MONITORING AND CONTROL OF A BIOPROCESS FOR MALARIA VACCINE PRODUCTION

Based on genetic manipulations, new strains of S. cerevisae are developed, which can be used for the production of pharmaceuticals. In this study, attention is focused on yeast fed-batch cultures dedicated to the production of a malaria vaccine. The efficient operation of this bioprocess requires on-line monitoring and regulation of the ethanol concentration at a low level (so as to maximize biomass productivity). This paper reports on the development of software sensors for the on-line reconstruction of biomass and ethanol, which are based on simple feedforward neural networks making only use of conventional bioprocess instrumentation (stirrer speed, base addition for pH regulation, etc.). This paper also discusses the design of a robust RST control strategy for regulating the ethanol concentration, which ensures setpoint tracking and asymptotic disturbance rejection. Robustification is achieved through the use of Youla parametrisation and on-line adaptation. This control strategy only requires the a priori knowledge about one yield coefficient and one on-line measurement sensor (i.e. an ethanol probe or the proposed software sensor). The software sensor and controller are tested successfully in real-case experimental runs.