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Title: Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation
Authors: Tay, Hui Min
Kharel, Sharad
Dalan, Rinkoo
Chen, Zhijie Joshua
Tan, Kah Kee
Boehm, Bernhard Otto
Loo, Say Chye Joachim
Hou, Han Wei
Keywords: Sub-micrometer Particles
Drug Release
Issue Date: 2017
Source: Tay, H. M., Kharel, S., Dalan, R., Chen, Z. J., Tan, K. K., Boehm, B. O., et al. (2017). Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation. NPG Asia Materials, 9(9), e434-.
Series/Report no.: NPG Asia Materials
Abstract: Efficient separation of sub-micrometer synthetic or biological components is imperative in particle-based drug delivery systems and purification of extracellular vesicles for point-of-care diagnostics. Herein, we report a novel phenomenon in spiral inertial microfluidics, in which the particle transient innermost distance (Dinner) varies with size during Dean vortices-induced migration and can be utilized for small microparticle (MP) separation; aptly termed as high-resolution Dean flow fractionation (HiDFF). The developed technology was optimized using binary bead mixtures (1–3 μm) to achieve ~100- to 1000-fold enrichment of smaller particles. We demonstrated tunable size fractionation of polydispersed drug-loaded poly(lactic-co-glycolic acid) particles for enhanced drug release and anti-tumor effects. As a proof-of-concept for microvesicles studies, circulating extracellular vesicles/MPs were isolated directly from whole blood using HiDFF. Purified MPs exhibited well-preserved surface morphology with efficient isolation within minutes as compared with multi-step centrifugation. In a cohort of type 2 diabetes mellitus subjects, we observed strong associations of immune cell-derived MPs with cardiovascular risk factors including body mass index, carotid intima-media thickness and triglyceride levels (P<0.05). Overall, HiDFF represents a key technological progress toward high-throughput, single-step purification of engineered or cell-derived MPs with the potential for quantitative MP-based health profiling.
ISSN: 1884-4057
DOI: 10.1038/am.2017.175
Rights: © 2017 The Author(s) (Nature Publishing Group). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
Fulltext Permission: open
Fulltext Availability: With Fulltext
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