Abstract
Extracellular vesicles (EVs) are becoming a promising biomarker in liquid biopsy of cancer. Separation EV from cell culture medium or biofluids with high purity and quality remains a technique challenge. EV manipulation techniques based on microfluidics have been developed in the last decade. Microfluidic-based EV separation techniques developed so far can be classified into two categories: surface biomarker-dependent and size-dependent approaches. Microfluidic techniques allow the integration of EV separation and analysis on a single chip. Integrated EV separation and on-chip analysis have shown great potential in cancer diagnosis and monitoring treatment of responses. In this review, we discuss the development of microfluidic chips for EV separation and analysis. We also detail the clinical application of these microfluidic chips in the liquid biopsy of various cancers.
Highlights
Tissue biopsy is still the standard procedure of cancer diagnosis
The results showed the levels of ephrin type-A receptor 2 (EPHA2) and EGFR were significantly higher in glioblastoma multiforme (GBM) patients than in healthy donors, while PDPN levels were similar in both groups
The potential of Extracellular vesicles (EVs) in cancer diagnosis, molecular classification, and monitoring treatment response have aroused a great deal of interest in the medical and bioengineering fields
Summary
Tissue biopsy is still the standard procedure of cancer diagnosis. several limitations of tissue biopsy exist [1,2]. Tissue biopsy is invasive and brings some risks to patients Liquid biopsy is a new technique that detects cancer cells or their products in the body fluids of cancer patients [3]. EV separation and concentration can be achieved by multiple technologies based on EV size or surface marker expression. These techniques include differential ultracentrifugation, density gradient centrifugation, immunoaffinity, ultrafiltration, polymer-based precipitation, and size-exclusion chromatography [17]. To confirm the purity of separated EVs electron microscopy, nanoparticle tracing analysis (NTA), and western blotting are usually performed to characterize EV shape, size, and biomarker expression [48]. A single EV could be characterized through two different but complementary techniques: microscopy (such as scanning-probe microscopy, atomic force microscopy, or super-resolution microscopy) or single particle analyzers (NTA, high resolution flow cytometry, and dynamic light scattering) [49]
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