Integrated Silicon-On-Insulator Based Mesh Membrane for Continuous Monitoring in Organs-on-a-chip

Abstract

Porous membranes play a crucial role in organ-on-chip (OOC) models mimicking barrier functions like e.g., brain, intestine, and lungs. These membranes act as basement membranes for cell growth and communication via their pores, while also serving as physical barriers between chip compartments. Integrating electrodes close to the cells will allow continuous cell culture monitoring, but direct integration into the membrane presents challenges. Moreover, while natural extracellular matrix protein-based membranes are beneficial over synthetic ones, electrode integration onto such biological membranes is challenging if not possible at all. To address these challenges, we present the silicon-on-insulator (SOI)-based mesh membrane (SMM) as a support for a biologically relevant collagen-based membrane for the cell culture. The SOI material of our SMM allows for electrode integration, thus facilitating the impedance monitoring of the cell culture. Here we integrated the SMM into well plates, Transwells, and OOC devices highlighting its versatile applicability across different in vitro setups. We demonstrate its biocompatibility by modeling vasculature utilizing human-induced pluripotent stem cell-derived endothelial cells. In the future, the electrical impedance of the cell culture will be monitored providing non-invasive measurement of the cell layer development in real time.