Integrating conductive electrodes into hydrogel-based microfluidic chips for real-time monitoring of cell response

Abstract

The conventional real-time screening in organs-on-chips is limited to optical tracking of pre-tagged cells and biological agents. This work introduces an efficient biofabrication protocol to integrate tunable hydrogel electrodes into 3D bioprinted-on-chips. We established our method of fabricating cell-laden hydrogel-based microfluidic chips through digital light processing-based 3D bioprinting. Our conductive ink includes poly-(3,4-ethylene-dioxythiophene)-polystyrene sulfonate (PEDOT: PSS) microparticles doped in polyethylene glycol diacrylate (PEGDA). We optimized the manufacturing process of PEDOT: PSS microparticles characterized our conductive ink for different 3D bioprinting parameters, geometries, and materials conditions. While the literature is limited to 0.5% w/v for PEDOT: PSS microparticle concentration, we increased their concentration to 5% w/v with superior biological responses. We measured the conductivity in the 3–15 m/m for a range of 0.5%–5% w/v microparticles, and we showed the effectiveness of 3D-printed electrodes for predicting cell responses when encapsulated in gelatin-methacryloyl (GelMA). Interestingly, a higher cellular activity was observed in the case of 5% w/v microparticles compared to 0.5% w/v microparticles. Electrochemical impedance spectroscopy measurements indicated significant differences in cell densities and spheroid sizes embedded in GelMA microtissues.