

• The Eulerian-Lagrangian method can capture the historical environmental conditions experienced by cells.
• It provides insights into physical and biological timescales, linking them through cell lifelines.
• Digitalization of bioreactors enables the reproduction of critical microenvironmental factors like gradients and shear stress.

Conclusions:

• The Eulerian-Lagrangian approach, coupled with particle tracking, offers a comprehensive method for understanding cellular behavior in bioreactors.
• It bridges the gap between cellular biological responses and the physical environment of the bioreactor.
• This methodology enhances bioprocess control, design, and strain engineering by revealing cell-specific environmental data.