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@PHDTHESIS{Stevanovic:1044500,
      author       = {Stevanovic, Jelena},
      title        = {{M}icrofluidic-{MEA} hybrid systems for
                      electrophysiological recordings of neuronal co-cultures},
      volume       = {295},
      school       = {RWTH Aachen University},
      type         = {Dissertation},
      address      = {Jülich},
      publisher    = {Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag},
      reportid     = {FZJ-2025-03237},
      isbn         = {978-3-95806-831-5},
      series       = {Schriften des Forschungszentrums Jülich Reihe
                      Schlüsseltechnologien / Key Technologies},
      pages        = {ix, 186},
      year         = {2025},
      note         = {Dissertation, RWTH Aachen University, 2025},
      abstract     = {The study of brain development and degeneration is
                      frequently observed in the scope of in vivo studies.
                      However, newly developed in vitro models offer better
                      precision and specificity in the investigation of neuronal
                      networks. For example, the use of microfluidic
                      microchannels, which have proven to be a successful method
                      of isolating axons and directing their growth. Building upon
                      the axon diode microchannel shape initially proposed by
                      Peyrin et al. in 2011, I developed a μFluidic-MEA device
                      with integrated microchannel structures on a recording
                      platform. The microchannels were fabricated using
                      photostructurable polymer, i.e. HD-8820, with the goal of
                      improving the precision of aligning the compartmentalized
                      microfluidic on top and facilitating the co-culturing of
                      cortical and striatal neuronal cells. The primary objective
                      of this thesis was to characterize the electrophysiological
                      activity of a cortico-striatal co-culture in a μFluidic-MEA
                      device, with variation of axon diode microchannel lengths. A
                      secondary objective was to enhance the unidirectionality of
                      the device and recordable activity yield by modifying the
                      microelectrode array layout and the number of electrically
                      active microchannels. The co-culture is then observed in a
                      newly proposed design μFluidic-r16MEA device following the
                      same conditions of reversible (RB) and irreversible (IRB)
                      final device assembly. The analysis of recorded
                      electrophysiological activity was focused on action
                      potential spike shapes classification, microchannel
                      amplification effect, and measuring of the signal
                      propagation velocities over the long-term cell culture
                      maintenance (up to DIV 35). One of the main findings in this
                      thesis is the definition and characterization of small in
                      peakto-peak amplitude monophasic spike shapes that, to the
                      best of our knowledge, have not been reported previously.
                      The significance of these results lies in the comprehensive
                      understanding of axonal dynamics within the microchannel
                      area. The occurrence of this shape is associated with the
                      boundary microchannel electrodes, indicating that the
                      axon-electrode coupling is less effective and results in a
                      less visible signal. Depending on the electrode pair and the
                      length of the microchannel observed for this type of
                      analysis, the signal propagation velocities range from 0.14
                      to 1.7 m/s. The size of the microchannels allows multiple
                      axons to pass through, making it challenging to determine
                      with certainty whether a given spike pair is correct. This
                      can be observed in recordings where the directionality of
                      signal propagation is atypical, with both forward and
                      backward spike pairs being detected in a train of spikes
                      that are labeled as belonging to the same axon. In
                      conclusion, the successful application of a novel
                      fabrication approach for microchannels on top of an MEA has
                      been demonstrated. The following effects of final device
                      assembly (RB vs. IRB) were observed on electrophysiological
                      activity from cortico-striatal co-culture. The introduced
                      changes in the overall microfluidic design have brought
                      benefits in terms of microchannel activity yield and
                      unidirectionality of axonal growth.},
      cin          = {IBI-3},
      cid          = {I:(DE-Juel1)IBI-3-20200312},
      pnm          = {5244 - Information Processing in Neuronal Networks
                      (POF4-524)},
      pid          = {G:(DE-HGF)POF4-5244},
      typ          = {PUB:(DE-HGF)3 / PUB:(DE-HGF)11},
      urn          = {urn:nbn:de:0001-2508150936299.999922666678},
      doi          = {10.34734/FZJ-2025-03237},
      url          = {https://juser.fz-juelich.de/record/1044500},
}