Sensor-embedded Kidney and Liver Microphysiological Systems for Drug and Disease Analysis

Abstract

Advanced cell culture technique, organ-on-a-chip (OoC) caters the capacity to mimic human physiology with reverse engineered biological formulation of human organs and multi-organs. The prime perspective of 3D cell culture is engineering human physiology for disease modeling to enhance drug screening analytics. Mimicking human physiology with complex in vitro model brings the prospect to replace the usage of laboratory animals for drug screening. Human metabolism is primarily carried out in liver with its excretion taking place in kidney makes these two organs vital for drug screen studies. Additionally, current OoC based MPS systems are mainly dependent upon conventional end-point bioassays comprising of PCR, western blots, and biochemical assays. It is challenging to perform conventional bioassays to analysis MPS systems owing to their complexity as well as reduced cell number and culture media quantity for sample collection. Such analytical limitation in MPS highlights the potential to integration the real-time or continuous sensors for efficient monitoring of cell conditions and responses. This thesis work encompasses the development of microfluidic liver and kidney MPS systems to emulate the development of disease and drug treatment with the integration of sensors. Liver and Kidney MPS were established with the integration of impedance-based transepithelial electrochemical resistance (TEER) sensor, optical pH sensor, and albumin immunosensor for monitoring of disease model development and drug efficacy measurements which were further validated by conventional bioassays. As albumin exhibits the function, the integrated microfluidic human serum albumin immunosensor facilitated the albumin screening for disease and drug analysis. This thesis contributes for the improvement of continuous monitoring of MPS by expanding the disease modeling capacity of OoC technology for a rapid development of drugs.