Nanostructure enabled extracellular vesicles separation and detection

Extracellular vesicles (EVs) have recently attracted significant research attention owing to their important biological functions, including cell-to-cell communication. EVs are a type of membrane vesicles that are secreted into the extracellular space by most types of cells. Several biological biomolecules found in EVs, such as proteins, microRNA, and DNA, are closely related to the pathogenesis of human malignancies, making EVs valuable biomarkers for disease diagnosis, treatment, and prognosis. Therefore, EV separation and detection are prerequisites for providing important information for clinical research. Conventional separation methods suffer from low levels of purity, as well as the need for cumbersome and prolonged operations. Moreover, detection methods require trained operators and present challenges such as high operational expenses and low sensitivity and specificity. In the past decade, platforms for EV separation and detection based on nanostructures have emerged. This article reviews recent advances in nanostructure-based EV separation and detection techniques. First, nanostructures based on membranes, nanowires, nanoscale deterministic lateral displacement, and surface modification are presented. Second, high-throughput separation of EVs based on nanostructures combined with acoustic and electric fields is described. Third, techniques combining nanostructures with immunofluorescence, surface plasmon resonance, surface-enhanced Raman scattering, electrochemical detection, or piezoelectric sensors for high-precision EV analysis are summarized. Finally, the potential of nanostructures to detect individual EVs is explored, with the aim of providing insights into the further development of nanostructure-based EV separation and detection techniques.