Published December 2023 | Version Published
Journal Article Open

Rapid integration of screen-printed electrodes into thermoplastic organ-on-a-chip devices for real-time monitoring of trans-endothelial electrical resistance

  • 1. ROR icon Terasaki Foundation
  • 2. ROR icon University of California, Riverside
  • 3. ROR icon University of Jordan
  • 4. ROR icon University of British Columbia
  • 5. ROR icon Ghent University
  • 6. ROR icon Royal Institute of Technology
  • 7. ROR icon University of California, San Francisco
  • 8. ROR icon California Institute of Technology
  • 9. ROR icon University of South Carolina

Abstract

Trans-endothelial electrical resistance (TEER) is one of the most widely used indicators to quantify the barrier integrity of endothelial layers. Over the last decade, the integration of TEER sensors into organ-on-a-chip (OOC) platforms has gained increasing interest for its efficient and effective measurement of TEER in OOCs. To date, microfabricated electrodes or direct insertion of wires has been used to integrate TEER sensors into OOCs, with each method having advantages and disadvantages. In this study, we developed a TEER-SPE chip consisting of carbon-based screen-printed electrodes (SPEs) embedded in a poly(methyl methacrylate) (PMMA)-based multi-layered microfluidic device with a porous poly(ethylene terephthalate) membrane in-between. As proof of concept, we demonstrated the successful cultures of hCMEC/D3 cells and the formation of confluent monolayers in the TEER-SPE chip and obtained TEER measurements for 4 days. Additionally, the TEER-SPE chip could detect changes in the barrier integrity due to shear stress or an inflammatory cytokine (i.e., tumor necrosis factor-α). The novel approach enables a low-cost and facile fabrication of carbon-based SPEs on PMMA substrates and the subsequent assembly of PMMA layers for rapid prototyping. Being cost-effective and cleanroom-free, our method lowers the existing logistical and technical barriers presenting itself as another step forward to the broader adoption of OOCs with TEER measurement capability.

Copyright and License

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Contributions

Satoru Kawakita, Shaopei Li and Huu Tuan Nguyen contributed equally.

Conceptualization: SK and SL; Methodology: SK, SL, and HTN; Validation: SK, SL, and HTN; Formal Analysis and Investigation: SK, SL, HTN, SM, RH, JB, NY, KM, PB, LM, ME, EK, AP, RN, AA, AN, RB, and YZ; Writing – Original Draft: SK; Writing – Review & Editing: all authors; Funding Acquisition: MRD and AK. Resources: AK. Supervision: VJ, MRD, and AK.

Conflict of Interest

The authors declare no competing interests.

Data Availability

Data is available upon reasonable request.

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Additional details

Identifiers

ISSN
1572-8781
URL
https://rdcu.be/dpQ75