Abstract

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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Change history

  • 28 August 2018

    In the version of this Article originally published, the affiliation for the author Francesca Santoro was incorrectly given; it should have been ‘Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia, Napoli, Italy’. This has now been corrected in all versions of the Article.

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Acknowledgements

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. [616213], CoG: Neuro-Plasmonics.

Author information

Affiliations

  1. Istituto Italiano di Tecnologia, Genova, Italy

    • Michele Dipalo
    • , Giovanni Melle
    • , Laura Lovato
    • , Andrea Jacassi
    • , Valeria Caprettini
    • , Denis Garoli
    • , Giulia Bruno
    • , Francesco Tantussi
    •  & Francesco De Angelis
  2. Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia, Napoli, Italy

    • Francesca Santoro
  3. Department of Electrical and Computer Engineering, Rice University, Houston, TX, USA

    • Andrea Schirato
    •  & Alessandro Alabastri

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Contributions

F.D.A. and M.D. conceived and designed the experiments. M.D., G.M. and L.L. performed the electrophysiology experiments. F.S. and V.C. performed the focused ion beam cross-sections and SEM imaging. A.J. and M.D. analysed the data. G.B., A.J. and D.G. characterized the porous meta-electrodes. G.B. and M.D. fabricated the passive MEA devices. M.D. and F.T. designed the experimental set-up. A.A. and A.S. performed the electromagnetic and thermal simulations. F.D.A. supervised the work. All the authors discussed the results and wrote the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Francesco De Angelis.

Supplementary information

  1. Supplementary Information

    Supplementary Methods, Supplementary Figures 1–15, Supplementary References

  2. Reporting Summary

  3. Supplementary Video 1

    Whole CMOS-MEA recording during optoacoustic poration on one electrode. The optoacoustic poration occurs at t = 5 s.

  4. Supplementary Video 2

    Propagation wave in extracellular mode of human-induced pluripotent stem cells-derived cardiomyocytes on CMOS-MEA. The pixel colours represent the signals’ amplitude.

  5. Supplementary Video 3

    Propagation wave in intracellular mode of human-induced pluripotent stem cells-derived cardiomyocytes on CMOS-MEA. The pixel colours represent the signals’ amplitude.

  6. Supplementary Video 4

    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.

  7. Supplementary Video 5

    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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DOI

https://doi.org/10.1038/s41565-018-0222-z

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