New Microfluidic System for Electrochemical Impedance Spectroscopy Assessment of Cell Culture Performance: Design and Development of New Electrode Material.

Electrochemical impedance spectroscopy (EIS) is widely accepted as an effective and non-destructive method to assess cell health during cell-culture. However, there is a lack of compact devices compatible with microfluidic integration and microscopy that could provide the real-time and non-invasive monitoring of cell-cultures using EIS. In this paper, we reported the design and characterization of a modular EIS testing system based on a patented technology. This device was fabricated using easily processable methodologies including screen-printing of the impedance electrodes and molding or micromachining of the cell culture chamber with an easy assembly procedure. Accordingly, to obtain processable, biocompatible and sterilizable electrode materials that lower the impact of interfacial impedance on TEER (Transepithelial electrical resistance) measurements, and to enable concomitant microscopy observations, we optimized the formulation of the electrode inks and the design of the EIS electrodes, respectively. First, electrode materials were based on carbon biocompatible inks enriched with IrOx particles to obtain low interfacial impedance electrodes approaching the performances of classical non-biocompatible Ag/AgCl second-species electrodes. Secondly, we proposed three original electrode designs, which were compared to classical disk electrodes that were optically compatible with microscopy. We assessed the impact of the electrode design on the response of the impedance sensor using COMSOL Multiphysics. Finally, the performance of the impedance spectroscopy devices was assessed in vitro using human airway epithelial cell cultures.