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...

Full description

Saved in:
Bibliographic Details
Main Authors: Tay, Hui Min, Kharel, Sharad, Dalan, Rinkoo, Chen, Zhijie Joshua, Tan, Kah Kee, Boehm, Bernhard Otto, Loo, Say Chye Joachim, Hou, Han Wei
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2017
Subjects:
Online Access:https://hdl.handle.net/10356/85809
http://hdl.handle.net/10220/43855
Tags: Add Tag
No Tags, Be the first to tag this record!
Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-85809
record_format dspace
spelling 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
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Sub-micrometer Particles
Drug Release
spellingShingle 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
description 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.
author2 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
format 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
_version_ 1683493510152454144