Consistent e-phys signals across multiple plates. Ncyte CardioPlate Maestro MEA 96 show stable beat rate of ~30-40 BPM with <1% beat-to-beat variation and physiological FPD < 1000 ms.
Very stable beat rate across multiple plates. Low inter-well variation <10% and very low intra-well beat irregularity <1% at day 11 post seeding.
hiPSC-derived cardiomyocytes seeded in the Ncyte Cardioplate express cardiac markers and exhibit cardiac sarcomeric structure. Immunofluorescence shows a cardiac population (low mag., left) with a sarcomeric myofibril organization (high mag., right).
Easily identifiable repolarization peak with Ncyte CardioPlate enable fast and accurate data analysis. hERG-trafficking inhibition by chronic exposure to Pentamidine. Flattening of repolarization peak amplitude over time highlighted by red arrows.
Spike amplitude activity map of hiPSC-derived cardiomyocytes showing 96-wells and 8 electrodes per well. Nearly 100% coverage is observed 6 days after plating. Depolarization peak amplitude of at least 300 µV is indicated by white over an electrode.
Isoproterenol activates the β-adrenergic receptor, which results in an increased beat rate. Left: ∆∆ % Change of beat rate
(baseline vs acute measurement at MEA day 11); Right: Beating pattern (baseline vs acute)
Immunofluorescence imaging of cTnT expression directly in Cytoview MEA plates allows additional assay flexibility. Images taken from the center of well, where cells were seeded as a droplet.
The chronic cardiotoxicant Pentamidine prolongs FPDc after long-term treatment. Left: Concentration-dependent effect of FPDc prolongation by hERG-trafficking inhibition 3 hours after exposure. The graph shows dd% change of FPDc normalized to baseline and time-matched vehicle after addition of 0.3, 10 and 30 uM Pentamidine. Right: example plots show prolongation of FPD and typical flattening of the repolarization peak over time at 10 uM.
Structural toxicity by chronic exposure with kinase inhibitor Ponatinib. Left: Concentration-dependency shows decreased beat rate to approx. 50% over time at 1 uM. Graph shows dd% change of beat rate normalized to baseline and time-matched vehicle after addition of 0.01, 0.1 and 1.0 uM. Right: Beating pattern shows decreased beat rate at 1.0 uM 48 hours after addition.
FPD detected in >60% electrodes per well using Ncardia recommended detection settings with a low 0.5% intra-well variation. Bottom: Table shows succession rates (total # of active electrodes vs FPD electrodes) using unsupervised FPD detection. Top: Low 0.5% intra-well variation using supervised detection with low <5% inter-well variation of FPD detection. Supervised vs unsupervised yield similar values supporting feasibility of unsupervised detection.
Representative example of beating pattern showing regular beating and clear de- and repolarization peaks.
Similar occurrence of arrhythmic events per plate and time point with 3 nM Dofetilide suggesting high reproducibility between plates and time points
Ncyte CardioPlate MEA 96 shows evidence of being a predictive model based on responses to a subset of CiPA-approved compounds. Electrophysiological effects detected in Ncyte CardioPlate by compounds with known risk levels (low, medium, and high) for clinical TdP risk. Drug-induced repolarization prolongation is shown as averaged baseline- and vehicle-controlled (red). Bars represent % of wells in which an event was observed. Event classifications are color coded.