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With the advancement of micro/nanotechnologies, multielectrodes arrays (MEAs) with different three‐dimensional (3D) micro/nanostructures have been developed to achieve intracellular action potential recording of cardiomyocytes. However, the effect of the 3D micro/nanostructures density on the intracellular recording has not been fully investigated. In this work, 3D tunable nanodensity electrode arrays (TNDEA) are fabricated by hydrothermal synthesis and standard microfabrication to explore the effect of nanodensity regulation on intracellular biosensing. By low‐voltage electroporation, the signal quality of intracellular potentials recorded by the low‐nanodensity TNDEA showed was significantly improved compared to those recorded by the high‐nanodensity TNDEA. The low‐nanodensity TNDEA improved the amplitude (up to 7.7 mV), signal‐to‐noise ratio (SNR) (up to 69.46 dB), recording duration (up to 83 min), and recording yield (∼100%). The 3D nanodensity regulating strategy has achieved sensitive and prolonged intracellular biosensing of action potentials and is expected to be a powerful electrophysiological research tool in the biomedical field. [ABSTRACT FROM AUTHOR]

Preclinical investigation of drug-induced cardiotoxicity is of importance for drug development. To evaluate such cardiotoxicity, in vitro high-throughput interdigitated electrode-based recording of cardiomyocytes mechanical beating is widely used. To automatically analyze the features from the beating signals for drug-induced cardiotoxicity assessment, artificial neural network analysis is conventionally employed and signals are segmented into cycles and feature points are located in the cycles. However, signal segmentation and location of feature points for different signal shapes require design of specific algorithms. Consequently, this may lower the efficiency of research and the applications of such algorithms in signals with different morphologies are limited. Here, we present a biosensing system that employs nonlinear dynamic analysis-assisted neural network (NDANN) to avoid the signal segmentation process and directly extract features from beating signal time series. By processing beating time series with fixed time duration to avoid the signal segmentation process, this NDANN-based biosensing system can identify drug-induced cardiotoxicity with accuracy over 0.99. The individual drugs were classified with high accuracies over 0.94 and drug-induced cardiotoxicity levels were accurately predicted. We also evaluated the generalization performance of the NDANN-based biosensing system in assessing drug-induced cardiotoxicity through an independent dataset. This system achieved accuracy of 0.85–0.95 for different drug concentrations in identification of drug-induced cardiotoxicity. This result demonstrates that our NDANN-based biosensing system has the capacity of screening newly developed drugs, which is crucial in practical applications. This NDANN-based biosensing system can work as a new screening platform for drug-induced cardiotoxicity and improve the efficiency of bio-signal processing. [ABSTRACT FROM AUTHOR]