More specifically, whereas the noise in nanopore systems was elucidated to stem from several sources such as surface charge fluctuations and dielectric loss, coupling between the device capacitance and the voltage noise in current amplifiers was found to be the most significant factor giving rise to high-frequency noise above 10 kHz. [25][26][27] Previous nanopore measurements often used low-pass filters to cut-off this fast noise for detecting resistive pulse signals, which has proven useful in studying translocation dynamics of small molecules. [28,29] Nonetheless, as the sensitivity of the nanosensor was improved by employing ultrathin membranes such as graphene [30,31] and MoS 2 , [19] it started to become possible to probe not only the size of objects but their shapes, surface charge densities, and even mass from the ionic current signals. [8,32] In this context, it turns out to be an important issue to reduce the high frequency noise without any pre-filters as it generally involves signal blunting that obscures the fine yet important ionic current profiles. One of the effective strategies was to employ highly insulating materials as low-capacitance substrates, for example quartz and polymers. [33] Later, it was also found that covering the membrane surface with a thick polymer layer can serve to reduce the noise. [34] These works indeed provided nanopore chip designs for diminishing the current fluctuations by more than an order of magnitude through tailoring surface reactions and capacitive coupling. [27,[34][35][36][37] Besides the material and device engineering for controlling the physical/chemical phenomena relevant to ionic current fluctuations, digital post processing has been utilized to mitigate the noise via band-pass filtering and wave transformations. [38,39] However, previous studies have found it to be a non-trivial task since the computation in frequency domains inevitably entails signal distortions thereby obscured the small yet important features occurring at variable time scales due to the stochastic and random nature of the translocation dynamics. [39] Here we report on a novel concept for post-denoising of ionic current in solid-state nanopores. Our method is based on a deep learning algorithm formulated to extract noise floor from ionic current (I ion ) versus time (t) curves without clean data (Figure 1). This strategy is known as Noise2Noise [40] proven to be useful in processing noisy digital images. [41] In the present study, we exploited it to demonstrate clarification of fine signatures in a resistive pulse signal that may otherwise be immersed in noise or completely smeared out under the conventional signal processing.Noise is ubiquitous in real space that hinders detection of minute yet important signals in electrical sensors. Here, the authors report on a deep learning approach for denoising ionic current in resistive pulse sensing. Electrophoretically-driven translocation motions of single-nanoparticles in a nanocorrugated nanopore are detected. The noise is reduced by a convo...