Fluidic Circuit Board with Modular Sensor and Valves Enables Stand-Alone, Tubeless Microfluidic Flow Control in Organs-on-Chips

Abstract

Organs-on-chips are a unique class of microfluidic in vitro cell culture models, in which the in vivo tissue microenvironment is mimicked. Unfortunately, its widespread use is hampered by their operation complexity and incompatibility with end-user research settings. To address these issues, many commercial and non-commercial platforms have been developed for semi-automated culture of organs-on-chips. However, these organ-on-chip culture platforms each represent a closed ecosystem, with very little opportunity to interchange and integrate components from different platforms or to develop new ones. The Translational Organ-on-Chip Platform (TOP) is a multi-institutional effort to develop an open platform for automated organ-on-chip culture and integration of components from various developers. Central to TOP is the fluidic circuit board (FCB), a microfluidic plate with the form factor of a typical well plate. The FCB enables microfluidic control of multiple components like sensors or organ-on-chip devices through an interface based on openly available standards. Here, we report an FCB to integrate commercial and in-house developed components forming a stand-alone flow control system for organs-on-chips. The control system is able to achieve constant and pulsatile flow recirculation through a connected organ-on-chip device. We demonstrate that this system is able to automatically perfuse a heart-on-chip device containing co-cultures of cardiac tissues derived from human pluripotent stem cell-derived cardiomyocytes and monolayers of endothelial cells for five days. Altogether, we conclude that open technology platforms allow the integration of components from different sources to form functional and fit-for-purpose organ-on-chip systems. We anticipate that open platforms will play a central role in catalysing and maturing further technological development of organ-on-chip culture systems.

Guiding organs-on-chips towards applications: a balancing act between integration of advanced technologies and standardization

“…This standard prompted the development of a multiinstitutional approach that developed the Translational Organ-on-Chip Platform (TOP). TOP employs a fluidic circuit board that serves as a microfluidic platform that connects several independent modules via standardized interfacing (Vivas et al, 2022). This approach has already been applied to cardiac and vascular OoC models (de Graaf et al, 2022;Vivas et al, 2022;de Graaf et al, 2023).…”

“…TOP employs a fluidic circuit board that serves as a microfluidic platform that connects several independent modules via standardized interfacing (Vivas et al, 2022). This approach has already been applied to cardiac and vascular OoC models (de Graaf et al, 2022;Vivas et al, 2022;de Graaf et al, 2023). Another important component of TOP is the inclusion of accessible software able to integrate control commands and sensor interfaces (de Graaf et al, 2022).…”

Dynamic and static biomechanical traits of cardiac fibrosis

“…Cardiac fibrosis biomechanical models have attracted extensive attention due to their inclusion of vital dynamic traits. By simulating dynamic stimulus on classic 2D models or stereoscopic 3D models (Bein et al, 2018;Yu and Choudhury, 2019;Vivas et al, 2022), we can mimic dynamic biomechanical traits of cardiac fibrosis in vitro well at the multiscale (Table 1).…”