title: Model-based derivation, analysis and control of unstable microaerobic steady-states--considering Rhodospirillum rubrum as an example.
abstract: Microaerobic (oxygen-limited) conditions are critical for inducing many important microbial processes in industrial or environmental applications. At very low oxygen concentrations, however, the process performance often suffers from technical limitations. Available dissolved oxygen measurement techniques are not sensitive enough and thus control techniques, that can reliable handle these conditions, are lacking. Recently, we proposed a microaerobic process control strategy, which overcomes these restrictions and allows to assess different degrees of oxygen limitation in bioreactor batch cultivations. Here, we focus on the design of a control strategy for the automation of oxygen-limited continuous cultures using the microaerobic formation of photosynthetic membranes (PM) in Rhodospirillum rubrum as model phenomenon. We draw upon R. rubrum since the considered phenomenon depends on the optimal availability of mixed-carbon sources, hence on boundary conditions which make the process performance challenging. Empirically assessing these specific microaerobic conditions is scarcely practicable as such a process reacts highly sensitive to changes in the substrate composition and the oxygen availability in the culture broth. Therefore, we propose a model-based process control strategy which allows to stabilize steady-states of cultures grown under these conditions. As designing the appropriate strategy requires a detailed knowledge of the system behavior, we begin by deriving and validating an unstructured process model. This model is used to optimize the experimental conditions, and identify properties of the system which are critical for process performance. The derived model facilitates the good process performance via the proposed optimal control strategy. In summary the presented model-based control strategy allows to access and maintain microaerobic steady-states of interest and to precisely and efficiently transfer the culture from one stable microaerobic steady-state into another. Therefore, the presented approach is a valuable tool to study regulatory mechanisms of microaerobic phenomena in response to oxygen limitation alone. Biotechnol. Bioeng. 2014;111: 734-747. © 2013 Wiley Periodicals, Inc.
authors.affiliation: Institute for Automation Engineering, Otto-von-Guericke University, Universitaetsplatz 2, Magdeburg, 39106, Germany; Max Planck Institute for Dynamics of Complex Technical Systems, Magdeburg, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Carius
authors.forename: Philipp
authors.initials: P
authors.lastname: Rumschinski
authors.forename: Timm
authors.initials: T
authors.lastname: Faulwasser
authors.forename: Dietrich
authors.initials: D
authors.lastname: Flockerzi
authors.forename: Hartmut
authors.initials: H
authors.lastname: Grammel
authors.forename: Rolf
authors.initials: R
authors.lastname: Findeisen
mesh_terms: D000332:Aerobiosis / Q000502:physiology*; D019149:Bioreactors; D018929:Cell Culture Techniques / Q000379:methods*; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism; D015203:Reproducibility of Results; D012247:Rhodospirillum rubrum / Q000378:metabolism / Q000502:physiology*; D049490:Systems Biology / Q000379:methods*
chemical_list: D010100:Oxygen
keywords: 2DOF control; continuous cultivation; microaerobic; model invalidation; model-based control; parameter estimation