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Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues

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Abstract

Real-time mapping and manipulation of electrophysiology in three-dimensional (3D) tissues could have important impacts on fundamental scientific and clinical studies, yet realization is hampered by a lack of effective methods. Here we introduce tissue-scaffold-mimicking 3D nanoelectronic arrays consisting of 64 addressable devices with subcellular dimensions and a submillisecond temporal resolution. Real-time extracellular action potential (AP) recordings reveal quantitative maps of AP propagation in 3D cardiac tissues, enable in situ tracing of the evolving topology of 3D conducting pathways in developing cardiac tissues and probe the dynamics of AP conduction characteristics in a transient arrhythmia disease model and subsequent tissue self-adaptation. We further demonstrate simultaneous multisite stimulation and mapping to actively manipulate the frequency and direction of AP propagation. These results establish new methodologies for 3D spatiotemporal tissue recording and control, and demonstrate the potential to impact regenerative medicine, pharmacology and electronic therapeutics.

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Figure 1: 3D spatiotemporal mapping of APs.
Figure 2: AP evolution during tissue development.
Figure 3: Arrhythmia induced by localized norepinephrine injection.
Figure 4: Active spatiotemporal regulation of APs.

Change history

  • 21 July 2016

    In the version of this Article originally published online, in Fig. 1e, the traces for devices (1,2) and (2,3) were incorrect. This has now been corrected in all versions of the Article. In addition, the original data for Fig. 1d (from which Fig. 1e was extracted) is now provided as Supplementary Data.

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Acknowledgements

The authors thank R. Liao and D. Zhang for the inspiring discussion on cardiac electrophysiology and tissue engineering. The authors thank J. L. Huang for the assistance on instrumentation. This work was supported by National Institutes of Health Director's Pioneer and National Security Science and Engineering Faculty Fellow awards (to C.M.L.).

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X.D., W.Z. and C.M.L. conceived and designed the experiments. X.D., W.Z., T.G. and J.L. performed the experiments and analysed the data. X.D., W.Z. and C.M.L. co-wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Charles M. Lieber.

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The authors declare no competing financial interests.

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Dai, X., Zhou, W., Gao, T. et al. Three-dimensional mapping and regulation of action potential propagation in nanoelectronics-innervated tissues. Nature Nanotech 11, 776–782 (2016). https://doi.org/10.1038/nnano.2016.96

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