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We report a label-free nanopore sensor for the detection of Zn 2+ ions. By taking advantage of the cleavage of a substrate peptide by zinc-dependent enzymes, nanomolar concentrations of Zn 2+ ions could be detected within minutes. Furthermore, structurally similar transition metals such as Ni 2+ , Co 2+ , Hg 2+ , Cu 2+ , and Cd 2+ did not interfere with their detection. The enzymatic reaction-based nanopore sensing strategy developed in this work may find potential applications in environmental monitoring and medical diagnosis. 

In this review, recent research efforts that aimed at developing nanopore sensors for detection of metal ions, which play a crucial role in environmental safety and human health, are highlighted. Protein pores use three stochastic sensing‐based strategies for metal ion detection. The first strategy is to construct engineered nanopores with metal ion binding sites, so that the interaction between the target analytes and the nanopore can slow the movement of metal ions in the nanochannel. Second, large molecules such as nucleic acids and especially peptides can be utilized as external selective molecular probes to detect metal ions based on the conformational change of the ligand molecules induced by the metal ion–ligand chelation/coordination interaction. Third, enzymatic reactions can also be used as an alternative to the molecule probe strategy in the situation that a sensitive and selective probe molecule for the target analyte is difficult to obtain. On the other hand, by taking advantage of steady‐state analysis, synthetic nanopores mainly use two strategies (modification and modification‐free) to detect metals. Given the advantages of high sensitivity and selectivity, and label‐free detection, nanopore‐based metal ion sensors should find useful application in many fields, including environmental monitoring, medical diagnosis, and so on.