On-chip bioelectronic platforms for direct current stimulation of single cells, cell collectives, and tissues

Abstract: General background: Bioelectricity is an innate and reprogrammable communication modality for excitable and non-excitable cells on multiple scales: from single cells to cell collectives to tissues.

Specific background: Exogenous direct current (DC) stimulation is a method that reprograms the way cells communicate with their environment (e.g., migration guidance cues) and with each other (e.g., neural plasticity).

Knowledge gap: The options of electrode materials and experimental setups meant for fundamental
investigation of biological DC stimulation is lacking in comparison to well-established stimulation counterparts, like alternating current (AC). As new biomaterials and engineering methods emerge, there is an opportunity to update, advance, and standardize DC stimulation materials and methods to investigate stimulation effects on the cellular and tissue levels.

Technology development: Conducting polymer hydrogels (i.e., poly(3,4-ethylenedioxythiophene) and its complex with poly(styrene sulfonate), PEDOT:PSS) integrated onto laser-induced graphene (LIG) is developed here as non-metal hybrid electrode meant for DC applications. On-chip (e.g., microfluidic) technology is leveraged here to enable a controlled platform for precisely delivering dosages of DC stimulation to cell or tissue cultures. The integration of the microfluidics and non-metal bioelectronics is the foundation of this dissertation.

Applications: DC stimulation-induced modulation of non-excitable and excitable cell types are explored here: epithelial keratinocytes and hippocampal pyramidal neurons. The non-excitable case investigates the influence of DC guidance cues on in vitro cell collective wound healing of healthy and diabetic-like human keratinocytes. The excitable case investigates the influence of in vitro DC dosages on acute and long-term changes in excitability within ex vivo organotypic hippocampal tissue cultures.

Results: In the non-excitable application, sustained DC electric fields (dcEFs, 12 h at 200 mV mm−1) triples the wound closure rate compared to non-stimulated controls. Motility-impaired diabetic-like keratinocytes also experience a threefold increase in wound closure rates when stimulated. In the excitable application, hippocampal CA1 neurons are acutely activated via increased calcium activity with strong supra-threshold pulsed dcEFs (0.1 s pulses, 16.7 % duty cycle, 2 min stimulation at 140 mV mm−1). Whereas, weak constant sub-threshold dcEFs (10 min stimulation at 4.7 mV mm−1) does not increase calcium activity nor alters synaptic transmission.

Significance: The translationally-focused PEDOT:PSS hydrogel-coated LIG electrodes offer an in vitro to in vivo bridge for skin-based DC stimulation due to large volumetric ionic capacitance compared to standard metal electrodes that rely on electrolyte gels and sponges. The on-chip wound healing platform offers electrotaxis and wound healing researchers a method to further investigate the influence of dcEFs (i.e., intensity and shape) on all cells involved in the wound healing process. The on-chip brain stimulation platform offers transcranial DC stimulation (tDCS) researchers a new paradigm to more reliably study mechanisms of DC-induced neural plasticity, which still remains an open question in the field

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Universität Freiburg, Dissertation, 2023

Classification and Topics

• Keyword: Lab on a Chip ; Bioelektronik ; Mikrofluidik ; Bioelektrizität ; Galvanische Abscheidung ; Polyethylendioxythiophen ; Gleichstrom ; Stimulation ; Lab on a Chip

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2023
• Creator: Shaner, Sebastian
• Contributor: Asplund, Maria ; Rapp, Bastian E. ; Albert-Ludwigs-Universität Freiburg. Institut für Mikrosystemtechnik ; BrainLinks-BrainTools. Körperschaft ; Albert-Ludwigs-Universität Freiburg. Fakultät für Angewandte Wissenschaften

Further information

• DOI: 10.6094/UNIFR/237338
• URN: urn:nbn:de:bsz:25-freidok-2373386
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 10:49 AM CEST