The trajectories, referred to as lifelines, of individual microorganisms in an industrial scale fermentor under substrate limiting conditions were studied using an Euler‐Lagrange computational fluid dynamics approach. The metabolic response to substrate concentration variations along these lifelines provides deep insight in the dynamic environment inside a large‐scale fermentor, from the point of view of the microorganisms themselves. We present a novel methodology to evaluate this metabolic response, based on transitions between metabolic “regimes” that can provide a comprehensive statistical insight in the environmental fluctuations experienced by microorganisms inside an industrial bioreactor. These statistics provide the groundwork for the design of representative scale‐down simulators, mimicking substrate variations experimentally. To focus on the methodology we use an industrial fermentation of Penicillium chrysogenum in a simplified representation, dealing with only glucose gradients, single‐phase hydrodynamics, and assuming no limitation in oxygen supply, but reasonably capturing the relevant timescales. Nevertheless, the methodology provides useful insight in the relation between flow and component fluctuation timescales that are expected to hold in physically more thorough simulations. Microorganisms experience substrate fluctuations at timescales of seconds, in the order of magnitude of the global circulation time. Such rapid fluctuations should be replicated in truly industrially representative scale‐down simulators.
CFD simulations of mixing in single-phase multi-Rushton stirred tanks based on the RANS methodology frequently show an over-prediction of the mixing time. This hints at an underprediction of the mass exchange between the compartments formed around the individual impellers. Some studies recommend tuning the turbulent Schmidt number to address this issue, but this appears to be an ad-hoc correction rather than physical adjustment, thereby compromising the predictive value of the method. In this work, we study the flow profile in between two Rushton impellers in stirred tank. The data hints at the presence of macroinstabilities, and a peak in turbulent kinetic energy in the region of convergent flow, which both may promote inter-compartment mass exchange. CFD studies using the steady-state multiple reference frame model (unsteady simulations are treated in part II) inherently fail to include the macro-instability, and underestimate the turbulent kinetic energy, thereby strongly overestimating mixing time. Furthermore, the results are highly mesh-sensitive, with increasing mesh density leading to a poorer prediction of the mixing time. Despite proper results for 1-impeller studies, we do not deem MRF-RANS models suitable for mixing studies in multi-impeller geometries.
• A comprehensive overview of the Euler-Lagrange bioreactor simulation approach. • Application of Euler-Lagrange CFD to three different case studies. • Different strategies to design scale-down experiments using CFD data are discussed. • Approach selection chart based on hydrodynamic characteristics of modeled reactor. • The potential of combining Euler-Lagrange CFD with microfluidics is discussed.
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