Standardizing TEER Measurements in Blood-Brain Barrier-on-Chip Systems: A Systematic Review of Electrode Designs and Configurations.

The blood-brain barrier (BBB) is one of the most selective physiological interfaces in the human body. Transendothelial electrical resistance (TEER) has become a widely adopted quantitative metric for assessing its in vitro structural and functional integrity. Although TEER measurements are routinely incorporated into BBB-on-chips, the absence of harmonized electrode architectures, measurement settings, and reporting standards continues to undermine reproducibility and translational reliability among laboratories. This systematic review provides the first comprehensive classification and critical comparison of electrode configurations used for TEER assessment, specifically within BBB-on-chip systems. Eligible studies were analyzed and categorized according to electrode design, fabrication method, integration strategy, and operational constraints. We critically evaluated six principal electrode architectures, highlighting their performance trade-offs in terms of uniformity of current distribution, long-term stability, scalability, and compatibility with dynamic shear conditions. Furthermore, we propose a bioinspired TEER reporting framework that consolidates essential metadata, including electrode specification, temperature control, viscosity effects, and blank resistance correction. Our analysis proposes screen-printed and hybrid silver-indium tin oxide (ITO) electrodes as promising candidates for next-generation BBB platforms. Moreover, our review provides a structured roadmap for standardizing TEER electrode design and reporting practices to facilitate interlaboratory consistency and accelerate the adoption of BBB-on-chip systems as truly biomimetic platforms for predictive neuropharmacological workflows.