A Surface-EnhancedRaman Scattering Platform for Rapid,Sensitive, and Cost-Effective Quantitative Analysis of Exosomes Basedon Titanium Dioxide Functionalized Nanomaterials

Exosomes have emerged as vital biomarkers for cancer diagnosis because they carry diverse biomolecules, reflecting the physiological state of their original cells. However, despite this potential, there are still challenges in developing highly sensitive, rapid, and efficient detection methods in clinical diagnosis. Here, we present a straightforward approach for the efficient enrichment and SERS quantification of exosomes via the interaction between titanium dioxide (TiO₂) and the phospholipid bilayer on the exosome membrane. First, Fe₃O₄@TiO₂ was employed for rapid exosome enrichment, enabling magnetic separation from biological fluids. Subsequently, surface-enhanced Raman scattering (SERS) tags, Ag@NTP@TiO₂, were applied to label exosomes for precise quantification. Ag@NTP@TiO₂ exhibited strong and homogeneous SERS signals. The TiO₂ shell of SERS tags not only facilitated the labeling of exosomes rapidly but also ensured the long-term stability of the SERS signals. It avoided the high cost and time-consuming disadvantages of the traditional method of recognizing exosomes with antibodies and aptamers. Our approach enabled quantitative detection of exosomes from capture to SERS measurement within 10 min. The quantification range spanned 5 orders of magnitude, with the detection limit as low as 640 particles/mL. In clinical plasma sample testing, this method exhibited good diagnosis ability in distinguishing cancer patients from healthy individuals, with an area under the curve (AUC) of 0.880. All these results suggest that our method may become a powerful tool for liquid biopsy based on the analysis of exosomes in clinics.