Abstract

Extracellular vesicles (EVs) are the cell-secreted nano- and micro-sized particles consisted of lipid bilayer containing nucleic acids and proteins for diagnosis and therapeutic applications. The inherent complexity of EVs is a source of heterogeneity in various potential applications of the biological nanovesicles including analysis. To diminish heterogeneity, EV should be isolated and separated according to their sizes and cargos. However, current technologies do not meet the requirements. We showed noninvasive and precise separation of EVs based on their sizes without any recognizable damages. We separated atto-liter volumes of biological nanoparticles through operation of the present system showing relatively large volume of sample treatment to milliliters within an hour. We observed distinct size and morphological differences of 30 to 100 nm of exosomes and apoptotic bodies through TEM analysis. Indeed, we confirmed the biological moiety variations through immunoblotting with noninvasively separated EVs opening new windows in study and application of the biological nanoparticles.

Highlights

  • The complexity of a biological system can be resolved by using its physicochemical properties to isolate and separate its specific constituent bio-organisms and -molecules, such as cells, bacteria, proteins, and DNA

  • The microdevice is composed of two inlets (Sample and Function channel), nine outlets, and a magnification channel that controls the overall flow pattern

  • With the ratio of 1:99 of Sample:Function, MR is more than 80% for every Qtotal condition

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Summary

Introduction

The complexity of a biological system can be resolved by using its physicochemical properties to isolate and separate its specific constituent bio-organisms and -molecules, such as cells, bacteria, proteins, and DNA. There is an emerging need to isolate and separate extracellular vesicles (EVs). EVs are lipid bilayer vesicles secreted by cells, and generally, the size ranges between hundreds of nanometers. Exosomes are membranous vesicles of endosomal origin with 50–200 nm hydrodynamic diameter and have biologically significant molecules[6]. Miniaturized fluidic channel offers a potential means for experimental biological research[14,15,16], including exosome separation[17,18,19]. Affinity-based EV separation catches only specific targets, missing unknown biological nanoparticles of potential value

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