Low-cost microelectrode array with integrated heater for extracellular recording of cardiomyocyte cultures using commercial flexible printed circuit technology

This article reports the use of commercial, flexible printed circuit technology for the fabrication of low-cost microelectrode arrays (MEAs) for recording extracellular electrical signals from cardiomyocyte cultures. A 36-electrode array has been designed and manufactured using standard, two-layer, polyimide-based flexible circuit technology, with electrode diameters of 75 and 100μm. Copper structures defined on the backside of the array have been used for low-power thermal regulation of the culture. Electrical characterization of the gold-plated electrodes showed impedances below 250kΩ at 1kHz. Functional testing was conducted using HL-1 cardiac myocytes. The arrays proved biocompatible, and supported the formation of functional syncytia, as demonstrated by electrical recordings of depolarization waves across the array. A comparison with conventional, glass-based MEAs is presented, which reveals differences in signal strength (smaller for larger electrode) and variability (less for larger electrodes), but no effect of the substrate types on culture parameters such as beat rate or conduction velocity. The performance of the on-chip heating was evaluated, with typical temperature settling times (to ±0.1°C) below 10s, for a power consumption around 1W (at 37°C). Accuracy and stability are discussed. HL-1 cell responses to various temperature profiles enabled by the on-chip heating are presented, showing a remarkable correlation between temperature and beat rate.