Bringing a scalable adaptive hybrid modeling framework closer to industrial use: Application on a multiscale fungal fermentation

Thomas Rydal, Jesper Frandsen, Gisela Nadal-Rey, Mads Orla Albæk, Pedram Ramin*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


Digitalization has paved the way for new paradigms such as digital shadows and digital twins for fermentation processes, opening the door for real-time process monitoring, control, and optimization. With a digital shadow, real-time model adaptation to accommodate complex metabolic phenomena such as metabolic shifts of a process can be monitored. Despite the many benefits of digitalization, the potential has not been fully reached in the industry. This study investigates the development of a digital shadow for a very complex fungal fermentation process in terms of microbial physiology and fermentation operation on pilot-scale at Novonesis and the challenges thereof. The process has historically been difficult to optimize and control due to a lack of offline measurements and an absence of biomass measurements. Pilot-scale and lab-scale fermentations were conducted for model development and validation. With all available pilot-scale data, a data-driven soft sensor was developed to estimate the main substrate concentration (glucose) with a normalized root mean squared error (N-RMSE) of 2%. This robust data-driven soft sensor was able to estimate accurately in lab-scale (volume < 20× pilot) with a N-RMSE of 7.8%. A hybrid soft sensor was developed by combining the data-driven soft sensor with a mass balance to estimate the glycerol and biomass concentrations on pilot-scale data with N-RMSEs of 11% and 21%, respectively. A digital shadow modeling framework was developed by coupling a mechanistic model (MM) with the hybrid soft sensor. The digital shadow modeling framework significantly improved the predictability compared with the MM. The contribution of this study brings the application of digital shadows closer to industrial implementation. It demonstrates the high potential of using this type of modeling framework for scale-up and leads the way to a new generation of in silico-based process development.
Original languageEnglish
Article number1609-1625
JournalBiotechnology and Bioengineering
Issue number5
Publication statusPublished - 2024


  • Data-driven modeling
  • Digitalization
  • Hybrid modeling
  • Industrial fermentation
  • Mechanistic modeling
  • Multiscale fermentation


Dive into the research topics of 'Bringing a scalable adaptive hybrid modeling framework closer to industrial use: Application on a multiscale fungal fermentation'. Together they form a unique fingerprint.

Cite this