Takaichi Watanabe

Microfluidic approach to the formation of internally porous polymer particles by solvent extraction.

We report the controlled formation of internally porous polyelectrolyte particles with diameters ranging from tens to hundreds of micrometers through selective solvent extraction using microfluidics. Solvent-resistant microdevices, fabricated by frontal photopolymerization, encapsulate binary polymer (P)/solvent (S1) mixtures by a carrier solvent phase (C) to form plugs with well-defined radii and low polydispersity; the suspension is then brought into contact with a selective extraction solvent (S2) that is miscible with C and S1 but not P, leading to the extraction of S1 from the droplets. The ensuing phase inversion yields polymer capsules with a smooth surface but highly porous internal structure. Depending on the liquid extraction time scale, this stage can be carried out in situ, within the chip, or ex situ, in an external S2 bath. Bimodal polymer plugs are achieved using asymmetrically inverted T junctions. For this demonstration, we form sodium poly(styrenesulfonate) (P) particles using water (S1), hexadecane (C), and methyl ethyl ketone (S2). We measure droplet extraction rates as a function of drop size and polymer concentration and propose a simple scaling model to guide particle formation. We find that the extraction time required to form particles from liquid droplets does not depend on the initial polymer concentration but is rather proportional to the initial droplet size. The resulting particle size follows a linear relationship with the initial droplet size for all polymer concentrations, allowing for the precise control of particle size. The internal particle porous structure exhibits a polymer density gradient ranging from a dense surface skin toward an essentially hollow core. Average particle porosities between 10 and 50% are achieved by varying the initial droplet compositions up to 15 wt % polymer. Such particles have potential applications in functional, optical, and coating materials.

Continuous fabrication of monodisperse polylactide microspheres by droplet-to-particle technology using microfluidic emulsification and emulsion–solvent diffusion

Monodisperse polylactide (PLA) microspheres were continuously fabricated by microfluidic emulsification and subsequent dilution in water. The diameter was precisely tuned from 6 to 50 μm by changing the flow rate of the fluids in microfluidics or the PLA concentration in the dispersed phase. The use of amphiphilic oil-soluble poly(ethylene glycol)-b-polylactide (o-PEG–PLA) as a matrix resulted in a highly porous microsphere morphology, and the porosity was controlled by blending PLA. Therefore, monodisperse PLA microspheres with the predetermined surface porosity were continuously produced by just enough reagents and energy.

Microfluidic Fabrication of Monodisperse Polylactide Microcapsules with Tunable Structures through Rapid Precipitation

We describe a versatile and facile route to the continuous production of monodisperse polylactide (PLA) microcapsules with controllable structures. With the combination of microfluidic emulsification, solvent diffusion, and internal phase separation, uniform PLA microcapsules with a perfluorooctyl bromide (PFOB) core were successfully obtained by simply diluting monodisperse ethyl acetate (EA)-in-water emulsion with pure water. Rapid extraction of EA from the droplets into the aqueous phase enabled the solidification of the polymer droplets in a nonequilibrium state during internal phase separation between a concentrated PLA/EA phase and a PFOB phase. Higher-molecular-weight PLA generated structural complexity of the microcapsules, yielding core-shell microcapsules with covered with small PFOB droplets. Removal of the PFOB via freeze drying gave hollow microcapsules with dimpled surfaces. The core-shell ratios and the diameter of these microcapsules could be finely tuned by just adjusting the concentration of PFOB and flow rates on emulsification, respectively. These biocompatible microcapsules with controllable size and structures are potentially applicable in biomedical fields such as drug delivery carriers of many functional molecules.

Augmented EPR effect by photo-triggered tumor vascular treatment improved therapeutic efficacy of liposomal paclitaxel in mice bearing tumors with low permeable vasculature.

The effects of photo-triggered tumor vascular treatment (PVT) on the structural and functional properties of tumor vasculature were assessed in Colon-26 (C26) and B16/BL6 (B16) tumor-bearing mice. Furthermore, anti-tumor efficacy of subsequently injected PEG liposomal paclitaxel (PL-PTX) was also evaluated. As a photosensitizer, a hydrophobic porphyrin derivative was used and formulated in polymeric nanoparticle composed of polyethylene glycol-block-polylactic acid to avoid its non-specific in vivo disposition. In the mice bearing C26 with high permeable vasculature, the prominent anti-tumor activity was confirmed by PVT alone, but the subsequently injected PL-PTX did not show any additive effect. PVT itself initially induced apoptotic cell death of tumor vascular endothelial cells and platelet aggregation, which would have subsequently induced apoptosis of C26 tumor cells surrounding the vasculature. On the other hand, in the mice bearing B16 with low permeable vasculature, PVT enhanced the anti-tumor activity of subsequently injected PL-PTX, which would be attributed to the tumor disposition amount and area of PEG liposomes enhanced by PVT. These results clearly indicated that the treatment would have made it possible to provide more efficient extravasation of PL-PTX, leading to its more potent anti-tumor effect.

Microfluidic-SANS: flow processing of complex fluids.

Understanding and engineering the flow-response of complex and non-Newtonian fluids at a molecular level is a key challenge for their practical utilisation. Here we demonstrate the coupling of microfluidics with small angle neutron scattering (SANS). Microdevices with high neutron transmission (up to 98%), low scattering background (), broad solvent compatibility and high pressure tolerance (≈3–15 bar) are rapidly prototyped via frontal photo polymerisation. Scattering from single microchannels of widths down to 60 μm, with beam footprint of 500 μm diameter, was successfully obtained in the scattering vector range 0.01–0.3 Å−1, corresponding to real space dimensions of . We demonstrate our approach by investigating the molecular re-orientation and alignment underpinning the flow response of two model complex fluids, namely cetyl trimethylammonium chloride/pentanol/D2O and sodium lauryl sulfate/octanol/brine lamellar systems. Finally, we assess the applicability and outlook of microfluidic-SANS for high-throughput and flow processing studies, with emphasis of soft matter.

Efficient anti-tumor effect of photodynamic treatment with polymeric nanoparticles composed of polyethylene glycol and polylactic acid block copolymer encapsulating hydrophobic porphyrin derivative

To develop potent and safer formulation of photosensitizer for cancer photodynamic therapy (PDT), we tried to formulate hydrophobic porphyrin derivative, photoprotoporphyrin IX dimethyl ester (PppIX-DME), into polymeric nanoparticles composed of polyethylene glycol and polylactic acid block copolymer (PN-Por). The mean particle size of PN-Por prepared was around 80nm and the zeta potential was determined to be weakly negative. In vitro phototoxicity study for PN-Por clearly indicated the significant phototoxicity of PN-Por for three types of tumor cells tested (Colon-26 carcinoma (C26), B16BL6 melanoma and Lewis lung cancer cells) in the PppIX-DME concentration-dependent fashion. Furthermore, it was suggested that the release of PppIX-DME from PN-Por would gradually occur to provide the sustained release of PppIX-DME. In vivo pharmacokinetics of PN-Por after intravenous administration was evaluated in C26 tumor-bearing mice, and PN-Por exhibited low affinity to the liver and spleen and was therefore retained in the blood circulation for a long time, leading to the efficient tumor disposition of PN-Por. Furthermore, significant and highly effective anti-tumor effect was confirmed in C26 tumor-bearing mice with the local light irradiation onto C26 tumor tissues after PN-Por injection. These findings indicate the potency of PN-Por for the development of more efficient PDT-based cancer treatments.

Monodisperse polylactide microcapsules with a single aqueous core prepared via spontaneous emulsification and solvent diffusion

A simple approach to preparing monodisperse poly(D,L-lactide) (PDLLA) microcapsules with a single aqueous core is developed. The method is based on automatic water-in-oil-in-water double emulsion formation from oil-in-water single emulsion via spontaneous emulsification which voluntarily disperses part of continuous aqueous phase into the dispersed oil phase dissolving oil-soluble amphiphilic diblock copolymer, poly(D,L-lactide)-b-poly(2-dimethylaminoethyl methacylate)(PDLLA-b-PDMAEMA), followed by coalescence of tiny water droplets within the polymer droplets, coupled with quick precipitation of polymers by diluting the emulsion with water. In this study, we have investigated the effect of PDLLA to PDLLA-b-PDMAEMA ratios and flow rates of each solution during preparing the emulsion on the final morphology and the size of the microcapsules. It was found that the polymer blend ratio played a crucial role in determining internal structure of the microcapsules. The microcapsules size decreased with the increment of the flow rate ratios of the continuous phase to the dispersed phase and eventually reached 10 μm, while maintaining narrow size distribution. In addition, we have demonstrated that the microcapsules can encapsulate both hydrophilic and hydrophobic compounds during the formation.

Polydopamine-Based 3D Colloidal Photonic Materials: Structural Color Balls and Fibers from Melanin-Like Particles with Polydopamine Shell Layers

Nature creates beautiful structural colors, and some of these colors are produced by nanostructural arrays of melanin. Polydopamine (PDA), an artificial black polymer produced by self-oxidative polymerization of dopamine, has attracted extensive attention because of its unique properties. PDA is a melanin-like material, and recent studies have reported that photonic materials based on PDA particles showed structural colors by enhancing color saturation through the absorption of scattered light. Herein, we describe the preparation of three-dimensional (3D) colloidal photonic materials, such as structural color balls and fibers, from biomimetic core-shell particles with melanin-like PDA shell layers. Structural color balls were prepared through the combined use of membrane emulsion and heating. We also demonstrated the use of microfluidic emulsification and solvent diffusion for the fabrication of structural color fibers. The obtained 3D colloidal materials, i.e., balls and fibers, exhibited angle-independent structural colors due to the amorphous assembly of PDA-containing particles. These findings provide new insight for the development of dye-free technology for the coloration of various 3D colloidal architectures.

Microfluidic devices for small-angle neutron scattering

A review of materials and fabrication methods provides recommendations for microdevices for small-angle neutron scattering.

Free-Standing Metal Films Prepared via Electroless Plating at Liquid–Liquid Interfaces

We report a simple preparation of free-standing metal films via electroless plating (ELP) at the liquid-liquid (L-L) interface between an aqueous electroless plating solution and an organic solvent. The use of ELP does not require any external energy in the form of heating and stirring. We find that the affinity of the organic solvent for the palladium nanoparticles (PdNPs) as catalysts and the vertical position of the organic and aqueous phases in the biphasic system are important considerations for synthesizing a robust copper film. Specifically, 1,2-dichloroethane which has an appropriate affinity for PdNPs and a higher density than water was found to be a good candidate for use as the organic phase in this system. However, a poor-quality copper film was obtained in the system with 1-hexanol as the organic phase. We also controlled the microscale surface structure of the copper films by using different concentrations of the injected PdNP dispersion. A high density of PdNPs caused smaller regions of metal growth, which contributed to the formation of smoother metal films. Moreover, under the optimal synthesis condition, we confirmed the electrical conductivity of the obtained copper film to be 1.16 × 10-7 Ωm. We believe that this metal film preparation represents a promising way to produce a range of metal film structures through the use of flexible L-L interfaces as templates.