Researchers at the University of Toronto have developed a novel, cost-effective method called Porous Membrane Electrical Cell–Substrate Impedance Spectroscopy (PM-ECIS) to assess the function of biological barriers in Petri dishes. In a subsequent study, the researchers characterized its sensitivity and further validated the method against a gold-standard barrier assessment technique. This new method could enhance research in fields like drug development and disease modeling.
The original study was published in ACS Applied Biomaterials and the follow-up study was published in the ACS Biomaterials Science & Engineering.
Biological barriers are often modeled in the lab using porous membrane inserts, which allow for well-controlled culture in a setup that facilitates the growth of and cross-talk between the different cell types making up a barrier. For example, the blood-brain barrier, essential for controlling the transport of substances into the brain, can be modeled in such setups using blood vessel cells on one side of the membrane, and support cells like astrocytes on the other side.
Traditional methods used to measure barriers grown on porous membrane inserts often require invasive manual handling, have low temporal resolution, and may disrupt barrier integrity. PM-ECIS adapts Electrical Cell–Substrate Impedance Sensing (ECIS) technology to porous membranes, in which cells are grown directly on measurement electrodes, allowing for sensitive, real-time measurement of changes in cell barrier impedance without damaging the cell layer.
The innovative approach involves high-fidelity patterning of electrodes on porous membranes and integrated into cell culture inserts, a fabrication process adaptable to well plates of various sizes. This method shows excellent cell biocompatibility, enabling multiple cell types to be grown in parallel and for direct comparison to standard approaches like the molecular permeability assay, as demonstrated in the original study.
In the follow-up study, led by Alisa Ugodnikov, Oleg Chebotarev, Henrik Persson, and Professor Craig Simmons, PM-ECIS was compared with the widely used trans-endothelial electrical resistance (TEER) method. TEER is commonly used to measure cell barrier integrity but has some limitations, especially in complex cell culture models.
Unlike TEER, PM-ECIS electrodes are in direct contact with the cells of interest, which makes them well-suited for detecting small changes in cell barriers and providing more precise measurements. Nevertheless, PM-ECIS results were consistent with TEER measurements, validating PM-ECIS as a reliable alternative for monitoring cell barriers. Additionally, PM-ECIS effectively detected disruptions in cell barriers caused by different substances, with tunable sensitivity based on electrode size, making it useful for various applications such as testing new drugs and studying diseases in lab-grown tissues.
PM-ECIS could significantly improve how scientists study cell barriers, offering a more accurate, non-invasive, and real-time method for monitoring changes. This has important implications for medical research, including developing new treatments and understanding diseases better.
“PM-ECIS provides a new, improved way to measure cell barrier integrity. This technology improves accuracy and allows continuous monitoring, which is crucial for advancing research in biological interfaces like the blood-brain barrier.” Said Alisa Ugodnikov, one of the authors of this study.