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A Novel Bioprocess Control Strategy Under Uncertainty via Operational Space Identification

Zhu, M.; Pennington, O.; Pincam, T.; Zarei, M.; Kay, S.; Liu, Y.-Q.; Short, M.; Zhang, D.

2026-02-08 microbiology
10.64898/2026.02.07.704591 bioRxiv
Show abstract

Bioprocesses are critical for sustainable industrial development but face challenges from their inherent uncertainties that affect efficiency and scalability. This study in-troduces a worst-case operational space design framework, integrating symbolic optimization with scenario-based validation, to preemptively mitigate uncertainties so that key performance indicators are consistently satisfied even under adverse conditions. The methodology is demonstrated through two case studies: a lab-scale fermentation for astaxanthin production and a site-scale anaerobic digestion for biogas production. Process uncertainty is quantified through model parameter variations (2% - 13%) to reflect real-world scenarios. The results indicate that highly flexible operational spaces are identified in both case studies, with control variables able to vary by up to 25% and 15% in the respective systems, while consistently adhering to system constraints. Validation over 10,000 scenarios confirmed 0 violation per case study. The proposed framework delivers validated operational flexibility with modest computational requirements, making it practical for lab-to-site deployment.

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