Président du jury Hanus, Raymond
Promoteur Bogaerts, Philippe
;Vande Wouwer, Alain Publication Non publié, 2006-12-07
| Résumé : | The exponential development of biotechnology has lead to a quasi unlimited number of potential products going from biopolymers to vaccines. Cell culture has therefore evolved from the simple cell growth outside its natural environment to its use to produce molecules that they do not naturally produce. This rapid development could not be continued without new control and supervising tools as well as a good process understanding. This requirement involves however a large diversity and a better accessibility of process measurements. In this framework, software sensors show numerous potentialities. The objective of a software sensor is indeed to provide an estimation of the system state variables and particularly those which are not obtained through in situ hardware sensors or laborious and expensive analysis. In this context, This work attempts to join the knowledge of increasing bioprocess complexity and diversity and the time scale of process developments and favours systematic modelling methodology, its flexibility and the speed of development. In the field of state observation, an important modelling constraint is the one induced by the selection of the state to estimate and the available measurements. Another important constraint is the model quality. The central axe of this work is to provide solutions in order to reduce the weight of these constraints to software sensors development. On this purpose, we propose four solutions to four main questions that may arise. The first two ones concern modelling uncertainties. 1."How to develop a software sensor using measurements easily available on pilot scale bioreactor?" The proposed solution is a static software sensor using an artificial neural network. Following this modelling methodology we developed static software sensors for the biomass and ethanol concentrations in a pilot scale S. cerevisae cell culture using the measurement of titrating base quantity, agitation rate and CO₂ concentration in the exhaust gas. 2."How to obtain a reaction scheme and a kinetic model to develop a dynamic observation model?". The proposed solution is to combine three elements: a systematic methodology to generate, identify and select the possible reaction schemes, a general kinetic model and a systematic identification procedure where the last step is particularly dedicated to the identification of observation models. Combining these methodologies allowed us to develop a software sensor for the concentrations of an allergen produced by an animal cell culture using the discrete measurement of glucose, glutamine and ammonium concentrations (which are also estimated in continuous time by the software sensors). The two other questions are dealing with kinetic model uncertainty. 3 "How to correct kinetic model parameters while keeping the system observability?". We consider the possibility to correct some model parameters during the process observation. We propose indeed an adaptive observer based on the theory of the most likely initial conditions observer and exploiting the information from the asymptotic observer. This algorithm allows to jointly estimate the state and some kinetic model parameters. 4 "How to avoid any state observer selection that requires an a priori knowledge on the model quality?". Answering this question lead us to the development of hybrid state observers. The general principle of a hybrid observer is to automatically evaluate the model quality and to select the appropriate state observer. In this work we focus on kinetic model quality and propose hybrid observers that evolves between the state observation from an exponential observer (free convergence rate tuning but model error sensitivity) and the one provided by an asymptotic observer (no kinetic model requirement but a convergence rate depending on the dilution rate). Two strategies are investigated in order to evaluate the model quality and to induce the state observation evolution. Each of them have been validated on two simulated cultures (microbial and animal cells) and one real industrial one (B. subtilis). \ |
