The ability to monitor electrogenic cells accurately plays a pivotal role in neuroscience, cardiology and cell biology. Despite pioneering research and long-lasting efforts, the existing methods for intracellular recording of action potentials on the large network scale suffer limitations that prevent their widespread use. Here, we introduce the concept of a meta-electrode, a planar porous electrode that mimics the optical and biological behaviour of three-dimensional plasmonic antennas but also preserves the ability to work as an electrode. Its synergistic combination with plasmonic optoacoustic poration allows commercial complementary metal–oxide semiconductor multi-electrode arrays to record intracellular action potentials in large cellular networks. We apply this approach to measure signals from human-induced pluripotent stem cell-derived cardiac cells, rodent primary cardiomyocytes and immortalized cell types and demonstrate the possibility of non-invasively testing a variety of relevant drugs. Due to its robustness and easiness of use, we expect the method will be rapidly adopted by the scientific community and by pharmaceutical companies.
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We thank M. Gandolfo and A. Maccione for discussions and for the impedance spectroscopy data of the CMOS-MEA electrodes. The research that led to these results received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement no. , CoG: Neuro-Plasmonics.
The authors declare no competing interests.
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Supplementary Methods, Supplementary Figures 1–15, Supplementary References
Whole CMOS-MEA recording during optoacoustic poration on one electrode. The optoacoustic poration occurs at t = 5 s.
Propagation wave in extracellular mode of human-induced pluripotent stem cells-derived cardiomyocytes on CMOS-MEA. The pixel colours represent the signals’ amplitude.
Propagation wave in intracellular mode of human-induced pluripotent stem cells-derived cardiomyocytes on CMOS-MEA. The pixel colours represent the signals’ amplitude.
Propagation wave in extracellular mode of human-induced pluripotent stem cells-derived cardiomyocytes on CMOS-MEA, including example extracellular waveforms from few electrodes. The brown vertical stripes in the graphs represent the time-bins used for calculating the amplitude for the pixel colouring in the map. The time-traces shown in the videos are highlighted by black square contours in the colour maps.
Propagation wave in intracellular mode of human-induced pluripotent stem cells-derived cardiomyocytes on CMOS-MEA, including example intracellular waveforms from few electrodes. The brown vertical stripes in the graphs represent the time-bins used for calculating the amplitude for the pixel colouring in the map. The time-traces shown in the videos are highlighted by black square contours in the colour maps.
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Dipalo, M., Melle, G., Lovato, L. et al. Plasmonic meta-electrodes allow intracellular recordings at network level on high-density CMOS-multi-electrode arrays. Nature Nanotech 13, 965–971 (2018). https://doi.org/10.1038/s41565-018-0222-z
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