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MEA and impedance measurements using the xCELLigence RTCA CardioECR system

Ncardia's expertise in MEA assays enables detailed electrophysiological detection of potential test compounds, in a broad throughput range. The xCELLigence RTCA CardioECR system is a noninvasive, label-free platform that combines impedance with microelectrode array technology to simultaneously assess cardiomyocyte contractility, viability and electrophysiology.

Case studies were performed to assess the effects of cardioactive compounds on the electrophysiology and cellular impedance of Pluricyte Cardiomyocytes using the xCELLigence RTCA CardioECR system. The cardiomyocytes show the expected pharmacological responses to reference compounds in a reproducible manner.

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Application

Cardiac safety assessment using hiPSC-derived cardiomyocytes in combination with the xCELLigence RTCA CardioECR system

The xCELLigence RTCA CardioECR instrument records cellular impedance and electrical field potential in parallel, using proprietary microelectrode array (MEA) technology. Changes in extracellular field potential are captured through ECR measurement, generated by the electrophysiological processes across the cell membrane. In addition, impedance of cells is recorded by sending a small electrical current through the cardiomyocyte monolayer.

Isoproterenol doesn't affect ion channels directly, but affects cardiomyocyte contraction through other mechanisms, still causing potential changes in the field potential signal and/or the contractility of the cells. Isoproterenol activates β-adrenergic receptors, resulting in increased beat rate and consequently a reduction in field potential duration. The figure below shows that isoproterenol indeed had a concentration-dependent effect on the firing rate of Pluricyte Cardiomyocytes, as well as on the absolute field potential duration.

Effects of isoproterenol on FPD and impedance on pluricyte cardiomyocytes

Isoproterenol activates the β-adrenergic receptor, which results in an increased beat rate (left panel). The impedance signal can be used to assess compound effects on cell contractility. Isoproterenol caused an increase in impedance peak amplitude in Pluricyte Cardiomyocytes (right panel), indicating a positive inotropic effect of isoproterenol.

Conclusion

This application note shows how we can assess the effects of a set of cardio-active compounds on electrophysiology by electrical field potential and Cellular Index measurements using the xCELLigence RTCA CardioECR.

Through our >10 years of expertise, our MEA assay services can support your Drug Discovery projects, providing you with detailed analyses of either patient derived or genetically modified iPSC models, to study your required disease phenotype and its response to compounds. Results are highly relevant for studying cardiac safety or efficacy profile of compounds through several stages of your drug development projects.

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