LAUSR

Nanopore analysis based on the resistive-pulse technique is an attractive tool for the single molecule detection in different fields, but it suffers the great drawback in selectivity. The common solution of this challenge is to add extra sensing aptamers and labels to analytes by improving the sensitivity of their pulses for distinguishment. Comparing to the labelling methods, we alternatively develop and demonstrate a novel data process for label-free nanopore analysis that enables the conversion of resistive current signals to more specific frequency domain phase angle features with the contribution from both sinusoidal voltage excitation and Fourier transform. In particular, we find that the transmural capacitance induced by nanoparticles translocations under a sinusoidal voltage plays an important role in this process, making phase angle features more pronounced. In practical applications, the method is successfully applied to directly distinguish the translocation events through a nanopipette by their unique phase angles for similarly sized SiO2, Ag and Au nanoparticles and soft living organisms of HeLa and LoVo, respectively, and even in a more complicated case of a SiO2, Ag and Au nanoparticle mixture.