Rapid and label-free exosome analysis by surface-enhanced Raman spectroscopy using silver nanoparticle substrate based on selective laser ablation and melting of silver nanowire

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 spectroscopy (SERS), which enables the detection of Raman scattering, has been proved as a promising tool for exosome detection but 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 Raman spectra using silver nanoparticle SERS substrate fabricated by selective laser ablation and melting. Employing silver nanowire and optimizing pulse repetition rate power enable rapid and energy-efficient fabrication of SERS substrate. The functionality including sensitivity, reproducibility, stability, and renewability was evaluated using rhodamine 6G as a probe molecule. Then, the feasibility of POCT was examined by the statistical analysis of Raman 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.