Quasi-In Vivo Electrocardiogram Measurement using Convolution of Field Potential Propagation in the On-Chip Cardiomyocytes Network Circuit

Abstract

Understanding the importance of spatial and temporal regulation of cellular community size and shape are keys to resolve mechanisms in highly complex heart system by new quasi-in vivo assay, which can predict the phenomenon in vivo using in vitro assay. For that, an on-chip cell network cultivation system has been developed, in which field potential (FP) of cardiomyocyts in geometrically patterning chambers have been recorded with a multielectrode array (MEA) system. We have fabricated ring-shaped microelectrode having 1 or 2 mm in diameter and 50 μm in width, and cultivated cardiomyocytes from mouse embryonic hearts on the electrode with same closed circuit shape assisted by agarose microstructures. After the confirmation of regular propagation of beatings, we added a 1μM Astemizole which is well known to raise ventricular arrhythmias, and found that the profile of FP changed to the abnormal beating shape and then reached to the fibrillation shape [1]. To investigate the propagation pathway of excitation on abnormal beating, we constructed the circuit on 16 electrodes with area of 50x50 μm in a similar geometry to ring electrode assay. When abnormal beating happened on convoluted FPs obtained from all the 16 channels, one directional block on propagation were occurred and induced “re-entry” [2]. These results suggest that abnormal propagation, such as re-entry, causes abnormal fibrillation-like signal on the ring electrode. In conclusion, a simple quasi-in vivo ECG measurement assay has been proposed and developed and the results showed the typical arrhythmia profiles, in which both the temporal depolarization information and the spatial beating propagation information were appeared. [1] Nomura F, et al. J. Nanobiotechnology. 9, 39, 2011. [2] Kaneko T, et al. Jpn. J. Appl. Phys., 50, 070213, 2011.