Real-time electrical monitoring and analysis of stem-cell proliferation and differentiation using organic microelectrode arrays.
Mustafeez Shah a, Achilleas Savva a
a Regenerative Bioelectronic Technologies (ReBooT) Group, Section Bioelectronics, Department of Microelectronics, Faculty of EEMCS, Delft University of Technology, Delft, The Netherlands.
Proceedings of Bioelectronic Interfaces: Materials, Devices and Applications (CyBioEl)
Limassol, Cyprus, 2024 October 22nd - 25th
Organizers: Eleni Stavrinidou and Achilleas Savva
Oral, Mustafeez Shah, presentation 044
Publication date: 28th June 2024

Therapy for peripheral nerve and spinal cord injuries as well as several neurodegenerative diseases remain a big clinical challenge due to poor regeneration of neural tissue in the damaged area. [1]. Within this context, human induced pluripotent stem cells  (hiPSC)-derived neuronal networks present an effective in-vitro model for the study of these physiological issues. However, the differentiation and maturation of hiPSCs is a complex and time-consuming process, thereby necessitating techniques for real-time monitoring of neuronal differentiation and maturation with high sensitivity.

Moreover, physical microenvironmental cues, such as electrical signals, have been increasingly recognized as crucial in regulating stem cell behaviour and fate as well as neuron regeneration processes [2]. However, the underlying molecular mechanism demand further investigation [3]. Furthermore, PEDOT: PSS based electrodes have been shown to lower the electrochemical impedance leading to an increased SNR [4] while recording in addition to promoting neurogenic differentiation [5].

In this work, we first designed a microelectrode array and compared the SNR, electrochemical stability, charge storage capacity and charge injection limit of different electrode materials, viz-a-viz, Gold, Gold/PEDOT: PSS and PEDOT: PSS only via Electrochemical Impedance Spectroscopy (EIS), Voltage Transients and Cyclic Voltammetry (CV) measurements.  This is followed by comparison of different electrode designs including inter-digitated, castellated and matrix based. The best electrode designs were used to monitor proliferation of (hiPSCs) followed by the differentiation to cortical neurons with the entire process being analysed by correlating the physiological variations during the process to the variation in impedance magnitude and phase at various frequency bands.

Further studies aim to make the in-vitro platform more biomimetic with flexible mesh-design based electrodes to bridge the dimensional gap between the 3D cultures and the monitoring system.


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