Biocalorimetry as a process analytical technology process analyser; robust in-line monitoring and control of aerobic fed-batch cultures of crabtree-negative yeast cells

摘要: Control of bioprocesses requires reliable and robust on- or in-line monitoring tools providing real-time information on process dynamics. Heat generation related to metabolic activity living systems is currently gaining importance in bioprocess industry due its non-invasive essentially instantaneous characteristics. This study deals with control pure aerobic fed-batch cultures three Crabtree-negative yeast strains, Kluyveromyces marxianus, Candida utilis Pichia pastoris, based measured, heat flow signals. A high resolution biocalorimeter (BioRC1) was developed from a standard bench-scale calorimeter (RC1). The BioRC1 equipped (dielectric spectroscopy, pH probe dissolved oxygen probe) at-line (exit gas analyser) sensors characterise the growth behaviour cells. Both biomass profiles exhibited similar proving significance employing signal as key-parameter for system under investigation. simple estimator concentration specific rate formulated values. In order evaluate potential calorimetry powerful tool, robustness, reliability well broad applicability estimators assessed through comparison off-line measurement techniques showed promising results general wide range bioprocesses.