A closed-loop modular multiorgan-on-chips platform for self-sustaining and tightly controlled oxygenation

Abstract

To mimic physiological microenvironments in organ-on-a-chip systems, physiologically relevant parameters are required to precisely access drug metabolism. Oxygen level is a critical microenvironmental parameter to maintain cellular or tissue functions and modulate their behaviors. Current organ-on-a-chip setups are oftentimes subjected to the ambient incubator oxygen level at 21%, which is higher than most if not all physiological oxygen concentrations. Additionally, the physiological oxygen level in each tissue is different ranging from 0.5 to 13%. Here, a closed-loop modular multiorgan-on-chips platform is developed to enable not only real-time monitoring of the oxygen levels but, more importantly, tight control of them in the range of 4 to 20% across each connected microtissue-on-a-chip in the circulatory culture medium. This platform, which consists of microfluidic oxygen scavenger(s), an oxygen generator, a monitoring/controller system, and bioreactor(s), allows for independent, precise upregulation and downregulation of dissolved oxygen in the perfused culture medium to meet the physiological oxygen level in each modular microtissue compartment, as needed. Furthermore, drug studies using the platform demonstrate that the oxygen level affects drug metabolism in the parallelly connected liver, kidney, and arterial vessel microtissues without organ–organ interactions factored in. Overall, this platform can promote the performances of organ-on-a-chip devices in drug screening by providing more physiologically relevant and independently adjustable oxygen microenvironments for desired organ types on a single- or a multiorgan-on-chip(s) configuration.