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In this study, we report a gold nanoparticle (AuNP)-amplified surface acoustic wave (SAW) sensor for exosome detection with high sensitivity. The SAW chip was self-assembled with mercapto acetic acid to generate carboxylic groups via the Au–S bond. Anti-CD63 was then anchored onto the chip by pretreatment with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide,1-hydroxypyrrolidine-2,5-dione (NHS). Due to the existence of a membrane protein, CD63, on the exosome surface, exosomes could be bound onto the antibody-immobilized SAW chip. To amplify the detection signal, both the biotin-conjugated epithelial cell adhesion molecule (EpCAM) antibody as a secondary antibody and AuNP-labeled streptavidin were applied onto the exosome-bound SAW chip, resulting in AuNP assembly on the chip through biotin–avidin recognition. The sensor was capable of detecting 1.1 × 103 particles/mL exosomes, which was about 2 orders of magnitude higher than those detected by the strategy without using signal amplification. The sensor also achieved a satisfactory specificity and could detect the low-abundance exosomes directly in blood samples from cancer patients with minimal disturbance. This makes the SAW sensor useful for early diagnosis of cancer.

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