Speaker
Description
Model-based design advances bioprocess development \cite{FBDURL, FBD2025}, yet multi-stage continuous microbial processes remain empirically designed due to poor system-level understanding. Here, we introduce a systems-level, physiology-based framework for analyzing multi-stage continuous bioprocesses, enabling early-stage screening with minimal experimental effort.
Starting from mass balance equations under substrate-limited conditions, we derive closed-form steady-state expressions for biomass, substrate, and product concentrations in reactor cascades. This analytical description enables interrogation of trade-offs between dilution rates, inter-stage coupling, and physiological constraints. We show that optimal cascade performance cannot be achieved by individual optimization, revealing a limitation of stage-wise design intuition.
From this analysis, we derive rules for globally optimal operation of multi-stage continuous processes. Optimal performance requires maximizing substrate feed to the production stage, minimizing downstream dilution, and selecting maximal upstream biomass concentrations.
The framework is implemented as an interactive web tool for design space exploration \cite{CDURL}. It can assess design modifications, like residence time redistribution and feed adjustments. By combining steady-state analysis with an accessible tool, the approach links mathematical modeling with practical process engineering.
Bibliography
@software{CDURL,
title = {{{ContiDesigner}}},
author = {Graf, Andrea and Zanghellini, Juergen},
date = {2026},
url = {https://chemnettools.anc.univie.ac.at/ContiDesigner/},
urldate = {2026-03-09},
}
@software{FBDURL,
title = {{{FedBatchDesigner}}},
author = {Graf, Andrea and Libiseller-Egger, Julian and Gotsmy, Mathias and Zanghellini, Juergen},
date = {2025},
url = {https://chemnettools.anc.univie.ac.at/FedBatchDesigner/},
urldate = {2026-03-09},
}
@article{FBD2025,
title = {Fedbatchdesigner: {{A User-Friendly Dashboard}} for {{Modeling}} and {{Optimizing Growth-Arrested Fed-Batch Processes}}},
shorttitle = {Fedbatchdesigner},
author = {Graf, Andrea C. and Libiseller-Egger, Julian and Gotsmy, Mathias and Zanghellini, Jürgen},
date = {2025-08-15},
journaltitle = {ACS Synthetic Biology},
shortjournal = {ACS Synth. Biol.},
volume = {14},
number = {8},
pages = {3252--3257},
publisher = {American Chemical Society},
doi = {10.1021/acssynbio.5c00357},
url = {https://doi.org/10.1021/acssynbio.5c00357},
urldate = {2026-03-09},
abstract = {Optimizing fed-batch fermentation strategies is key to maximizing bioprocess efficiency. While mathematical modeling can aid process design, its complexity often limits accessibility for experimental scientists. We present FedBatchDesigner, a user-friendly web tool for optimizing fed-batch processes with a growth-arrested production stage. With minimal input requirements, FedBatchDesigner enables rapid exploration of a process’s titer, rate, and yield (TRY) landscape for constant, linear, and exponential feeding strategies. Interactive visualizations allow users to assess trade-offs between productivity and titer, supporting rational decision-making without the need for extensive modeling expertise. We demonstrate FedBatchDesigner’s utility via two case studies: synthesis of (i) l-valine with a microaerobic production stage in Escherichia coli and (ii) ethanol under nitrogen starvation in Saccharomyces cerevisiae. FedBatchDesigner is freely available at https://chemnettools.anc.univie.ac.at/FedBatchDesigner, with the source code provided at https://github.com/julibeg/FedBatchDesigner under the MIT license.},
}
