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Journal ArticleDOI

An industrial perspective on bioreactor scale-down: What we can learn from combined large-scale bioprocess and model fluid studies

Henk Noorman
- 01 Aug 2011 - 
- Vol. 6, Iss: 8, pp 934-943
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TLDR
Here it is tried to highlight what can be learned from real large-scale bioprocess in combination with model fluid studies, and to provide suitable computation tools to overcome data restrictions.
Abstract
For industrial bioreactor design, operation, control and optimization, the scale-down approach is often advocated to efficiently generate data on a small scale, and effectively apply suggested improvements to the industrial scale. In all cases it is important to ensure that the scale-down conditions are representative of the real large-scale bioprocess. Progress is hampered by limited detailed and local information from large-scale bioprocesses. Complementary to real fermentation studies, physical aspects of model fluids such as air-water in large bioreactors provide useful information with limited effort and cost. Still, in industrial practice, investments of time, capital and resources often prohibit systematic work, although, in the end, savings obtained in this way are trivial compared to the expenses that result from real process disturbances, batch failures, and non-flyers with loss of business opportunity. Here we try to highlight what can be learned from real large-scale bioprocess in combination with model fluid studies, and to provide suitable computation tools to overcome data restrictions. Focus is on a specific well-documented case for a 30-m(3) bioreactor. Areas for further research from an industrial perspective are also indicated.

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Citations
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Consistent development of bioprocesses from microliter cultures to the industrial scale

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References
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Journal ArticleDOI

Substrate gradient formation in the large-scale bioreactor lowers cell yield and increases by-product formation

TL;DR: IPTG induction of a recombinant protein was shown to influence important cell parameters and considerably increased the yield of carbon dioxide per glucose added, indicating an increased maintenance in the large-scale bioreactor.
Journal ArticleDOI

Mixing in large-scale vessels stirred with multiple radial or radial and axial up-pumping impellers: modelling and measurements

TL;DR: In this article, the authors used the Compartment Model Approach (CMA) to develop a flow model based on the general knowledge of the hydrodynamics of both unaerated and aerated stirred vessels.
Journal ArticleDOI

Numerical simulation of the dynamics of two-phase gas—liquid flows in bubble columns

TL;DR: In this article, a two-dimensional computational fluid dynamics study of the two-phase gas-liquid flow in bubble columns is presented, where the flow is modelled by a Navier-Stokes system of equations in an Eulerian representation, whereas the motion of the gas is modeled on a smaller scale by tracking individual bubbles or bubble clusters through the liquid in a Lagrangian way.
Journal ArticleDOI

Substrate gradients in bioreactors: origin and consequences

TL;DR: In this paper, a 30 m3 cultivation of Saccharomyces cerevisiae grown in minimal medium to a cell density of 20 gl−1 was studied, with glucose as limiting component which was fed continuously to the process.
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