Homogenous Magneto-Fluorescent Nanosensor for Tumor-Derived Exosome Isolation and Analysis

Tumor-derived exosomes carrying unique surface proteins have shown great promise as novel biomarkers for liquid biopsies. However, point-of-care analysis for tumor-derived exosomes in the blood with low-cost and easy processing is still challenging. Herein, we develop an integrated approach, homogenous magneto-fluorescent exosome (hMFEX) nanosensor, for rapid and on-site tumor-derived exosomes analysis. Tumor-derived exosomes are captured immunomagnetically, which further initiates the aptamer-triggered assembly of DNA three-way junctions in homogenous solution containing aggregation-induced emission luminogens and graphene oxide, resulting in an amplified fluorescence signal. By integrating magnetic isolation and enhanced fluorescence measurement, the hMFEX nanosensor detects tumor-derived exosomes in the dynamic range spanning 5 orders of magnitude with high specificity, and the limit of detection is 6.56 × 10⁴ particles/μL. Analyzing tumor-derived exosomes in limited volume plasma from breast cancer patients demonstrates the excellent clinical diagnostic efficacy of the hMFEX nanosensor. This study provides new insights into the point-of-care testing of tumor-derived exosomes for cancer diagnostics.