Shin-Hyun Kim

Synthesis and assembly of structured colloidal particles

Synthesis and self-assembly of structured colloids is a nascent field. Recent advances in this area include the development of a variety of practical routes to produce robust photonic band-gap materials, colloidal lithography for nanopatterns, and hierarchically structured porous materials with high surface-to-volume ratios for catalyst supports. To improve their properties, non-conventional suprastructures have been proposed, which could be built up using binary or bimodal mixtures of spherical particles and particles with internal or surface nanostructures. This Feature Article will describe the state-of-the-art in colloidal particles and their assemblies. The paper consists of three main sections categorized by the type of colloid, namely shape-anisotropic particles, chemically patterned particles and internally structured particles. In each section, we will discuss not only synthetic routes to uniform colloids with a range of structures, features and shapes, but also self-organization of these colloids into macrocrystalline structures with varying nanoscopic features and functionalities. Finally, we will outline future perspectives for these colloidal suprastructures.

Multicompartment Polymersomes from Double Emulsions

Polymersomes are vesicles which consist of compartments surrounded by membrane walls that are composed of lamellae of block copolymers; these are important for numerous applications in encapsulation and delivery of active ingredients such as food additives, drugs, fragrances and enzymes [2] . Polymersomes are typically prepared by precipitating block copolymers from their solvents through addition of a poor solvent for the copolymers, or by rehydrating a dried film of the copolymers. The unfavorable interactions between blocks in the copolymer and the poor solvent induce formation of aggregate structures ranging from micelles, wormlike micelles and vesicles. However, the resultant polymersomes are highly polydisperse and have poor encapsulation efficiency. Recently, a new approach has been developed to fabricate monodisperse polymersomes by using double emulsions as templates. Water-in-oil-in-water (W/O/W) double emulsions with a core-shell structure are first prepared in capillary microfluidic devices. Diblock copolymers, dissolved in the oil shell phase, assemble onto the walls of the polymersomes upon removal of the oil by evaporation 7] after adhesion of the diblock copolymeradsorbed interfaces. This approach leads to polymersomes with high size uniformity and excellent encapsulation efficiency; it also enables precise tuning of the polymersome structures. Advances in techniques for fabricating polymersomes have led to controlled spherical polymersomes with a single compartment. However, non-spherical capsules with multiple compartments also have great potential for encapsulation and delivery applications. By storing incompatible actives or functional components separately, polymersomes with multiple compartments can achieve encapsulation of multiple actives in single capsules and reduce the risk of cross contamination. Moreover, multiple reactants can be encapsulated separately to allow reaction upon triggering. By tuning the number of compartments containing each reactant, the stoichiometric ratio of the reactants for each reaction can be manipulated. These multi-compartment polymersomes will create new opportunities to deliver not only multiple functional components, but also multiple reactants for reactions on demand. In addition, with the versatility of synthetic polymer chemistry to tune properties such as polymer length, biocompatibility, functionality and degradation rates, non-spherical polymersomes with multiple compartments can be tailored for specific delivery targets. However, polymersomes that have been reported to date are almost exclusively spherical in shape, and have only one compartment; since most conventional polymersome fabrication processes rely on self-assembly of the block copolymer lamellae, little control over the size and structure of the resultant polymersomes is achieved. With the conventional emulsion-based methods, non-spherical droplets are also not favored because interfacial tension between the two immiscible phases favors spherical droplets, which have the smallest surface area for a given volume. Recent advances in microfluidic technologies enable high degree of control in droplet generation, and ease in tuning the device geometry; this offer a new opportunity to fabricate double emulsion with controlled morphology, which serve as templates for fabricating the nonspherical multi-compartment polymersomes. However, such investigations have not, as yet, been carried out. In this work, we demonstrate the generation of non-spherical polymersomes with multiple compartments. We use glass capillary microfluidics to prepare W/O/W double emulsions with different number of inner aqueous drops. These emulsions are initially stabilized by the amphiphilic diblock copolymers in the oil shells, which consist of a mixture of a volatile good solvent and a less volatile poor solvent for the copolymers. As the good solvent evaporates, the copolymers at the W/O and the O/W interfaces are attracted towards each other to form the membranes. As a result, neighboring inner droplets adhere to one another; this leads to formation of multi-compartment polymersomes, as schematically illustrated in Scheme 1. We also use a modified glass capillary device for generating double emulsions with two distinct inner phases containing different encapsulants; this process leads to the fabrication of non-spherical polymersomes with multiple compartments for separate encapsulation of multiple actives. A glass capillary microfluidic device is used to generate double emulsions with controlled morphology. (See Fig. S1 in Supporting Information) Due to the high degree of control afforded by microfluidics, the number of inner droplets in a W/O/W double emulsion system can be controlled by varying the flow rates of the three phases independently; 12] an example of the process is shown in Fig. 1A. The thickness of the double emulsion shells can be adjusted by changing the flow rates; however, as long as the flow rates are not altered enough to change the number of inner droplets of the double emulsion templates, change in shell thickness does not affect the morphology of the final polymersomes since all solvents in the shells is removed in subsequent steps. To prepare the double emulsion templates, multiple inner droplets are dispersed in drops of a mixture of chloroform and hexanes (36:65 v/v) with 10 mg/mL poly(ethylene-glycol)-b-poly(lactic acid), (PEG(5000)-bPLA(5000)); the drops-in-drops are suspended and stabilized in a poly(vinyl alcohol) (PVA) solution. A homopolymer, PEG, is added [] Prof. D. A. Weitz, Dr. H. C. Shum, Dr. S. H. Kim School of Engineering and Applied Sciences, Department of Physics and Kavli Institute for Bionano Science and Technology, Harvard University, Cambridge, Massachusetts 02138 (USA) Fax: (+1) 617-495-0426 E-mail: weitz@seas.harvard.edu Homepage: http://www.seas.harvard.edu/projects/weitzlab/

Characterizing and tracking single colloidal particles with video holographic microscopy

We use digital holographic microscopy and Mie scattering theory to simultaneously characterize and track individual colloidal particles. Each holographic snapshot provides enough information to measure a colloidal spheres radius and refractive index to within 1%, and simultaneously to measure its three-dimensional position with nanometer in-plane precision and 10 nanometer axial resolution.

Multiple Polymersomes for Programmed Release of Multiple Components

Long-term storage and controlled release of multiple components while avoiding cross-contamination have potentially important applications for pharmaceuticals and cosmetics. Polymersomes are very promising delivery vehicles but cannot be used to encapsulate multiple independent components and release them in a controlled manner. Here, we report a microfluidic approach to produce multiple polymersomes, or polymersomes-in-polymersome by design, enabling encapsulation and programmed release of multiple components. Monodisperse polymersomes are prepared from templates of double-emulsion drops, which in turn are injected as the innermost phase to form the second level of double-emulsion drops, producing double polymersomes. Using the same strategy, higher-order polymersomes are also prepared. In addition, incorporation of hydrophobic homopolymer into the different bilayers of the multiple polymersomes enables controlled and sequential dissociation of the different bilayer membranes in a programmed fashion. The high encapsulation efficiency of this microfluidic approach, as well as its programmability and the biocompatibility of the materials used to form the polymersomes, will provide new opportunities for practical delivery systems of multiple components.

Double-emulsion drops with ultra-thin shells for capsule templates

We introduce an emulsification technique that creates monodisperse double-emulsion drops with a core-shell geometry having an ultra-thin wall as a middle layer. We create a biphasic flow in a microfluidic capillary device by forming a sheath flow consisting of a thin layer of a fluid with high affinity to the capillary wall flowing along the inner wall of the capillary, surrounding the innermost fluid. This creates double-emulsion drops, using a single-step emulsification, having a very thin fluid shell. If the shell is solidified, its thickness can be small as a hundred nanometres or even less. Despite the small thickness of this shell, these structures are nevertheless very stable, giving them great potential for encapsulation. We demonstrate this by creating biodegradable microcapsules of poly(lactic acid) with a shell thickness of a few tens of nanometres, which are potentially useful for encapsulation and delivery of drugs, cosmetics, and nutrients.

Janus microspheres for a highly flexible and impregnable water-repelling interface.

As part of the evolutionary drive to survive and reproduce, some organisms have developed unique surface morphologies. For example, mosquitoes have anti-fog compound eyes that are decorated with small boss arrays, and some desert beetles have patterned wings that enable them to collect water droplets from the atmosphere. Geckos can climb vertical walls and even hang upside down from the ceiling because of spatula arrays on their footpads. 4] Many researchers have sought to mimic such natural surface morphologies to develop useful materials. Artificial superhydrophobic surfaces, which are a representative group of biomimetic materials, have great potential in a wide range of industrial applications owing to their self-cleaning, antifogging, and anti-biofouling properties. Natural waterrepelling objects, such as sundews and lotus leaves, butterfly wings, and duck feathers, have inspired researchers to explore various morphologies, ranging from disordered to highly textured surfaces, in efforts to prepare superhydrophobic surfaces on solid films. However, most studies on superhydrophobic materials performed to date have focused on methods for preparing flat solid surfaces in an inexpensive and simple manner. Herein, we have sought to develop superhydrophobic materials that do not require flat substrates. Taking inspiration from superhydrophobic small objects, such as the scales of butterflies or moths and the legs of water striders, 21] we fabricated and investigated superhydrophobic microspheres with a complex surface morphology in conjunction with hydrophobic surface moieties. The high mobility of the superhydrophobic microspheres gives rise to unique interfacial properties that cannot be achieved using conventional superhydrophobic materials of solid film type. To create the complex surface morphology on the microspheres, we employed emulsion droplets (a Pickering emulsion) decorated with silica particles as a template. Droplets of the photocurable resin ethoxylated trimethylolpropane triacrylate (ETPTA) containing silica particles were generated, and microspheres with silica particle arrays on their surfaces were obtained after photopolymerization of the droplet phase. Through subsequent selective removal of the silica particles by a wet-etching process, we obtained microspheres with surfaces covered with cavity arrays. Further to creating the complex morphology, we incorporated a hydrophobic moiety on the surface to achieve superhydrophobicity, which was achieved simply by applying reactive ion etching (RIE) with sulfur hexafluoride. These procedures are summarized in Figure 1a.

25th Anniversary Article: Double Emulsion Templated Solid Microcapsules: Mechanics And Controlled Release

How droplet microfluidics can be used to fabricate solid-shelled microcapsules having precisely controlled release behavior is described. Glass capillary devices enable the production of monodisperse double emulsion drops, which can then be used as templates for microcapsule formation. The exquisite control afforded by microfluidics can be used to tune the compositions and geometrical characteristics of the microcapsules with exceptional precision. The use of this approach to fabricate microcapsules that only release their contents when exposed to a specific stimulus--such as a change in temperature, exposure to light, a change in the chemical environment, or an external stress--only after a prescribed time delay, and at a prescribed rate is reviewed.

Optofluidic Encapsulation of Crystalline Colloidal Arrays into Spherical Membrane

Double emulsion droplets encapsulating crystalline colloidal arrays (CCAs) with a narrow size distribution were produced using an optofluidic device. The shell phase of the double emulsion was a photocurable resin that was photopolymerized downstream of the fluidic channel within 1 s after drop generation. The present optofluidic synthesis scheme was very effective for fabricating highly monodisperse spherical CCAs that were made structurally stable by in situ photopolymerization of the encapsulating shells. The shell thickness and the number of core emulsion drops could be controlled by varying the flow rates of the three coflowing streams in the dripping regime. The spherical CCAs confined in the shell exhibited distinct diffraction patterns in the visible range, in contrast to conventional film-type CCAs. As a result of their structure, the spherical CCAs exhibited photonic band gaps for normal incident light independent of the position on the spherical surface. This property was induced by heterogeneous nucleation at the smooth wall of the spherical emulsion drop during crystallization into a face-centered cubic (fcc) structure. On the other hand, the solidified shells did not permit the penetration of ionic species, enabling the CCAs to maintain their structure in a continuous aqueous phase of high ionic strength for at least 1 month. In addition, the evaporation of water molecules inside the shell was slowed considerably when the core-shell microparticles were exposed to air: It took approximately 6 h for a suspension encapsulated in a thick shell to evaporate completely, which is approximately 1000 times longer than the evaporation time for water droplets with the same volume. Finally, the spherical CCAs additionally exhibited enhanced stability against external electric fields. The spherical geometry and high dielectric constant of the suspension contributed to reducing the electric field inside the shell, thereby inhibiting the electrophoretic movement of the charged particles.

Droplet Microfluidics for Producing Functional Microparticles

Isotropic microparticles prepared from a suspension that undergoes polymerization have long been used for a variety of applications. Bulk emulsification procedures produce polydisperse emulsion droplets that are transformed into spherical microparticles through chemical or physical consolidation. Recent advances in droplet microfluidics have enabled the production of monodisperse emulsions that yield highly uniform microparticles, albeit only on a drop-by-drop basis. In addition, microfluidic devices have provided a variety of means for particle functionalization through shaping, compartmentalizing, and microstructuring. These functionalized particles have significant potential for practical applications as a new class of colloidal materials. This feature article describes the current state of the art in the microfluidic-based synthesis of monodisperse functional microparticles. The three main sections of this feature article discuss the formation of isotropic microparticles, engineered microparticles, and hybrid microparticles. The complexities of the shape, compartment, and microstructure of these microparticles increase systematically from the isotropic to the hybrid types. Each section discusses the key idea underlying the design of the particles, their functionalities, and their applications. Finally, we outline the current limitations and future perspectives on microfluidic techniques used to produce microparticles.

Controlled Origami Folding of Hydrogel Bilayers with Sustained Reversibility for Robust Microcarriers

Microencapsulation and controlled release have long been studied because of the high demand for practical delivery systems in the pharmaceutics and cosmetics fields. Multiphase emulsion drops have provided efficient templates for microcapsules, and various feasible methods have been developed for controlled release. However, the emulsion-based approach has limitations for the in situ control of membrane permeability. Micro-origami has emerged as one of the most promising alternative approaches for producing tunable microcapsules with the potential to be applied, for example as drug carriers, actuators, microcontainers, and microrobots. Inspired by living organisms in nature such as the ice plant and Venus flytrap, two different micro-origami approaches have been employed to make various microstructures. One approach uses solid patches connected by active hinge materials. Typical examples use various metal– metal, metal–polymer, and polymer–polymer combinations. The patch and hinge system has enabled the capture, release, and gripping of target materials, showing the feasibility of micro-origami structures. However, the microcapsule is limited to polyhedral shapes in this approach, and complete sealing of the gaps between patches requires exquisite control of the folding angles. Moreover, the delicate and complex fabrication processes make practical applications difficult. The second approach uses a bilayer structure composed of two different materials. For example, a metal– polymer bilayer can show bending/unbending when the polymeric active layer suffers significant volume change, but the metal layer remains unchanged. 13] Polymer materials have been employed in both layers to make biocompatible microcapsules. 15] However, complete sealing of the gaps in the bilayer contact regions remains an important, yet unmet, need. In addition, a simple and effective method for the fabrication of practical microcapsules has not yet been developed, and remains highly desirable. This is the main thrust of the present study. Herein, we report the use of biocompatible bilayer structures for the fabrication of tunable microcapsules based on micro-origami. Monodisperse bilayer microstructures were prepared using a facile photolithographic procedure, without employing photomask alignment. In addition, highly flexible hydrogels were selected as both active and passive layers, facilitating tight contact between patches. The bilayer structure therefore enabled in situ encapsulation, through a reversible transformation to microcapsules with a closed compartment. The resultant microcapsules showed negligible leakage of encapsulants and triggered release of the encapsulants could be achieved simply by inducing the unfolding of the hydrogel bilayer. The essential strategy of our approach relies on the anisotropic volume change of a hydrogel bilayer. As shown in Scheme 1a, the active hydrogel layer shows significant volume expansion under external stimuli by swelling, whereas the passive hydrogel layer remains in a constant volume. Therefore, mechanical stress drives the bending of the bilayer, resulting in microcapsules with a closed compartment. The hydrogel swelling behavior is highly reversible, enabling repeated transformations. The hydrogel bilayer structure was prepared on a glass substrate, using photolithography with an amorphous silicon photomask, as shown in Scheme 1b. Here, we propose poly(2hydroxyethyl methacrylate-co-acrylic acid), p(HEMA-coAA), and poly(2-hydroxyethyl methacrylate), p(HEMA), as model components because they are widely used, FDAapproved (FDA = Food and Drug Administration) biocompatible materials. One monomer solution for p(HEMA-coAA) was infiltrated into the space between the photomask and a polydimethylsiloxane (PDMS) microchannel of 25 mm thickness; this monomer solution was then polymerized by UV irradiation through the photomask. The second monomer solution for p(HEMA) was infiltrated into the space between the same photomask and a PDMS microchannel 50 mm in thickness, after washing out the previously unpolymerized solution. Upon the second round of UV irradiation, bilayer structures consisting of a p(HEMA) layer on a p(HEMA-coAA) layer were formed; alignment of the photomask was unnecessary, because each layer was fabricated on the photomask. The resultant bilayer structures were released from the photomask through immersion in a pH 9 buffer solution. To exploit the structural transformation of the bilayer microparticles, we used two different shapes of microparticle: snowman-shaped and flower-shaped. The shape and dimensions of these microparticles were carefully determined to ensure a fully closed compartment in the swollen state; both the snowmanand flower-shaped microparticles were 50 mm [*] T. S. Shim, Dr. S.-H. Kim, Dr. C.-J. Heo, H. C. Jeon, Prof. S.-M. Yang National Creative Research Initiative Center for Integrated Optofluidic Systems and Department of Chemical and Biomolecular Engineering KAIST Daejeon, 305-701 (Korea) E-mail: smyang@kaist.ac.kr Homepage: http://msfl.kaist.ac.kr