Actuation & Sensing Modules for Standardized Organ-on-Chip Platforms
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About this event
Organ-on-chip (OoC) platforms are advanced cell culture systems that can emulate human tissues and diseases for mechanistic studies, potentially conducive to improved drug development and personalized therapy guidance. These platforms provide a representative tissue microenvironment including microfluidic perfusion and controlled mechanical stimulation to synthetically replicate in vivo-like conditions that static in vitro models cannot provide. This is particularly relevant for barrier tissues, where function is tied directly to flow, transport dynamics, and integrity of cell layers. Translating OoC technology into routine laboratory practice requires platforms that are not only biologically relevant but also modular in design, compatible with standardized formats, and capable of continuous functional readout. This thesis contributes to realizing such a platform through the development of three technical modules with integrated functionalities tailored for perfusion and electrical barrier sensing, each designed for biological, mechanical and electrical compatibility with an ISO-compatible OoC platform. The first module introduces magnetic artificial cilia (MAC) as a tubeless on-chip micropumping mechanism. Flexible magnetic elastomeric cilia integrated in a microfluidic chip perform tilted conical motion when driven by an external rotating permanent magnet, and this motion generates net fluid displacement at low Reynolds number. Prior work has demonstrated MAC-driven fluid pumping in closed microfluidic loops. Here, the mechanism is adopted within a MAC module and characterized within a standardized OoC platform, achieving flow rates of up to 40 uL/min across a range of hydraulic loads, tunable through actuation frequency. A key result is the continuous circulation of human monocytes at actuation frequencies up to 100 Hz. Cell viability and cytokine secretion profiles remain statistically comparable to static controls, proving that the gentle nature of MAC actuation is compatible with circulating mechanically sensitive cells in suspension. The second module targets transepithelial electrical resistance (TEER) measurement, the standard label-free metric for tight-junction integrity in epithelial and endothelial barriers. A silicon-microfabricated sensor chip with titanium nitride electrodes patterned on slanted sidewalls, combined with a silicon nitride microporous membrane, implements four-electrode impedance spectroscopy with a geometry designed to achieve uniform current distribution across the cell layer. Reusable packaging with magnetic clamping and leak-free microfluidic interconnects allows repeated disassembly and assembly of the module without loss of measurement integrity. Electrode functionality and stability is confirmed over multi-day culture periods, providing the performance baseline needed for the module to serve as reliable sensor in standardized barrier assays. The third module uses organic electrochemical transistors (OECTs) for continuous barrier monitoring under perfusion. OECTs amplify the ionic signal from the cell layer through volumetric electrochemical doping of the transistor channel, offering a sensitivity advantage over passive impedance measurements at physiologically relevant signal levels. Photo-patterned PEDOT:PSS and p(g2T-TT) channels are evaluated, and gate configurations are systematically compared. A separated Ag/AgCl gate compartment coupled through a poly(vinyl alcohol)/KCl salt bridge is identified as the most suitable configuration, decoupling gate polarization and decreasing silver leaching into the cell culture medium. Integrated on the standardized platform, the OECT module can track Caco-2 tight-junction formation continuously and it can resolve pharmacological disruption of the barrier in real time. The work presented in this thesis demonstrates that actuation and sensing functions can be realized as modular, independently characterized units within a single ISO-compatible platform. Together, the three modules provide controlled tubeless perfusion and cell circulation, continuous impedance-based barrier monitoring, and transistor-based sensing with stable performance under fluid flow. More broadly, this thesis shows how these functions can be combined within a shared standardized framework, providing a foundation for reproducible and scalable OoC workflows in circulating cells and barrier tissue research.
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