Functional Nanosensor‐Integrated System Based on Molecularly Imprinted Quartz Crystal Microbalance for Rapid In Situ Detection of 3‐Chloro‐1,2‐Propanediol in Paper‐Based Food Contact Materials

ABSTRACT To address the limitations of traditional methods in detecting 3‐chloro‐1,2‐propanediol (3‐MCPD) in food contact materials (FCMs)—notably complex operations, prolonged detection cycles, and low sensitivity—this study introduces a novel Molecularly Imprinted Polymer‐based Nano‐Analytical System (MNAS). This integrated system enables rapid, in situ, and derivatization‐free detection of 3‐MCPD in paper‐based FCMs. The MNAS innovatively combines molecularly imprinted polymers (MIPs) with a quartz crystal microbalance (QCM) sensing mechanism. Guided by density functional theory (DFT), a “pre‐organized recognition” strategy was employed to design highly selective imprinting interfaces through precise monomer‐template hydrogen bonding configurations. Further insights into the hydrogen bond‐driven recognition mechanism were obtained using variable‐temperature infrared spectroscopy and multimodal interference validation. This synergistic approach of interfacial molecular configuration control and enhanced mass response mechanisms endows the system with exceptional selectivity and anti‐interference capabilities in complex matrices. The detection limit achieved is 0.006 µM, significantly surpassing that of traditional GC‐MS methods (2.2 µM). Moreover, the overall detection process time is reduced by over 75%, eliminating the need for organic extraction and derivatization steps inherent in conventional methods, thereby greatly enhancing operational simplicity and practicality. The MNAS system not only broadens the application scope of MIPs in detecting non‐intentionally added substances but also offers a novel strategy for high‐throughput, on‐site rapid screening of chlorinated contaminants in paper‐based materials. This advancement holds significant implications for early warning systems and risk assessment in food safety.