A Modular Microfluidic Organoid Platform Using LEGO® -like Bricks

The convergence of organoid and organ-on-a-chip (OoC) technologies is urgently needed to overcome limitations of current 3D in vitro models. However, integrating organoids in standard OoCs faces several technical challenges as it is typically laborious, lacks flexibility and often results in even more complex and less efficient cell culture protocols. Therefore, specifically adapted and more flexible microfluidic platforms need to be developed to facilitate the incorporation of complex 3D in vitro models. Here, we developed a modular, tubeless fluidic circuit board (FCB) coupled with reversibly sealed cell culture bricks for dynamic culture of embryonic stem cell (ESC)-derived thyroid follicles. The FCB was fabricated by milling channels in a polycarbonate (PC) plate followed by thermal bonding against another PC plate. LEGO -like fluidic interconnectors allowed plug-and-play connection between a variety of cell culture bricks and the FCB. Lock-and-play (LnP) clamps were integrated in the organoid brick to enable easy (un)loading of organoids. A multiplexed perfusion experiment was conducted with six FCBs, where thyroid organoids were transferred on-chip within minutes and cultured up to 10 days without losing their structure and functionality, thus validating this system as a flexible, easy-to-use platform, capable of synergistically combining organoids with advanced microfluidic platforms. This article is protected by copyright. All rights reserved.