Ultrasensitive Detection of Organophosphorus Pesticides Using Single-Molecule Conductance Measurement

Detection of organophosphorus pesticides (OPs) with high sensitivity in environmental samples is of vital importance for environmental safety and human health. However, it remains a challenge to achieve fM (10–15 mol/L) sensitivity for detecting OPs. Herein, we developed an acetylcholinesterase sensor based on 3,3′,5,5′-tetramethylbenzidine (TMB) combining an enzyme-mediated strategy and scanning tunneling microscopy break junction (STM-BJ). Benefiting from the enzyme inhibition kinetics of OPs and the customized spectral clustering analysis method, our new strategy achieved the detection of methamidophos (MTMP) with a limit of 10 aM (10–17 mol/L) and 3 times higher selectivity in mixed OPs. As applied to natural lake waters, it also exhibited high reproducibility, high stability, and good recovery. This work paves a new avenue toward the application of single-molecule conductance characterizations for biochemical analysis and environmental monitoring.