Measurement-based Optimization of a Fed-Batch Fermenter

Dominique Bonvin, Bala Srinivasan, Sergio Valentinotti

Optimal operation of fed-batch bio-transformations calls for a time-varying feed profile that varies from one batch to the next due to the presence of unavoidable disturbances. The idea used in this work is to choose a process variable, the tracking of which implies optimality. In fed-batch fermenters with the possible production of overflow metabolite, maximal rate of biomass production can be ensured by regulating the metabolite concentration at a low value. Similarly, in fermenters with inhibition, optimal operation corresponds to maintaining a constant substrate concentration. The next issue is to design a controller that is capable of maintaining constant metabolite or substrate concentration while allowing the biomass to grow exponentially with unknown growth rate. Biomass growth can be considered as an unknown unstable disturbance that needs to be rejected, for the solution of which standard PID controllers are inadequate, and modern control techniques are too complex to implement. In this work, the fed-batch fermentation is considered as the combination of two simple-linear models, the first related to biomass growth, and the second to the overflow metabolite. Since the exponential growth rate is unknown, the controller needs to be adjusted on-line. The potential benefits of implementing this control strategy are illustrated with two different experimental applications. In the first application, the ethanol concentration in a Saccharomyces cerevisiae fed-batch fermentation is maintained constant at a very low concentration, thereby maximizing biomass growth. In the second application, the substrate concentration is maintained constant in a fed-batch culture of Phaffia rhodozyma. The same controller can be used when the controlled signal is changed from glucose to xylose, thereby illustrating the robustness of the control scheme. This project is in collaboration with LGCB of EPFL.

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Valentinotti S., B. Srinivasan , U. Holmberg , D. Bonvin , C. Cannizzaro , M. Rhiel and U. von Stockar. Optimal Operation of Fed-Batch Fermentations via Adaptive Control of Overflow Metabolite. Control Engineering Practice, (June 2003), 11 (6), 665-674

Cannizzaro C., S. Valentinotti , M. Rhiel , D. Bonvin and U. von Stockar. Fed-Batch Control of S. Cerevisiae and E. Coli at Critical Point Using Mid-FTIR Spectroscopy. European Symposium on Biochemical Engineering Science ESBES-3, Copenhagen, Denmark (September 2000)

Valentinotti S., C. Cannizzaro, M. Rhiel, U. Holmberg, U. von Stockar and D. Bonvin. Optimal Control of Fed-Batch Fermenters. Biotechnology 2000, The World Congress on Biotechnology, Berlin (September 2000)

Valentinotti S., U. Holmberg, C. Cannizzaro and D. Bonvin. Modeling for Control of Fed-Batch Fermenters. ADCHEM 2000, Pisa, Italy (June, 2000), 491-496