The integration of molecular imprinting and surface-enhanced Raman scattering for highly sensitive detection of lysozyme biomarker aided by density functional theory

Surface-enhanced Raman scattering (SERS) is a powerful bioanalytical technique that opens opportunities for early disease diagnosis and treatment by detecting biomarkers. However, the low sensitivity, selectivity, and reproducibility in the bioanalytical SERS are the main obstacles for clinical use. Herein, we demonstrate a high sensitive and selective label-free lysozyme biomarker detection platform based on coupling of SERS with molecular imprinting technique. The hierarchical silver microspheres with dendritic structure are controllably fabricated by a wet-chemical self-assembly approach. Based on selection of surface-active regions by density functional theory (DFT) simulations, a thin MIPs film (thickness < 15 nm) is then grafted on Ag microsphere surface through surface imprinting. As a result, the final synthesized Ag@MIPs hybrid exhibits as low as 5 ng mL⁻¹ detection limit for target lysozyme, and high selectivity and reproducibility. Intensive “hot spots” in Ag@MIPs confirmed by Raman mapping give rise to the high-performance SERS. Meanwhile, DFT calculations are employed to investigate the SERS spectra and assist the assignment for the characteristic peaks of lysozyme. We believe that the present study provides a reliable and high-sensitive protocol for label-free protein biomarkers detection.