Exosomes are potential and promising natural noninvasive biomarkers for liquid biopsies and can be involved in various biological and pathological processes in early-stage cancer. Thus, there is an urgent demand to develop low-cost, small-size, remarkable-specificity, and ultrasensitive exosome biosensors for early clinical point-of-care (POC) testing. Although various conventional tumor exosome detection methods have been generally proposed, the low detection sensitivity and specificity significantly hinder their use in cancer clinical diagnosis and prognosis. To address the above challenges, an optical microfiber integrated with MoSe2-supported gold nanorods is proposed. To tune the strong localized surface plasmon resonance (LSPR) of the nanointerfaces on the optical microfiber to be in accordance with the operating wavelength of the silica optical microfiber in the telecommunication band, gold nanorods with a high aspect ratio of approximately 10:1 are proposed. Due to the interaction between the excited LSPR effect and the evanescent field of the optical microfiber, the sensor can detect clear cell renal cancer exosomes within a wide concentration range from 100 particles/mL to 108 particles/mL, with an extremely low limit of detection (LOD) of 9.32 particles/mL, which is lower than that of current various state of the art methods. More importantly, the microfiber with high specificity can successfully differentiate pathological plasma and healthy controls, exhibiting very promising clinical applications in renal cancer diagnosis and prognosis. This work opens up a new approach for the in situ detection and quantification of exosomes with ultrahigh sensitivity in early clinical screening and diagnosis.
Keywords: CA9 protein; LSPR; clear cell renal cancer exosomes; evanescent field; optical microfiber biosensor; ultralow LOD.