We report an SERS-based method for the screening and multiple detection of cancer exosomes in solution and real blood samples.

Exosomes play an important role in intercellular communications. Here, we present a surface-enhanced Raman scattering (SERS) based detection method for tumor-derived exosomes using SERS nanoprobes and magnetic nanobeads. The SERS nanoprobe has a core–shell structure, with gold core–silver shell nanorods (Au@Ag NRs) as the SERS active core, Raman molecules as the SERS reporter and a silica layer as the protecting shell. The outmost surface of the SERS nanoprobe is decorated with exosome-specific antibodies. Each magnetic nanobead is fabricated by coating Fe₃O₄ nanoparticles (NPs) with a silica shell and attaching specific antibodies to the silica shell. With target exosomes present, the magnetic nanobeads and SERS nanoprobes can capture the exosomes by forming a sandwich-type immunocomplex. The immunocomplex (as well as the SERS nanoprobes) can be precipitated with a magnet, and thus SERS signals can be detected in the precipitates. With no target exosomes present, no immunocomplex can be formed, and thus quite weak SERS signals will be detected in the precipitates. Hence, the SERS signal of the final magnetic separation product can be used to detect exosomes. In the experiment, using one kind of tumor cells and one kind of normal cells, we proved that the presented method can be used for both qualitative and quantitative detection of tumor-derived exosomes.