The new advance of exosome-based liquid biopsy for cancer diagnosis

Abstract

Liquid biopsy is a minimally invasive method that uses biofluid samples instead of tissue samples for cancer diagnosis. Exosomes are small extracellular vesicles secreted by donor cells and act as mediators of intercellular communication in human health and disease. Due to their important roles, exosomes have been considered as promising biomarkers for liquid biopsy. However, traditional methods for exosome isolation and cargo detection methods are time-consuming and inefficient, limiting their practical application. In the past decades, many new strategies, such as microfluidic chips, nanowire arrays and electrochemical biosensors, have been proposed to achieve rapid, accurate and high-throughput detection and analysis of exosomes. In this review, we discussed about the new advance in exosome-based liquid biopsy technology, including isolation, enrichment, cargo detection and analysis approaches. The comparison of currently available methods is also included. Finally, we summarized the advantages and limitations of the present strategies and further gave a perspective to their future translational use.

Keywords: Biomarker; Cancer; Diagnosis; Exosomes; Liquid biopsy.

Fig. 1

New isolation and enrichment methods for exosomes. A. Separation based on acoustofluidic platform. B. Separation based on deterministic lateral displacement. C. Separation based on negative magnetophoretic technique. D. Viscoelasticity-based separation. E. Separation based on asymmetric-flow field-flow fractionation. F. Dielectrophoretic separation. G. Separation by magnetic beads modified with antibodies. H. Separation based on aptamer targeting surface proteins. I. Separation based on paper-based device. J. Nanowire-array-based separation. K. Phospholipid-based separation. L. Separation based on Tim4 beads targeting PS

Fig. 2

Single exosome detection technology based on total internal reflection fluorescence (TIRF) imaging system

Fig. 3

New technology for analyzing exosomal cargoes. A. Using electrochemical sensor to detect proteins. B. Using surface plasmon resonance or localized surface plasmon resonance biosensor to detect proteins. C. Protein detection based on surface enhanced raman spectra. D. Protein detection based on flow cytometry. E. Protein detection based on fluorescence signals. F. Nucleic acids detection based on CRISPR/Cas system. G. Nucleic acids detection based on drop digital PCR. H. Nucleic acids detection based on rolling circle amplification. I. Nucleic acids detection based on hairpin probes. J. Nucleic acids detection based on DNA polyhedral probes