Fig. 6: Self-referencing assessment of pharmacological compounds using nanocrown electrodes.

A A raw data trace of intracellular action potentials (iAPs) with sequential addition of pharmacological compounds (Dofetilide for the displayed trace). DMSO is added first as a control, after which an increasing dose of the selected drug is added every 3–4 min while iAPs are continuously being recorded. The large variations in the signal trace are due to vibrations associated with exchanging lipids when new doses of the drug are added (indicated by arrows). B Overlay of amplitude-normalized and self-referencing iAPs, i.e., the same cell before and after adding increasing doses of each drug. The high risk drugs Dofetilide and D,L-Sotalol caused dose-dependent prolongation of iAPs, while the low-risk drugs Verapamil and Nifedipine caused dose-dependent shortening of iAPs. The medium-risk drug Cisapride caused early after-depolarization (EAD). The increasing doses for each drug (Dose1, Dose2, Dose3, and Dose4) were as follows: Dofetilide (0.3 nM, 1 nM, 3 nM and 10 nM), D-L-Sotalol (0.1 µM, 1 µM, 10 µM, 100 µM), Verapamil and Nifedipine (1 nM, 10 nM, 100 nM, 1000 nM), and Cisapride (1 µM). C Dose-dependent changes in APD 90 for three cells showing distinct responses to Dofetilide. iAP waveforms at various time points during the pharmacology experiments at 60 s (DMSO), 600 s (Dose3), and 900 s (Dose4) are shown. D Self-referencing iAPs alignments for cells 1, 2 and 3 show different dose-dependent responses to Dofetilide at doses 3 and 4. E Self-referencing iAPs from 40–84 cells show dose-dependent changes in APD90, APD90-30 (triangulation), and rising time in response to Dofetilide. Data are presented as mean values ± SD.