Real-time physiological sensor-based liver-on-chip device for monitoring drug toxicity

摘要

Organ-on-chip models, known as microphysiological systems, are created to mimic the anatomy and physiology of a human organ at the micro-level. Besides being pivotal in the reverse engineering of human organs and pathogenesis studies, they serve as an alternative to animal testing and the development of pharmaceutics. Monitoring the extracellular stromal environment is the basis for gaining in-depth knowledge of the pathophysiology of cell culture. Hence, it is extensively employed as an essential tool in the fields of organ-on-chip andin vitrotoxicology. In this study, we explore the vitality of a microfluidic system for the automated, online detection of drug-induced physical changes in cellular viability by continual monitoring of a microfluidic 2D monolayer cell culture. Trans-epithelial electrical resistance (TEER) values and pH changes of the immortal HepG2 cell line were measured continuously using microfluidic-based electrical and photoelectric sensors. A chip-embedded transparent, flat, non-toxic sensor and in-house 3D manufactured portable digital microscope supersedes the conventional manual, expensive confocal microscopic assays, and off-line operated isolated sensor systems. The cytotoxicity was induced by various concentrations of doxorubicin, epirubicin and lapatinib, and the acute metabolic and physical response of cells was examined by detecting the variations in TEER, pH and other biological markers. Thus, our liver-on-chip device provides real-time online data on drug-induced liver injuryin vitro.