Microfluidic platforms with monolithically integrated hierarchical apertures for the facile and rapid formation of cargo-carrying vesicles

Cho, Hyesung; Kim, Junsoo; Suga, Kazuyoshi; Ishigami, Takaaki; Park, Hyunchul; Bang, Jung Won; Seo, Soonmin; Choi, Mansoo; Chang, Pahn–Shick; Umakoshi, Hiroshi; Jung, Ho‐Sup; Suh, Kahp Y.

doi:10.1039/c4lc01096e

Cited by 17 publications

(17 citation statements)

References 26 publications

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“…8 Over the last few decades, researchers have proposed the use of bottom-up methodologies to build liposomes from scratch using elemental organic and inorganic components. Previously developed methods include: hydrodynamic flow focusing, 12,13 pulsed jetting, 14,15 droplet emulsion transfer in static solution 16,17 or in a microchannel network, [18][19][20] and double emulsion templates with oil phase removal. 11 These traditional liposome preparation techniques allow for relatively facile production of large amounts of membrane material.…”

Section: Introductionmentioning

confidence: 99%

Continuous microfluidic fabrication of synthetic asymmetric vesicles

Schertzer

Chiarot

2015

Lab Chip

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We report on a novel microfluidic strategy for the continuous fabrication of monodisperse asymmetric vesicles with customized membrane composition, size, and luminal content. The microfluidic device encompasses a triangular post region and two flow-focusing regions. The major steps involved in the vesicle fabrication process include: (1) forming highly uniform water emulsions in an oil/inner-leaflet-lipid solution, (2) replacing the inner-leaflet-lipid solution with an outer-leaflet-lipid solution inside the microchannel network, (3) forming water-in-oil-in-water double emulsions, and (4) extracting excess oil/outer-leaflet-lipid solution from the double emulsions. Bilayer membrane asymmetry and unilamellarity are evaluated using a fluorescence quenching assay and a transmembrane protein insertion assay, respectively. Our approach addresses many of the deficiencies found in existing technologies for building vesicles, and yields strong membrane asymmetry. The ability to create and sustain membrane asymmetry is an important feature, as it is a characteristic of nearly all natural membranes. Over 80% of the vesicles remain stable for at least 6 weeks and the membrane asymmetry is maintained for over 30 hours. The asymmetric vesicles built using this strategy are collected off-chip and hold the potential to be used as model systems in membrane biology or as vehicles for drug delivery.

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Section: Introductionmentioning

confidence: 99%

Continuous microfluidic fabrication of synthetic asymmetric vesicles

Schertzer

Chiarot

2015

Lab Chip

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“…during the shift of the pressure and temperature above the critical point of the system. A continuous vesicle preparation method using microfluidics 23 also requires a liquid-liquid interface (e.g., IPA/water) to form a membrane, although the prepared vesicle suspension must be heat treated to remove IPA. Nonsolvent methods for vesicle preparation are preferred in the research fields of biochemistry, drug delivery systems, food, and cosmetics.…”

Section: Discussionmentioning

confidence: 99%

“…20 Based on vesicle characterization protocols, a variety of vesicles prepared by several methods have been investigated. [21][22][23][24] The membrane properties, such as the phase state, membrane fluidity, and membrane polarity, are possible factors to recruit the guest molecules on the membrane surface. 25,26 However, it is assumed that a specific assembled state (i.e., interdigitated membrane) might form in the liquid-liquid-surfactant ternary system.…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, the microchannel method requires heterogeneous liquid systems, such as isopropyl alcohol (IPA)/ water. 23 Although such liquid-liquid two phase (heterogeneous) systems have advantages from the viewpoint of energy loss, organic solvents in the product must be removed when the vesicles are used in medical applications, cosmetics, and food. Therefore, the nonsolvent CO 2 method is an ideal method to provide environmentally friendly vesicles.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of the physicochemical properties of phospholipid vesicles prepared in CO2/water systems at high pressure

et al. 2015

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Phospholipid vesicles were prepared by the nonsolvent method using high-pressure CO2/water systems. The membrane properties of vesicles prepared at different pressures and temperatures were mainly characterized based on analysis of the membrane fluidity and membrane polarity, using the fluorescent probes 1,6-diphenyl-1,3,5-hexatriene and 6-dodecanoyl-N,N-dimethyl-2-naphthylamine, respectively. The CO2(liquid)/water(liquid) and the CO2(supercritical)/water(liquid) two-phase (heterogeneous) systems resulted in the formation of vesicles with high yield (ca. 85%–88%). The membrane fluidity and polarity of the vesicles were similar to those of liposomes prepared by the conventional method. It is suggested that high-pressure CO2 can be used to form an appropriate hydrophobic–hydrophilic interface where phospholipid molecules as a self-assembled membrane.

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“…By utilizing these intriguing properties of each nano‐ and microstructures simultaneously, multiscale hierarchical structures can provide multifunctional effects to the system and maximize their function without the need for any further physicochemical processes. Thus, there have been many attempts to use multiscale hierarchical structures in diverse fields and applications, including micro/nanofluidics, wearable devices, optical devices, and energy systems with various materials including polymers, metals, and ceramics …”

Section: Introductionmentioning

confidence: 99%

Multiscale Hierarchical Patterning by Sacrificial Layer‐Assisted Creep Lithography

Jang

Choi

Shin

et al. 2019

Adv Materials Inter

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to the expectation that technological breakthroughs can be achieved. [1][2][3] As is well known in literature, nanostructures exhibit unique properties such as plasmonic effects, [4] antireflection, [5] structural color, [6] super-hydrophobicity, [7] adhesion, [8] superior catalytic activity, [9] and charge transport. [10] Microstructures lend mechanical properties (e.g., stress-strain relationship, hardness, and flexibility) [7] to the system and enable the control of light, liquid, and gas pathways. [11][12][13][14] By utilizing these intriguing properties of each nanoand microstructures simultaneously, multi scale hierarchical structures can provide multifunctional effects to the system and maximize their function without the need for any further physicochemical processes. Thus, there have been many attempts to use multiscale hierarchical structures in diverse fields and applications, including micro/nanofluidics, [15] wearable devices, [16] optical devices, [17,18] and energy systems [19,20] with various materials including polymers, metals, and ceramics. [21,22] Our recent study showed that multiscale hierarchical structure can be simply and easily fabricated with the aid of creep behavior of a polymer, [23] which is a permanent deformation of the material due to the viscoelastic behavior of the polymer under long-term stress below the glass transition temperature. In this work, nanostructures were first carved onto polymer films by hot-embossing nanoimprint lithography (NIL) and then followed by a second imprinting with a micropattern mold using the creep deformation characteristic of the polymer film. This facile multiscale patterning method does not require any sophisticated process and equipment. Further, by using Nafion as a substrate that has a low modulus (≈250 MPa) and large creep deformation property, [24,25] we can use diverse polymeric molds instead of metallic molds that require very high pressures for conformal contact with the substrate. However, this method had a weakness that previously carved nanostructures also inevitably underwent creep deformation during the second imprinting process, which led to deformation of the original morphologies of the nanostructures.To address this issue, we introduced a poly(methyl methacrylate) (PMMA) sacrificial layer to protect the preformed structures before the secondary creep-based imprinting process. The PMMA sacrificial layer has a larger modulus (≈3 GPa) [26] The capability to fabricate various multiscale structures without limitations of size, morphology, and number of hierarchies via a simple process is highly desired in modern research. This work reports a powerful multiscalepatterning method called sacrificial layer-assisted creep lithography (SCL). Multiscale structures are successfully obtained by introducing a sacrificial layer, which has low creep compliance and preferential solubility in a nonpolar solvent, on a Nafion film during an additional creep-based imprinting process. Through this method, deformation or geometrical loss of preformed st...

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Microfluidic platforms with monolithically integrated hierarchical apertures for the facile and rapid formation of cargo-carrying vesicles

Cited by 17 publications

References 26 publications

Continuous microfluidic fabrication of synthetic asymmetric vesicles

Continuous microfluidic fabrication of synthetic asymmetric vesicles

Characterization of the physicochemical properties of phospholipid vesicles prepared in CO2/water systems at high pressure

Multiscale Hierarchical Patterning by Sacrificial Layer‐Assisted Creep Lithography

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