Tang_2025_Talanta_293_128086

The establishment of a fast, simple-yet-practical, cost-effective and reliable sensing method for the detection of acetylcholinesterase (AChE) activity and inhibition is always desired in clinical Alzheimer's disease (AD) diagnosis and drug screening. Herein, a CoOOH nanosheet-isolated SERS nanoprobe (Ag-Au NPs@4-MBA@CoOOH, AAMC) with core-shell-molecule-shell structure was developed for sensitive and selective quantification of AChE. Experimental results indicated that the CoOOH shell can effectively impede the penetration of the external illuminated laser and block the internal SERS signal of Raman molecules. When AChE and its substrate were present, the specific AChE-catalyzed reaction would be rapidly triggered, resulting in the decomposition of CoOOH in AAMC probe and the generation of greatly enhanced SERS signal. By taking advantage of a portable Raman spectrometer, the AAMC nanoprobe is capable for rapid, sensitive and specific detection of AChE in the range 1 x 10(-5) - 10 U/mL (LOD of 7.9 x 10(-6) U/mL). Moreover, the measurement of AChE activity in complex human serum samples (with recoveries ranging from 98.0 to 103.3 %) and effective detection of its inhibition activity with the developed strategy were also successfully realized, showing great promise for on-site and point-of-care testing.