A dual-recognition electrochemical impedance sensor based on an aptamer-MIP strategy for sensitive detection of...

The increasing prevalence of methamphetamine (METH) abuse necessitates analytical methods capable of ultra-trace detection in complex matrices. However, single-recognition strategies often suffer from limited selectivity and susceptibility to environmental interference. Herein, we present a highly sensitive electrochemical impedance sensor based on a synergistic aptamer-molecularly imprinted polymer (MIP) dual-recognition strategy constructed on a AuNPs@COF nanostructured interface. This dual-recognition system operates through complementary mechanisms. A newly screened METH-specific aptamer (K _D = 213 nM), achieving an approximately 2.7-fold improvement in affinity over a recently reported aptamer (K _D = 570 nM), provides primary molecular recognition. Concurrently, the electropolymerized MIP layer introduces spatial complementarity that imposes stringent steric constraints on target binding, enabling a "dual verification" mechanism that effectively discriminates against structurally analogous interferents. Moreover, the MIP matrix is expected to provide physical shielding of the aptamer from nuclease degradation, as previously reported for such hybrid recognition systems, thereby potentially enhancing sensor stability in complex biological matrices. The AuNPs@COF interface further maximizes aptamer immobilization and facilitates electron transfer, ensuring efficient signal transduction. Benefiting from this synergistic interplay, the sensor enables label-free detection of METH via electrochemical impedance spectroscopy (EIS), achieving an ultralow detection limit of 33 aM (S/N = 3) and a wide dynamic range from 0.1 fM to 0.5 nM. The sensor exhibits excellent selectivity, reproducibility, and long-term stability, along with reliable performance in complex matrices including wastewater and biological fluids. This work establishes a versatile dual-recognition sensing paradigm, offering significant potential for ultra-trace detection of small-molecule contaminants in environmental and biomedical applications.