Liang-Yin Chu

Designer emulsions using microfluidics

We describe new developments for the controlled fabrication of monodisperse emulsions using microfluidics. We use glass capillary devices to generate single, double, and higher order emulsions with exceptional precision. These emulsions can serve as ideal templates for generating well-defined particles and functional vesicles. Polydimethylsiloxane microfluidic devices are also used to generate picoliter-scale water-in-oil emulsions at rates as high as 10 000 drops per second. These emulsions have great potential as individual microvessels in high-throughput screening applications, where each drop serves to encapsulate single cells, genes, or reactants.

Nano-structured smart hydrogels with rapid response and high elasticity

Smart hydrogels, or stimuli-responsive hydrogels, are three-dimensional networks composed of crosslinked hydrophilic polymer chains that are able to dramatically change their volume and other properties in response to environmental stimuli such as temperature, pH and certain chemicals. Rapid and significant response to environmental stimuli and high elasticity are critical for the versatility of such smart hydrogels. Here we report the synthesis of smart hydrogels which are rapidly responsive, highly swellable and stretchable, by constructing a nano-structured architecture with activated nanogels as nano-crosslinkers. The nano-structured smart hydrogels show very significant and rapid stimuli-responsive characteristics, as well as highly elastic properties to sustain high compressions, resist slicing and withstand high level of deformation, such as bending, twisting and extensive stretching. Because of the concurrent rapid and significant stimuli-response and high elasticity, these nano-structured smart hydrogels may expand the scope of hydrogel applications, and provide enhanced performance in their applications.

Preparation of thermo-responsive core-shell microcapsules with a porous membrane and poly(N-isopropylacrylamide) gates

Abstract A thermo-responsive core-shell microcapsule with a porous membrane and poly(N-isopropylacrylamide) (PNIPAM) gates was prepared using interfacial polymerization to prepare polyamide core-shell microcapsules, and plasma-graft pore-filling polymerization to graft PNIPAM into the pores in the microcapsule wall. The proposed thermo-responsive microcapsule could be a positive thermo-response controlled-release one or a negative thermo-response one by changing the PNIPAM graft yield. When the graft yield is low, the release rate from the microcapsules is higher at temperatures above the lower critical solution temperature (LCST) than that below the LCST, due to the opened/closed pores in the microcapsule membranes controlled by the PNIPAM gates. In contrast, when the graft yield is high, the release rate is lower at temperatures above the LCST than that below the LCST, due to the hydrophilic/hydrophobic phase transition of the PNIPAM gates.

Membranes and membrane processes for chiral resolution

This critical review is devoted to an active field of research on chiral separation, membrane-based enantioseparation technique, which has potential for large-scale production of single-enantiomer compounds. Adsorption-type enantioselective membranes and membrane-assisted resolution systems with non-enantioselective solid membranes have attracted much attention recently. The principles and recent developments of both enantioselective liquid and solid membranes and membrane-assisted processes for chiral resolution will be summarized comprehensively in this review, in which the contents are of interest to a wide range of readers in a variety of fields from analytical, organic and medicinal chemistry, to pharmaceutics and materials, to process engineering for fabricating pharmaceuticals, agrochemicals, fragrances and foods, and so on (148 references).

Controllable microfluidic production of multicomponent multiple emulsions

A hierarchical and scalable microfluidic device constructed from a combination of three building blocks enables highly controlled generation of multicomponent multiple emulsions. The number, ratio and size of droplets, each with distinct contents being independently co-encapsulated in the same level, can be precisely controlled. The building blocks are a drop maker, a connector and a liquid extractor; combinations of these enable the scale-up of the device to create higher-order multicomponent multiple emulsions with exceptionally diverse structures. These multicomponent multiple emulsions offer a versatile and promising platform for precise encapsulation of incompatible actives or chemicals, for synergistic delivery and biochemical and chemical reactions, and for engineering multicompartment materials with controlled internal phases.

Fabrication of monodisperse thermosensitive microgels and gel capsules in microfluidic devices

We use droplet-based microfluidic techniques to produce monodisperse poly(N-isopropylacrylamide) gel particles in the size range of 10–1000 µm. Our techniques offer exquisite control over both outer dimensions and inner morphology of the particles. We demonstrate this control by fabricating conventional microgels, microgels with embedded materials and voids, and gel microcapsules with single- and multi-phase cores. These techniques should be applicable for the synthesis of particles and capsules of a variety of chemical compositions and for the generation of higher order “supraparticles” by directed assembly of colloidal particles in droplets.

Monodisperse core-shell chitosan microcapsules for pH-responsive burst release of hydrophobic drugs

Monodisperse core-shell microcapsules based on crosslinked chitosan membrane with acid-triggered burst release properties are successfully developed. The microcapsules are fabricated from double emulsion precursors that are prepared with a microfluidic approach. In neutral medium (pH 7.1), the microcapsules maintain a good spherical shape and structural integrity; while, in acidic medium (pH 1.5 ∼ 4.7), the microcapsules decompose rapidly and release the encapsulated contents completely in short periods varying from 39 s to 22 min. The acid-triggered burst release pattern from the proposed chitosan microcapsules may make them capable for stomach-specific drug delivery systems with quick and complete release characteristics in a controllable pH-responsive manner.

Smart thermo-triggered squirting capsules for nanoparticle delivery

A squirting capsule is designed to deliver nanoparticles inspired by the squirting cucumber ejecting its seeds. The capsule has a thermo-sensitive hydrogel shell, and encapsulates nanoparticles by emulsifying the nanoparticle aqueous suspension in the water-in-oil emulsion core. The squirting capsule can completely squirt out the encapsulated nanoparticles with a high momentum, just like a nanoparticle bomb, by the dramatic shrinkage and sudden rupture of the capsule membrane upon heating.

Study of SPG membrane emulsification processes for the preparation of monodisperse core-shell microcapsules

Experimental investigations on the Shirasu-porous-glass (SPG)-membrane emulsification processes for preparing monodisperse core-shell microcapsules with porous membranes were carried out systematically. The results showed that, to get monodisperse oil-in-water (O/W) emulsions by SPG membrane emulsification, it was more important to choose an anionic surfactant than to consider hydrophile-lipophile balance (HLB) matching. Increasing the viscosity of either the disperse phase or the continuous phase or decreasing the solubility of the disperse phase in the continuous phase could improve both the monodispersity and the stability of emulsions. With increasing monomer concentration inside the disperse phase, the monodispersity of emulsions became slightly worse and the mean diameter of emulsions gradually became smaller. Monodisperse monomer-containing emulsions were obtained when the SPG membrane pore size was larger than 1.0 micro m, and from these emulsions satisfactory monodisperse core-shell microcapsules with a porous membrane were prepared. On the other hand, when the SPG membrane pore size was smaller than 1.0 mciro m, no monodisperse emulsions were obtained because of the formation and chokage of solid monomer crystals in the pores or at the end of the pores of the SPG membrane. This was due to the remarkable solvation and diffusion of the solvent in water. With increasing the emulsification time the average emulsion diameter generally decreased, and the monodispersity of the emulsions gradually became worse.

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/