Microphysiological system with continuous analysis of albumin for hepatotoxicity modeling and drug screening

Abstract

In microfluidics, the emerging field of microphysiological systems (MPS) is overcoming the challenge of physiological irrelevancy by animal models for drug discovery and development. Liver function is critically influenced by drugs owing to its role in drug metabolism and detoxification. Human serum albumin (HSA) is one of the most important secreted biomarkers which indicate normal liver function. A microfluidic albumin immunosensor was developed to be integrated with liver-on-a-chip MPS for continuous feedback over disease modeling and treatment. A gold-electrode based electrochemical immunosensor was established by anti-HSA antibody immobilization. The liver MPS was found to be efficient for live monitoring of disease modelling and drug treatment over the period of 6 days. The system emulated and analyzed real-time toxicity modeling with HSA sensing. The detection limit of integrated sensor was 1μg/ml with successive reproducibility. The proposed sensor was also validated with metabolic biomarkers’ assays. Molecular assays supported the sensor monitoring and depicted liver injury and recovery. The liver MPS with combined albumin sensor chip may be a promising platform to mimic real-time drug assessment.