Exploring Aptamer‐Based Metasurfaces for Label‐Free Plasmonic Biosensing of Breast Tumor‐Derived Exosomes

Abstract Exosomes are critical tumor biomarkers, which can be detected by label‐free sensing of plasmonic metasurfaces with expensive antibody functionalization. Due to their low cost and small size, aptamers should be promising to replace antibodies in plasmonic metasensing of exosomes. However, research on aptamer‐based plasmonic metasensing of exosomes is still unexplored. Here, the optical near‐field sensing mechanism of aptamer‐based plasmonic metasurface (APM) is investigated. Based on the study of the evanescent field of APM, using thiol‐modified aptamer boosts the utilization rate of resonance wavelength shift from 27.5% to 83.3% compared to biotinylated aptamers, attributed to a significant reduction in the near‐field occupation of the biofunction layer. Moreover, APM biosensors effectively detect clinical serum exosomes for breast cancer (BC) diagnosis and classification. The receiver operating characteristic analysis shows an area under the curve of 99.3% for APM diagnosis, surpassing the 79.1% for hematological tests of the conventional BC biomarker CA153. The results also indicate that APM biosensors can be a noninvasive tool for molecular classification of BC with great distinguishment of P < 0.0001. The research demonstrates that APM biosensors are enabling a reliable and convenient platform to facilitate clinical hematological tests of exosomes for auxiliary diagnosis of cancer.