Intracellular access with high spatiotemporal resolution can enhance our understanding of how neurons or cardiomyocytes regulate and orchestrate network activity, and how this activity can be affected with pharmacology or other interventional modalities. Nanoscale devices often employ electroporation to transiently permeate the cell membrane and record intracellular potentials, which tend to decrease rapidly to extracellular potential amplitudes with time. Here, we report innovative scalable, vertical, ultra-sharp nanowire arrays that are individually addressable to enable long-term, native recordings of intracellular potentials. We report large action potential amplitudes that are indicative of intracellular access from 3D tissue-like networks of neurons and cardiomyocytes across recording days and that do not decrease to extracellular amplitudes for the duration of the recording of several minutes. Our findings are validated with cross-sectional microscopy, pharmacology, and electrical interventions. Our experiments and simulations demonstrate that individual electrical addressability of nanowires is necessary for high-fidelity intracellular electrophysiological recordings. This study advances our understanding of and control over high-quality multi-channel intracellular recordings, and paves the way toward predictive, high-throughput, and low-cost electrophysiological drug screening platforms.
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