Responsive nanopore-based sensors have evolved to be powerful analytical tools in biosensing territory. Although taking advantages including label-free, low-cost, and analytical universality, the detection sensitivity is hampered by recognition efficiency of the responsive element in the nanoconfinement. Here, we show that improving the sensing performance for ATP molecules can be realized by a dual-site recognition strategy. We engineered a functionalized glass nanopipette using DNA grafted zeolitic iminazolate framework-90 (ZIF-90) as a dual-recognition nanoprobe. By virtue of the rigidity of MOF materials, ZIF-90 was shown to produce a remarkable pore-blockage effect and ion gating function. Particularly, the skeleton of ZIF-90 can be specifically induced to collapse by ATP molecules, resulting in remarkable signal-on ionic-current modulation. Collaborated with the aptamer units, the nanopipette allowed dual-site binding of ATP, thus greatly enhancing the sensing efficiency, with the linear response down to 0.1 nM ATP, compared to traditional single-site recognition mode. This method enabled us to directly probe the ATP concentration level in cells without the need of time-consuming and labor-intensive signal amplification strategies currently widely used. Reasonably, this nanopipette sensor should be promising to be a generalized sensing platform, provided that feasible responsive elements are used.
Song et al. (2026) studied this question.