Nanopore-based sensing and analysis: beyond the resistive-pulse method

Solid-state nanopores are generally considered as an indispensable element in the research field of fundamental ion transport and molecular sensing. The improvement in fabrication and chemical modification of the solid-state nanopores remains increasingly updated. During the last decades, numerous works have been reported on the nanopore-based sensing applications. More and more new analytical methods using nanopore-based devices are emerging. In this review, we highlight the recent progress on the analytical methods for the interdisciplinary and fast-growing area of nanopore research. According to the different types of the electrical readout, whether it is steady-state ionic current or transient current fluctuation, the nanopore-based sensing and analysis can be generally divided into two categories. For the first type, the electrical readout shows a stable blockade or reopening of the nanopore conductance in the presence of target analytes, termed steady-state analysis, including the conductance change, electrochemical analysis, and two-dimensional scanning and imaging. The other type is based on the transient fluctuation in the transmembrane ionic current, termed transient-state analysis, including the noise analysis, transient ion transport, and transverse tunneling current. The investigation of solid-state nanopores for chemical sensing is just in its infancy. For further research work, not only new nanopore materials and chemical modifications are needed, but also other non-electric-based sensing techniques should be developed. We will focus our future research in the framework of bio-inspired, smart, multiscale interfacial materials and extend the spirit of binary cooperative complementary nanomaterials.