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Integration of Physiology and Fluid Dynamics

  • Sven Schmalzriedt
  • Marc Jenne
  • Klaus Mauch
  • Matthias Reuss
Chapter
Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 80)

Abstract

The purpose of strategies for the integration of fluid dynamics and physiology is the development of more reliable simulation tools to accelerate the process of scale-up. The rigorous mathematical modeling of the richly interactive relationship between the dynamic response of biosystems and the physical environment changing in time and space must rest on the link between coupled momentum, energy and mass balances and structured modeling of the biophase. With the exponential increase in massive computer capabilities hard- and software tools became available for simulation strategies based on such holistic integration approaches. The review discusses fundamental aspects of application of computational fluid dynamics (CFD) to three-dimensional, two-phase turbulence flow in stirred tank bioreactors. Examples of coupling momentum and material balance equations with simple unstructured kinetic models for the behavior of the biophase are used to illustrate the application of these strategies to the selection of suitable impeller configurations. The examples reviewed in this paper include distribution of carbon and energy source in fed batch cultures as well as dissolved oxygen fields during aerobic fermentations.

A more precise forecasting of the impact of the multitude of interactions must, however, rest upon a rigorous understanding of the response of the cell factory to the complex dynamic stimulation due to space- and time-dependent concentration fields.The paper also introduces some ideas for fast and very fast experimental observations of intracellular pool concentrations based on stimulus response methods. These observations finally lead to a more complex integration approach based on the coupling of CFD and structured metabolic models.

Keywords

Computational fluid dynamics (CFD) Intracellular metabolites Integration of CFD with unstructured and structured kinetic models 

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References

  1. 1.
    Jenne M, Reuss M (1999) Chem Eng Sci 54:3921CrossRefGoogle Scholar
  2. 2.
    Launder BE, Spalding DB (1972) Mathematical models of turbulence. Academic PressGoogle Scholar
  3. 3.
    Launder BE, Spalding DB (1974) Comp Meth Appl Mech Eng 3:269CrossRefGoogle Scholar
  4. 4.
    Kim JJ (1978) Three dimensional turbulent flow-field in a turbine stirred tank. PhD thesis, Louisiana State UniversityGoogle Scholar
  5. 5.
    Pope SB (1978) AIAA J 16:279CrossRefGoogle Scholar
  6. 6.
    Hanjalick, Launder BE (1980) Trans ASME 102:34Google Scholar
  7. 7.
    Kline SJ, Cantwell BJ, Lilley GM (1981) The 1980-1981 HFOSR-HTMM-Stanford Conference on Complex Turbulent Flow, Stanford University, I, II, IIIGoogle Scholar
  8. 8.
    Roback R, Johnson BV (1983) NASA CR-168252Google Scholar
  9. 9.
    Chen YS, Kim SW (1987) NASA CR-179204Google Scholar
  10. 10.
    Patankar SV (1980) Numerical heat transfer and fluid flow. Mc Graw-HillGoogle Scholar
  11. 11.
    Van’t Riet K, Smith JM (1975) Chem Eng Sci 30:1093CrossRefGoogle Scholar
  12. 12.
    Perng CY, Murthy JY (1993) AIChE Symp Ser 89:37Google Scholar
  13. 13.
    Takeda H, Narasaki K, Kitajima H, Sudoh S, Onofusa M, Iguchi S (1993) Comput Fluids 22:223CrossRefGoogle Scholar
  14. 14.
    Brucato A, Ciofalo M, Grisafi F, Micale G (1998) Chem Eng Sci 53:3653CrossRefGoogle Scholar
  15. 15.
    Placek J, Tavlarides LL (1985) AIChE J31:1113CrossRefGoogle Scholar
  16. 16.
    Gosman AD (1998) Trans I Chem Eng 76:153CrossRefGoogle Scholar
  17. 17.
    Issa RI, Gosman AD (1981) The computation of three-dimensional turbulent two phase flows in mixer vessels. In: Numerical methods in laminar and turbulent flow. Pineridge Press, Swansea, p 829Google Scholar
  18. 18.
    Trägardh C (1988) A hydrodynamic model for the simulation of an aerated agitated fed-batch fermentation. In: Bioreactor fluid dynamics. Elsevier, p 117Google Scholar
  19. 19.
    Politis S, Issa RI, Gosman AD, Lekakon C, Looney MK (1992) AIChE J 38:1946CrossRefGoogle Scholar
  20. 20.
    Morud K, Hjertager BH (1993) Computational fluid dynamics simulations of bioreactors. In: Mortensen U, Noorman H (eds) Bioreactor performance. IDEON, Lund, Sweden, p 47Google Scholar
  21. 21.
    Ishii M (1975) Thermo-fluid dynamic theory of two-phase-flow. EyrollesGoogle Scholar
  22. 22.
    Ranade VV, van den Akker HEA (1994) Chem Eng Sci 49:5175CrossRefGoogle Scholar
  23. 23.
    Kuo JT, Wallis GB (1988) Int J Multiphase Flow 14:547CrossRefGoogle Scholar
  24. 24.
    Ishii M, Zuber N (1979) AIChE J 25:843CrossRefGoogle Scholar
  25. 25.
    Drew DA, Lahey TJ (1987) Int J Multiphase Flow 13:113CrossRefGoogle Scholar
  26. 26.
    Lopez de Bertodano M, Lahey TJ, Jones OCC (1994) Trans SME 116:128Google Scholar
  27. 27.
    Watanabe T, Hirano M, Tanabe F, Kamo H (1990) Nuclear Engng Design 120:181CrossRefGoogle Scholar
  28. 28.
    Huang B (1989) Modelisation numérique d’écoulements disphasiques à bulles dans des réacteurs chimiques. PhD thesis, LyonGoogle Scholar
  29. 29.
    Kowe R, Hunt JCR, Hunt A, Couet B, Bradbury LJS (1988) Int J Multiphase Flow 14:587CrossRefGoogle Scholar
  30. 30.
    Lopez de Bertodano M. Lee SJ, Lahey RT, Drew DA (1990) ASME J Fluids Enging 112:107CrossRefGoogle Scholar
  31. 31.
    Svendsen HF, Jakobsen HA, Torvik R (1992) Chem Eng Sci 47:3297CrossRefGoogle Scholar
  32. 32.
    Johansen ST, Boysan F (1988) Metall Trans B 19B:755CrossRefGoogle Scholar
  33. 33.
    Lahey RT, Lopez de Bertodano M, Jones OC (1993) Nuclear Enging Des 141:177CrossRefGoogle Scholar
  34. 34.
    Sato Y, Adatomi M, Sekoguchi K (1981) Int J Multiphase Flow 7:167CrossRefGoogle Scholar
  35. 35.
    Rousar I, van den Akker HEA (1994) Proceedings of the 8th European conference on mixing, Cambridge, UK, p 89Google Scholar
  36. 36.
    Reuss M, Bajpai R (1991) Stirred tank models. In: Schügerl K (ed) Biotechnology, a multivolume comprehensive treatise, vol 4, measuring, modelling and control. VCH, Weinheim, p299Google Scholar
  37. 37.
    Joshi JB, Pandit AB, Sharma MM (1982) Chem Eng Sci 37:813CrossRefGoogle Scholar
  38. 38.
    Bombac A (1994) PhD thesis, University of LjubljanaGoogle Scholar
  39. 39.
    Bombac A, Zun I, Filipic B, Zumer M (1997) AIChE J 43:2921CrossRefGoogle Scholar
  40. 40.
    Hinze JO (1955) AIChE J 3:289CrossRefGoogle Scholar
  41. 41.
    Bakker A, van den Akker HEA (1994) Trans I Chem Eng 72:594Google Scholar
  42. 42.
    Greaves M, Barigou M (1988) Proceedings of the 6th European conference on mixing, Pavia, Italia, p 313Google Scholar
  43. 43.
    Jenne M (1999) Modellierung und Simulation der Strömungsverhältnisses in begasten Rührkesselreaktoren. PhD thesis, Universität StuttgartGoogle Scholar
  44. 44.
    Reuss M, Schmalzriedt S, Jenne M (2000) In: Schügerl, Bellgardt (eds) Bioreaction engineering. Springer-Verlag (in press)Google Scholar
  45. 45.
    Bouafi M, Roustan M, Djebbar R (1997) Mixing IX, multiphase systems. Récents Progrès en génie des procédés 11(52):137Google Scholar
  46. 46.
    John AH, Bjalski W, Nienow AW (1997) Mixing IX, multiphase Systems. Récents Progrès en génie des procédés 11(52): 169Google Scholar
  47. 47.
    Nienow AW, Elson TP (1988) Chem Eng Res Des 66:5Google Scholar
  48. 48.
    Cooke M, Middleton JC, Bush JR (198) Proceedings of the 2nd international conference on bioreactor fluid dynamics, BHRA/Elsevier, p 37Google Scholar
  49. 49.
    Abradi V, Rovera G, Baldi G, Sicardi S, Conti R (1990) Trans I Chem E 68:516Google Scholar
  50. 50.
    Harvey PS, Greaves M (1982) Trans I Chem Eng 60:201Google Scholar
  51. 51.
    Friberg PC (1988) PhD Thesis, NTNU Trondheim, NorwayGoogle Scholar
  52. 52.
    Noorman H (1993) Bioreactor performance on 30 m3 scale: verification of a scale-down/CFS approach. Technical report, Instituttet for Bioteknologi, Damarks Tekniske Hojskole, Lyngy, DenmarkGoogle Scholar
  53. 53.
    Cui YQ, van der Lans RGJM, Noorman HJ, Luybenk ChAM (1996) Trans/Chem E 74:261Google Scholar
  54. 54.
    Voncken RM (1966) Circumlatie stromingen en menjing in geroerde vaten. PhD thesis, Delft University of TechnologyGoogle Scholar
  55. 55.
    Hoogendoorn CJ, Hartog AP (1967) Chem Eng Sci 22:1689CrossRefGoogle Scholar
  56. 56.
    Landau J, Prochazka J (1961) Coll Czechoslov Chem Commun 26:1976Google Scholar
  57. 57.
    Khang SJ, Levenspiel O (1976) Chem Eng Sci 31:569CrossRefGoogle Scholar
  58. 58.
    Tatterson GB (1991) Fluid mixing and gas dispersion in agitated tanks. McGraw Hill, New YorkGoogle Scholar
  59. 59.
    Groen DJ (1994) Macromixing in bioreactors. PhD thesis, Delft University of TechnologyGoogle Scholar
  60. 60.
    Bajpai R, Reuss M (1982) Can J Chem Eng 60:384Google Scholar
  61. 61.
    Kawase Y, Moo-Young M (1990) ChemEng I 43:B19Google Scholar
  62. 62.
    Van’t Riet K (1979) Ind Eng Chem Proc Des Dev 18:367CrossRefGoogle Scholar
  63. 63.
    Theobald U, Mailinger W, Reuss M (1998) Anal Biochem 214:31CrossRefGoogle Scholar
  64. 64.
    Rizzi M, Theobald U, Querfurth E, Rohrhirsch T, Baltes M, Reuss M (1996) Biotechnol Bioeng 49:316CrossRefGoogle Scholar
  65. 65.
    Theobald U, Mailinger W, Baltes M, Rizzi M, Reuss M (1997) Biotechnol Bioeng 55:305CrossRefGoogle Scholar
  66. 66.
    Vaseghi S, Baumeister A, Rizzi M, Reuss M (1999) Metabolic Eng 1:128CrossRefGoogle Scholar
  67. 67.
    Schaefer U, Boos W, Takors R, Weuster-Botz D (1999) Anal Biochem 270:88CrossRefGoogle Scholar
  68. 68.
    Buziol S, Bashir I, Baumeister A, Claasen W, Noisommit-Rizzi N, Mailinger W, Reuss M (2002) Biotechnol Bioeng 80:632CrossRefGoogle Scholar
  69. 69.
    Mailinger W, Baumeister A, Reuss M, Rizzi M (1998) J Biotechnol 63:155CrossRefGoogle Scholar
  70. 70.
    Rizzi M, Baltes M,Theobald U, Reuss M (1997) Biotechnol Bioeng 55:592CrossRefGoogle Scholar
  71. 71.
    Mauch K, Hieber SE, Reuss M (2000) Proceedings of the 4th international congress on biochemical engineering, Stuttgart, Fraunhofer IRB Verlag, ISBN 3-8167-5570-4:57Google Scholar
  72. 72.
    de Koning W, van Dam K (1992) Anal Biochem 204:118CrossRefGoogle Scholar
  73. 73.
    Liao JV, Hou S-Y, Chao Y-P (1996) Biotechnol Bioeng 52:129CrossRefGoogle Scholar
  74. 74.
    Schäfer K, Boos W, Takors R, Weuster-Botz D (1999) Anal Biochem 270:88CrossRefGoogle Scholar
  75. 75.
    Kaback H R (1969) Physiology 63:724Google Scholar
  76. 76.
    Larsson G, Törnkvist M, Stahl Wernersson E, Trägardh C, Noorman H, Enfors S-O (1996) BioprocEng 14:281CrossRefGoogle Scholar
  77. 77.
    Griot M (1987) Maßstabsvergrößerung von Bioreaktoren mit einer sauerstoffempfind-lichen Testkultur. PhD Thesis, ETH ZürichGoogle Scholar
  78. 78.
    Moes J (1985) Untersuchung von Mischphänomenen mit Hilfe von Bacillus subtilis. PhD Thesis, ETH ZürichGoogle Scholar
  79. 79.
    Moes J, Griot M, Keller J, Heinzle E, Dunn LJ, Bourne JR (1985) Biotechnol Bioeng 27:482CrossRefGoogle Scholar
  80. 80.
    Kossen NWF (1992) In: Vardar-Sukan F, Suha Sukan S (eds) Recent advances in biotechnology. NATO Asi series, Kluwer Academic Publisher, p 147Google Scholar
  81. 81.
    Cui YQ, van der Lans RGJM, Noorman HJ, Luyben KCAM (1996) Trans IChemE 74(A):261Google Scholar
  82. 82.
    Alves S, Vasconcelos JMT, Barata J (1997) Trans IChemE 75(A):334CrossRefGoogle Scholar
  83. 83.
    Vrabel P, van der Lans RGJM, Cui YQ, Luyben KCAM (1999) Trans IChemE 77(A4):291CrossRefGoogle Scholar
  84. 84.
    Chassagnole C, Noisommit-Rizzi N, Schmid J-W, Mauch K, Reuss M (2002) Biotechnol Bioeng 79:53CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2003

Authors and Affiliations

  • Sven Schmalzriedt
    • 1
  • Marc Jenne
    • 1
  • Klaus Mauch
    • 1
  • Matthias Reuss
    • 1
  1. 1.Institute of Biochemical EngineeringUniversity of StuttgartStuttgartGermany

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