Regulating Gold Nanobipyramid Morphology via Au⁺-Disproportionation System on Paper Toward a Paper-Based Multicolor Sensor for Sensitive Visual Detection of Acetylcholinesterase Activity

On-site quick detection of acetylcholinesterase (AChE) activity is of great significance for diagnosing nervous diseases, screening drugs, and monitoring poisoning. Herein, we developed a system for sensitively regulating gold nanobipyramid (AuNBP) morphology on a paper-based analytical device (PAD) via an Au+-disproportionation system, and further developed a high-resolution paper-based multicolor sensor (PMS) for both on-site visual detection and laboratory precision quantification of AChE activity using the system as a signal reporter and a dual-enzyme strategy as a receptor. The paper-based Au+ disproportionation-mediated AuNBP morphology system not only has excellent stability, reproducibility, and robust resistibility against reducing substances existing in biological samples but also can effectively suppress the color interference from reagents and greatly improve the sensitivity of regulating AuNBP morphology transformation, making it capable of generating long-term stable and more colorful/clearer color changes corresponding to Au+ concentrations. The developed PMS exhibited eight color changes corresponding to AChE activity within 0.0–1.0 U/L and the color changes could be stably maintained for 30 days, which makes both on-site visual detection and laboratory sensitive quantification possible. The PMS was successfully used to detect AChE activity in serum and erythrocyte samples with a visual detection limit (LOD) of 50 mU/L, a spectrometry LOD of 26 mU/L, and a recovery of 81–102%. The results obtained with the PMS were consistent with those obtained with Ellman’s method, verifying its reliability. All of the above features make the PMS a promising assay for the rapid detection of AChE activity in clinical diagnosis. Importantly, the proposed paper-based Au+ disproportionation-mediated AuNBP morphology system can serve as a promising general signal reporter for developing various sensitive multicolor colorimetric sensors for target detection in various fields.