A spheroid-based biosensor for the label-free detection of drug-induced field potential alterations

Abstract A valuable method for evaluating the functional effects of promising candidates in cardiac drug discovery is the analysis of electrophysiological characteristics. In vitro techniques facilitate the investigation of physiological parameters, including action potential generation, conduction, arrhythmia and QT duration, to chemical provocation and at the same time benefit from defined experimental conditions as well as enhanced accessibility. A widespread approach to studying the electrophysiological properties of developing and mature cellular networks in vitro is the multichannel recording of cardiac cells cultured as monolayers on microelectrode arrays. However, common two-dimensional monolayer cell cultures do not accurately reflect in vivo conditions. Cells within a tissue are organized into a complex three-dimensional pattern, and cellular interactions are not limited to a two-dimensional environment. Here, we report on a biosensor that combines the microelectrode array technique with cardiac three-dimensional cellular networks. Fully dissociated primary cells from chicken embryonic hearts were re-aggregated into spheroids. We found that action potentials could be recorded with an excellent signal-to-noise-ratio for up to several weeks. The administration of cardioactive drugs significantly altered the electrophysiological characteristics of the spheroids. Cellular responses were investigated along with the biosensor's potential as a tool for estimating the effectiveness and the risk of adverse reactions of drugs.

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