Highlights

A lung cancer-on-chip platform was developed for real-time physiological monitoring.

All the biosensors were developed in-house including pH, and TEER impedance sensors.

Transparent ITO electrode allowed for visual monitoring using 3D-printed microscope.

The toxicity of anticancer drugs doxorubicin and docetaxel was evaluated.

A comparison of impedimetric and live/dead cell viabilities was also analyzed.

Abstract

Numerous micro-physiological systems have been reported to successfully mimic the organ microenvironment. However, there are currently only a few systems that focus on real-time physiological monitoring for preclinical cytotoxicity assessment of drug candidates. We developed a multi-sensor lung cancer-on-chip platform for trans-epithelial electrical (TEER) impedance based cytotoxicity evaluation of drug candidates. The excellent transparency of ITO electrodes allowed for visual monitoring of cells on chip using a 3D-printed digital microscope, which has not been previously reported. An optical pH sensor was used for online monitoring of media pH. As a proof of concept, lung cancer NCI-H1437 cells were cultured on glass-based microfluidic chip and biosensors data were obtained in real-time. The toxicity of different concentrations of drugs doxorubicin (DOX) and docetaxel was then monitored in real-time using the TEER impedance sensor. The TEER impedance response was evaluated in terms of cell index (CI), whereas a live/dead assay was performed for the comparison of cell viability at the end of the experiments. The cell index assessment suggested that the increasing concentrations of doxorubicin resulted in a higher cell death rate than docetaxel. The pH response and microscopic images were also recorded during drug treatment. The platform we developed here, is a promising tool for the cytotoxicity evaluation of novel drug compounds for future micro-physiological systems and development of personalized medicine.