Perfused organs-on-a-chip integrated with teer measurement technique: a novel approach towards studying non-targeted drug induced organ toxicity
PORTable STaNDOuTs aims to develop a multiple Organs-on-a-Chip (MOOC) microfluidic device integrated with electrodes for carrying out Transepithelial electrical resistance (TEER) measurements. The key motivation for adopting such an approach is to develop a rapid, versatile and cost-effective prototype with ability for real-time monitoring to replace the conventional long and cost-ineffective preclinical procedures involved in the drug development process. On administration of an oral pharmaceutical drug, major organs that are involved in the absorption and metabolism of drug are intestine and liver. The drug is then distributed to different target organs such as brain, heart, lung, etc. Finally, the drug metabolites are eliminated from the human system with the help of kidney.  Additionally, it has also been found that certain drug metabolites produced by the liver cause non-target drug induced organ toxicity. TEER measurement is a rapid and non-invasive technique for the real-time detection of pathophysiology. TEER indicates the integrity of the cell membrane barrier of different organs that is necessary for maintaining homeostasis within the human body. In view of this, we intend to fabricate a physiologically-mimicking perfused intestine-liver-kidney microfluidic chip with provision for carrying out in-chip TEER measurements. The device will be designed to consist of three compartments for organs namely, intestine, liver and kidney, independently equipped with electrodes for measuring TEER values to detect the integrity of cell membrane barriers in each organ compartment. The developed device will be then subsequently validated for its ability to study drug-induced nephrotoxity. Furthermore, the device will also be made versatile to incorporate other organs of interest to study non-target organ toxicity. Thus, the developed MOOC microfluidic device will surely boost the drug development process that will successively improve the health security of the society.