The xCELLigence® RTCA Cardio system uses non-invasive, label-free impedance monitoring to quantitatively evaluate cardiomyocyte health/function in real-time. Cardiomyocytes are seeded in a 96-well electronic microtiter plate (E-Plate® Cardio 96) that contains gold microelectrode arrays fused to the bottom of each well. Application of a low voltage (less than 20 mV) establishes an electric current between the electrodes, which is differentially modulated by the number of cells covering the electrodes, the morphology of those cells, and the strength of cell attachment (Figure 1A). Because the cardiomyocyte contraction/relaxation cycle involves substantial changes in cell morphology and adhesion, it can be dynamically monitored using impedance (Fig. 1B). The fast data acquisition rate (12.9 ms for the entire 96-well plate) of the xCELLigence®RTCA Cardio system provides high temporal resolution for viewing subtleties of the cardiomyocyte contraction/relaxation continuum. Because impedance measurement is noninvasive, the millisecond time scale data can be combined with longer-term monitoring (hours/days) to study both the short- and long-term effect of compounds on cardiomyocyte health and function.

Figure 1. Using real-time impedance monitoring to quantitatively evaluate cardiomyocyte health and function. (A) The principle of real-time impedance monitoring. The E-Plate Cardio 96 is a 96-well microtiter plate containing gold microelectrodes integrated into the bottom of each well. Application of a low-voltage creates a current between the electrodes. The presence of adherent cells on the surface of the electrodes impedes this current in a manner which is proportional to the number of cells inside the well and the morphologic and adhesive characteristics of the cells. The impedance signal (Z) is displayed as an arbitrary, unitless parameter called Cell Index, which is a ratio that compares the impedance value in the presence of cells vs. the absence of cells. (B) Because the size/shape and attachment strength of cardiomyocytes fluctuate rhythmically during the contraction/relaxation cycle, impedance is capable of tracking this process. (C) Video of beating cardiomyocytes on an E-Plate Cardio 96.