Chiroptical detection and mutation analysis of cancer-associated extracellular vesicles using microfluidics with oriented chiral nanoparticles

Abstract

Cancer-cell-secreted small extracellular vesicles, known as exosomes, represent a rapidly emerging family of cancer biomarkers. However, the current protocols for exosome analysis require complex equipment and lengthy procedures, which prevents their broad utilization for cancer diagnosis. We have engineered plasmonic gold nanoparticles combining molecular and nanoscale chirality, and have demonstrated that such nanoparticles in self-assembled films in a microfluidic device can isolate and analyze exosomes directly from blood plasma due to marker-specific chiroptical responses and volumetric electromagnetic resonance. Cancer exosomes can be distinguished from those from healthy donors by their giant polarization rotation signatures, and the observed dependence of plasmonic resonances on mutations of epidermal growth factor receptor suggests the possibility of in-line mutation/deletion analysis of protein cargo based on molecular chirality. The present microfluidic chips eliminate ultracentrifugation and improve the sensitivity and detection speed by at least 14 times and 10 times, respectively, enabling the rapid liquid biopsy of cancer.