Process development and scale-up from shake flask to fermenter of suspended and immobilized aerobic microorganisms

  • Prozessentwicklung und Maßstabsvergrößerung vom Schüttelkolben zum Fermenter suspendierter und immobilisierter aerober Mikroorganismen

Seletzky, Juri Martin; Büchs, Jochen (Thesis advisor)

Aachen : Publikationsserver der RWTH Aachen University (2009)
Dissertation / PhD Thesis

Aachen, Techn. Hochsch., Diss., 2007


The aim of this study was to develop and advance techniques required to carry out process developments with suspended and immobilized aerobic microorganisms cultivated in batch or continuous mode. The applicability is demonstrated with the biological model system Corynebacterium glutamicum grown on lactic acid. Respiration measurement in shake flasks is introduced as a screening method to characterize the behavior of microorganisms exposed to stress factors such as carbon starvation, anaerobic conditions, organic acids, osmolarity and pH. It is evaluated and compared with the standard measuring methods, exhaust gas analysis and respirometry. A simple and inexpensive shake flask screening method to perform immobilization studies with solid supports is introduced. This method is applied to study the adhesion of dormant and growing cells to ceramic and glass support materials with different porosities and surface modifications. A novel everyday scale-up strategy from shake flasks to fermenters based on empirical correlations of the volumetric mass transfer coefficient and the pH change of the medium is developed and applied for batch and continuous cultures. Mixing time, gas-liquid mass transfer, the influence of antifoam agent, power input, gas hold-up, productivity, and long term behavior of a novel external loop biofilm reactor with a honeycomb ceramic monolith as immobilization carrier are determined. With modeling the productivities of biofilm and standard reactors are compared for aerobic processes with growth associated product formation. To identify optimal operating conditions, the influences of dilution rate, mass transfer, carbon source concentration, and surface area on the productivity is modeled.