Synthesis of Size‐Tunable Polymeric Nanoparticles Enabled by 3D Hydrodynamic Flow Focusing in Single‐Layer Microchannels

Rhee, Minsoung; Valencia, Pedro M.; Rodríguez, María Isabel Hernández; Langer, Robert; Farokhzad, Omid C.; Karnik, Rohit

doi:10.1002/adma.201004333

Cited by 215 publications

(226 citation statements)

References 38 publications

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“…Moreover, the manually folded 3D channels had smooth turns to avoid abrupt velocity changes, ensuring that no clogging occurs inside microchannels for over several hours. 18 The cellular uptake of PLGA-DOX nanoparticles was compared against free DOX solution by using two human carcinoma cell lines, MCF-7 and HeLa. The PLGA-DOX nanoparticles of 100 nm in size were synthesized by 3D double spiral microchannels at 2.5 mL h À1 .…”

mentioning

confidence: 99%

A microfluidic origami chip for synthesis of functionalized polymeric nanoparticles

Sun

Xianyu

et al. 2013

Nanoscale

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mentioning

confidence: 99%

A microfluidic origami chip for synthesis of functionalized polymeric nanoparticles

Sun

Xianyu

et al. 2013

Nanoscale

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“…3B) (Rhee et al, 2011). NPs of different polymer concentrations and M w that were otherwise difficult to assemble by either 2D HFF or bulk preparation methods were successfully fabricated using this 3D HFF method.…”

Section: Synthesis Of Nanostructures and Their Applications 221 Synmentioning

confidence: 99%

“…Microfluidics is attractive for making chitosan nanoparticles. Although fast mixing in microfluidics remains a challenge due to its laminar flow characteristics (Rhee et al, 2011), it has been demonstrated computationally (Kamat et al, 2015) and experimentally (Cetin et al, 2014;Chen et al, 2014b;Majedi et al, 2014) that introducing active mixers can facilitate rapid mixing through chaotic advection and diffusion. Cetin et al designed a microfluidic device (Fig.…”

Section: Natural Polymer Nanoparticlesmentioning

confidence: 99%

Multiphase microfluidic synthesis of micro- and nanostructures for pharmaceutical applications

Ran

Sun

Baby

et al. 2017

Chemical Engineering Science

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Multiphase microfluidics has attracted significant interest in making micro-and nanostructures for various applications because of its capabilities in precisely controlling and manipulating a small volume of liquids. In this review, we introduce the recent advances in making micro-and nanostructures for pharmaceutical applications, including microparticles and microcapsules for controlled release, nanoparticles for drug delivery and microgels for 3D cell culture. With the development of more advanced microfluidic systems, the research focus in this field has shifted from making simple micro-and nanostructures to multifunctional systems to achieve more desirable functions. However, these multifunctions may lose their advantages that have been demonstrated in vitro once they are applied in vivo or later in human. The key challenge is a lack of fundamental understanding of the interactions between the micro-and nanomaterials and the biology systems. Consequently, the translation of these advanced materials lags far behind their extensive laboratory research.To better understand the micro-or nano-bio interactions, the development of new in vivomimicking models is imperative. Microfluidics has demonstrated its great potential in creating physiologically relevant models including 3D cell culture, tumor-on-a-chip and organs-on-a-chip. Therefore, efforts towards developing 3D cell culture and biomimetic chips including tumor-on-a-chip and organs-on-chips for faster and reliable evaluation of these micro-and nanosystems are also highlighted.

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“…2 In microparticle fabrication, conventional 'bottom-up' self-assembly emulsification techniques yield a broad particle size distribution, which can affect the drug release kinetics and biotransport in blood. 3,4 Although well-controlled and monodisperse particles can be produced by 'top-down' approaches using specific lithographic techniques 5,6 and microfluidics, 7,8 microfabricated particles are prone to damage during mechanical harvesting, a problem further aggravated at the smaller/nanoscale level. Similarly, microfluidic synthesis of drug-loaded polymeric particles requires compatible drug/surfactant chemistry with additional steps to remove solvent prior use.…”

Section: Introductionmentioning

confidence: 99%

Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation

et al. 2017

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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 (D inner ) 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 (Po0.05). Overall, HiDFF represents a key technological progress toward highthroughput, single-step purification of engineered or cell-derived MPs with the potential for quantitative MP-based health profiling. NPG Asia Materials (2017) 9, e434; doi:10.1038/am.2017.175; published online 29 September 2017 INTRODUCTIONEnabling technologies for continuous, size-based separation of submicrometer engineered or biological components are highly desirable in clinical applications, such as particle-based drug delivery systems 1 and the purification of extracellular vesicles in clinical diagnostics. 2 In microparticle fabrication, conventional 'bottom-up' self-assembly emulsification techniques yield a broad particle size distribution, which can affect the drug release kinetics and biotransport in blood. 3,4 Although well-controlled and monodisperse particles can be produced by 'top-down' approaches using specific lithographic techniques 5,6 and microfluidics, 7,8 microfabricated particles are prone to damage during mechanical harvesting, a problem further aggravated at the smaller/nanoscale level. Similarly, microfluidic synthesis of drug-loaded polymeric particles requires compatible drug/surfactant chemistry with additional steps to remove solvent prior use. Developing novel tools to achieve tunable size fractionation of polydispersed synthetic particles would enable optimal biodistribution and controlled drug release. Such technologies also facilitate physical isolation of smaller biological targets (o2 μm) including platelets, microbes and extracellular vesicles in a label-free manner for unbiased downstream analysis.

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Synthesis of Size‐Tunable Polymeric Nanoparticles Enabled by 3D Hydrodynamic Flow Focusing in Single‐Layer Microchannels

Cited by 215 publications

References 38 publications

A microfluidic origami chip for synthesis of functionalized polymeric nanoparticles

A microfluidic origami chip for synthesis of functionalized polymeric nanoparticles

Multiphase microfluidic synthesis of micro- and nanostructures for pharmaceutical applications

Rapid purification of sub-micrometer particles for enhanced drug release and microvesicles isolation

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