Synovial fluid research based on SERS and SERRS for enhanced detection of biomarkers in staged osteoarthritis

Abstract Surface‐enhanced (resonance) Raman scattering (SER(R)S) can extremely enhance Raman intensity of samples, which is helpful for detecting synovial fluid (SF) that does not show Raman activity under normal conditions. In this study, SER(R)S spectra of SF from three different osteoarthritis (OA) stages were collected and analyzed for OA progress, finding that the content of collagen increased throughout the disease, while non‐collagen proteins and polysaccharides decreased sharply at advanced OA stage accompanied by the increase of phospholipid. The spectral features and differences were enhanced by salting‐out and centrifugation. Much more information on biomolecules at different OA stages was disclosed by using SERRS for the first time, these main trace components (β‐carotene, collagen, hyaluronic acid, nucleotide, and phospholipid) can be used as potential biomarkers. It indicates that SERRS has a more comprehensive ability to assist SERS in seeking micro(trace) biomolecules as biomarkers and facilitating accurate and efficient diagnosis and mechanism research of OA.