Improved trans-endothelial Electrical Resistance sensing using microfluidic low-temperature co-fired ceramics

Trans-endothelial Electrical Resistance (TEER) and cellular impedance measurements are widely used to evaluate the barrier properties and functional change of endothelial cell monolayers. In the current work, low temperature cofired ceramics (LTCC) are applied enabling the incorporation of TEER and impediametric measurements in an integrated microfluidic chip. LTCC materials are an ideal substrate for biomedical and cell-based microfluidics due to their biocompatibility and ability to combine complex three dimensional structures with optical, fluidic, and electrical functionality. Multilayer microfluidic ceramic devices incorporating gold measurement electrodes where prepared using standard LTCC manufacturing procedures. The sensitivity of the resulting LTCC devices were compared to systems currently on the market for TEER measurements. These results indicate the LTCC device is able to effectively detect the growth of an endothelial cell monolayer. Results further evaluate endothelial cell viability using electrical resistance and Live/Dead assay. Finally, the results from this study also display improved sensitivity through the optimization of the electrode geometry and use of a lock-in amplifier. These results provide a solid basis for using low temperature co-fired ceramic materials for microfluidic TEER devices.