Gabriel Werr: On-chip sensing

Abstract

With Organ-on-chip (OoC) systems being developed for the last 15 years, they have started to establish themselves as the more in-vivo like alternative to standard cell-culturing methods. With their ability to replicate mechanical and chemical stimulus more accurately, they are promised to improve research predictions and start reducing animal testing. Their more in-vivo like features although come with more settings to be adjusted, more dynamic behaviour, and more complexity in the results. Most of the OoCs produce only very little sample volume compared to the effort of running them, which makes it more difficult to track their status with conventional measurement techniques. Therefore, this thesis is focused on integrating and improving sensing methods for OoC applications. An in-line cytokine detection chip was built, using bead-based immunoassays and acoustic trapping to reduce the necessary sample volume by 97% to 1.5 µl, while reducing the assay time by 80% to 35 min and retaining a detection limit of 1.2 ng/ml. The internal temperature profile of acoustofluidic devices was characterised using integrated thin-film resistive temperature devices, with sensitivities <10mK. One chip was built to compare internal measurements to external measurements, allowing the cytokine detection chip to operate within safe margins at high acoustic energies and without the need to integrate its own temperature sensor. Another chip was built to measure the temperature gradient in an acoustophoresis channel to provide validation data for streaming simulations at high acoustic powers, with the thought to optimise the sample exposure of the cytokine detection chip. Lastly, a flexible thin-film electrode fabrication based on polyimide tape was developed to integrate electrodes into OoCs, the method was demonstrated by integrating multiple electrodes in a gut-on-chip model and performing impedance spectroscopies to determine the TEER value of the cell layer.