Abstract
Submersed cultures are increasingly being used for fermentation with animal cells. Reactor design is particularly important in these operations, because of the sensitivity of the cells to shear. In addition to the usual aeration methods, open-pore membranes or pure diffusion membranes are used for oxygenation in order to avoid gas bubbles. The various oxygenation methods are described in the present article [1]. Design principles for surface aeration, bubble columns, loop reactors, and stirred tanks, as well as oxygenation with Accurel or silicone membranes, are presented and discussed specifically for the low oxygen inputs desired in cell cultures. The scale laws are formulated, and special reference is made to problems of scale up. The various oxygenation methods are finally compared on the basis of the design principles presented, with particular attention to mechanical stress on the cells and to the laws of scale translation.
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Abbreviations
- A :
-
Interfacial area
- a :
-
=A/V, Specific interfacial area
- c * :
-
Saturation concentration
- c :
-
Gas concentration in the liquid phase
- d :
-
Impeller diameter
- d 2 :
-
Outside diameter of tubular membrane
- d 1 :
-
Inside diameter of tubular membrane
- d′:
-
Diameter under stretched conditions
- d p :
-
Particle diameter
- d L :
-
Diameter of sparger holes
- D :
-
Reactor diameter
- D L :
-
Draught tube diameter
- \(\mathbb{D}\) :
-
Gas/liquid diffusion coefficient
- e :
-
Eccentricity
- Fr :
-
Froude number
- G :
-
Mass flow
- g :
-
Acceleration due to gravity
- h :
-
Height of impeller blade
- H :
-
Filling height
- Hy :
-
Henry constant for the liquid phase
- Hy s :
-
Henry constant of the membrane material
- k :
-
Overall mass transfer coefficient
- k L :
-
Gas-liquid interface mass transfer coefficient
- L :
-
Length of the tubular membrane
- L′:
-
Length of the streched turbulare membrane
- n :
-
Impeller speed
- Ne :
-
P/ϱ n3d5, Newton number
- \(\mathcal{P}{\text{o}}_{\text{2}} \) :
-
O2-partial pressure in the membrane
- \({\text{(}}\mathcal{P}{\text{o}}_{\text{2}} )_R \) :
-
O2-partial pressure in the reactor
- P :
-
Impeller power
- q :
-
Gas throughput
- r :
-
Cell specific respiration rate
- Re :
-
Reynolds number
- Sc :
-
\(v/\mathbb{D}\), Schmidt number
- Sh :
-
\(/\mathbb{D}\), Sherwood number
- u :
-
Liquid velocity
- \(\sqrt {u'^2 } \) :
-
Root mean square velocity of turbulent fluctuations Superficial gas velocity
- V :
-
Filled reactor volume
- V s :
-
Sparged volume
- X :
-
Cell concentration
- ɛ :
-
Energy dissipation
- η :
-
Dynamic viscosity
- ϑ :
-
Temperature
- ν :
-
Kinematic viscosity
- ϱ :
-
Density of the liquid
- σ :
-
Surface tension
- τ :
-
Shear stress
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Henzler, HJ., Kauling, D.J. Oxygenation of cell cultures. Bioprocess Eng. 9, 61–75 (1993). https://doi.org/10.1007/BF00369033
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DOI: https://doi.org/10.1007/BF00369033