Narrow-interval chemical enhancement (NICE) factors for improving the robustness and transferability of SERS data: a proof-of-concept demonstration using amphetamines adsorbed on large-area gold substrates.

Surface-enhanced Raman scattering (SERS) is widely used for detecting various analytes; however, the transferability and comparability of spectral data are limited by the complex interplay between electromagnetic and chemical enhancement mechanisms. In particular, mode-selective chemical enhancement within narrow spectral intervals can significantly distort relative band intensities, complicating comparisons across different substrates and experimental platforms. In this study, we measured amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine molecules adsorbed on electrochemically prepared large-scale gold substrates and evaluated the related extent of narrow-interval chemical enhancement. Compared to colloidal gold nanoparticle substrates, large-scale substrates exhibit a substantially attenuated narrow-interval chemical enhancement response, which is attributed to hotspot heterogeneity and spatial signal averaging across the extended surface. To quantitatively describe and compare these effects, a modified narrow-interval chemical enhancement factor is introduced, enabling systematic evaluation of substrate-dependent chemical enhancement contributions. The results demonstrate that this factor can be extended beyond concentration-dependent analyses and employed as a methodological parameter for improving the robustness and transferability of SERS data. This approach provides a framework for more reliable cross-platform comparison of SERS spectra and supports the development of reproducible spectroscopic protocols for forensic applications.