Real-time impedance monitoring of epithelial cultures with inkjet-printed interdigitated-electrode sensors

Abstract

From electronic devices to large-area electronics, from individual cells to skin substitutes, printing techniques are providing compelling applications in wide-ranging fields. Research has thus fueled the vision of a hybrid, printing platform to fabricate sensors/electronics and living engineered tissues simultaneously. Following this interest, we have fabricated interdigitated-electrode sensors (IDEs) by inkjet printing to monitor epithelial cell cultures. We have fabricated IDEs using flexible substrates with silver nanoparticles as a conductive element and SU-8 as the passivation layer. Our sensors are cytocompatible, have a topography that simulates microgrooves of 300 µm width and ~4 µm depth, and can be reused for cellular studies without detrimental in the electrical performance. To test the inkjet-printed sensors and demonstrate their potential use for monitoring laboratory-growth skin tissues, we have developed a real-time system and monitored label-free proliferation, migration, and detachment of keratinocytes by impedance spectroscopy. We have found that variations in the impedance correlate linearly to cell densities initially seeded and that the main component influencing the total impedance is the isolated effect of the cell membranes. Results obtained show that impedance can track cellular migration over the surface of the sensors, exhibiting a linear relationship with the standard method of image processing. Our results provide a useful approach for non-destructive in-situ monitoring of processes related to both in vitro epidermal models and wound healing with low-cost ink-jetted sensors. This type of flexible sensor as well as the impedance method are promising for the envisioned hybrid technology of 3D-bioprinted smart skin substitutes with built-in electronics.