A dual aptamer recognition-based fluorescent biosensor for extracellular vesicles assays with high sensitivity and specificity

Cancer-derived extracellular vesicles (EVs) play a crucial role in intercellular information transmission, tumor metastasis and invasion, which has become one of the most promising biomarkers for tumor liquid biopsy. Herein, we propose a novel dual aptamer recognition-based fluorescent biosensor assisted by functionalized metal−organic frameworks (MOFs) and rolling circle amplification (RCA) method for ultrasensitive cancer-derived EVs assay. This approach exhibits excellent specificity and sensitivity toward EVs. The linear range of EVs detection was 5 × 104 particles/μL to 1 × 107 particles/μL and the limit of detection (LOD) was 2.2 × 104 particles/μL, which is superior to those of most reported methods. Moreover, double aptamer recognition improved the accuracy of this strategy in practical application. This method has been successfully used for the diagnosis of leukemia by detecting EVs from the normal and leukemia patient’s serum, which is expected to be applied as an effective tool for EVs research and has considerable potential for early clinical diagnosis of disease.