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Hybrid modeling for industrial fermentation processes with an "Intra-Batch Experimental Design".

Marc Lemperle1, Pedram Ramin1, Julian Kager1

  • 1Process and Systems Engineering Center (PROSYS), Department of Chemical and Biochemical Engineering, Technical University of Denmark Søltofts Plads, DK-2800 Kgs. Lyngby, Denmark.

Journal of Industrial Microbiology & Biotechnology
|June 2, 2026
PubMed
Summary
This summary is machine-generated.

This study introduces a new framework for modeling fungal fermentation viscosity, reducing experimental costs and offline measurements. The hybrid model improves process optimization and supports automated model development for industrial applications.

Keywords:
experimental designhybrid modelingindustrial fermentationoxygen transfer rate

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Area of Science:

  • Biotechnology
  • Chemical Engineering
  • Process Systems Engineering

Background:

  • Accurate modeling of oxygen transfer rate is crucial for fungal fermentation optimization.
  • Traditional viscosity models are complex, requiring extensive offline measurements.
  • Digital twins/shadows for fermentation require high-fidelity process models.

Purpose of the Study:

  • To develop a novel, cost-effective framework for modeling fungal fermentation viscosity.
  • To reduce reliance on tedious offline rheological measurements.
  • To integrate online sensor data for improved predictive modeling.

Main Methods:

  • Developed a model for oxygen mass transfer coefficient (kLa) using reduced fermentation runs.
  • Evaluated three machine learning algorithms as soft sensors for online viscosity prediction.
  • Created a hybrid model combining mechanistic and data-driven approaches.

Main Results:

  • Achieved R² of 0.92 with online data vs. 0.67 with offline data for kLa modeling.
  • Reduced experimental effort for kLa model development from nine to two fermentations.
  • Hybrid model accurately predicted fermentation dynamics across various conditions with modest accuracy improvements.

Conclusions:

  • Online sensor integration significantly enhances mathematical model development.
  • The proposed framework lowers costs and effort for model development.
  • This work advances automated model development for industrial fermentation processes.