Abstract

Surface-enhanced Raman scattering (SERS) is a powerful molecular fingerprinting technique widely applied across physical chemistry, environmental monitoring, and public safety. While hotspot engineering has driven significant advances, a critical limitation persists: the reliable detection of analytes lacking affinity for plasmonic surfaces remains challenging. Despite extensive reviews on SERS substrates and hotspots (>300 in recent years), none systematically address analyte manipulation as a complementary paradigm for overcoming this universal detection barrier.

This review uniquely synthesizes the rapidly evolving field of analyte enrichment strategies—categorized as chemical, physical, and macroscopic force field approaches—and demonstrates their integration with engineered hotspots as a multifaceted solution. We highlight how this synergy achieves unprecedented sensitivity enhancements (104–1015 fold), unattainable through hotspot engineering alone.

Finally, we emphasize the current challenges in this research area and propose new research directions aimed at developing efficient SERS designs that are critical for real-world applications.