Controlling the specific growth rate via biomass trend regulation in filamentous fungi bioprocesses

•Viable biomass concentration is predicted online via dielectric spectroscopy.•The method is applicable for filamentous fungi process in growth and decline phase.•Holding µ on a constant level is based on controlling biomass trends.•The control strategy adapts automatically to changing biomass yields.•The method is robust to changing process parameters, physiology and morphology.

Increasing pressure on product quality and quantity pushes solutions of process control to be a central issue in pharmaceutical bioprocesses. Especially online biomass estimation, and further control of the specific growth rate are of central importance because they describe the catalyst of the reaction. For penicillin producing bioprocesses with filamentous microorganisms, this was underlined by recent findings describing the influence of the specific growth rate on the specific production rate. Hence, the specific growth rate needs to be controlled on a certain level to achieve high productivity.In this study, we developed a control strategy for the specific growth rate based on online estimation of viable biomass via dielectric spectroscopy. The method was verified using an at-line staining method for viability measurement. The online viable biomass estimation is applicable in the growth and decline phase, coping with physiological and morphological changes of filamentous fungi. Furthermore, the control strategy adapts to changing biomass yields, which is a big issue in the bioprocess for penicillin production applied in this study.Two application runs were conducted, yielding in proper online viable biomass estimation and control of the specific growth rate at a constant level of 0.012 h−1. We achieved biomass predictions with an average error of 1.5 g/l over the whole fed-batch process. In the decline phase, the control of specific growth rates was not possible due to physiological constrains. However, in the growth phase, a total specific growth rate of 0.013 h−1 was achieved, which met the pre-defined acceptance criterion for this method.The method is thus ready for viable biomass estimation in the growth and in the decline phase of the penicillin production process. Furthermore, the method is applicable to control the specific growth rate during the growth phase.

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