Building upon the impedance-only xCELLigence® RTCA Cardio system, the new CardioECR system combines impedance recording (for evaluating contractility and viability) with both multi electrode array (MEA) technology and a pacing function (for evaluating integrated ion channel activity). Cardiomyocytes are seeded in a 48-well electronic microtiter plate (E-Plate® CardioECR 48) that contains gold microelectrode arrays fused to the bottom of each well (Figures 1A-C). 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. Because the cardiomyocyte contraction/relaxation cycle involves substantial changes in cell morphology and adhesion, it can be dynamically monitored using impedance (Figures 2A-B). The enhanced impedance measurement rate (every 1 ms) of the xCELLigence® RTCA CardioECR system provides extremely high temporal resolution for viewing subtleties of the cardiomyocyte contraction/relaxation continuum. In addition to this ability to monitor cell viability and contractile activity, additional point electrodes in the well bottoms (Figure 1C) allow for extracellular field potential (FP) measurements at 10 kHz, which can be performed in tandem with impedance recording (Figure 2B).

Figure 1. E-Plate CardioECR 48 compatible with the xCELLigence RTCA CardioECR system. (A) E-Plate CardioECR 48. The footprint of this plate complies with ANSI/SBS 1-2004 requirements, and the spacing of the wells in each column is 9 mm center-to-center as per the ANSI/SBS 4-2004 standard. (B) Zoomed in view of E-Plate CardioECR 48 wells. (C) Graphic depiction of a confluent layer of cardiomyocytes interacting with both types of recording electrodes (impedance and field potential electrodes).

Figure 2. Simultaneously using impedance and field potential to monitor cardiomyocyte health and function. (A) Comparison of the contracted vs. relaxed states of two cardiomyocytes adhered to a single electrode. The differences in cell size/shape, and the manner in which cells contact the electrode cause these two states to impede the flow of electric current differently. (B) Simultaneously monitoring cardiomyocyte contraction (red, green, blue, and pink traces) and field potential (integrated ion channel activity; black traces) in real-time. Compared to the negative control (upper set of traces), the three different drugs being evaluated here (bottom three sets of traces) have distinct effects on both contraction and field