Tunable Au@SiO<sub>2</sub>/Au Film Metasurface as Surface Plasmon Resonance Enhancer for Direct and Ultrasensitive Detection of Exosomes
Yangyang Zhou, Yawen Liu, Yindian Wang, Xiaojun Hu, Kwangnak Koh, Hongxia Chen
Abstract
Surface plasmon resonance (SPR) spectroscopy with non-labelling, sensitive, and real-time properties is critical for clinical diagnosis applications. However, conventional SPR sensors face the challenge of lower sensitivity and selectivity for trace exosomes assay in complex serum. We proposed a core–shell Au@SiO 2 –Au film (Au@SiO 2 –Au film) metasurface to enhance SPR signal based on systematic study on the relationship between gap modes and SPR enhancement. The self-assembled multifunctional peptide was designed as recognition layer with antifouling properties for ultrasensitive and selective detection of PD-L1 + exosomes in serum. The tuning electromagnetic (EM) field model by manipulating the gap was established to guide the preparation of Au@SiO 2 –Au film metasurface. The in-plane and out-of-plane coupling of Au@SiO 2 nanoparticles (NPs) could greatly enlarge and enhance three-dimensional EM field to meet the size of exosomes located in the evanescent field. At the structural level, we achieved high sensitivity (0.16 particles/mL) and a broad response range (10–5 × 10 3 particles/mL) through optimizing the thickness of SiO 2 and surface coverage of Au@SiO 2 . Furthermore, clinical sample assay achieved the optimal diagnostic accuracy (AUC = 0.97) for differentiating cancer patients from healthy controls. This work provides an opportunity for the construction of a tunable gap mode as SPR enhancer in a total internal reflection architecture. The systematic study on the relationship between gap modes and SPR sensitivity provides a broad scope for promoting direct, efficient, highly selective, and sensitive detection of SPR sensors for clinical application.