Organs-on-chips constitute an emerging class of microfluidic models of functional units of human organs. They combine the advantage to provide a more controllable environment than in vivo models while generating a more realistic physiological and pathological behavior of cells than conventional in vitro models made for drug discovery 1,2. Impedance spectroscopy is a widely accepted technique for dynamic quantification of tight junction integrity in cell culture models. It is mostly performed using a two electrodes configuration. The transepithelial/transendothelial electrical resistance (TEER) extracted is a strong indicator of cell barrier integrity for high throughput toxicology screening3. However, for organ-on-chips the measurement of ionic cell barrier resistance require cells to be cultivated on a flat porous membrane otherwise the high resistance of the channel masks TEER value. This configuration is limiting parameters like cell curvature and cell-matrix interaction, which improve cell barrier characteristics particularly in the case of blood brain barrier (BBB) models 4,5. Here we show the use of PEDOT.PSS based organic electrochemical transistors (OECTs) integrated with a 3D model of the BBB for monitoring of endothelial cell barrier resistance with high resolution. Our device combines microvasculature made of collagen and human brain capillary endothelial cells (hCMEC/D3) with OECT in an optically transparent platform. The application of physiologically relevant fluid shear stress on the endothelial cells has shown to increase ZO-1 tight junction expression compare to usual 2D cell culture and can be related to cell resistance measurements. Rat astrocytes could also be integrate in the collagen structure in order to biochemically interact with endothelial cells allowing a more relevant BBB model. This platform will enable high-content screening for in vitro drug discovery and toxicology testing and could also be easily adapted to other tissue models like gut or intestine.
1. Bhatia, S. N. & Ingber, D. E. Microfluidic organs-on-chips. Nat. Biotechnol. 32, 760–772 (2014).
2. Esch, E. W., Bahinski, A. & Huh, D. Organs-on-chips at the frontiers of drug discovery. Nat. Rev. Drug Discov. 14, 248–260 (2015).
3. Srinivasan, B. et al. TEER measurement techniques for in vitro barrier model systems. J. Lab. Autom. 20, 107–126 (2015).
4. Ye, M. et al. Brain microvascular endothelial cells resist elongation due to curvature and shear stress. Sci. Rep. 4, (2014).
5. Adriani, G., Ma, D., Pavesi, A., Kamm, R. D. & Goh, E. L. K. A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as a blood–brain barrier. Lab Chip (2017).