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

Organ-on-chip (OOC) technologies, also called microphysiological systems (MPS), offer dynamic microenvironments that improve upon static culture systems, yet widespread adoption has been hindered by fabrication complexity, reliance on polydimethylsiloxane (PDMS), and limited modularity. Here, we present a modular MPS platform designed for ease of use, reproducibility, 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 workflows. We validated the system using dual epithelial and endothelial 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