Label‐Free Exosome Analysis by Surface‐Enhanced Raman Scattering Spectroscopy with Laser‐Ablated Silver Nanoparticle Substrate

Abstract Early diagnostics of breast cancer is crucial to reduce the risk of cancer metastasis and late relapse. Exosome, which contains distinct information of its origin, can be the target object as a liquid biopsy. However, its low sensitivity and inadequate diagnostic tools interfere with the point‐of‐care testing (POCT) of the exosome. Recently, Surface‐enhanced Raman Scattering (SERS) spectroscopy, which amplifies the Raman scattering, has been proved as a promising tool for exosome detection. However, the fabrication process of SERS probe or substrate is still inefficient and far from large‐scale production. This study proposes rapid and label‐free detection of breast cancer‐derived exosomes by statistical analysis of SERS spectra using silver‐nanoparticle‐based SERS substrate fabricated by selective laser ablation and melting (SLAM). Employing silver nanowires and optimizing laser process parameters enable rapid and low‐energy fabrication of SERS substrate. The functionalities including sensitivity, reproducibility, stability, and renewability are evaluated using rhodamine 6G as a probe molecule. Then, the feasibility of POCT is examined by the statistical analysis of SERS spectra of exosomes from malignant breast cancer cells and non‐tumorigenic breast epithelial cells. The presented framework is anticipated to be utilized in other biomedical applications, facilitating cost‐effective and large‐scale production performance.