Microfluidic Strategies for Extracellular Vesicle Isolation: Towards Clinical Applications

Abstract

Extracellular vesicles (EVs) are double-layered lipid membrane vesicles released by cells. Currently, EVs are attracting a lot of attention in the biological and medical fields due to their role as natural carriers of proteins, lipids, and nucleic acids. Thus, they can transport useful genomic information from their parental cell through body fluids, promoting cell-to-cell communication even between different organs. Due to their functionality as cargo carriers and their protein expression, they can play an important role as possible diagnostic and prognostic biomarkers in various types of diseases, e.g., cancers, neurodegenerative, and autoimmune diseases. Today, given the invaluable importance of EVs, there are some pivotal challenges to overcome in terms of their isolation. Conventional methods have some limitations: they are influenced by the starting sample, might present low throughput and low purity, and sometimes a lack of reproducibility, being operator dependent. During the past few years, several microfluidic approaches have been proposed to address these issues. In this review, we summarize the most important microfluidic-based devices for EV isolation, highlighting their advantages and disadvantages compared to existing technology, as well as the current state of the art from the perspective of the use of these devices in clinical applications.

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications

“…These devices contain microchannels with precise filtering structures, allowing larger particles to pass through while capturing EVs. 361 Miniaturized microfluidic devices can be used at the point of care for rapid and sensitive diagnostics of brain-related conditions. These devices may incorporate EV capture and analysis within a portable and easy-to-use format.…”

“…This allows for the examination of individual vesicles, providing insights into their heterogeneity. , Microfluidic devices can utilize size-based filtration to selectively capture EVs based on their size. These devices contain microchannels with precise filtering structures, allowing larger particles to pass through while capturing EVs . Miniaturized microfluidic devices can be used at the point of care for rapid and sensitive diagnostics of brain-related conditions.…”

Recent research on material-based methods for isolation of extracellular vesicles

“…It also leads to the introduction of pollutants such as miscellaneous proteins and polymer particles, which greatly impacts the downstream analysis of EVs. In addition to the above traditional methods, microuidic devices have become a new method for the isolation of EVs 18,19 that further improved the recovery and specicity of isolation. However, the operating conditions of these pieces of equipment were complex, and the sample number it could handle was limited.…”

Physiological and pathological consequences of exosomes at the blood–brain-barrier interface

“…Despite the ease of use, the Exo values such as purity, number, and size distribution are so variable [ 54 ]. Along with approaches, other modalities such as membrane-based separation, microfluidics, and other modalities can be used for the isolation of Exo [ 55 ].…”