Development of microelectrodes for electrical measurements in a microfluidic system

Abstract: Transendothelial electrical resistance (TEER) measurements are used to quantitatively monitor cell barrier formation in in vitro models of the blood-brain barrier. TEER measurements in microfluidic in vitro systems are technically problematic and have suffered from poor measurement reproducibility. The aim of this Master’s thesis project was to develop fully integrated electrodes for measuring TEER in a microfluidic blood-brain barrier model. Two patterns of thin film electrodes – one with electrodes placed in the microfluidic channels, and one with electrodes directly above and below the cell culture membrane – were designed, fabricated and embedded in the microfluidic system. Electrodes were fabricated in silver and in platinum, and their reproducibility was evaluated using impedance spectroscopy. Results showed that electrodes fabricated in platinum and placed directly over the membrane could measure impedance with the highest precision. Measurement variation from the electrodes placed in the channels was shown to effectively be reduced by employing a technique of combining six measurements from four electrodes. Based on the reproducibility studies presented in this report, both types of electrodes were believed to have sufficient sensitivity and robustness to be used for TEER measurements. A robust technique to measure TEER enables real-time monitoring of cells in microfluidic systems, and offers a quantitative validation parameter for easy comparison and benchmarking of different system.