Perfused Organs-on-a-Chip intergrated with TEER measurement technique:

There is growing global concern over the outbreak of new diseases and disease conditions. This makes it pertinent to synthesise new drugs to protect the society from any undesirable health conditions. The developmental process of a new drug molecule is cost-ineffective involving more than a billion Euros and particularly time-consuming taking about 10 to 15 years. In order to consider a newly synthesised drug molecule safe for human administration, the drug must undergo two stages, namely, preclinical and clinical trials in the drug developmental process. During the preclinical stages, the efficacy, toxicity and pharmacokinetics-pharmacodynamics (PK-PD) based data of the drugs are collected. It has been found that one out of ten drugs tested fail in the clinical trials owing to inefficient and unsuitable models available for the preclinical trial stage of the drug development process [1].

Conventionally, the preclinical stage in the drug developmental process involves implementation of two techniques namely, in vitro cell culture assay and in vivo animal experimentation. The preliminary in vitro cell culture assays performed using human-derived cells, facilitate to understand the cytotoxic effect of a chosen drug molecule [2]. However, the 2D cell culture assay that involves culturing of human-derived cells in petri dishes and multi-well plates does not mimic the physiological environment as the cells suffer from incomplete maturation, in addition, also lack complete functional development due to their confinement and growth in 2D space. Most importantly, 2D cell culture assay lack the organ-organ or tissue-tissue interaction and as a result cannot predict the complex drug metabolism and the effect of metabolite activity on non-target tissues [1,3]. Use of suitable animal models to test the in vivo drug efficacy and toxicity is another generally used method in the preclinical stage of drug development. Performing drug efficacy and toxicity experiments on animals take into consideration the multi-organ interaction and non-target organ toxicity. Nevertheless, there are ethical concerns over using animals. The use of animals also generates erroneous pharmacological data owing to the inaccuracies involved in extrapolating the results obtained due to species differences. Additionally, performing animal tests involves longer experimentation time and cost-ineffective [1-3].

Therefore, a new emerging contemplation of fabrication of multiple Organs-on-a-Chip (MOOC) is gaining attention considering the aforementioned drawbacks of the existing in vitro and in vivo preclinical drug testing methods. An Organs-on-a-chip is a micro-engineered biomimetic device that contains microfluidic channels and chambers populated by living cells, which replicate key functional units of living organs to reconstitute integrated organ-level pathophysiology in vitro. In the European Union, it is believed that in vitro methods will play a major role in future legislation on testing chemicals and also in relation to the seventh amendment to the Cosmetic Directive. Thus, both of these policies demand for an alternative technique to replace animal experiments. Therefore, an extensive interest has been shown by many biotech, pharmaceutical, food and cosmetic industries in applying Organs-on-a-Chip for studying drug, nutrient and xenobiotic absorption and their possible toxic effects [4]. On administration of an oral pharmaceutical drug, major organs that are involved in the drug absorption and metabolism are intestine and liver. The drug is then distributed to different target organs such as brain, heart, lungs, etc. Finally, the drug metabolites are eliminated from the human system with the help of kidney.