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

**Authors:** Nazanin Ghane, Reza Jafari, Naser Valipour Motlagh

PMC · DOI: 10.3390/biomimetics11020119 · Biomimetics · 2026-02-05

## TL;DR

This paper reviews and compares different electrode designs for measuring TEER in BBB-on-chip systems to improve consistency and reliability across labs.

## Contribution

The paper introduces a comprehensive classification of electrode configurations and proposes a standardized framework for TEER reporting in BBB-on-chip systems.

## Key findings

- Six electrode architectures were evaluated for performance trade-offs in current distribution and stability.
- Screen-printed and hybrid silver-ITO electrodes are recommended for future BBB platforms.
- A bioinspired reporting framework is proposed to enhance interlaboratory consistency.

## Abstract

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.

## Full-text entities

- **Genes:** FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, MRPL58 (mitochondrial ribosomal protein L58) [NCBI Gene 3396] {aka DS-1, DS1, ICT1, MRP-L58, mL62}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, TJP3 (tight junction protein 3) [NCBI Gene 27134] {aka ZO-3, ZO3}, TJP1 (tight junction protein 1) [NCBI Gene 7082] {aka ZO-1}, TJP2 (tight junction protein 2) [NCBI Gene 9414] {aka C9DUPq21.11, DFNA51, DUP9q21.11, FHCA1, PFIC4, X104}, CGN (cingulin) [NCBI Gene 57530], OCLN (occludin) [NCBI Gene 100506658] {aka BLCPMG, PPP1R115, PTORCH1}, CLDN5 (claudin 5) [NCBI Gene 7122] {aka AWAL, BEC1, CPETRL1, TMDVCF, TMVCF}
- **Diseases:** cytotoxicity (MESH:D064420), multiple sclerosis (MESH:D009103), inflammatory (MESH:D007249), injury to (MESH:D014947), Parkinson's disease (MESH:D010300), Alzheimer's disease (MESH:D000544), traumatic brain injury (MESH:D000070642), stroke (MESH:D020521)
- **Chemicals:** ITO (MESH:C109984), dextran (MESH:D003911), Al (MESH:D000535), graphene (MESH:D006108), AZ 100 (-), LY (MESH:C017475), Cr (MESH:D002857), carbon nanotubes (MESH:D037742), sodium fluorescein (MESH:D019793), Evans Blue (MESH:D005070), PDMS (MESH:C013830), polypropylene (MESH:D011126), lipid (MESH:D008055), PET (MESH:D011093), oxide (MESH:D010087), saline (MESH:D012965), Au (MESH:D006046), Pt (MESH:D010984), metal (MESH:D008670), polymer (MESH:D011108), carbon (MESH:D002244), PMMA (MESH:D019904), water (MESH:D014867), Al2O3 (MESH:D000537), AgCl (MESH:C037548), Ag (MESH:D012834)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** hCMECs/D3 — Mus musculus (Mouse), Embryonic stem cell (CVCL_4378)

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12938208/full.md

## References

103 references — full list in the complete paper: https://tomesphere.com/paper/PMC12938208/full.md

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Source: https://tomesphere.com/paper/PMC12938208