Highly Sensitive Glass Nanopipette Sensor Using Composite Probes of DNA-Functionalized Metal–Organic Frameworks

Pore structure-based analytical techniques have great potential applications for the detection of biological molecules. However, the sophistication of traditional pore sensors is restricted in their applicability of analytical chemistry due to a lack of effective carrier probes. Here, we used porous coordination network-224 (PCN-224) composite probes in conjunction with a glass nanopipette (GN) as a sensing platform. The sensor exhibits a good fluorescence signal and a change in GN’s ionic current at the same time. Due to the volume exclusion mechanism coming from PCN-224, the detection limit of target DNA reaches 10 fM in a GN with a diameter of up to ca. 260 nm, outperforming a simple probe. The structure of the composite probe is optimized by the probe’s pairing efficiency. Furthermore, the sensor can also discriminate between 1-, 3-, and 5-mismatch DNA sequences and capture the target DNA from a complex mixture. Based on the GN platform, a series of techniques for detecting biomolecules are expected to emerge because of its simplicity, robustness, and universality by incorporating advanced nanoprobes.