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@PHDTHESIS{Habicher:801742,
      author       = {Habicher, Tobias},
      othercontributors = {Büchs, Jochen and Schwaneberg, Ulrich},
      title        = {{S}mall-scale shaken bioreactors for fed-batch cultivation
                      with parallel online monitoring},
      school       = {Rheinisch-Westfälische Technische Hochschule Aachen},
      type         = {Dissertation},
      address      = {Aachen},
      reportid     = {RWTH-2020-09055},
      pages        = {1 Online-Ressource (XIII, 135 Seiten) : Illustrationen,
                      Diagramme},
      year         = {2020},
      note         = {Deutsche und englische Zusammenfassung. - Veröffentlicht
                      auf dem Publikationsserver der RWTH Aachen University;
                      Dissertation, Rheinisch-Westfälische Technische Hochschule
                      Aachen, 2020},
      abstract     = {Small-scale shaken bioreactors, such as shake flasks and
                      microtiter plates, are the most frequently used reactor
                      systems during initial bioprocess development. Originally,
                      they were designed to be operated in batch mode. However,
                      batch mode causes adverse effects like overflow metabolism,
                      substrate inhibition or catabolite repression. Fed-batch
                      mode can prevent these effects, and thus, it is
                      predominantly applied in production processes. Consequently,
                      the implementation of fed-batch mode at small scale is
                      crucial to obtain physiological conditions that are
                      comparable to fed-batch production processes. In shake
                      flasks, fed-batch mode was realized with the previously
                      introduced 250 mL membrane-based fed-batch shake flasks.
                      Within this thesis, the system was standardized regarding
                      its dimensions and optimized in design, handling and
                      robustness. Furthermore, the operating principle was
                      successfully scaled-up to 500 mL shake flasks. The
                      application of membrane-based fed-batch shake flasks allowed
                      to introduce carbon- and nitrogen-limited fed batch
                      conditions to overcome catabolite repression and substrate
                      inhibition in a protease producing Bacillus licheniformis
                      strain. In microtiter plates, carbon-limited fed-batch
                      conditions were realized with polymer-based
                      controlled-release fed-batch microtiter plates. Special
                      emphasis was paid to the possibilities for online monitoring
                      of the fed-batch operated small-scale shaken bioreactors.
                      Membrane-based fed-batch shake flasks and polymer-based
                      controlled-release fed-batch microtiter plates have been
                      tailored to be compatible with the RAMOS and µRAMOS device,
                      respectively. In order to have access to additional culture
                      parameters, a fed-batch microtiter plate with polymer rings
                      was designed. The polymer rings make the culture broth
                      optically accessible, enabling online monitoring with the
                      established BioLector device. In conclusion, the presented
                      small-scale shaken bioreactors enable fed-batch operation
                      with parallel online monitoring of the most important
                      culture parameters. This allows to mimic the physiological
                      conditions relevant for fed-batch production processes
                      already during initial bioprocess development, which saves
                      time and cost, and accelerates bioprocess development.},
      cin          = {416510},
      ddc          = {620},
      cid          = {$I:(DE-82)416510_20140620$},
      typ          = {PUB:(DE-HGF)11},
      doi          = {10.18154/RWTH-2020-09055},
      url          = {https://publications.rwth-aachen.de/record/801742},
}