Issue 19, 2022

Size-selective filtration of extracellular vesicles with a movable-layer device

Abstract

This paper presents a microfluidic device that can isolate extracellular vesicles (EVs) with multiple size intervals in a simple, effective, and automated manner. We accomplish this size-selective separation using a vertically movable plunger and a rotationally movable chip. The chip has open chambers with nanoporous filters that are sequentially connected by check valves. The plunger speed is adjusted to reduce chamber pressurization in order to prevent EV deformation, thereby achieving a high separation resolution. Herein, high-purity EVs with a purity ten times higher than that of ultracentrifugation were obtained by washing three times with a high EV recovery rate of 89%. For the analysis of device performance, we used polymer nanobeads, preformed liposomes, and canine blood plasma. To demonstrate the utility of the device, we applied size-selective isolation to EVs that were secreted by endothelial cells under shear flow. The results revealed that the cells secreted more EVs of larger size, the expression of CD63 protein was higher for EVs with a larger size, and a high amount of TSG101 protein was expressed under the condition of no shear flow. This device is envisioned to facilitate molecular analysis and EV-based biomarker discovery that use various biofluids, including blood plasma, urine, and cell culture supernatants. Our device automates size-selective EV filtration that requires laborious multiple washing and separation steps.

Graphical abstract: Size-selective filtration of extracellular vesicles with a movable-layer device

Supplementary files

Article information

Article type
Paper
Submitted
13 מאי 2022
Accepted
12 אוג 2022
First published
16 אוג 2022

Lab Chip, 2022,22, 3699-3707

Size-selective filtration of extracellular vesicles with a movable-layer device

I. Seder, H. Moon, S. J. Kang, S. Shin, W. J. Rhee and S. Kim, Lab Chip, 2022, 22, 3699 DOI: 10.1039/D2LC00441K

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