Chip modularity enables molecular information access from organ-on-chip devices with quality control

Organ-on-chip (OOC) devices are envisioned to replace animal models in preclinical toxicity and efficacy testing. Although significant progress has been made towards ensuring the biofidelity of these devices, analyzing samples from within these miniaturized structures remains a challenge. Based on the concept of modularity, we developed accessorial modular functional units that facilitate molecular information access to and from OOCs. Specifically, we developed three mutually independent microfluidic modules: a mixer, a "molecular- electronic" sensor, and a quality control unit. Each module can be interconnected/disconnected, replicated or replaced as needed. As a proof of concept, we developed a cytotoxicity assay comprised of two modules and linked these to a model OOC providing near real time molecular information on OOC function. Additionally, we developed sensor design criteria for generic use, particularly for on-chip measurements that require substrates and enzymes. We monitored sensor function during long-term experiments and, by design, maintained assay consistency by switching out fouled sensors. Importantly, using electrobiofabrication, our sensor assembly with biological components and its connection to the OOC requires only minutes and no bulky instrumentation. We believe a modular strategy wherein various chips are assembled in situ and subsequently interrogated in real time could provide an alternative and promising path to enhance functionality, reproducibility, and utility. They will enrich our abilities to access biological information in a variety of contexts.