Surface-enhanced Raman spectroscopy for protein detection: Challenges and countermeasures.

Proteins, as the core functional molecules of life activities, are of significant value in disease diagnosis. However, the low concentration of proteins in body fluids presents challenges for their clinical application. Surface-enhanced Raman spectroscopy (SERS), with its label-free and ultrasensitive detection advantages, has garnered extensive attention in the field of protein analysis in recent years. This review systematically elaborates on the application progress of SERS technology in protein detection, covering research breakthroughs in novel SERS substrates, single-molecule detection, and multi-component simultaneous analysis techniques. It also discusses the combined strategies of SERS with other technologies and the application of machine learning in spectral interpretation, while analyzing the application challenges of this technology in disease diagnosis and prospecting its future development directions.