Ultrasensitive SERS-based detection of prostate cancer exosome using Cu₂O-CuO@Ag composite nanowires

Exosome is a recently emerging cancer-associated biomarker for early diagnostic and prognostic owing to their noninvasive, intrinsic stability, and representativeness of primitive cell state. However, the development of convenient and quantitative methods for exosome analysis remains technically challenging. Here, we proposed a cost-effective assay for the direct capture and rapid monitoring of exosomes utilizing the multifunctional surface enhanced Raman scattering (SERS) substrate, which consisted of Cu₂O-CuO nanowires prepared by a simple thermo-oxidative growth method and subsequently sputtered with Ag NPs. This reticulate substrate made up of interlaced one-dimensional nanowires that highly favored for exosome recognition and collection. Particularly, the electromagnetic hotspots with high density were uniformly distributed on the nanowires due to uniform physical deposition, facilitating robust SERS property with an enhancement factor (EF) of 3.3 × 10⁸ and signal reproducibility with a relative standard deviation (RSD) of 13%. In addition, the presence of Cu₂O-CuO heterojunction enabled further elevation of the SERS performance attributed to the effective charge transfer, triggering a significant chemical enhancement effect. Finally, clinical validation with the serum specimens of prostate cancer patients indicated that the proposed immunosensor possessed great potential for application in rapid cancer screening and diagnosis.