Mixed-Dimensional Heterostructure Material-Based SERS for Trace Level Identification of Breast Cancer-Derived Exosomes

[Image: see text] Raman spectroscopy has capability for fingerprint molecular identification with high sensitivity if weak Raman scattering signal can be enhanced by several orders of magnitudes. Herein, we report a heterostructure-based surface-enhanced Raman spectroscopy (SERS) platform using 2D graphene oxide (GO) and 0D plasmonic gold nanostar (GNS), with capability of Raman enhancement factor (EF) in the range of ∼10(10) via light–matter and matter–matter interactions. The current manuscript reveals huge Raman enhancement for heterostructure materials occurring via both electromagnetic enhancement mechanism though plasmonic GNS nanoparticle (EF ∼10(7)) and chemical enhancement mechanism through 2D-GO material (EF ∼10(2)). Finite-difference time-domain (FDTD) simulation data and experimental investigation indicate that GNS allows light to be concentrated into nanoscale “hotspots” formed on the heterostructure surface, which significantly enhanced Raman efficiency via a plasmon–exciton light coupling process. Notably, we have shown that mixed-dimensional heterostructure-based SERS can be used for tracking of cancer-derived exosomes from triple-negative breast cancer and HER2(+) breast cancer with a limit of detection (LOD) of 3.8 × 10(2) exosomes/mL for TNBC-derived exosomes and 4.4 × 10(2) exosomes/mL for HER2(+) breast cancer-derived exosomes.