Isolation of exosomes from biological samples provides a minimally-invasive alternative for basic understanding, diagnosis, and prognosis of metastatic cancers. The biology and clinical values of exosomes are under intensive investigation, yet most studies are limited by technical challenges in recovering these exosomes with heterogeneous sizes and cargos from biological samples. We report a novel method based on “particle ferrohydrodynamics” and its associated microfluidic device, termed as the FerroChip, which can separate exosome-like nanoparticles from microliters of cell culture media and human serum in a label-free, continuous-flow and size-dependent manner, and achieves a high recovery rate (94.3%) and a high purity (87.9%). Separated exosome-like nanoparticles had diameters, morphology, and protein expressions that were consistent with other reports. This method, upon further molecular characterization, could potentially facilitate basic understanding of exosomes and its clinical application in blood liquid biopsy.

Overview of the label-free ferrohydrodynamic nanoparticle separation principle and the FerroChip device design. <b>a</b> Schematic of an extracellular vesicle (EV, 30–1000 nm in diameter) experiencing both diffusion and “particle ferrohydrodynamics” in a colloidally-stable magnetic nanoparticle (∼10 nm particle diameter) suspension (<i>i.e.</i>, ferrofluids). <b>b</b> Work principle of a label-free continuous-flow EV focusing/separation device, termed as FerroChip. <b>c</b> Top-view schematic drawing of the FerroChip's microchannel. <b>d</b> A photo of a microchannel (left, blue ink indicating the channel geometry) and assembled FerroChip with four permanent magnets in quadrupole configuration inside a holder (right). The microfluidic device and permanent magnets were placed within an aluminum manifold during its operation.

Overview of the label-free ferrohydrodynamic nanoparticle separation principle and the FerroChip device design. a Schematic of an extracellular vesicle (EV, 30–1000 nm in diameter) experiencing both diffusion and “particle ferrohydrodynamics” in a colloidally-stable magnetic nanoparticle (∼10 nm particle diameter) suspension (i.e., ferrofluids). b Work principle of a label-free continuous-flow EV focusing/separation device, termed as FerroChip. c Top-view schematic drawing of the FerroChip's microchannel. d A photo of a microchannel (left, blue ink indicating the channel geometry) and assembled FerroChip with four permanent magnets in quadrupole configuration inside a holder (right). The microfluidic device and permanent magnets were placed within an aluminum manifold during its operation.

Wujun Zhao

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