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Hepatic fibrosis is a foreshadowing of future adverse events like liver cirrhosis, liver failure, and cancer. Hepatic stellate cell activation is the main event of liver fibrosis, which results in excessive extracellular matrix deposition and hepatic parenchyma's disintegration. Several biochemical and molecular assays have been introduced for in vitro study of the hepatic fibrosis progression. However, they do not forecast real-time events happening to the in vitro models. Trans-epithelial electrical resistance (TEER) is used in cell culture science to measure cell monolayer barrier integrity. Herein, we explored TEER measurement's utility for monitoring fibrosis development in a dynamic cell culture microphysiological system. Immortal HepG2 cells and fibroblasts were co-cultured, and transforming growth factor β1 (TGF-β1) was used as a fibrosis stimulus to create a liver fibrosis-on-chip model. A glass chip-based embedded TEER and reactive oxygen species (ROS) sensors were employed to gauge the effect of TGF-β1 within the microphysiological system, which promotes a positive feedback response in fibrosis development. Furthermore, albumin, Urea, CYP450 measurements, and immunofluorescent microscopy were performed to correlate the following data with embedded sensors responses. We found that chip embedded electrochemical sensors could be used as a potential substitute for conventional end-point assays for studying fibrosis in microphysiological systems.

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 and in vitro toxicology. 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 injury in vitro.