Issue 14, 2023

Steady-state monitoring of oxygen in a high-throughput organ-on-chip platform enables rapid and non-invasive assessment of drug-induced nephrotoxicity

Abstract

High-throughput, rapid and non-invasive readouts of tissue health in microfluidic kidney co-culture models would expand their capabilities for pre-clinical assessment of drug-induced nephrotoxicity. Here, we demonstrate a technique for monitoring steady state oxygen levels in PREDICT96-O2, a high-throughput organ-on-chip platform with integrated optical-based oxygen sensors, for evaluation of drug-induced nephrotoxicity in a human microfluidic co-culture model of the kidney proximal tubule (PT). Oxygen consumption measurements in PREDICT96-O2 detected dose and time-dependent injury responses of human PT cells to cisplatin, a drug with known toxic effects in the PT. The injury concentration threshold of cisplatin decreased exponentially from 19.8 μM after 1 day to 2.3 μM following a clinically relevant exposure duration of 5 days. Additionally, oxygen consumption measurements resulted in a more robust and expected dose-dependent injury response over multiple days of cisplatin exposure compared to colorimetric-based cytotoxicity readouts. The results of this study demonstrate the utility of steady state oxygen measurements as a rapid, non-invasive, and kinetic readout of drug-induced injury in high-throughput microfluidic kidney co-culture models.

Graphical abstract: Steady-state monitoring of oxygen in a high-throughput organ-on-chip platform enables rapid and non-invasive assessment of drug-induced nephrotoxicity

Supplementary files

Article information

Article type
Paper
Submitted
10 Mar 2023
Accepted
05 Jun 2023
First published
12 Jun 2023

Analyst, 2023,148, 3204-3216

Author version available

Steady-state monitoring of oxygen in a high-throughput organ-on-chip platform enables rapid and non-invasive assessment of drug-induced nephrotoxicity

S. H. Kann, E. M. Shaughnessey, X. Zhang, J. L. Charest and E. M. Vedula, Analyst, 2023, 148, 3204 DOI: 10.1039/D3AN00380A

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