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@ARTICLE{Tuber:909652,
      author       = {Täuber, Sarah and Blöbaum, Luisa and Steier, Valentin and
                      Oldiges, Marco and Grünberger, Alexander},
      title        = {{M}icrofluidic single‐cell scale‐down bioreactors: {A}
                      proof‐of‐concept for the growth of {C}orynebacterium
                      glutamicum at oscillating p{H} values},
      journal      = {Biotechnology $\&$ bioengineering},
      volume       = {119},
      number       = {11},
      issn         = {0006-3592},
      address      = {New York, NY [u.a.]},
      publisher    = {Wiley},
      reportid     = {FZJ-2022-03320},
      pages        = {3194-3209},
      year         = {2022},
      abstract     = {In large-scale bioreactors, gradients in cultivation
                      parameters such as oxygen, substrate, and pH result in
                      fluctuating cell environments. pH fluctuations were
                      identified as a critical parameter for bioprocess
                      performance. Traditionally, scale-down systems at the
                      laboratory scale are used to analyze the effects of
                      fluctuating pH values on strains and thus process
                      performance. Here, we demonstrate the application of dynamic
                      microfluidic single-cell cultivation (dMSCC) as a novel
                      scale-down system for the characterization of
                      Corynebacterium glutamicum growth using oscillating pH
                      conditions as a model stress factor. A detailed comparison
                      between two-compartment reactor (two-CR) scale-down
                      experiments and dMSCC was performed for one specific pH
                      oscillation between reference pH 7 (~8 min) and disturbed
                      pH 6 (~2 min). Similar reductions in growth rates were
                      observed in both systems (dMSCC $21\%$ and two-CR $27\%)$
                      compared to undisturbed cultivation at pH 7. Afterward,
                      systematic experiments at symmetric and asymmetric pH
                      oscillations, between pH ranges of 4–6 and 8–11 and
                      different intervals from 1 to 20 min, were performed to
                      demonstrate the unique application range and throughput of
                      the dMSCC system. Finally, the strength of the dMSCC
                      application was demonstrated by mimicking fluctuating
                      environmental conditions of a putative large-scale
                      bioprocess, which is difficult to conduct using two-CRs},
      cin          = {IBG-1},
      ddc          = {570},
      cid          = {I:(DE-Juel1)IBG-1-20101118},
      pnm          = {2172 - Utilization of renewable carbon and energy sources
                      and engineering of ecosystem functions (POF4-217)},
      pid          = {G:(DE-HGF)POF4-2172},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {35950295},
      UT           = {WOS:000848750900001},
      doi          = {10.1002/bit.28208},
      url          = {https://juser.fz-juelich.de/record/909652},
}