TEER in a microfluidic gut-on-a-chip device
Paper can be found here
I am working on developing an analytical model to understand how to accurately post-process the resistance values I obtain from my TEER measurements. This paper addresses a similar issue and comes up with a correction factor to match the TEER values obtained in a microsystem with the ones obtained from a transwell configuration.
Model: The authors have a made a coculture microlfuidic device with a porous PDMS membrane as a cell growth substrate [Caco-2 cells]. The device design is almost same as Henry’s flow device, with fluid access on both the sides of the porous membrane. They essentially a 4 point resistance measurement system, with two electrodes for electric current and potential measurements respectively. They model apical and basal resistances in series, with tight junctions, intercellular junction resistances in parallel. An extra addition to this regular model was the addition of a gap resistance in parallel, and understanding the effects of cell coverage on the net TEER values
Results and Analysis: They obtained TEER values higher than the ones in the transwell device. They attributed this increase to the non-uniformity in the electric field distribution across their channel, leading to the overestimation of the TEER. The current distribution profile matches to the fluid flow profile obtained by Henry in his paper. In order to beat this discrepancies, authors presented an one-to-one mapping function; they generated a calibration curve comparing TEER from their device to the transwell TEER. This calibration curve can then be used to inter-convert from one system to other.
Take-home: Any microfluidic device will have a different geometrical dependency of the TEER. One can accurately model the device and vary multiple parameters to get an exact (or empirical) behavior of TEER. Once this function is determined, one can then predict TEER values for different input conditions like membrane active area, electrode geometry etc. This model then needs to be experimentally validated by mimicking similar conditions in the lab. Alternatively, one can just come-up with a mapping function and map all their TEER values in the transwell domain, and then use them for further analysis.
The presentation for this paper can be found here
This is good stuff, i wondered on reading whether there’s any merit in looking at equivalent circuit analysis, or even impedance-based methods which might allow the various components to be disentangled from each other? Ideally the series resistance of the cells would dominate the contributions of the bath and electrode couplings, which should make recordings from “tight” cells more reliable than leaky ones – however this won’t save you early in the piece before the cells make a patent layer..