Unlocking new possibility of Fe 3 O 4 @C@Ag nanostructures as an advanced SERS substrate for ultrasensitive detection of low-cross-section urea biomolecules

Surface-enhanced Raman spectroscopy (SERS) is widely recognized as a powerful analytical technique, offering molecular identification by amplifying characteristic vibrational signals, even at the single-molecule level. While SERS has been successfully applied for a wide range of targets including pesticides, dyes, bacteria, and pharmaceuticals, it has struggled with the detection of molecules with inherently low Raman scattering cross-sections. Urea, a key nitrogen-containing biomolecule and the diamide of carbonic acid, is a prime example of such a challenging target. Found in human urine and blood, urea serves as an essential biomarker for diagnosing kidney dysfunction, liver disease, and heart failure, while its residue in water poses significant health risks. However, due to its low Raman cross-section, SERS has faced challenges in achieving high sensitivity for urea detection, limiting its potential in diagnosis and residual analysis. In this study, we present Fe 3 O 4 @C@Ag nanostructures as an advanced SERS substrate engineered for ultrasensitive urea detection. Our results reveal that Fe 3 O 4 @C@Ag nanostructures enable the detection of urea with a good limit of 5.68 × 10 −9 M and a high enhancement factor of 3.67 × 10 6 . In addition, the substrate demonstrated high reliability, with repeatability and reproducibility showing relative standard deviations below 10%. Furthermore, the practicality of the Fe 3 O 4 @C@Ag nanostructures was evaluated in real-world scenarios using artificial urine and tap water samples as representative matrices for early disease diagnosis and water quality monitoring. The sensor successfully detected urea across concentrations as low as 10 −8 M, with excellent recovery rates ranging from 90% to 99%, even in complex sample environments. These results highlight the remarkable sensitivity and versatility of Fe 3 O 4 @C@Ag nanostructures, overcoming SERS's traditional limitations in urea detection and unlocking new possibilities for clinical diagnostics and environmental monitoring.