Research output per year
Research output per year
Cees Haringa, Wenjun Tang, Guan Wang, Amit T. Deshmukh, Wouter A. van Winden, Ju Chu, Walter M. van Gulik, Joseph J. Heijnen, Robert F. Mudde, Henk J. Noorman*
Research output: Contribution to journal › Article › Scientific › peer-review
We assess the effect of substrate heterogeneity on the metabolic response of P. chrysogenum in industrial bioreactors via the coupling of a 9-pool metabolic model with Euler-Lagrange CFD simulations. In this work, we outline how this coupled hydrodynamic-metabolic modeling can be utilized in 5 steps. (1) A model response study with a fixed spatial extra-cellular glucose concentration gradient, which reveals a drop in penicillin production rate qp of 18–50% for the simulated reactor, depending on model setup. (2) CFD-based scale-down design, where we design a 1-vessel scale down simulator based on the organism lifelines. (3) Scale-down verification, numerically comparing the model response in the proposed scale-down simulator with large-scale CFD response. (4) Reactor design optimization, reducing the drop in penicillin production by a change of feed location. (5) Long-term fed-batch simulation, where we verify model predictions against experimental data, and discuss population heterogeneity. Overall, these steps present a coupled hydrodynamic-metabolic approach towards bioreactor evaluation, scale-down and optimization.
Original language | English |
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Pages (from-to) | 12-24 |
Number of pages | 13 |
Journal | Chemical Engineering Science |
Volume | 175 |
DOIs | |
Publication status | Published - 2018 |
Research output: Contribution to journal › Article › Scientific › peer-review
Research output: Contribution to journal › Article › Scientific › peer-review
Research output: Contribution to journal › Article › Scientific › peer-review