Recent
discoveries reveal that extracellular vesicles (EVs) play
an important role in transmitting signals. Although this emerging
transcellular pathway enables a better understanding of neural communication,
the lack of techniques for effectively isolating EVs impedes their
studies. Herein, we report an emergent high-throughput platform consisting
of three-dimensional carbon nanotube arrays that rapidly capture different
EVs based on their sizes, without any labels. More importantly, this
label-free capture maintains the integrity of the EVs when they are
excreted from a host cell, thus allowing comprehensive downstream
analyses using conventional approaches. To study neural communication,
we developed a stamping technique to construct a gradient of nanotube
herringbone arrays and integrated them into a microdevice that allowed
us processing of a wide range of sample volumes, microliters to milliliters,
in several minutes through a syringe via manual hand pushing and without
any sample preparation. This microdevice successfully captured and
separated EVs excreted from glial cells into subgroups according to
their sizes. During capture, this technology preserved the structural
integrity and originality of the EVs that enabled us to monitor and
follow internalization of EVs of different sizes by neurons and cells.
As a proof of concept, our results showed that smaller EVs (∼80
nm in diameter) have a higher uptake efficiency compared to larger
EVs (∼300 nm in diameter). In addition, after being internalized,
small EVs could enter endoplasmic reticulum and Golgi but not the
largest ones. Our platform significantly shortens sample preparation,
allows the profiling of the different EVs based on their size, and
facilitates the understanding of extracellular communication. Thus,
it leads to early diagnostics and the development of novel therapeutics
for neurological diseases.