Nanoplasmonic Sensing Technologies for Molecular Analysis of Extracellular Vesicles

Exosomes, or more broadly extracellular vesicles (EVs), have emerged as promising cancer biomarkers and present new opportunities for cancer diagnoses and treatment monitoring through liquid biopsies. These cell-derived membrane-bound vesicles are abundantly present and easily accessible in biological fluids. More importantly, they carry various biomaterials, such as proteins, lipids, and genetic materials, which reflect their originating cells and thus can be used as surrogate markers accessible through noninvasive liquid biopsies. Despite the clinical potential, routine, reliable, and sensitive EV analyses are still challenging due to their small sizes under micron and the low sensitivity of conventional analytical methods such as western blotting and enzyme-linked immunosorbent assay ELISA for EV detection. To address these unmet needs, we developed nanoplasmonic sensing technologies to sensitively detect EVs directly from clinical samples. Termed “nPLEX” nano-plasmonic exosomes, it harnesses surface plasmon resonances excited by periodic gold nanohole arrays tuned to have matched sensing range to the size of EVs, maximizing the sensitivity while simplifying the assay procedures. We demonstrated that nPLEX could sensitively detect and profile EVs directly from clinical samples. Using the nPLEX sensors, we showed that i tumor-derived EVs contain protein markers reflective of primary tumor cells; ii nPLEX sensors can rapidly and sensitively detect tumor EVs directly from clinical samples; iii EV analyses offer great clinical potential for cancer diagnostics and longitudinal monitoring of tumor response to therapy.