A customizable continuous and near real-time TEER platform to study anti-cancer drug toxicity in barrier tissues
Year: 2025
Type: article
Abstract: Barrier tissues such as the endothelium are critical in the regulation of mass transfer throughout the body. Trans-endothelium/epithelium electrical resistance (TEER) is an important bioelectrical measurement technique to monitor barrier integrity. Although available on the market, TEER sensors are usually expensive and bulky and do not allow customization around experimental setups like specific microfluidic settings. We recently reported a customizable TEER sensor built on Arduino. In this paper, we significantly advanced a new generation of TEER sensors characterized by 1) a large dynamic range of 242–11,880 Ω·cm 2 with high accuracy (>95%), which covers common needs for TEER studies, 2) a coupling three-dimensional (3D)-printed microfluidic system enabling modular cell integration and flow-based barrier studies, 3) customizable on-off cycles to significantly reduce cell exposure to the current, and 4) automated continuous measurements with customizable intervals. With this sensor system, we investigated how doxorubicin could impair the endothelium layer’s permeability, at a 1-min interval for 24 h. Endothelium toxicity is a new research direction under cardiotoxicity, with many aspects unknown. We found that a clinically relevant dosage did not change the endothelium integrity significantly until approximately 16 h of treatment, after that, the TEER started to drop (showing higher permeability), followed by a slight restoration of its barrier integrity. With an excess dosage (2.5 μM), the TEER started to drop significantly after 5 h and did not show recovery afterward, indicating endothelium toxicity. Overall, we report a new TEER sensor that can monitor continuous drug toxicity on barrier tissues. The customizable features make it translational for various other studies, such as personalized dosage determination on stem cell-derived tissue barriers, and transient barrier permeability variations under diseased conditions. • This paper reports an unprecedented TEER sensor system to investigate drug toxicity in barrier tissues. • This system included a customizable and near real-time TEER sensor and a modular microfluidic device to integrate endothelium in relevant extracellular matrices. • We report for the time how doxorubicin, a common anti-cancer drug, could impact endothelium permeability in 1-min resolution. • Because the system was based on low-cost parts and 3D printing (engineering sketches provided in the SI) with vast customization room.
Authors: Curtis G. Jones, Chengpeng Chen
Institution: University of Maryland, Baltimore County
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,950
OpenAlex ID: W4408476273