Developing rational scale-down simulators for mimicking substrate heterogeneities based on cell lifelines in...

Area of Science:

• Biotechnology
• Biochemical Engineering
• Cellular Metabolism

Background:

• Extracellular variations significantly impact cellular metabolism and large-scale bioprocess performance.
• Accurately mimicking cell lifelines (flow paths and experiences) in large bioreactors using scale-down simulators presents a major challenge.
• Understanding these dynamics is crucial for optimizing industrial fermentation.

Purpose of the Study:

• To develop a novel scale-down simulator application (SDSA) that accurately replicates cell lifelines.
• To validate the SDSA's ability to reproduce industrially relevant metabolic regimes at laboratory scale.
• To provide a tool for both educational and research purposes in bioprocess development.

Main Methods:

• Developed a scale-down simulator application (SDSA) based on a black box model and process reaction model for Penicillium chrysogenum.
• Utilized cell lifeline/trajectory data from an industrial-scale fermentor to guide SDSA design.
• Employed a laboratory-scale three-compartment scale-down (SD) system to test the SDSA.

Main Results:

• Successfully reproduced industrial metabolic regimes (substrate excess, limitation, starvation) at the laboratory scale using the SDSA.
• The SDSA accurately mimicked the cell lifelines and metabolic experiences of cells in large-scale bioreactors.
• The SDSA demonstrated the ability to display individual process dynamics within each compartment.

Conclusions:

• The developed SDSA effectively bridges the gap between large-scale bioprocesses and laboratory-scale studies by accurately simulating cell lifelines.
• The SDSA enables the precise reproduction of critical metabolic conditions, facilitating research and optimization of bioprocesses.
• This tool enhances understanding of how individual factors influence overall bioprocess performance, supporting both education and research.