Euler-Lagrangian Simulations: A Proper Tool for Predicting Cellular Performance in Industrial Scale Bioreactors

Microbial lifelines in bioprocesses: From concept to application

“…Siebler et al, 2019). Using the lifeline, the metabolic state of a cell can be assessed (Hajian et al, 2020;Haringa et al, 2018b;Wang et al, 2020b;Wang et al, 2020a). The third concept is closely related to the second: a lifeline can also be an intracellular condition-vs-time series (Haringa et al, 2016).…”

“…All research on lifelines has in common, that it aims to assess the metabolic impact of large-scale gradients on microorganisms and microbial populations. This information can be valuable for insights into bioreactor performance (Siebler et al, 2019), guiding future strain engineering (Zieringer and Takors, 2018), bioreactor design and operation (Hajian et al, 2020;Kuschel et al, 2017;Lapin et al, 2004) and paving the way for efficient and successful bioprocess scale-up (Wang et al, 2020b;Wang et al, 2020a).…”

“…For this, a minimum of two models are needed, which interact with each other: a model for the bioreactor environment and a model that describes the cell. Most common for calculating fluid flow for gradient or lifeline modelling is the use of CFD models (Hajian et al, 2020), either using the finite volume approach (often with a frozen flowfield) (Haringa et al, 2016;Kuschel et al, 2017;Zieringer et al, 2021) or, more recently, with Lattice-Boltzmann (Haringa, 2022), but less calculation-intensive approaches gain attention like CFD-based compartment models (Haringa et al, 2022;Nadal-Rey et al, 2021).…”

“…The fluid dynamics of the bioreactor are typically modelled using an Eulerian approach wherein the flow and distribution of other relevant parameters, like gas holdup or nutrient concentration, are described by a continuum (field based) approach. In this framework, equations for fluid motion, like the Navier-Stokes equation, and the equations to calculate turbulence, mass transfer and substrate distribution can be included (Hajian et al, 2020). As substrate uptake of microbes alters the nutrient distribution, unstructured black-box substrate uptake kinetics are often applied in the Euler framework (Hajian et al, 2020), where the local nutrient specific uptake rate q s is directly linked to the local nutrient concentration C s .…”

“…In this framework, equations for fluid motion, like the Navier-Stokes equation, and the equations to calculate turbulence, mass transfer and substrate distribution can be included (Hajian et al, 2020). As substrate uptake of microbes alters the nutrient distribution, unstructured black-box substrate uptake kinetics are often applied in the Euler framework (Hajian et al, 2020), where the local nutrient specific uptake rate q s is directly linked to the local nutrient concentration C s .…”