Bioprocess Engineering

, Volume 9, Issue 2–3, pp 61–75 | Cite as

Oxygenation of cell cultures

  • H.-J. Henzler
  • D. J. Kauling
Originals

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.

List of Symbols

A

Interfacial area

a

=A/V, Specific interfacial area

c*

Saturation concentration

c

Gas concentration in the liquid phase

d

Impeller diameter

d2

Outside diameter of tubular membrane

d1

Inside diameter of tubular membrane

d

Diameter under stretched conditions

dp

Particle diameter

dL

Diameter of sparger holes

D

Reactor diameter

DL

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

Hys

Henry constant of the membrane material

k

Overall mass transfer coefficient

kL

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

Vs

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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References

  1. 1.
    Henzler, H.-J.; Kauling, J: Sauerstoffversorgung von Zellkulturen. Lecture presented at Fachausschußsitzung. Bioverfahrenstechnik der GVC in Würzburg Mai 1990 and Preprints of 2. Taunustagung in Bad Soden Febr. 1991Google Scholar
  2. 2.
    Thilly, W. G.: Mammalian Cell Technology. Butterworths 1986Google Scholar
  3. 3.
    Bailey, J. E.; Ollis, D. F.: Biochemical Engineering Fundamentals. McGraw-Hill Book Company 1987Google Scholar
  4. 4.
    Brunner, H.; Comer, M. J.; Kearns, M. J.: Preprints of 2. BMFT Statusseminar “Produktion natürlicher Substanzen aus tierischen Zellen” 1985 Herausgeber Bundesministerium für Forschung und Technologie in BonnGoogle Scholar
  5. 5.
    Miller, W. M.; Wilke, C. R.; Blanch, H. W.: Journal of Cellular Physiologie. 132 (1987) 524–530Google Scholar
  6. 6.
    Bödeker, B.; u.a.: see 4.Google Scholar
  7. 7.
    Fiedl, P.; u.a.: Different oxygen sensitivities of vascular endothelical cells in an stirred bioreactor. Bericht der GBF BraunschweigGoogle Scholar
  8. 8.
    Hülscher, M.; Pauli, J.; Onken, U.: Biotechnology Letters. 10 (1988) 689–694Google Scholar
  9. 9.
    Lehmann J.; Piehl, W.; Schulz, R.: Biotech-Forum 2 (1985) 112–117Google Scholar
  10. 10.
    Bräutigam, H.-J.; Sekoulov, I.: Forum Mikrobiologie 9 (1986) 269–272Google Scholar
  11. 11.
    Bräutigam, H.: Preprints der 2. Taunustagung Membrantechnologie. Bad Soden 26 27.2.1991Google Scholar
  12. 12.
    Bräutigam, H.-J.: “Untersuchungen zum Einsatz von nichtporösen Kunststoff membranen als Sauerstoffeintragssystem” Dissertation TH Hamburg-Harburg 1985Google Scholar
  13. 13.
    Zlokarnik, M.: Korrespondenz Abwasser 27 (1980) 14–21Google Scholar
  14. 14.
    Vorlop, J.; Lehmann, J.: Chem. Eng. Technol. 11 (1988) 171–178Google Scholar
  15. 15.
    Brauer, H.; Mewes, D.: Stoffaustausch einschließlich chemischer Reaktion" in Grundlagen der Chemischen Verfahrenstechnik. Verlag Sauerländer, Aarau und Frankfurt am Main 1971Google Scholar
  16. 16.
    Perkins, H. C.; Leppert, G.: Trans. ASME C.J. Heat Transfer. 84 (1962) 257–63Google Scholar
  17. 17.
    Henzler, H.-J.: Chem.-Ing.-Tech. 52 (1980) 643–652Google Scholar
  18. 18.
    Zlokarnik, M.: Acta Biotechnologica 1 (1981) 311–325Google Scholar
  19. 19.
    Henzler, H.-J.: Chem.-Ing.-Tech. 45 (1982) 461–476Google Scholar
  20. 20.
    Henzler, H.-J.: VDI-Forschungsheft 587. 1978. VDI-VerlagGoogle Scholar
  21. 21.
    Calderbank, P. H., Moo-Young, M. B.: Chem. Engng. Sci. 16 (1961) 39–54Google Scholar
  22. 22.
    Hinze, J. O.: Turbulence. Mc Graw-Hill, New York 1975Google Scholar
  23. 23.
    Liepe, F.: “Stoffvereinigen in fluiden Phasen” in Verfahrenstechnishen Berechnungsunterlagen VCH Verlagsgesellschaft 1988Google Scholar
  24. 24.
    Möckel, H.-O.: Hydrodynamische Untersuchungen in Rührmaschinen. Dissertation Ingenieurhochschule Köthen 1978Google Scholar
  25. 25.
    Laufhütte, H.-D.: Turbulenzparameter in gerührten Fluiden. Dissertation TU München 1986Google Scholar
  26. 26.
    Geißler, R. K.: Fluiddynamik und Leistungseintrag in turbulent gerührten Suspensionen. Dissertation TU München 1991Google Scholar
  27. 27.
    Handa, A.: Ph.D. Thesis, University of Birmingham. 1986Google Scholar
  28. 28.
    Tramper, J., Vlak, J. M.: Preprints der GVC-Vortragstagung in Tübingen 1987, 189–201Google Scholar
  29. 29.
    Hülscher, M.: Fortschritt-Bericht Verfahrenstechnik. Reihe 3 (1990) 229 VDI-VerlagGoogle Scholar
  30. 30.
    Riquarts, H. P.: Chem.-Ing. Tech. 54 (1982) MS1023/82Google Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • H.-J. Henzler
    • 1
  • D. J. Kauling
    • 1
  1. 1.Zentrale Forschung/Bioverfahrenstechnik BAYER AGWuppertalGermany

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