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.

Supported Lipid Bilayer Assembly on PEDOT:PSS Films and Transistors

“…OECTs have been used to monitor not only the integrity of highly resistant barrier‐type tissue layers, but also the coverage of adherent but leaky, nonbarrier cell layers . In the OECT, holes in the channel between the source and drain electrodes are depleted by cations pushed from the electrolyte into the channel due to a bias at a gate electrode ( V G ).…”

“…A variety of different OECT channel geometries were used, including 10 × 10 μm, 10 × 100 μm, and 50 × 50 μm. Previous studies have shown that data can be compared between transistors of different channel geometry …”

Organic electrochemical transistors

“…OECTs have been shown to monitor cell coverage 107 as well as barrier tissue formation and health. [108][109][110][111][112] The majority of these measurements involve the growth of a cell monolayer between the channel and the gate, which introduces an extra barrier for ion motion in the electrolyte and alters the characteristics of the OECT. 113 The same principle was applied to study ion channels in supported lipid bilayers assembled on PEDOT:PSS channels.…”

In Vitro Models for Studying Respiratory Host–Pathogen Interactions

“…[ 185 ] Of note are poly (3,4‐ethlyenedioxythiophene) doped (p‐type) with poly (styrene sulfonate) (PEDOT:PSS)‐based electrodes or organic electrochemical transistors (OECTs). The detailed physical theory of OECT operation is explored elsewhere, [ 186,187 ] but such technology has been integrated into a variety of biological formats, including Transwell ALI culture, [ 178 ] planar and microfluidic devices, [ 188–191 ] PEDOT:PSS bio‐scaffolds, [ 192,193 ] self‐rolling sensors, [ 194 ] and neuromorphic devices. [ 195 ] In vivo examples include bioresorbable patches [ 196,197 ] and implantable electrocorticography devices for monitoring neuronal epileptiform discharge.…”