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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.

International audience; The development of an acoustic wave device for biological detection poses several challenges, notably, the operation in water- based complex media that reduces the performance of such devices due to acoustic wave radiation and viscous losses. Good performance in liquid media is however indispensable for biological applications1.The present work focuses on the development of a micro-electro-mechanical system (MEMS) based on Love wave resonators fabricated on a LiNbO3 substrate and a waveguide SiO2 layer. The SiO2 layer on top of the substrate also plays two other essential roles acting as an electrical insulator and offering a surface on which to graft bioreceptors. Love wave devices are commonly found in the literature with a delay-line configuration and LiTaO3/Quartz being the preferred substrates with polymers, such as Novolac, as the waveguiding layer2.We used a numerical model to first evaluate the Love wave confinement into the SiO2 layer, and second to evaluate the acoustic wave radiation when the resonator is in contact with water. PECVD (Plasma-Enhanced Chemical Vapor Deposition) and PVD (Physical Vapor Deposition) processes were used to deposit the SiO2 layer with the PECVD method showing better agreement to numerical simulations. Figure 1 shows a comparison between numerical and experimental Love wave resonators electrical response in a vacuum with a SiO2 PECVD layer. It shows good agreement in resonance frequency prediction for the Rayleigh and Bulk waves. The slight frequency shift of the Love wave is attributed to deviations in the density and stiffness of the SiO2 film deposited compared to theoretical expectations.Numerical simulations show that a relatively thick SiO2 layer is necessary to achieve high quality factors when operating in water, which is confirmed by experiments as shown in Figure 2. Other parameters such as the number of electrodes and acoustic aperture were evaluated but showed little experimental impact on the quality factors.

This work reports the design of a live-cell monitoring platform based on a macroporous scaffold of a conducting polymer, poly(3,4-ethylene dioxythiophene): poly(styrenesulfonate). The conducting polymer scaffolds support 3D cell cultures due to their biocompatibility and tissue-like elasticity, which can be manipulated by inclusion of biopolymers such as collagen. Integration of a media perfusion tube inside the scaffold enables homogenous cell spreading and fluid transport throughout the scaffold, ensuring long term cell viability. This also allows for co-culture of multiple cell types inside the scaffold. The inclusion of cells within the porous architecture affects the impedance of the electrically conducting polymer network and, thus, is utilized as an in situ tool to monitor cell growth. Therefore, while being an integral part of the 3D tissue, the conducting polymer is an active component, enhancing the tissue function, and forming the basis for a bioelectronic device with integrated sensing capability.