Photonic Crystal-Enhanced Surface-Enhanced Raman Scattering Biosensor with an Amphipathic Dendritic Supermolecule...

Exosomes hold great promise for tumor diagnosis, but their efficient isolation and sensitive in situ detection from biofluids remain challenging. Surface-enhanced Raman scattering (SERS) is an ideal solution due to its high sensitivity, yet conventional SERS biosensors face a trade-off between complex nanostructures for strong hotspots and practical fabrication. Here, we developed a novel strategy combining a highly stable large-sized opal photonic crystal (OPC) substrate with an amphipathic dendritic supermolecule probe (ADSP) for exosome capture and detection. The OPC substrate enhances SERS performance by modulating incident light, enabling a simple Au nanolayer to achieve detection limits as low as 1 × 10^-9 M. Meanwhile, ADSP ensures efficient exosome capture from plasma. Together, this approach allows direct isolation and sensitive in situ detection using a structurally simple device. Significant differences between patient and healthy donor groups were observed in practical sample detection, highlighting the potential of this exosome capture and detection platform for clinical applications.