Size Sorting of Exosomes by Tuning the Thicknesses of the Electric Double Layers on a Micro-Nanofluidic Device

Abstract

Exosomes, a type of extracellular vesicle with a diameter of 30–150 nm, perform key biological functions such as intercellular communication. Recently, size sorting of exosomes has received increasing attention in order to clarify the correlation between their size and components. However, such sorting remains extremely difficult. Here, we propose to sort their size by controlling their electrokinetic migration in nanochannels in a micro-nanofluidic device, which is achieved by tuning the thickness of the electric double layers in the nanochannels. This approach was demonstrated experimentally for exosomes smaller than 250 nm. Using different running buffer concentrations (1 × 10−3, 1 × 10−4, and 1 × 10−5 M), most of the exosomes larger than 140, 110, and 80 nm were successfully cut off at the downstream of the nanochannels, respectively. Therefore, it is clarified that the proposed method is applicable for the size sorting of exosomes.

Microfluidic‐Based Exosome Analysis for Liquid Biopsy

“…developed a method to sort exosomes in the nanochannels by controlling the thickness of the electric double layers. [ 91 ] Under optimized conditions, different cutoffs of the exosomes are separated. In addition, a nanopipette tip based on DEP was used to trap exosomes with high yield.…”

Permeability and selectivity analysis for affinity‐based nanoparticle separation through nanochannels

“…The length of the nanochannel is set as L ¼ 11σ 1 and width W ranges from 5σ 1 to 7σ 1 . The choice of this dimension in our calculation is comparative with that in the practical case 55 where the nanochannel can be reasonably modeled as a slit channel 51 as the width of the nanochannel is four times larger than the depth. Effects of channel length on permeability are not considered here, because this effect has been studied by other researchers.…”

Nanofluidic Devices and Applications for Biological Analyses

“…129 electric double layers of fused silica surfaces of nanochannels to sort exosomes derived from the HEK293 human embryonic kidney cell line. 130 In this study, size-selective separation of exosomes was performed by nanogates, which had a height restriction determined by the depth of the nanochannels as well as thickness of the electric double layers controlled by electrolyte concentration of a running buffer. Quantitation of subcellular vesicles is also possible with nanostructures.…”

“…This nanofluidic device sorted electroosmotic flow (EOF)-driven vesicles by nanopillars that induced displacement of vesicles in the direction perpendicular to the EOF based on vesicle size. Another example used electric double layers of fused silica surfaces of nanochannels to sort exosomes derived from the HEK293 human embryonic kidney cell line . In this study, size-selective separation of exosomes was performed by nanogates, which had a height restriction determined by the depth of the nanochannels as well as thickness of the electric double layers controlled by electrolyte concentration of a running buffer.…”