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Intracellular access with high spatiotemporal resolution can enhance ourunderstanding of how neurons or cardiomyocytes regulate and orchestrate networkactivity, and how this activity can be affected with pharmacology or otherinterventional modalities. Nanoscale devices often employ electroporation totransiently 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 thatare individually addressable to enable long-term, native recordings ofintracellular potentials. We report large action potential amplitudes that areindicative of intracellular access from 3D tissue-like networks of neurons andcardiomyocytes across recording days and that do not decrease to extracellularamplitudes for the duration of the recording of several minutes. Our findingsare validated with cross-sectional microscopy, pharmacology, and electricalinterventions. Our experiments and simulations demonstrate that individualelectrical addressability of nanowires is necessary for high-fidelityintracellular electrophysiological recordings. This study advances ourunderstanding of and control over high-quality multi-channel intracellularrecordings, and paves the way toward predictive, high-throughput, and low-costelectrophysiological drug screening platforms.

Ultra-Sharp Nanowire Arrays Natively Permeate, Record, and Stimulate Intracellular Activity in Neuronal and Cardiac Networks