LAPSE:2026.0402
Published Article

LAPSE:2026.0402
Advancing Industrial Fermentation across scales: Model Development, Cost Analysis, and Predictive Control
June 12, 2026
Abstract
The bioprocess industry is actively exploring technologies associated with the fourth industrial revolution, with modeling offering considerable potential for process optimization. Nevertheless, model adoption in industry remains limited. This is partly because model development continues to depend heavily on offline sampling, and because relatively few industrial applications convincingly demonstrate their practical value. This study therefore first examines the benefits of online rheology and online biomass measurements for model development and demonstrates, among other aspects, that online biomass significantly improves model fidelity. The second part examines how electricity prices affect process conditions, a key factor in production, and finds that, contrary to common practice, maximizing all operating parameters is not the most cost-effective strategy. Finally, an insilico framework for model predictive control, applied to a reactor endfill scenario, demonstrates that oxygencontrolled processes can be dynamically optimized, highlighting the strong potential of bioprocess models for industrial usage.
The bioprocess industry is actively exploring technologies associated with the fourth industrial revolution, with modeling offering considerable potential for process optimization. Nevertheless, model adoption in industry remains limited. This is partly because model development continues to depend heavily on offline sampling, and because relatively few industrial applications convincingly demonstrate their practical value. This study therefore first examines the benefits of online rheology and online biomass measurements for model development and demonstrates, among other aspects, that online biomass significantly improves model fidelity. The second part examines how electricity prices affect process conditions, a key factor in production, and finds that, contrary to common practice, maximizing all operating parameters is not the most cost-effective strategy. Finally, an insilico framework for model predictive control, applied to a reactor endfill scenario, demonstrates that oxygencontrolled processes can be dynamically optimized, highlighting the strong potential of bioprocess models for industrial usage.
Record ID
Keywords
Bioprocess Modelling, Cost Analysis, Model Predictive Control
Subject
Suggested Citation
Lemperle M, Ramin P, Kager J, Cassells B, Stocks S, Gernaey KV. Advancing Industrial Fermentation across scales: Model Development, Cost Analysis, and Predictive Control. Systems and Control Transactions 5:1582-1591 (2026) https://doi.org/10.69997/sct.190048
Author Affiliations
Lemperle M: Process and Systems Engineering Center (PROSYS), department of Chemical and Biochemical Engineering, Technical University of Denmark, Building 228A, 28000 Kgs. Lyngby [ORCID]
Ramin P: Process and Systems Engineering Center (PROSYS), department of Chemical and Biochemical Engineering, Technical University of Denmark, Building 228A, 28000 Kgs. Lyngby
Kager J: Process and Systems Engineering Center (PROSYS), department of Chemical and Biochemical Engineering, Technical University of Denmark, Building 228A, 28000 Kgs. Lyngby
Cassells B: Novonesis, Fermentation Pilot Plant, Krogshoejvej 36, 2880 Bagsværd, Denmark
Stocks S: Novonesis, Fermentation Pilot Plant, Krogshoejvej 36, 2880 Bagsværd, Denmark
Gernaey KV: Process and Systems Engineering Center (PROSYS), department of Chemical and Biochemical Engineering, Technical University of Denmark, Building 228A, 28000 Kgs. Lyngby
[Login] to see author email addresses.
Ramin P: Process and Systems Engineering Center (PROSYS), department of Chemical and Biochemical Engineering, Technical University of Denmark, Building 228A, 28000 Kgs. Lyngby
Kager J: Process and Systems Engineering Center (PROSYS), department of Chemical and Biochemical Engineering, Technical University of Denmark, Building 228A, 28000 Kgs. Lyngby
Cassells B: Novonesis, Fermentation Pilot Plant, Krogshoejvej 36, 2880 Bagsværd, Denmark
Stocks S: Novonesis, Fermentation Pilot Plant, Krogshoejvej 36, 2880 Bagsværd, Denmark
Gernaey KV: Process and Systems Engineering Center (PROSYS), department of Chemical and Biochemical Engineering, Technical University of Denmark, Building 228A, 28000 Kgs. Lyngby
[Login] to see author email addresses.
Journal Name
Systems and Control Transactions
Volume
5
First Page
1582
Last Page
1591
Year
2026
Publication Date
2026-06-12
Version Comments
Original Submission
Other Meta
PII: 1582-1591-125-SCT-5-2026, Publication Type: Journal Article
Record Map
Published Article

LAPSE:2026.0402
This Record
External Link

https://doi.org/10.69997/sct.190048
Publisher Version
Download
Meta
Record Statistics
Record Views
219
Version History
[v1] (Original Submission)
Jun 12, 2026
Verified by curator on
Jun 12, 2026
This Version Number
v1
Citations
Most Recent
This Version
URL Here
https://psecommunity.org/LAPSE:2026.0402
Record Owner
PSE Press
Links to Related Works
References Cited
- P. Stanbury, A. Whitaker, and S. Hall, Principles of fermentation technology. Elsevier, 2013.
- Villadsen J, Nielsen J, Lidén G. Bioreaction engineering principles. Springer US (2011) https://doi.org/10.1007/978-1-4419-9688-6
- Doran PM. Reactor engineering. Bioprocess Engineering Principles :333-391 (1995) https://doi.org/10.1016/b978-012220855-3/50013-4
- Rydal T, Frandsen J, Nadal?Rey G, Albæk MO, Ramin P. Bringing a scalable adaptive hybrid modeling framework closer to industrial use: application on a multiscale fungal fermentation. Biotech & Bioengineering 121:1609-1625 (2024) https://doi.org/10.1002/bit.28670
- Albino M, Gargalo CL, Nadal-Rey G, Albæk MO, Krühne U, Gernaey KV. Hybrid modeling for on-line fermentation optimization and scale-up: a review. Processes 12:1635 (2024) https://doi.org/10.3390/pr12081635
- Albaek MO, Gernaey KV, Hansen MS, Stocks SM. Modeling enzyme production with aspergillus oryzae in pilot scale vessels with different agitation, aeration, and agitator types. Biotech & Bioengineering 108:1828-1840 (2011) https://doi.org/10.1002/bit.23121
- Kager J, Herwig C, Stelzer IV. State estimation for a penicillin fed-batch process combining particle filtering methods with online and time delayed offline measurements. Chemical Engineering Science 177:234-244 (2018) https://doi.org/10.1016/j.ces.2017.11.049
- Pu Y, Chaudhry S, Parikh M, Berry J. Application of in-line viscometer for in-process monitoring of microcrystalline cellulose-carboxymethylcellulose hydrogel formation during batch manufacturing. Drug Development and Industrial Pharmacy 41:28-34 (2014) https://doi.org/10.3109/03639045.2013.845837
- Bergin A, Carvell J, Butler M. Applications of bio-capacitance to cell culture manufacturing. Biotechnology Advances 61:108048 (2022) https://doi.org/10.1016/j.biotechadv.2022.108048
- Fehrenbach R, Comberbach M, Pêtre JO. On-line biomass monitoring by capacitance measurement. Journal of Biotechnology 23:303-314 (1992) https://doi.org/10.1016/0168-1656(92)90077-m
- Konakovsky V, Yagtu A, Clemens C, Müller M, Berger M, Schlatter S, Herwig C. Universal capacitance model for real-time biomass in cell culture. Sensors 15:22128-22150 (2015) https://doi.org/10.3390/s150922128
- Herwig C, Pörtner R, Möller J. Digital twins. Springer International Publishing (2021) https://doi.org/10.1007/978-3-030-71660-8
- Udugama IA, Lopez PC, Gargalo CL, Li X, Bayer C, Gernaey KV. Digital twin in biomanufacturing: challenges and opportunities towards its implementation. Syst Microbiol and Biomanuf 1:257-274 (2021) https://doi.org/10.1007/s43393-021-00024-0
- Mears L, Stocks SM, Albaek MO, Sin G, Gernaey KV. Mechanistic fermentation models for process design, monitoring, and control. Trends in Biotechnology 35:914-924 (2017) https://doi.org/10.1016/j.tibtech.2017.07.002
- Mears L, Stocks SM, Albaek MO, Cassells B, Sin G, Gernaey KV. A novel model?based control strategy for aerobic filamentous fungal fed?batch fermentation processes. Biotech & Bioengineering 114:1459-1468 (2017) https://doi.org/10.1002/bit.26274
- Ferreira RG, Azzoni AR, Freitas S. Techno-economic analysis of the industrial production of a low-cost enzyme using E. coli: the case of recombinant ?-glucosidase. Biotechnol Biofuels 11: (2018) https://doi.org/10.1186/s13068-018-1077-0
- M. Lemperle, P. Ramin, J. Kager, B. Cassells, S. Stocks, and K. V. Gernaey, "Hybrid bioprocess model towards the development of a digital twin for an industrial fermentation process, " ESCAPE 35: 35th European Symposium on Computer Aided Process Engineering 2025, pp. 199-200, 2025.
- Esener AA, Veerman T, Roels JA, Kossen NWF. Modeling of bacterial growth; formulation and evaluation of a structured model. Biotech & Bioengineering 24:1749-1764 (2004) https://doi.org/10.1002/bit.260240803
- CONTOIS DE. Kinetics of bacterial growth: relationship between population density and specific growth rate of continuous cultures. Journal of General Microbiology 21:40-50 (1959) https://doi.org/10.1099/00221287-21-1-40
- O'Brien CM, Zhang Q, Daoutidis P, Hu WS. A hybrid mechanistic-empirical model for in silico mammalian cell bioprocess simulation. Metabolic Engineering 66:31-40 (2021) https://doi.org/10.1016/j.ymben.2021.03.016
- Abimbola M Enitan . Food processing optimization using evolutionary algorithms. Afr. J. Biotechnol. 10: (2011) https://doi.org/10.5897/ajb11.410
- Wagner N, Bosshart A, Wahler S, Failmezger J, Panke S, Bechtold M. Model-based cost optimization of a reaction-separation integrated process for the enzymatic production of the rare sugar d-psicose at elevated temperatures. Chemical Engineering Science 137:423-435 (2015) https://doi.org/10.1016/j.ces.2015.05.058
- Statista, "Denmark: Monthly wholesale electricity price." Accessed: Jan. 13, 2026. [Online]. Available: https://www.statista.com/statistics/1271525/denmark-monthly-wholesale-electricity-price/
- R. Davis et al., "Process Design and Economics for the Conversion of Lignocellulosic Biomass to Hydrocarbons: Dilute-Acid and Enzymatic Deconstruction of Biomass to Sugars and Catalytic Conversion of Sugars to Hydrocarbons, " Mar. 2015.
- J. Wimble, R. Ashizawa, and E. W. Swartz, "Analysis of the economic viability and environmental impacts of a conceptual process model for the recovery of lactic acid from spent media in cultivated meat production, " Biotechnol. Prog., 2025, doi: 10.1002/btpr.70094.
- R. Storn and K. Price, "Differential Evolution - A Simple and Efficient Heuristic for Global Optimization over Continuous Spaces, " Journal of Global Optimization, vol. 11, no. 4, pp. 341-359, 1997, doi: 10.1023/A:1008202821328/METRICS.
(0.11 seconds)
[0.11 s]

