Over the past two decades, Organ-on-a-Chip (OoC) technology has advanced significantly, and with the recent shift by the FDA toward favouring this technology over traditional animal testing for drug development, research in this field has accelerated. At TU Delft, this research continues with a focus on Gut-on-a-Chip (GoC) systems. Building on the earlier work of Tawade et al. on a silicon-based tissue-barrier-on-a-chip, and in line with the long-term goal of developing a multi-sensor integrated GoC, the present work focuses on the development of a silicon-based spatial transepithelial electrical resistance Gut-on-a-Chip (s-TEER GoC).
The “spatial” aspect refers to the ability to obtain localised TEER measurements through the integration of multiple 4-point electrode setups within the GoC design. A novel feature of the s-TEER GoC is the introduction of current windows, which guide and focus the current density fields generated by the electrode setups to specific regions of the tissue barrier. In addition, the chip design has been optimised to require only one-sided fluidic access, enabling compatibility with a standardised multi-organ-on-a-chip Translational OoC Platform (TOP) module developed by Yeh et al. This is achieved through the implementation of two vertically-stacked Z-shaped microfluidic channels, inspired by previously-reported polymer-based designs.
In this work, detailed design parameters were established to meet both the microphysiological modelling and biosensing requirements of the chip, using a theoretical framework and COMSOL simulations to analyse fluidic, mechanical, and electrical performance. A large part of the fabrication of the s-TEER GoC was carried out using microfabrication techniques available at the Else Kooi Laboratory on the TU Delft campus. In addition, a PCB and microfluidic packaging were developed to connect the chip to external fluidic and electrical control and measurement systems in a standardised way. Results include the executed fabrication steps and preliminary validation of the mechanical, optical, and fluidic functionality of the device.
This work demonstrates the feasibility of a silicon-based Gut-on-a-Chip platform with spatially resolved TEER sensing, providing a foundation for future development of multi-sensor integrated systems. The s-TEER GoC represents a step toward more physiologically relevant, high-resolution in vitro models, supporting the ongoing transition away from animal models in preclinical research.