Background-Free SERS Nanosensor for Endogenous Hydrogen Sulfide Detection Based on Prussian Blue-Coated Gold Nanobipyramids

Surface-enhanced Raman scattering (SERS) has great potential in biological analysis due to its specificity, sensitivity, and non-invasive nature. However, effectively extracting Raman information and avoiding spectral overlapping from biological background interference remain major challenges. In this study, we developed a background-free SERS nanosensor consisting of gold nanobipyramids (Au NBPs) core-Prussian blue (PB) shell (Au NBPs@PB), for endogenous H₂S detection. The PB shell degraded quickly upon contact with endogenous H₂S, generating a unique Raman signal response in the Raman silent region (1800–2800 cm^–1). By taking advantage of the high SERS-activity of Au NBPs and H₂S-triggered spectral changes of PB, these SERS nanosensors effectively minimize potential biological interferences. The nanosensor exhibits a detection range of 2.0 μM to 250 μM and a limit of detection (LOD) of 0.34 μM, with good reproducibility and minimal interference. We successfully applied this background-free SERS platform to monitor endogenous H₂S concentrations in human serum samples with satisfied results.