Early Detection of NephrotoxicityIn VitroUsing a Transparent Conducting Polymer Device

Abstract

Electrical methods for monitoring cell toxicity are becoming increasingly popular because of their amenability for longer-term, continuous, and label-free monitoring. Microfabrication techniques are also opening the way for miniaturization of devices and integration with microphysiometer or lab-on-chip–type devices. In the present work, we demonstrate the use of a transparent conducting polymer device, termed the “organic electrochemical transistor” (OECT), which we have used to monitor the effects of a subset of known nephrotoxicants (cisplatin, tobramycin, and gentamycin) on cell integrity in vitro. Based on a similar principle to traditional electronic impedance spectroscopy, the OECT provides an even more sensitive way to detect small changes in ionic currents in an electrolyte, as a result of inherent amplification of signal provided thanks to the transistor format. The device monitored the ability of the human renal proximal tubular epithelial cells, a human primary cell culture model of the kidney proximal tubule, to act as a barrier to ion flow (analogous to transepithelial resistance), even though this was not possible with a commercially available instrument (cellZscope). Further, the device demonstrated extremely rapid nephrotoxicity even at low concentrations, the transparency of the device allowed in situ monitoring of cells on the device, as well as immunofluorescence staining of key biomarkers of kidney tubule function: KIM-1 and ZO-1. Correlation of electrical and optical data was demonstrated as a powerful tool for validation of the method. In summary, the OECT is presented as an extremely versatile tool for highly sensitive nephrotoxicity monitoring, amenable for future integration into microfabricated lab-on-chip platforms.