Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation
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 trans...
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sg-ntu-dr.10356-858092020-11-01T05:17:36Z Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation Tay, Hui Min Kharel, Sharad Dalan, Rinkoo Chen, Zhijie Joshua Tan, Kah Kee Boehm, Bernhard Otto Loo, Say Chye Joachim Hou, Han Wei Lee Kong Chian School of Medicine (LKCMedicine) School of Materials Science & Engineering Singapore Centre for Environmental Life Sciences and Engineering Sub-micrometer Particles Drug Release 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. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) MOH (Min. of Health, S’pore) Published version 2017-10-10T08:53:48Z 2019-12-06T16:10:37Z 2017-10-10T08:53:48Z 2019-12-06T16:10:37Z 2017 Journal Article 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-. 1884-4057 https://hdl.handle.net/10356/85809 http://hdl.handle.net/10220/43855 10.1038/am.2017.175 en NPG Asia Materials © 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 http://creativecommons.org/licenses/by/4.0/. 10 p. application/pdf |
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Sub-micrometer Particles Drug Release Tay, Hui Min Kharel, Sharad Dalan, Rinkoo Chen, Zhijie Joshua Tan, Kah Kee Boehm, Bernhard Otto Loo, Say Chye Joachim Hou, Han Wei Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation |
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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. |
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Lee Kong Chian School of Medicine (LKCMedicine) |
author_facet |
Lee Kong Chian School of Medicine (LKCMedicine) Tay, Hui Min Kharel, Sharad Dalan, Rinkoo Chen, Zhijie Joshua Tan, Kah Kee Boehm, Bernhard Otto Loo, Say Chye Joachim Hou, Han Wei |
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Article |
author |
Tay, Hui Min Kharel, Sharad Dalan, Rinkoo Chen, Zhijie Joshua Tan, Kah Kee Boehm, Bernhard Otto Loo, Say Chye Joachim Hou, Han Wei |
author_sort |
Tay, Hui Min |
title |
Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation |
title_short |
Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation |
title_full |
Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation |
title_fullStr |
Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation |
title_full_unstemmed |
Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation |
title_sort |
rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation |
publishDate |
2017 |
url |
https://hdl.handle.net/10356/85809 http://hdl.handle.net/10220/43855 |
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1683493510152454144 |