title: Adding the 'heart' to hanging drop networks for microphysiological multi-tissue experiments.
abstract: Microfluidic hanging-drop networks enable culturing and analysis of 3D microtissue spheroids derived from different cell types under controlled perfusion and investigating inter-tissue communication in multi-tissue formats. In this paper we introduce a compact 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 at the liquid-air-interface for flow actuation. Control of the pneumatic protocol provides a wide range of unidirectional pulsatile and continuous flow profiles. With the proposed concept several independent hanging-drop networks can be operated in parallel with only one single pneumatic actuation line at high fidelity. Closed-loop medium circulation between different organ models for multi-tissue formats and multiple simultaneous assays in parallel are possible. Finally, we implemented a real-time feedback control-loop of the pump actuation based on the beating of a human iPS-derived cardiac microtissue cultured in the same system. This configuration allows for simulating physiological effects on the heart and their impact on flow circulation between the organ models on chip.
authors.affiliation: ETH Zurich, Department of Biosystems Science and Engineering, Bio Engineering Laboratory, Mattenstrasse 26, CH-4058 Basel, Switzerland. olivier.frey@bsse.ethz.ch.
authors.forename: Saeed
authors.initials: S
authors.lastname: Rismani Yazdi
authors.forename: Amir
authors.initials: A
authors.lastname: Shadmani
authors.forename: Sebastian C
authors.initials: SC
authors.lastname: Bürgel
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Misun
authors.forename: Andreas
authors.initials: A
authors.lastname: Hierlemann
authors.forename: Olivier
authors.initials: O
authors.lastname: Frey
mesh_terms: D004867:Equipment Design; D006801:Humans; D057446:Hydrodynamics; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D009206:Myocardium / Q000166:cytology*; D011312:Pressure; D018874:Spheroids, Cellular; D013500:Surface Tension; D013696:Temperature