Towards parallel and automated hanging drop networks. Integration of an hanging drop pump

Microfluidic hanging-drop networks enable culturing and analysis of different 3D microtissue spheroids derived from different cell types under controlled perfusion and investigating inter-tissue communication in multi-tissue formats. In this thesis, I introduce an on-chip pumping approach for flow control in hanging-drop networks. The pump includes one pneumatic chamber located directly above one of the hanging drops and uses the surface tension of the liquid-air-interface for flow actuation. The fabrication of the integrated pump adds no complex steps to standard fabrication procedures of microfluidic devices from PDMS using common microfabrication techniques such as photolithography and soft lithography. Numerical simulation of the hanging drop network with the integrated pump has been performed using a developed analytical model to estimate fluid dynamics and the behavior of the system at various external conditions. Operational and design parameters were optimized to reach maximum performances. Control of the pump actuation protocol provides a wide range of uni-directional pulsatile and continuous flow profiles. Further, with the proposed concept several independent hanging-drop networks can be operated in parallel with only one single pneumatic actuation line with high fidelity. In this way, long-term closed-loop medium circulation between different organ models for body-on-a-chip applications and multiple simultaneous assays in parallel are made possible. Finally, I implemented a real-time feedback control-loop of the pump actuation based on the beating of a cardiac microtissue cultured in the same system. This configuration allows simulating physiological effects on the heart and its impact on flow circulation between organ models on-chip. The integrated pump system overcomes limitations of external pumps and current on-chip micropumps which limit their use for open microfluidics such as hanging-drop network.