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Zusammenfassung

Die industrielle Verwertung Erfolg versprechender Bioreaktionen scheitert oft an der Übertragung der Ergebnisse vom Schüttelkolben in den m3-Maßstab. Der technischen Auslegung des hierfür notwendigen Reaktors sowie der Produktisolation und -reinigung sind deshalb die folgenden Kapitel gewidmet (7 bis 12).

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Literatur

  1. Adler, I. (1986): Valuation of bioreactors for low viscous media and high oxygen transfer demand. Bioproc. Eng. 1: 51–59CrossRefGoogle Scholar
  2. Adler, I., Fiechter, A. (1983): Charakterisierung von Bioreaktoren mit biologischen Testsystemen. Chem.-Ing.-Tech. 4: 322–323CrossRefGoogle Scholar
  3. Anderlei, T., Büchs, J. (2001): Device for sterile online measurement of the oxygen transfer rate in shaking flasks. Biochem. Eng. J. 7: 157–162PubMedCrossRefGoogle Scholar
  4. Anderlei, T., Zang, W., Papaspyrou, M., Büchs, J. (2004): Online respiration activity measurement (OTR, CTR, RQ) in shake flasks. Biochem. Eng. J. 17: 187–194CrossRefGoogle Scholar
  5. Anton, F., Suck, K., Diederichs, S., Behr, L., Hitzmann, B., van Griensven, M., Scheper, T., Kasper, C. (2008): Design and characterization of a rotating bed system bioreactor for tissue engineering applications. Biotechnol. Prog. 24: 140–147PubMedCrossRefGoogle Scholar
  6. Behie, L. A., Kalogerakis, N., Gaucher, G. M. (1987): The Application of Continous Three Phase Fluidized Bed Bioreactors to the Production of Pharmaceuticals. In: Chmiel, H., Hammes, W. P., Bailey, J. E. (Hrsg.): Biochemical Engineering. Gustav Fischer Verlag, StuttgartGoogle Scholar
  7. Blenke, H. (1979): Loop reactors. Adv. Biochem. Eng. 13: 121–214Google Scholar
  8. Blenke, H. (1984): Strömung, Dispergierung und Stoffübertragung bei G-L-Systemen in Schlaufenreaktoren. Preprints „Technik der Gas-Flüssig-und der Dreiphasenströmung“. GVC VDI-Gesellschaft Verfahrenstechnik und ChemieingenieurwesenGoogle Scholar
  9. Blenke, H. (1985): Biochemical Loop Reactors. In Biotechnology Vol. 2, VCH Verlagsgesellschaft, WeinheimGoogle Scholar
  10. Blenke, H. (1987): Process engineering contributions to bioreactor design and operation. In: Chmiel, H., Hammes, W. P., Bailey, J. E. (Hrsg.): Biochemical Engineering. Gustav Fischer Verlag, StuttgartGoogle Scholar
  11. Blenke, H. (1988): Verfahrenstechnische Beiträge zur Entwicklung von Bioreaktoren. BTF Biotech-Forum 1: 5Google Scholar
  12. Buchenauer, A., Funke, M., Büchs, J., Mokwa, W., Schnakenberg, U. (2009): Microbioreactors with microfluidic control and a user-friendly connection to the actuator hardware. J. Micromech. Microeng. 19: 074012 (8pp)CrossRefGoogle Scholar
  13. Chu, L., Robinson, D. K. (2001) Industrial choices for protein production by large-scale cell culture. Curr. Opin. Biotechnol. 12: 180–187PubMedCrossRefGoogle Scholar
  14. Dhariwal (2007): The significance of submerged ceramic membrane systems for production oriented bioprocesses. Dissertation, Universität des SaarlandesGoogle Scholar
  15. Diederichs, S., Freiberger, F., van Griensven, M. (2009): Effects of Repetitive and Short Time Strain in Human Bone Marrow Stromal Cells. J Biomed Mater Res A 88: 907–915PubMedGoogle Scholar
  16. Eibl, R., Eibl, D. (2009): Application of disposible bag bioreactors in tissue engineering and for the production of therapeutic agents. Adv. Biochem. Engin./Biotechnol. 112: 183–207CrossRefGoogle Scholar
  17. Funke, M., Buchenauer, A., Schnakenberg, U., Mokwa, W., Diederichs, S., Mertens, A., Müller, C., Kensy, F., Büchs, J. (2010): Microfluidic BioLector-Microfluidic Bioprocess Control in Microtiter Plates. Biotechnol. Bioeng. 107:497–505PubMedCrossRefGoogle Scholar
  18. Furchner, B. (1988): Die Zerstörung wässriger Tensidschäume durch rotierende Einbauten. Dissertation, Technische Universität MünchenGoogle Scholar
  19. Gebauer, A. (1985): Untersuchungen zum Wachstum und zur Enzymproduktion von E. coli. Dissertation, Universität HannoverGoogle Scholar
  20. Geisler, R. K. (1991): Fluiddynamik und Leistungseintrag in turbulent gerührten Suspensionen, Dissertation TU MünchenGoogle Scholar
  21. Gruber, T., Chmiel, H., Käppeli, O., Sticher, P., Fiechter, A. (1993): Integrated process for continuous rhamnolipid biosynthesis. In: Kosaric, N. (Hrsg.) Biosurfactants. Production — Properties — Applications. Surfactant Science Series, Vol. 48. Marcel Dekker, Inc., New York, 157–173Google Scholar
  22. Heijnen, J. J. (1984): Technik der anaeroben Abwasserreinigung. Chem.-Ing.-Tech. 56: 526–532CrossRefGoogle Scholar
  23. Henkel, H. J. (1992): Reaktionstechnische Untersuchung eines Dreiphasenfließbettreaktors..., Dissertation, Universität StuttgartGoogle Scholar
  24. Henzler, H.-J. (1982): Verfahrenstechnische Auslegungsunterlagen für Rührbehälter als Fermenter. Chem.-Ing.-Tech. 5: 461–476CrossRefGoogle Scholar
  25. Hiby, J. W. (1979): Definition und Messung der Mischgüte in flüssigen Gemischen. Chem.-Ing.-Tech. 7: 704–709CrossRefGoogle Scholar
  26. Hortsch, R., Stratmann, A., Weuster-Botz, D. (2010): New milliliter-scale stirred tank bioreactors for the cultivation of mycelium forming microorganisms. Biotechnol. Bioeng. 106: 443–451PubMedGoogle Scholar
  27. Hortsch, R., Weuster-Botz, D. (2010): Power consumption and maximum energy dissipation in a milliliter-scale bioreactor. Biotechnol. Prog. 26: 595–599PubMedGoogle Scholar
  28. Hortsch, R. (2011): Miniaturisierte Rührreaktoren zur Kultivierung morphologisch veränderlicher Mikroorganismen. Dissertation TU München, Lehrstuhl für BioverfahrenstechnikGoogle Scholar
  29. Huber, R., Ritter, D., Hering, T., Hillmer, A.-K., Kensy, F., Müller, C., Wang, L., Büchs, J. (2009): Robo-Lector — a novel platform for automated high-throughput cultivations in microtiter plates with high information content. Microbial Cell Factories 8: 42PubMedCrossRefGoogle Scholar
  30. Jaramillo, A. (1985): Fluid dynamic and oxygen transfer during the cultivation of Trichosporon cutaneum in jet loop bioreactors. Dissertation Nr. 7899, ETH ZürichGoogle Scholar
  31. Jeude, M., Dittrich, B., Niederschulte, H., Anderlei, T., Knocke, C., Klee, D., Büchs. J. (2006): Fed-batch mode in shake flasks by slow-release technique. Biotechnol. Bioeng. 95: 433–445PubMedCrossRefGoogle Scholar
  32. Judat, H. (1976): Zum Dispergieren von Gasen. Dissertation, Universität DortmundGoogle Scholar
  33. Judat, H. (1982): Stoffaustausch Gas/Flüssigkeit im Rührkessel — eine kritische Bestandsaufnahme. Chem.-Ing.-Tech. 5: 520–521CrossRefGoogle Scholar
  34. Karrer, D. (1978): Der total gefüllte Bioreaktor. Optimierung, physikalisch-chemische und biologische Charakterisierung. Dissertation Nr. 6254, ETH ZürichGoogle Scholar
  35. Kaskas, A. (1969): Partikelbewegung bei der Sedimentation von Mehrkornsuspensionen. Chem.-Ing.-Tech. 18Google Scholar
  36. Kasper, C. (2005): Tissue Engineering; Ersatzteillager Mensch. Chem. Unserer Zeit 39: 394–401CrossRefGoogle Scholar
  37. Kasper, C., van Griensven, M., Pörtner, M. (2009): Bioreactor systems for tissue engineering. Biochem. Eng. Technol. 112: 1–271Google Scholar
  38. Kensy, F., Engelbrecht, C., Büchs, J. (2009a): Scale-up from microtiter plate to laboratory fermenter: evaluation by online monitoring techniques of growth and protein expression in Escherichia coli and Hansenula polymorpha fermentations. Microbial Cell Factories 8: 68PubMedCrossRefGoogle Scholar
  39. Kensy, F., Zang, E., Faulhammer, C., Tan, R.-K., Büchs, J. (2009b): Validation of a high-throughput fermentation system based on online monitoring of biomass and fluorescence in continuously shaken microtiter plates. Microbial Cell Factories 8: 31PubMedCrossRefGoogle Scholar
  40. Kintzios, S., Makri, O., Pistola, E., Matakiadis, T., Shi, H. P., Economou, A. (2004): Scale-up production of puerarin from hairy roots of Pueraria phaseoloides in an airlift bioreactor. Biotechnol. Lett. 26: 1057–1059PubMedCrossRefGoogle Scholar
  41. Kipke, K. (1985a): Rührtechnische Auslegungsaspekte von Industriefermentern. Biotech-Forum 2: 65–72Google Scholar
  42. Kipke, K. (1985b): Auslegung von Industrierührwerken. Chem.-Ing.-Tech. 57: 813–823CrossRefGoogle Scholar
  43. Knorr, B., Schlieker, H., Hohmann, H. P., Weuster-Botz, D. (2007): Scale-down and parallel operation of the riboflavin production process with Bacillus subtilis. Biochem. Eng. J. 33: 263–274CrossRefGoogle Scholar
  44. Kolla, M. (1984): Vergleich des Stoffübergangs beim Wachstum einer Hefe und eines Bakteriums im Airlift-Schlaufenfermenter. Dissertation, Universität DortmundGoogle Scholar
  45. Krahe, M. (2000): Biochemical Engineering. Ullmann’s Encyclopedia of Industrial ChemistryGoogle Scholar
  46. Kraume, M. (2002): Mischen und Rühren, Grundlagen und moderne Verfahren, Wiley-VCH Verlag, WeinheimCrossRefGoogle Scholar
  47. Kresta, S. M., Wood, P. E. (1993): The flow field produced by a pitched blad turbine, Characterization of the turbulence and estimation of the dissipation rate. Chem. Eng. Sci. 48: 1761–1774CrossRefGoogle Scholar
  48. Kusterer, A., Krause, C., Kaufmann, K., Arnold, M., Weuster-Botz, D. (2008): Fully automated single-use stirred-tank bioreactors for parallel microbial cultivations. Bioprocess Biosys. Eng. 31: 207–215CrossRefGoogle Scholar
  49. Linek, V., Vacek, V. (1986): Recommended procedure for the measurement of the volumetric mass transfer coefficient kLa in aerated agitated vessels. Report for the Working Party on Mixing of EFChE, Prague Inst. Chem. TechnologyGoogle Scholar
  50. Lohmann, T., Pahl, M. H. (1993): Mechanische Schaumzerstörung feststoffhaltiger Schäume. Chem.-Ing.-Tech. 11: 1362–1365CrossRefGoogle Scholar
  51. Manna, L. (1997): Comparison between physical and chemical methods for the measurement of mixing times. Chem. Eng. J. 67: 167–173CrossRefGoogle Scholar
  52. Märkl, H., Lechner, M., Götz, F. (1990): A new dialysis fermentor for the production of high concentrations of extracellular enzymes. J. Ferment. Bioeng. 69: 244–249CrossRefGoogle Scholar
  53. Martin, I., Wendt, D., Heberer, M. (2004): The role of bioreactors in tissue engineering. Trends Biotechnol. 22: 80–86PubMedCrossRefGoogle Scholar
  54. Meusel, W. (1989): Beitrag zur Modellierung von Gas-Flüssigkeits-Reaktoren auf der Basis relevanter Mikroprozesse. Dissertation B, Ingenieurhochschule KöthenGoogle Scholar
  55. Naicker, M. (1999): Design and commissioning of the oscillatory mixer, Thesis Report, Department of Chemical Engineering University of QueenslandGoogle Scholar
  56. Pierce, L. N., Shabram, P. W. (2004): Scalability of a disposable bioreactor from 12L–500L run in perfusion mode with a CHO-based cell line: A tech review. BioProcessing J. 3(4): 1–6Google Scholar
  57. Pörtner, R., Fassnacht, D., Märkl, H. (1999): Immobilization of mammalian cells in fixed bed reactors. BIOforum International 4: 140–141Google Scholar
  58. Posten, C. (2009): Design principles of photo-bioreactors for cultivation of microalgae. Engineering in Life Sciences 9: 145–177CrossRefGoogle Scholar
  59. Puskeiler, R., Weuster-Botz, D. (2004): Rührkesselreaktoren im mL-Maßstab: Kultivierung von Escherichia coli. Chem.-Ing.-Tech. 76: 1865–1869CrossRefGoogle Scholar
  60. Puskeiler, R., Kaufmann, K., Weuster-Botz, D. (2005): Development, parallelization, and automation of a gas-inducing milliliter-scale bioreactor for high-throughput bioprocess design (HTBD). Biotechnol. Bioeng. 89: 512–523PubMedCrossRefGoogle Scholar
  61. Reule, W. (1983): Zur Sauerstoffübertragung im Strahl-Schlaufenreaktor mit dem Sulfitsystem. Dissertation, Universität StuttgartGoogle Scholar
  62. Richardson, J. F., Zaki, W. N. (1954): Sedimentation and fluidisation. Part I. Trans. Instn. Chem. Engrs. 32: 35–53Google Scholar
  63. Richardson, J. F., Mirza, S. (1979): Sedimentation of suspensions of particles of two or more sizes. Chem. Eng. Sci. 34: 447–454CrossRefGoogle Scholar
  64. Riesenberg, D., Menzel, K., Schulz, V., Schumann, K., Veith, G., Zuber, G., Knorre, W. A. (1990): High cell-density fermentation of recombinant Escherichia coli expressing human interferon alpha 1. Appl. Microbiol. Biotechnol. 34: 77–82PubMedCrossRefGoogle Scholar
  65. Samorski, M., Müller-Newen, G., Büchs, J. (2005): Quasicontinuous combined scattered light and fluorescence measurements: a novel measurement technique for shaken microtiter plates. Biotechnol. Bioeng. 92: 61–68PubMedCrossRefGoogle Scholar
  66. Sandoval-Basurto, E. A., Gosset, G., Bolivar, F., Ramirez, O. T. (2005): Culture of Escherichia coli under dissolved oxygen gradients simulated in a two-compartment scaledown system: Metabolic response and production of recombinant protein. Biotechnol. Bioeng. 89: 453–463PubMedCrossRefGoogle Scholar
  67. Scheidle, M., Jeude, M., Dittrich, B., Denter, S., Kensy, F., Suckow, M., Klee, D., Büchs, J. (2010): High-throughput screening of Hansenula polymorpha clones in batch compared to controlled-release fed-batch mode on small scale. FEMS Yeast Res. 10: 83–92PubMedCrossRefGoogle Scholar
  68. Schügerl, K. (1989): Biofluidization: Application of the fluidization technique in biotechnology. Canad. J. Chem. Eng. 67: 178–184CrossRefGoogle Scholar
  69. Seipenbusch, R., Blenke, H. (1980): The loop reactor for cultivating yeast on n-paraffin substrate. Adv. Biochem. Eng. 15: 1–40CrossRefGoogle Scholar
  70. Seletzky, J. M., Noack, U., Fricke, J., Welk, E., Eberhard, W., Knocke, C., Büchs, J. (2007): Scale-up from shake flasks to fermenters in batch and continuous mode with Corynebacterium glutamicum on lactic acid based on oxygen transfer and pH. Biotechnol. Bioeng. 98: 800–811PubMedCrossRefGoogle Scholar
  71. Siclaff, T. D, Hu, M. Z., Amiot, B., Rollins, M. D., Rao, S., McGuire, B., Bloomer, J. R., Hu, W. S., Cerra, F. B.(1995): Gel-entrapment bioartificial liver therapy in galactosamine hepatitis. J. Surg. Res. 59: 179–184CrossRefGoogle Scholar
  72. Sierra, E., Acien, F.G., Fernandez, J.M., Garcia, J.L., Gonzalez, C., Molina Grima, E. (2008): Characterization of a flat plate photobioreactor for the production of microalgae. Chem. Eng. J. 138(1–3): 136–147.CrossRefGoogle Scholar
  73. Stephens, E., Ross, I. L., King, Z., Mussgnug, J. H., Kruse, O., Posten, C., Borowitzka, M. A., Hankamer, B. (2010): An Economic and Technical Evaluation of Microalgal Biofueles. Nat. Biotechnol. 28(2): 4–6CrossRefGoogle Scholar
  74. Sternad, W. (1988): Beitrag zur Berechnung der Fluiddynamik von Mammut-Schlaufenreaktoren. Dissertation, Universität StuttgartGoogle Scholar
  75. Sternad, W. (1991): Bioreaktoren. In: Chmiel. H. (Hrsg.) Bioprozeßtechnik. Fischer-VerlagGoogle Scholar
  76. Sternad, W., Blenke, H. (1986): Untersuchung und Optimierung von Schlaufenreaktor-Varianten. Abschlussbericht zum AIF-Forschungsprojekt 5363, StuttgartGoogle Scholar
  77. Sternad, W., Blenke, H. (1989a): Zur Berechnung der Fluiddynamik von Mammut-Schlaufenreaktoren. Chem.-Ing.-Tech. 6: 479–482CrossRefGoogle Scholar
  78. Sternad, W., Blenke, H. (1989b): Hydrodynamische Schaumverhütung bei Gas-Liquid-Systemen. Forum Mikrobiologie 10: 465–473Google Scholar
  79. Stöckmann, C., Scheidle, M., Klee, D., Dittrich, B., Merckelbach, A., Hehmann, G., Melmer, G., Büchs, J., Kang, H. A., Gellissen, G. (2009): Process development in Hansenula polymorpha and Arxula adeninivorans, a re-assessment. Microbial Cell Factories 8: 22PubMedCrossRefGoogle Scholar
  80. Stöckmann, C., Maier, U., Anderlei, T., Knocke, C., Gellissen, G., Büchs, J. (2003): The oxygen transfer rate as key parameter for the characterisation of Hansenula polymorpha screening cultures. J. Ind. Microbiol. Biotechnol. 30(10): 613–622PubMedCrossRefGoogle Scholar
  81. Storhas, W. (1994): Bioreaktoren und periphere Einrichtungen, Vieweg Lehrbuch BiotechnologieGoogle Scholar
  82. Tredici, M. R. (2010): Photobiology of microalgae mass cultures: understanding the tools for the next green revolution. Biofuels 1(1): 143–162CrossRefGoogle Scholar
  83. Trick, I., Schneider, W., Sternad, W., Henkel, H. J., Trösch, W. (1989): Abwasserreinigung mit immobilisierten Mikroorganismen unter Verwendung von porösen, kugeligen Sinterglasträgern. Dechema-Jahrestagung der Biotechnologen, FrankfurtGoogle Scholar
  84. Trick, I., Sternad, W., Reuter, G., Johl, H. J., Gebicke, W., Trösch, W., Chmiel, H. (1991): Comparative investigations on the production of glutamic acid with Corynebacterium glutamicum in stirred tank and propeller loop reactors. In: Reuss, M., Chmiel, H., Gilles, E. D., Knackmuss, H.-J. (Hrsg.): Biochemical Engineering. Gustav Fischer Verlag, StuttgartGoogle Scholar
  85. Timmins, N., Scherberich, A., Früh, J., Heberer, M., Martin, I., Jakob M. (2007): Three-dimensional cell culture and tissue engineering in a T-CUP (tissue culture under perfusion). Tissue Eng. 13: 2021–2028PubMedCrossRefGoogle Scholar
  86. Vester, A., Hans, M., Hohmann, H. P., Weuster-Botz, D. (2009): Discrimination of riboflavin producing Bacillus subtilis strains based on their fed-batch process performances on a millilitre-scale. Appl. Microbiol. Biotechnol. 84: 71–76PubMedCrossRefGoogle Scholar
  87. Wagner, B. (1987): Leistungsvergleich von Bioreaktoren für Mycelförmiges Wachstum. Dissertation Nr. 8225, ETH ZürichGoogle Scholar
  88. Weiland, P. (1984): Einflu das Betriebsverhalten von Airlift-Schlaufenreaktoren. Chem.-Ing.-Tech. 56: 64–65CrossRefGoogle Scholar
  89. Wendt, D., Jakob, M., Martin, I. (2005): Bioreactor-based engineering of osteochondral grafts: from model systems to tissue manufacturing. J. Biosci. Bioeng. 100: 489–494PubMedCrossRefGoogle Scholar
  90. Weuster-Botz, D., Puskeiler, R., Kusterer, A., Kaufmann, K., John, G. T., Arnold, M. (2005): Methods and milliliter scale devices for high-throughput bioprocess design. Bioprocess Biosys. Eng. 28: 109–119CrossRefGoogle Scholar
  91. Yuan, Y.-J., Wie, Z.-J., Wu, Z.-L., Wu, J.-C. (2001): Improved taxol production in suspension cultures of Taxus chinensis var. mairei by in situ extraction combined with precursor feeding and additional carbon source introduction in an airlift loop reactor. Biotechnol. Lett. 23: 1659–1662CrossRefGoogle Scholar
  92. Zlokarnik, M. (1978): Sorption characteristics for gas-liquid contacting in mixing vessels. Adv. Biochem. Eng. 8: 133–151Google Scholar
  93. Zlokarnik, M. (1984): Auslegung und Dimensionierung eines mechanischen Schaumzerstörers. Chem.-Ing.-Tech. 11: 839–844CrossRefGoogle Scholar
  94. Zlokarnik, M. (1985): Tower-shaped reactors for aerobic biological waste water treatment. In: Rehm, H.-J., Reed, G. (Hrsg.) Biotechnology, Vol. 2. VCH Verlagsgesellschaft, WeinheimGoogle Scholar
  95. Zlokarnik, M. (1999): Rührtechnik. Springer-Verlag, BerlinCrossRefGoogle Scholar
  96. Zlokarnik, M. (2000a): Mixing, Ullmann’s Encyclopedia of Industrial Chemistry, Verlag Chemie, Weinheim, 6. Auflage, Vol. B2Google Scholar
  97. Zlokarnik, M. (2000b): Scale-up; Modellübertragung in der Verfahrenstechnik. Wiley-VCH, WeinheimCrossRefGoogle Scholar

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© Spektrum Akademischer Verlag Heidelberg 2011

Authors and Affiliations

  • Horst Chmiel
    • 1
  1. 1.audita Unternehmensberatung GmbHMünchen

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