Applications of dielectrophoresis in microfluidic-based exosome separation and detection

Exosomes are small vesicles secreted by most cells with contents such as primitive cell proteins, lipids, and RNAs, which play a key role in cell communication and could be detected as biomarkers in disease diagnosis and treatment monitoring. However, it is difficult to isolate and detect exosomes in real time due to their small size and density. Recently developed microfluidic methods and devices have demonstrated the potential for effective separation and detection of exosomes using a compact device. Meanwhile, dielectrophoresis (DEP) provides a broad prospect for use in microfluidic-based exosome separation and biomarker detection due to its advantages of high specificity, easy control, label-free, and no mechanical damage, which has attracted broad attention over the past decade. In this review, recent advances in DEP-based microfluidic isolation and detection of exosomes are reviewed in four categories, using a single DEP (p-DEP or n-DEP); using dual-DEP forces; combining the DEP force with other forces; combining with immunoaffinity reaction. The development of these strategies enables the detection and analysis of exosomes from "sample-to-answer". Moreover, these devices can be used in early cancer screening and prognosis monitoring in liquid biopsy, as well as the application of exosome-based point-of-care (POC) applications.