Plasmonic liquid biopsy for breast cancer detection via small extracellular vesicle counting in plasma

Abstract

Small extracellular vesicles (sEVs, aka, exosomes) are potential biomarkers for breast cancer liquid biopsy, but their nanoscale size and the complexity of plasma make sensitive, reproducible, and scalable measurements challenging. Here we report plasmonic nano-aperture label-free imaging (PANORAMA) assay implemented on arrayed-gold-nanodisk- on-invisible-substrate (AGNIS) chip to digitally quantify sEVs captured from human plasma. Using brightfield imaging with a narrowband light source (660 nm) and an automated workflow, we detect and localize sEV, track retention after a wash step to reduce nonspecific binding and quantify sEV count and contrast distributions. In a pilot cohort of 20 plasma samples (10 breast cancer, 10 controls) with five technical repeats per sample, sEV counts were significantly higher in cases (Student’s t-test p = 0.00009) and provided an area under the ROC curve (AUC) of 0.92. These results establish potential of PANORAMA as a high-throughput, label-free, and scalable route to digital sEV quantification for breast cancer liquid biopsy.