Mao-Jie Zhang

Hole–Shell Microparticles from Controllably Evolved Double Emulsions

Polymeric core–shell microparticles with hollow interiors have great potential for use as microencapsulation systems for controlled load/release, active protection, and confined microreaction. Core–shell structures with solid shells provide effective encapsulation; however, transport of the encapsulated molecule through the shell is more difficult. Addition of holes to the shell can provide more versatility for the microparticles by facilitating mass transport through the shell based on the size or functional selectivity of the holes; this produces microparticles with porous shells for a myriad of uses including controlled capture of particles, controlled release of active molecules and small particles, and removal of pollutants. Additional uses for these microparticles can be achieved through finer control of the holes in the shell: for example, a single, defined hole can provide a very versatile structure for selectively capturing particles for classification and separation, or capturing cells for confined culture. Even more versatility can be obtained through control of the shape of the hollow core: for example, microparticles with a dimple-shaped core are useful for sizeselective capture of colloidal particles, whereas microparticles with a fishbowl-shaped core are more useful for loading objects such as cells and confining a microreaction. Finally, to make these structures fully functional, it is also desirable to control the interfacial properties of the core to enable precise interactions between encapsulated molecules and the solid shell. Colloidal-scale core–shell microparticles with a single hole in the shell are typically made with particle or emulsiontemplate methods: polymerization-induced buckling of silicon drops, freeze-drying solvent-swollen polymeric particles, self-assembly of phase-separated polymers, diffusion-induced escape of monomers or solvents from the microparticles during fabrication, selective polymerization of phase-separated drops, and other means to control the phase behavior of the templates. These microparticles provide excellent performance when sizes less than a few microns are required. By contrast, larger microparticles provide additional versatility when the size requirements are not constrained to very small particles. These microparticles are typically formed using emulsion drops as templates and have sizes of tens of micrometers or larger. Even finer control over the monodispersity of the microparticles is achieved using microfluidic techniques to produce the emulsion templates. The microparticle structure strongly depends on the configuration between the coredrop and shell-drop in the emulsion templates. With the shelldrop partially wetted on the core-drop, organic-biphasic Janus drops produce truncated-sphere-shaped microparticles. With completely wetted core–shell configurations, aqueousbiphasic drops and water-in-oil-in-water (W/O/W) double emulsions respectively produce bowl-shaped and fishbowlshaped microparticles. Surface modification of these microparticles was recently achieved by introducing functional nanoparticles such as SiO2 nanoparticles into the organic phase of the emulsion templates. Complete versatility of the microparticles requires accurate and independent control of the shape and size of both the single-hole and the hollow-core, as well as the functionality of the core surface; this requires precise control of the configurations and interfacial properties of the emulsion templates. However, techniques to achieve this sort of fine control do not exist. Herein, we report a versatile strategy for fabrication of highly controlled hole–shell microparticles with a hollow core and a single, precisely determined hole, and with simultaneous, independent control of the properties of the core interface. W/O/W double emulsions from capillary microfluidics were used as the initial templates for the microparticles. By controlling the composition of the organic middle phase, we varied the adhesion energy DF between the inner drop and outer phase to control the evolution of the emulsions from initial core-shell to the desired acorn-shaped configuration; this produces versatile emulsion templates for controllable fabrication of monodisperse hole-shell microparticles with advanced shapes. Further adjustment of the hole–shell structures can be achieved by changing the size and [*] Dr. W. Wang, M.-J. Zhang, Dr. R. Xie, Dr. X.-J. Ju, C. Yang, C.-L. Mou, Prof. L.-Y. Chu School of Chemical Engineering, Sichuan University Chengdu, Sichuan, 610065 (China) E-mail: chuly@scu.edu.cn Homepage: http://teacher.scu.edu.cn/ftp_teacher0/cly/

Microfluidic fabrication of monodisperse microcapsules for glucose-response at physiological temperature

Hydrogel-based hollow microcapsules with good monodispersity and repeated glucose-response under physiological temperature and glucose concentration conditions have been fabricated by a simple emulsion-template approach. Double emulsions from microfluidic devices are used as templates to synthesize the monodisperse glucose-responsive microcapsules. In the poly(N-isopropylacrylamide-co-3-aminophenylboronic acid-co-acrylic acid) (P(NIPAM-co-AAPBA-co-AAc)) hydrogel shell of the microcapsules, the thermo-responsive PNIPAM network and the glucose-responsive AAPBA moiety are respectively used for actuation and glucose response, and the AAc moiety is used for adjusting the volume phase transition temperature of the shell. Glucose-responsive microcapsules prepared with 2.4 mol% AAc exhibit reversible and repeated swelling/shrinking response to glucose concentration changes within the physiological blood glucose concentration range (0.4–4.5 g L−1) at 37 °C. Rhodamine B and fluorescein-isothiocyanate-labeled insulin are used as model molecules and model drugs to demonstrate the potential application of the microcapsules for glucose-responsive controlled release. The microcapsules provide a promising and feasible model for developing glucose-responsive sensors and self-regulated delivery systems for diabetes and cancer therapy. Moreover, the microfluidic fabrication approach and research results presented here provide valuable guidance for the design and fabrication of monodisperse glucose-responsive microcapsules.

Thermo-responsive monodisperse core–shell microspheres with PNIPAM core and biocompatible porous ethyl cellulose shell embedded with PNIPAM gates

Monodisperse microspheres composed of thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) core and biocompatible porous ethyl cellulose (EC) shell embedded with PNIPAM gates have been successfully prepared by microfluidic emulsification, solvent evaporation and free radical polymerization. Attributing to the coating of EC shell, the mechanical strength and biocompatibility of the core-shell microsphere are much better than those of the PNIPAM core itself. Fourier transform infrared (FT-IR) spectrometer and scanning electron microscopy (SEM) are employed to examine chemical compositions and microstructures of prepared microparticles. By the cooperative action of EC shell with PNIPAM gates and PNIPAM core, the proposed core-shell microspheres exhibit satisfactory thermo-responsive controlled release behaviors of model drug molecules rhodamine B (Rd B) and VB12. At temperatures above the volume phase transition temperature (VPTT) of PNIPAM, the release rate of solute molecules is much faster than that at temperatures below the VPTT. The controlled factor of the prepared core-shell microspheres for VB12 release reaches to as high as 11.7. The proposed microspheres are highly attractive for controlled drug delivery.

Uniform Microparticles with Controllable Highly Interconnected Hierarchical Porous Structures.

A simple and versatile strategy is developed for one-step fabrication of uniform polymeric microparticles with controllable highly interconnected hierarchical porous structures. Monodisperse water-in-oil-in-water (W/O/W) emulsions, with methyl methacrylate, ethylene glycol dimethacrylate, and glycidyl methacrylate as the monomer-containing oil phase, are generated from microfluidics and used for constructing the microparticles. Due to the partially miscible property of oil/aqueous phases, the monodisperse W/O/W emulsions can deform into desired shapes depending on the packing structure of inner aqueous microdrops, and form aqueous nanodrops in the oil phase. The deformed W/O/W emulsions allow template syntheses of highly interconnected hierarchical porous microparticles with precisely and individually controlled pore size, porosity, functionality, and particle shape. The microparticles elaborately combine the advantages of enhanced mass transfer, large functional surface area, and flexibly tunable functionalities, providing an efficient strategy to physically and chemically achieve enhanced synergetic performances for extensive applications. This is demonstrated by using the microparticles for oil removal for water purification and protein adsorption for bioseparation. The method proposed in this study provides full versatility for fabrication of functional polymeric microparticles with controllable hierarchical porous structures for enhancing and even broadening their applications.

Microfluidic approach for encapsulation via double emulsions

Double emulsions, with inner drops well protected by the outer shells, show great potential as compartmentalized systems to encapsulate multiple components for protecting actives, masking flavor, and targetedly delivering and controllably releasing drugs. Precise control of the encapsulation characteristics of each component is critical to achieve an optimal therapeutic efficacy for pharmaceutical applications. Such controllable encapsulation can be realized by using microfluidic approaches for producing monodisperse double emulsions with versatile and controllable structures as the encapsulation system. The size, number and composition of the emulsion drops can be accurately manipulated for optimizing the encapsulation of each component for pharmaceutical applications. In this review, we highlight the outstanding advantages of controllable microfluidic double emulsions for highly efficient and precisely controllable encapsulation.

Thermo-driven microcrawlers fabricated via a microfluidic approach

A novel thermo-driven microcrawler that can transform thermal stimuli into directional mechanical motion is developed by a simple microfluidic approach together with emulsion-template synthesis. The microcrawler is designed with a thermo-responsive poly(N-isopropylacrylamide) (PNIPAM) hydrogel body and a bell-like structure with an eccentric cavity. The asymmetric shrinking–swelling circulation of the microcrawlers enables a thermo-driven locomotion responding to repeated temperature changes, which provides a novel model with symmetry breaking principle for designing biomimetic soft microrobots. The microfluidic approach offers a novel and promising platform for design and fabrication of biomimetic soft microrobots.

Beta-cyclodextrin-based molecular-recognizable smart microcapsules for controlled release

Novel molecular-recognizable smart microcapsules for controlled release are successfully fabricated in two steps. Firstly, monodispersed poly(N-isopropylacrylamide-co-acrylic acid) microcapsules are prepared via microfluidic emulsion template synthesis; and then, β-cyclodextrin groups are introduced onto the microcapsules by a condensation reaction. The results of Fourier transform infrared spectrometry confirm that β-cyclodextrin moieties are successfully immobilized onto microcapsules by the condensation reaction between carboxylic groups of acrylic acid components on the microcapsules and amino groups of modified β-cyclodextrin monomers. The resultant poly(N-isopropylacrylamide-co-acrylic acid/aminated β-cyclodextrin) (PNA-ECD) microcapsules show a narrow size distribution. The volume phase transition temperature of prepared PNA-ECD microcapsules exhibits a positive shift in the solution containing model guest molecules 2-naphthalenesulfonic acid (NS). Upon recognizing the guest molecules NS, the PNA-ECD microcapsules show an isothermal and reversible molecular-recognizable swelling behavior. Moreover, the release rate of model drug molecules Fluorescein isothiocyanate-labeled dextran loaded in the microcapsules dramatically increases upon recognizing NS molecules. The results provide valuable guidance for the design and fabrication of monodispersed molecular-recognizable microcapsules for controlled release.

Controllable Microfluidic Fabrication of Microstructured Materials from Nonspherical Particles to Helices

This work reports on a facile and flexible strategy based on the deformation of encapsulated droplets in fiber-like polymeric matrices for template synthesis of controllable microstructured materials from nonspherical microparticles to complex 3D helices. Monodisperse droplets generated from microfluidics are encapsulated into crosslinked polymeric networks via an interfacial crosslinking reaction in microchannel to in situ produce the droplet-containing, fiber-like matrices. By stretching and twining the dried fiber-like matrices, the encapsulated droplets can be flexibly engineered into versatile shapes for template synthesis of controllable nonspherical microparticles and helices. Moreover, magnetic helices can be fabricated by simply dispersing magnetic Fe3 O4 nanoparticles in the droplets to achieve rotational and translational motion under a rotated magnetic field. This work provides a simple and versatile strategy for the template synthesis of advanced functional microstructured materials with flexible shapes.