Nanoplasmonic On-Chip Immunoassay for Cancer-Derived Exosome Profiling and Exosome-Mediated Cell Communication Analysis

Exosomes are nano-sized extracellular vesicles (EVs) that carry unique surface compositions derived from their cells of origin. Tumor cell-derived exosomes play a vital role in the development of cancer by creating a biological milieu in which primary tumor cells can interact with their microenvironment to enhance cancer cell survival, proliferation, and the evasion of immune surveillance. Recent studies suggest that tumor cells can evade immune inspection by secreting excessive exosomes with surface expression of programmed death ligand 1 (PD-L1). Moreover, tumor cell-derived exosomes can stimulate immune cells to secrete cytokines with pro-tumorigenic function. Therefore, we have developed on-chip immunoassays to analyze the role of tumor cell-derived exosomes in the immune system. First, Au@Ag core-shell nano-bipyramids and gold nanorods based on-chip nanoplasmonic sandwich immunoassay provide rapid, sensitive quantification of exosomes and also accurate subtyping exosomes upon PD-L1 expression levels. Second, a specially designed on-chip device consists of cell isolation chambers and a gold nanosphere-based nanoplasmonic digital immunoassay, rendering <i>in situ </i>remote cell communication and immune analysis of cellular secretions and traces. These developed platforms provide new methods for tumor cell-derived exosome detection and analysis that have high potential as a future clinical diagnostic tool for monitoring cancer progression and as an analytical tool for accurate and comprehensive analysis of the immune system.