Abstract
Effective scale-up is essential for successful bioprocessing. While it is desirable to keep as many operating parameters constant as possible during the scale-up, the number of constant parameters realizable is limited by the degrees of freedom in designing the large-scale operation. Scale-up of aerobic fermentations is often carried out on the basis of a constant oxygen transfer coefficient, k L a, to ensure the same oxygen supply rate to support normal growth and metabolism of the desired high cell populations. In this paper, it is proposed to replace the scale-up criterion of constant k L by a more direct and meaningful criterion of equal oxygen transfer rate at a predetermined value of dissolved oxygen concentration. This can be achieved by using different oxygen partial pressures in the influent gas streams for different scales of operation. One more degree of freedom, i.e., gas-phase oxygen partial pressure, is thus added to the process of scale-up. Accordingly, one more operating factor can be maintained constant during scale-up. It can be used to regulate the power consumption in large-scale fermentors for economical considerations or to describe the fluid mixing more precisely. Examples are given to show that the results of optimization achieved in the bench-scale study can be translated to the production-scale fermentor more successfully with only a small change in the gas-phase oxygen partial pressure employed in the bench-scale operation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- a m2/m3 :
-
Specific gas/liquid interfacial area
- C L mole/m3 :
-
Dissolved oxygen concentration in bulk liquid phase
- C * mole/m3 :
-
Equilibrium oxygen concentration at gas/liquid interface
- D i m:
-
Impeller diameter
- D T m:
-
Bioreactor diameter
- H L mole/m3 · atm:
-
Henry's-law constant
- k L m/s:
-
Liquid-phase mass transfer coefficient
- N 1/s:
-
Impeller agitation speed
- N i :
-
Number of impellers
- OTR mole/s · m3 :
-
Oxygen transfer rate per unit volume of the medium
- P g kW:
-
Power input in aerated fermentation
- P o kW:
-
Power input in non-gassed fermentation
- p g atm:
-
Gas-phase oxygen partial pressure
- Q m3/s:
-
Volumetric gas flow rate
- Re i :
-
Impeller Reynolds number
- T Q Joule:
-
Torque applied to the mixer shaft
- V m3 :
-
Liquid volume
- v s m/s:
-
Superficial gas velocity
- μ kg/m · s:
-
Liquid viscosity
- ϱ kg/m3 :
-
Liquid density
References
Hubbard, D. W.: Scale-up strategies for bioreactors. In: Ho, C. S.; Oldshue, J. Y. (Eds.): Biotechnology processes. Scale-up and mixing, pp. 168–184. New York: AIChE 1987
Cooney, C. L.: Bioreactors: Design and operation. Science 219 (1983) 728–733
Wang, D. I. C.; Cooney, C. L.; Demain, A. L.; Dunnill, P.; Humphrey, A. E.; Lilly, M. D.: Fermentation and enzyme technology, pp. 194–211. New York: John Wiley & Sons, Inc. 1979
Fox, F. A.; Gex, V. E.: Single-phase blending of liquids. AIChE Journal 2 (1956) 539–544
Uhl, V. W.; Von Essen, J. A.: Scale-up of fluid mixing equipment. In: Uhl, V. W.; Gray, J. B. (Eds.): Mixing: Theory and practice, Vol. III, pp. 155–167. New York: Academic Press 1986
Einsele, A.: Scaling of bioreactors, theory and reality. Paper 4.13 presented at the 5th International Fermentation Symposium, Berlin 1976
Rushton, J. H.: Mixing — present theory and practice. Chem. Eng. Prog. 49 (1953) 161–168 and 267–275
Blakebrough, N.; Sambamurthy, K.: Mass transfer and mixing rates in fermentation vessels. Biotechnol. Bioeng. 8 (1966) 25–32
Steel, R.; Maxon, W. D.: Dissolved oxygen measurements in pilot and production-scale novobiocin fermentations. Biotechnol. Bioeng. 4 (1962) 231–240
Aiba, S.; Humphrey, A. E.; Millis, N. F.: Biochemical Engineering, 2nd edition, pp. 195–217. New York: Academic Press 1973
Gaden, E. L.: Aeration and agitation in fermentation. Sci. Rep. Ist. Super. Sanita 1 (1961) 161
Penney, W. R.: Recent trends in mixing equipment. Chem. Eng. 78(7) (1971) 86–98
Moo-Young, M.; Blanch, H. W.: Design of biochemical reactors. Mass transfer criteria for simple and complex systems. In: Ghose, T. K.; Fiechter, A.; Blakebrough, N. (Eds.): Advances in biochemical engineering, Vol. 19, pp. 1–69. Berlin: Springer-Verlag 1981
Oldshue, J. Y.: Fermentation mixing scale-up technique. Biotechnol. Bioeng. 8 (1966) 3–24
Cooper, C. M.; Fernstrom, G. A.; Miller, S. A.: Performance of agitated gas-liquid contactors. Ind. Eng. Chem. 36 (1944) 504–509
Bailey, J. E.; Ollis, D. F.: Biochemical engineering fundamentals, 2nd edition, pp. 508–512. New York: McGraw-Hill 1986
Finn, R. K.: Agitation and aeration. In: Blakebrough, N. (Ed.): Biochemical and biological engineering science, Vol. 1, pp. 69–99. New York: Academic Press 1967
Taguchi, H.; Miyamoto, S.: Power requirement in non-Newtonian fermentation broth. Biotechnol. Bioeng. 8 (1966) 43–54
Niitsu, H.; Fujita, M.; Terui, G.: Tryptophan fermentation with an improved strain of Hansenula anomala under the control of dissolved oxygen concentration. J. Ferm. Technol. 47 (1969) 194–202
Sumino, Y.; Kanzaki, T.; Fukuda, H.: Oxygen transfer in L-glutamic acid fermentation by an oleic acid-requiring organism. II. Effects of dissolved oxygen. J. Ferm. Technol. 46 (1968) 1040–1047
Connolly, J. R.; Winter, R. L.: Approaches to mixing operation scale-up. Chem. Eng. Prog. 65(8) (1969) 70–78
Fukuda, H.; Sumino, Y.; Kansaki, T.: Scale-up of fermentors. I. Modified equations for volumetric oxygen transfer coefficient. J. Ferment. Tech. (Japan) 46 (1968) 829–837
Fukuda, H.; Sumino, Y.; Kansaki, T.: Scale-up of fermentors. II. Modified equations for power requirement. J. Ferment. Tech. (Japan) 46 (1968) 838–845
Michel, B. J.; Miller, S. A.: Power requirements of gas-liquid systems. AIChE Journal 8 (1962) 262–266
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ju, L.K., Chase, G.G. Improved scale-up strategies of bioreactors. Bioprocess Eng. 8, 49–53 (1992). https://doi.org/10.1007/BF00369263
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00369263