Multimodal Biosensors with Flexible-Concentration Adaptability Based on Single-Component Nanozymes for Highly Accurate BChE Analysis and Concatenated Logic Circuit-Programmed Inhibitor Screening

The accurate analysis and programmed regulation of butyrylcholinesterase (BChE) activity are of paramount significance for many normal physiological activities and disease diagnosis. Nevertheless, there still exist non-negligible drawbacks in previous works, such as the tedious synthesis of frequently used hybridized/doped nanozymes, unsatisfactory accuracy/reliability and adaptability induced by limited output channels, and inferior point-of-care sensing ability. Therefore, development of versatile multimodal biosensors based on cost-effective single-component nanozymes for portable analysis of BChE, intelligent screening of inhibitors, and potential disease diagnosis are urgently needed yet still challenging. To break the above obstacles, herein, taking MnSiO₃ nanoparticles with superior OXD-like activity as representative economical single-component nanozymes, we achieved the efficient catalytic oxidation toward a series of optical substrates under broad pH ranges. Collaborative results of experiments and density functional theory calculations elucidated the detailed catalytic mechanism of the MnSiO₃ nanozyme. By exploiting the rational natural enzyme/nanozyme tandem catalysis, we constructed a versatile colorimetric-photothermal-fluorescent-RGB quadri-modal platform with flexible-concentration adaptability and realized the portable analysis of BChE in real samples, accompanied by excellent selectivity and competitive LODs. More surprisingly, the clinical diagnosis of patients with aberrant hepatocyte function was validly performed via XNOR-logic-assisted multimodal synergistic validation. Furthermore, taking advantage of the unique interaction between BChE and inhibitors, we fabricated concatenated logic circuits with multichannel outputs and achieved the intelligent logical identification of typical inhibitor drugs. This work not only represented an innovative protocol of multimodal biosensors based on economical and high-performance nanozyme but also enlightened unique horizons for logic-encoded smart analysis of drugs and clinical diagnostics.