Flexible Organic Clip as an Adapter to Enhance Host–Guest Nanopore Single-Molecule Sensing

The host–guest nanopore analysis method provided an avenue for hydrophobic analytes detection. However, the fixed cavity of conventional rigid hosts restricted the size range of detectable analytes, thereby partly limiting their further development. Herein, an organic clip (OC) was used as a flexible host to enhance the host–guest nanopore method in sensing hydrophobic drugs with various sizes. With the help of OC-assisted WT α-HL nanopores, differently sized hydrophobic drugs were detected and displayed distinguishable Level 2 signals, offering an effective approach to accomplish “one for more” analysis for hydrophobic analytes with various sizes. To explore the resolution of this method, the OC-assisted nanopore method was further used to simultaneously identify structurally similar antibiotics, including enoxacin, enrofloxacin, and moxifloxacin. Assisted by a machine learning algorithm, the validation accuracy for these three antibiotics reached up to 96.1%. Furthermore, the calibration curve for moxifloxacin was built based on the nanopore event frequency, through which moxifloxacin in commercial pharmaceuticals was accurately quantified. The OC-assisted nanopore method displayed the capability to extend the detection range across analyte sizes and demonstrated good resolution in distinguishing antibiotics with similar structures.