Abstract
This study evaluated the scale-up of Pseudomonas putida
fed-batch fermentation from a 2 L benchtop-scale stirred bioreactor to a
200 L pilot-scale tank by using a validated computational fluid dynamic
(CFD) model. One of the major concerns in this fermentation process is
the potential reduction in mixing quality with increasing scale, leading
to lower yield or product quality. For a low-risk scale-up, a
multiphase Euler-Euler CFD model was developed that simulated the
hydrodynamics of the fed-batch system at various filling volumes,
representing different stages of the fermentation process. The model was
validated using experimental data of mixing time and mass transfer
coefficient. The hydrodynamic model was then coupled with a Monod
kinetic model of P. putida ‘s fermentation. Response surface
methodology was used to generate a performance map of the pilot
bioreactor at various aeration, agitation, and bioreactor filling
volumes. The study considered different established scale-up approaches,
such as constant tip speed and aeration rate across scales, constant KLa
as well as constant power to unit of liquid volume (P/V). The
performance of the bioreactor was assessed, and the optimum operating
ranges of the input parameters were obtained at different stages of the
fermentation. Using performance map the possibility of substrate and
oxygen gradient formation, and the gradient severity inside the pilot
bioreactor at different working volumes were evaluated.
Original language | English |
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Article number | 109549 |
Journal | Biochemical Engineering Journal |
Volume | 213 |
Number of pages | 18 |
ISSN | 1369-703X |
DOIs | |
Publication status | Published - 2024 |
Keywords
- CFD
- Fermentation
- Gradients
- Kinetics
- Multiphase
- Scale-up