Interference-free detection of glucose in human urine based on a core-shell structured SERS nanoprobe

Non-invasive glucose monitoring plays a key role in the diagnosis and management of diabetes and related diseases. However, the application of conventional SERS glucose sensors in complex biofluids is often limited by spectral overlap between Raman signals from the reporter molecules and those of endogenous biomolecules. To overcome this issue, we developed a SERS nanoprobe capable of interference-free glucose detection. The probe comprises a gold-core silver-shell nanostructure (Au@Ag NPs), with 4-mercaptobenzonitrile (MBN) as the Raman reporter embedded between the core and the shell, and glucose oxidase (GOx) immobilized on the outer silver surface via electrostatic adsorption. Glucose is oxidized under GOx catalysis to generate H₂O₂, which etches the silver shell and consequently attenuates the SERS signal intensity. Accordingly, the intensity of the characteristic peak at 2226 cm^-1 decreases as the glucose concentration increases from 0 to 2 mM, enabling quantitative detection. The excellent interference-free capability of the nanoprobe originates from two structural and molecular designs. First, MBN produces exclusive Raman signals within the biological Raman-silent window (1800-2800 cm^-1), completely eliminating spectral overlap with endogenous biomolecules. Second, the core-shell structure physically isolates the internal Raman reporter from external biological matrices, effectively maintaining signal stability and accuracy. These design features endow the probe with outstanding selectivity for glucose over its structural analogues (e.g., fructose and lactose). The probe was further applied to glucose detection in human urine samples, supporting its potential utility in clinical urinalysis.