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bioRxiv · 10.1101/2025.04.30.651503

Democratizing Organ-on-Chip Technologies with a Modular, Reusable, and Perfusion-Ready Microphysiological System

Minahan, D. J.·Nelson, K. M.·Ribeiro, F.·Ferrick, B. J.·Zurzolo, A. M.·Byers, K.·Gleghorn, J. P.
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Abstract

Organ-on-chip (OOC) technologies, also called microphysi-ological systems (MPS), offer dynamic microenvironments that improve upon static culture systems, yet widespread adoption has been hindered by fabrication complexity, reliance on poly-dimethylsiloxane (PDMS), and limited modularity. Here, we present a modular MPS platform designed for ease of use, re-producibility, and broad applicability. The system comprises layered elastomeric inserts for dual monolayer cell culture, which is clamped within a reusable acrylic cassette for perfusion studies. This enables researchers to decouple model establishment from flow experiments and streamline their work-flows. We validated the system using dual epithelial and en-dothelial cell co-culture under static and perfused conditions, including shear-induced alignment of HUVECs. Material testing confirmed biocompatibility, while vinyl cutting reproducibility demonstrated high manufacturing fidelity. The platform reliably supported long-term culture (up to 14 days), and the open insert format facilitated uniform seeding and imaging access. This approach enables parallelized experimentation, minimizes pump usage, and is well-suited for labs without microfabrication infrastructure. By combining fabrication flexibility with biological robustness, this work establishes a generalizable platform for modular tissue-chip development adapted to diverse organ systems and serves as a foundational framework for democratizing advanced in vitro model systems. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=159 SRC="FIGDIR/small/651503v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1e5fed3org.highwire.dtl.DTLVardef@bcf27eorg.highwire.dtl.DTLVardef@d46f33org.highwire.dtl.DTLVardef@d0912f_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Minahan, D. J., Nelson, K. M., Ribeiro, F., Ferrick, B. J., Zurzolo, A. M., Byers, K., Gleghorn, J. P.. 2025-05-07. Democratizing Organ-on-Chip Technologies with a Modular, Reusable, and Perfusion-Ready Microphysiological System. https://doi.org/10.1101/2025.04.30.651503

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