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A Microfluidic Barrier-on-Chip Platform with Integrated Porous Membrane Cell-Substrate Impedance Spectroscopy.

Alisa Ugodnikov1,2, Joy Lu1, Bhaskar Yechuri1,2

  • 1Translational Biology & Engineering Program, Ted Rogers Centre for Heart Research, Toronto, Ontario M5G 1M1, Canada.

ACS Applied Materials & Interfaces
|August 4, 2025
PubMed
Summary
This summary is machine-generated.

We developed a new method using porous membrane electrical cell-substrate impedance sensing (PM-ECIS) to accurately measure organ-on-chip barrier function, overcoming limitations of previous techniques.

Keywords:
ECISTEERbiological barriersblood−brain barrierimpedance spectroscopymicrofluidicsorgan-on-chip

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Area of Science:

  • Biomedical Engineering
  • Cellular and Molecular Physiology
  • Microfluidics

Background:

  • Organ-on-chip (OOC) systems model biological barriers using microenvironmental features.
  • Trans-endothelial/epithelial electrical resistance (TEER) is commonly used for OOC barrier integrity but has limitations.
  • TEER is affected by current distribution and biomaterials, hindering accurate measurements in complex OOC models.

Purpose of the Study:

  • To develop and validate a novel impedance sensing method for OOC barrier integrity.
  • To overcome the limitations of TEER in OOC systems with biomaterials and fluid shear stress.
  • To establish a sensitive and noninvasive real-time measurement technique for OOC barrier function.

Main Methods:

  • Incorporated gold leaf porous membrane electrical cell-substrate impedance sensing (PM-ECIS) electrodes into a tape-based barrier-on-chip (BOC) platform.
  • Tested PM-ECIS robustness to fluid shear stress in cell-free and endothelial barrier models.
  • Evaluated PM-ECIS sensitivity in hydrogel coculture models, comparing it to trans-endothelial/epithelial electrical resistance (TEER).

Main Results:

  • PM-ECIS measurements were unaffected by fluid shear stress (5 dyn/cm²) in cell-free devices.
  • Perfusion (0.06 dyn/cm²) significantly decreased impedance and resistance in endothelial barrier models (p < 0.01).
  • PM-ECIS demonstrated robustness to hydrogels and superior sensitivity compared to TEER in detecting endothelial monolayers.

Conclusions:

  • Porous membrane electrical cell-substrate impedance sensing (PM-ECIS) provides a robust and sensitive method for measuring organ-on-chip barrier function.
  • This technique overcomes limitations of traditional TEER, especially in complex OOC models with biomaterials and shear stress.
  • PM-ECIS is well-suited for real-time, noninvasive monitoring of barrier integrity in advanced organ-on-chip applications.