Noise in nanopore sensors: Sources, models, reduction, and benchmarking

Label-free nanopore sensors have emerged as a new generation technology of DNA sequencing and have been widely used for single molecule analysis. Since the first α-hemolysin biological nanopore, various types of nanopores made of different materials have been under extensive development. Noise represents a common challenge among all types of nanopore sensors. The nanopore noise can be decomposed into four components in the frequency domain (1/f noise, white noise, dielectric noise, and amplifier noise). In this work, we reviewed and summarized the physical models, origins, and reduction methods for each of these noise components. For the first time, we quantitatively benchmarked the root mean square (RMS) noise levels for different types of nanopores, demonstrating a clear material-dependent RMS noise. We anticipate this review article will enhance the understanding of nanopore sensor noises and provide an informative tutorial for developing future nanopore sensors with a high signal-to-noise ratio.