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www.rsc.org/csr CRITICAL REVIEW

Anisotropic particles with patchy, multicompartment and Janus architectures: preparation and application

Jianzhong Du*a and Rachel K. O’Reilly*b

Received 17th December 2010 DOI: 10.1039/c0cs00216j

Anisotropic particles, such as patchy, multicompartment and , have attracted significant attention in recent years due to their novel morphologies and diverse potential applications. The non-centrosymmetric features of these particles make them a unique class of nano- or micro-colloidal materials. Patchy particles usually have different compositional patches in the corona, whereas multicompartment particles have a multi-phasic anisotropic architecture in the core domain. In contrast, Janus particles, named after the double-faced Roman god, have a strictlybiphasicgeometryofdistinct compositions and properties in the core and/or corona. The term Janus particles, multicompartment particles and patchy particles frequently appears in the literature, however, they are sometimes misused due to their structural similarity. Therefore, in this critical review we classify the key features of these different anisotropic colloidal particles and compare structural properties as well as discuss their preparation and application. This review brings together and highlights the significant advances in the last 2 to 3 years in the fabrication and application of these novel patchy, multicompartment and Janus particles (98 references).

a School of Materials Science and Engineering, Tongji University, 1. Introduction 4800 Caoan Road, Shanghai, 201804, China. 1.1 Patchy, multicompartment and Janus particles E-mail: [email protected]; Fax: +86 (021) 6958 4723; Tel: +86 (021) 6958 0239 The past few years have seen an almost unbelievable revolution Downloaded by Tsinghua University on 20 April 2011 b Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK. E-mail: [email protected]; in materials science, especially in the preparation and design of

Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J Fax: +44 (0)247 652 4112; Tel: +44 (0)247 652 3236 nano- or micro-sized anisotropic particles such as patchy,

Dr Jianzhong Du is an ‘Eastern Dr Rachel O’Reilly is an Scholar’ professor at Tongji EPSRC career acceleration University in Shanghai. He fellow in the Chemistry received his PhD in 2004 from Department at the University Institute of Chemistry, Chinese of Warwick. She graduated Academy of Sciences (CAS), from the University of under the supervision of Prof. Cambridge in 1999 and went Yongming Chen. His PhD on to complete her PhD at thesis was awarded ‘The Top Imperial College London in 50 PhD Dissertations in CAS’ 2003. She then moved to the in 2005 and ‘The Nominated US under the joint direction of National Top 100 PhD Professors Craig J. Hawker Dissertations in China’ in and Karen L. Wooley. In 2006. He was also an Alexander 2004 she was awarded a Jianzhong Du von Humboldt Fellow in 2006. Rachel K. O’Reilly research fellowship from the He immediately moved to Royal Commission for the Prof. Steve Armes group at the University of Sheffield as a Exhibition for 1851 and in 2005 she took up a Royal Society postdoctoral fellow in 2004. Then in 2008 he moved to Rachel Dorothy Hodgkin Fellowship at the University of Cambridge. In O’Reilly’s group at Cambridge. In 2009 he was appointed a 2009 she moved to her current position. Her research focuses on special appointment professorship at Shanghai institutions of bridging the interface between creative synthetic, polymer and higher learning based at Tongji University. His research interests catalysis chemistry, to allow for the development of materials include controlled radical polymerization and stimuli-responsive that are of significant importance in medical, materials and and functional polymeric materials such as polymer vesicles and nanoscience applications. , and their biomedical applications.

2402 Chem. Soc. Rev., 2011, 40, 2402–2416 This journal is c The Royal Society of Chemistry 2011 转载 中国科技论文在线 http://www.paper.edu.cnView Online

developed for the fabrication of Janus particles such as surface coating by deposition of evaporated metal particles,11,16–19 pickering emulsion methods,20,21 layer-by-layer self-assembly,22,23 biphasic electrified jetting,24 photo-polymerization in a micro- fluidic channel,25–27 olefin metathesis,28 polymer self-assembly,29–31 protonation/deprotonation cycling,32 surface-initiated free- radical polymerization,33 and in situ ‘‘click chemistry’’.34 However, achieving perfect biphasic Janus character is still problematic and challenging for materials scientists. Thus, recent research focus has gradually shifted towards the applica- Fig. 1 Scanning electron microscopy images of pollen grains. The tions of Janus particles and the fabrication of asymmetric center in the left image is a pumpkin pollen grain which has a patchy colloidal structures without perfect biphasic architectures, such 1 structure. The right image is an Indian mallow pollen grain. as multicompartment particles and patchy particles.35

multicompartment and Janus particles. These anisotropic 1.2 Definition of patchy, multicompartment and Janus particles have attracted much attention, although real world particles applications of these materials appear to still be far from realiza- Patchy particles are defined as particles with precisely con- tion. In nature, there are a number of structural analogues to trolled patches of varying surface and interaction properties.36 the recently developed anisotropic particles in modern materials As schematically described in Fig. 2, Janus particles (Fig. 2A) science. For example, in 2009, Oeggerli presented scanning have equal phase-separated domains which can be located electron microscopy (SEM) images of pollen grains, which either in the core or in the corona (if present), whereas multi- have beautiful anisotropic patches, as shown in Fig. 1.1 It is compartment particles (Fig. 2B) can be generally defined as believed that these patches not only help the pollen cling to colloidal structures which are composed of multiple phase- bird feathers, but also may cause hay fever.1 A further example separated domains in the core. Particles with patches on the of a natural anisotropic structure is heme which is classified surface are called patchy particles (Fig. 2C), and have potential as Janus-like.2 Janus-like structures can also form in nature applications in electronics37 and targeted drug delivery.38 through self-assembly processes such as the assembly of Furthermore Janus or multicompartment particles with patches hydrophobin proteins through the characteristic eight cysteine on the surface can be called ‘‘patchy Janus particles’’ (Fig. 2D) residues in their primary sequence.3 Due to this pattern, or ‘‘patchy-multicompartment particles’’ (Fig. 2E), respectively. hydrophobins have a non-centrosymmetric arrangement of Through the self-assembly of amphiphiles to a number of hydrophilic and hydrophobic patches, which undergoes self- interesting nanostructure morphologies can be accessed including assembly in aqueous solution to form Janus-like structures, spherical micelles, vesicles, cylinders (amongst many others) which are important in several different tasks in the growth Downloaded by Tsinghua University on 20 April 2011 all of which have a phase separated core–corona structure.39–41 and development of filamentous fungi.4 For example, they can However, in recent years there has been great interest in the Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J form coatings on spores, hyphae, and fruiting bodies and can synthesis of more complex morphologies such as toroids, have roles in the attachment of fungi to different surfaces.5 discs and also nanostructures with more complex domains They also play a role in breaking the surface tension of water such as multicomponent structures, Janus and patchy particles. to enable the formation of fungal aerial structures.6 This has become a rapidly advancing field and a number of Furthermore, in the biological cell, compartmentalization excellent reviews covering each of these particles have been plays an important role and enables an enormous number of published in recent years. Most notably in 2005, Lutz and reactions and transport processes to be executed in parallel.7 Laschewsky reviewed the area of multicompartment polymer Given the importance of compartmentalization in nature and micelles.42 In 2008, Walther and Mueller highlighted the recent the recent development of synthetic analogues there is great interest in exploring multicompartment particles for the transport of several compounds for a wide variety of processes such as controlled/targeted drug/gene delivery, cosmetics, imaging techno- logy, selective entrapment and release of dyes, pesticides, perfume, etc.8 Indeed it has been proposed that the different subdomains in a multicompartment particle’s core may cosolubilize and transport several different and immiscible molecules selectively, preventing any undesired interactions before delivery. Generally, Janus particles have a strict 50 : 50 distinct coverage in shape, composition, chemistry, polarity, functionality, electrical and other properties, making them suitable for applications in switchable display devices,9 interface stabilizers,10 self-motile micro-particles,11 controllable pores in lipid membranes12 and smart nanomaterials such as biological sensors, nanomotors, Fig. 2 Schematic representation of anisotropic particles: (A) Janus 13 14 antireflection coatings, optical sensors, and anisotropic building particles; (B) multi-compartment particles; (C) patchy particles; blocks for complex structures.15 Many techniques have been (D) patchy Janus particles; (E) patchy multi-compartment particles.

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advances in the preparation of Janus particles, focusing on to the nanostructure. Particles which demonstrate incomplete preparation pathways and higher order self-assembly of Janus segregation are more accurately classified as patchy particles. particles.43 More recently in 2009, Wurm and Kilbinger reviewed the Janus particles with a focus on the polymer 2. Fabrication of anisotropic particles self-assembly.44 In 2010, Jiang et al. highlighted recent progress in Janus particles with a focus on the experiment and theory of The preparation of highly ordered, defect-free structures of the synthesis and self-assembly of Janus particles and Wang nano- or micro-size is a key target in modern materials science et al. reported the self-assembly of colloidal anisotropic and nanotechnology. Most commonly, bottom-up fabrication particles.45,46 In the same year, Pawar and Kretzschmar approaches such as self-assembly techniques are utilized to reviewed the preparation, self-assembly and application of prepare such materials. However, these methods require building patchy particles.47 However, to the best of our knowledge, blocks of precisely defined size and shape to ensure specific no review articles have been published focusing on the and predictable interactions and assembly products. In this comparison between patchy, multi-compartment and Janus section we aim to summarize the fabrication techniques used particles. There is usually some overlap in the definition of to prepare different classes of anisotropic particles. these particles, for example anisotropic polymer micelles could 2.1 Patchy particles be classified according to their morphology in the core and/or coronas and this is highlighted in Fig. 3. Hence, There are many methods for the fabrication of patchy particles. anisotropic micelles could be classified as: (1) Janus micelles; In 2010, Pawar and Kretzschmar reviewed the recent advances in (2 and 3) Janus–Janus micelles; (4) Janus multi-compartment this area and hence readers are referred to this excellent review.35 micelles; (5) patchy Janus micelles; (6) multi-compartment In this review the authors highlighted six main techniques, as micelles; (7) patchy multi-compartment micelles; (8) Patchy summarized in Fig. 4, for fabricating patchy particles.47 micelles. Another recently developed method for the preparation of To clarify the difference between terms generally, a multi- patchy particles is through block copolymer self-assembly. In compartment micelle is defined as a 2004, Du and Chen reported a patchy multicompartment composed of a hydrophilic shell and a phase-separated hydro- organic–inorganic hybrid large compound vesicle by simple phobic core. Importantly, Lutz and Laschewsky48 proposed self-assembly of a reactive amphiphilic block copolymer, poly- that for a multicompartment micelle, a key feature is that the (ethylene oxide)-block-poly[3-(trimethoxysilyl)propyl methacrylate] various sub-domains of the micellar core must be substantially (PEO-b-PTMSPMA) in a DMF/water solution, followed by a different to behave as separate compartments. Furthermore in stabilization step using a sol–gel process catalyzed by triethyl- the literature there is some confusion as to the distinction amine. Owing to the crosslinking reaction in the preformed between a patchy and a Janus particle and given the definition polymer vesicle, the particles were very stable and shape- of Janus particles outlined above a key feature is that there is persistent and the patchy nature of the surface could be readily visualized by TEM and SEM analyses, as shown in Fig. 5.49

Downloaded by Tsinghua University on 20 April 2011 complete segregation of the domains to form 2 opposing faces The multicompartment nature of the core can be seen in the

Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J TEM image (A) and further confirmed by a TEM study of the microtomed sample where separate small cavities were clearly visible in the core. Using a different approach to the kinetically controlled assembly of micelles,50 Mueller and coworkers in 2009

Fig. 3 Schematic representation of anisotropic polymer micelles: Fig. 4 Techniques for the fabrication of patchy particles. (a) templating; (1) Janus micelles; (2–3) Janus–Janus micelles; (4) Janus multi- (b) colloidal assembly; (c) particle lithography; (d) glancing-angle compartment micelles; (5) patchy Janus micelles; (6) multi-compartment deposition; (e) nanosphere lithography; (f) electrospray using a biphase micelles; (7) patchy multi-compartment micelles; (8) patchy micelles. nozzle.35

2404 Chem. Soc. Rev., 2011, 40, 2402–2416 This journal is c The Royal Society of Chemistry 2011 中国科技论文在线 http://www.paper.edu.cnView Online

solvent for the PtBMA block induces aggregation into branched, undulated cylinders with core domains with multi- compartment character. More recently, Du and Armes prepared patchy multi- compartment micelles by direct dissolution of a triblock copolymer in water at pH 7.52 The primary amine-based triblock copolymer, poly(ethylene oxide)-b-poly(e-caprolactone)- b-poly(2-aminoethyl methacrylate), PEO-PCL-PAMA, was dissolved in water to form patchy micelles with PCL chains forming the micellar cores and the PEO and PAMA chains forming phase-segregated patchy or hemispherical coronas. By selectively silicifying the PCL cores with tetramethyl orthosilicate (TMOS), the phase-separated character of these Fig. 5 TEM image (A) and the corresponding SEM image (B) of a micelles was revealed by TEM analysis. However, at pH 4.8, patchy large compound vesicle by self-assembly of block copolymers.49 the triblock copolymer was observed to form a mixture of Janus micelles, patchy micelles, patchy Janus micelles and reported patchy cylindrical micelles with compartmentalized patchy multi-compartment micelles. The authors found that coronas through the self-assembly of a linear block terpolymer, it was very difficult to make exclusively Janus micelles but poly(4-tert-butoxystyrene)-b-polybutadiene-b-poly(tert-butyl relatively easy to make exclusive patchy micelles using this methacrylate) (PtBSt-PB-PtBMA), where the central PB block block copolymer self-assembly approach. was modified with a fluorinated side group by the thiolene Based on coarse grain molecular dynamic simulations, reaction of the vinyl groups with 1-mercapto-1H,1H,2H,2H- Srinivas and Pitera proposed a simple approach to obtain perfluorooctane (Fig. 6).51 In organic fluorophobic media, the soft patchy .53 They used two different diblock fluorinated block forms the micellar core and maintains copolymers with a common hydrophobic block and dissimilar sufficient dynamics for reorientation of the coronal block hydrophilic blocks. Upon mixing the two diblock copolymers during annealing. Hence, in dioxane, a common solvent for together, patchy spherical micelles were formed in water. The both outer blocks, micelles with patchy coronas are obtained patchy sphere geometry was immobilized by subsequent cross- due to this reorganization. Subsequent transfer into a selective linking. The morphologies were observed to change from ‘‘patchy spheres’’ to ‘‘patchy cylinders’’, and the number and size of the patches changed upon altering the hydrophilic versus hydrophobic ratio. Furthermore, by choosing different solvents, the patches can be selectively placed either on the

Downloaded by Tsinghua University on 20 April 2011 outer surface or inside the core of the micelle. Molecular simulations were also performed by Zhang and

Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J Glotzer to explore the self-assembly of particles with discrete, attractive interactive sites or patches to form higher order patchy materials.36 Morphologies such as chains, sheets, rings, icosahedra, square pyramids, tetrahedra, twisted and staircase structures were obtained through suitable design of the surface pattern of the patches. Their simulations predicted that the spontaneous formation of two-dimensional sheets and icosahedra occurs via a first-order transition while the forma- tion of chains occurred via a continuous disorder-to-order transition as observed in equilibrium polymerizations. Their results showed how precise arrangements of patches combined with patch ‘‘recognition’’ or selectivity may be used to control the relative position of particles within a higher order structure and thus influence the overall structure of particle assemblies. In this context, patchy particles may represent a new class of precisely tunable building block for the fabrication of well- defined hierarchical structures.

2.2 Multicompartment particles In 1999, Stahler et al. reported a series of polymerizable hydrocarbon and fluorocarbon cationic acrylamido surfactants, which were used as comonomers for the synthesis of multi- Fig. 6 Preparation of undulated multi-compartment cylinders by compartment polymeric micelles, as confirmed by fluorescence directed stacking polymer micelles with a compartmentalized corona.51 spectroscopy.54 They found that the nature of the amido

This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 2402–2416 2405 中国科技论文在线 http://www.paper.edu.cnView Online

group of the surfactant, either N-monosubstituted (CONRH)

or disubstituted (CONRC2H5) was one of the key parameters governing the solution behavior of the surfactant. Radical polymerization of the acrylamide functionality in aqueous solution fixed the multicomponent micelle core into well segregated hydrocarbon and fluorocarbon segments.54 However, it was only in 2004 that the direct evidence of self- assembled multicompartment polymer micelles by cryo-TEM was first reported by Lodge, Hillmyer and coworkers55,56 and then in 2005 was highlighted by Lutz and Laschewsky.48 Since 2006, Lodge and Hillmyer have reported numerous elegant examples of multicompartment polymer micelles using self- assembly techniques.57–60 These systems are mainly based on the self-assembly of miktoarm ABC star polymers. One key feature of these star polymers is that there is a strong effective repulsion between each pair of blocks, such that A, B, and C segregate into distinct nanodomains. A typical star polymer used in their work consists of a water-soluble poly(ethylene oxide) block, a saturated hydrocarbon polyethylethylene block, Fig. 7 Chemical structure of triblock copolymer (EHA)120-(OEGA)50- and a hydrophobic, lipophobic poly(perfluoropropylene oxide) (FDA)40 and cryo-TEM image of its 0.5 wt% aqueous dispersion. The block.55 These miktoarm star polymers afford elegant multi- micelles appear as high-contrast spherical particles surrounded by a fringed corona (indicated by arrows).70 component structures; however, their synthesis is somewhat difficult compared with the preparation of linear triblock of the PISC block) to form regular patchy micelles, with a PS copolymers.61 Hence, recently the self-assembly of linear core and a mixed shell formed by PEO and PISC blocks.67 triblock copolymers has been investigated and has shown In 2009, Mueller and coworkers reported a dynamic multi- great potential in the preparation of multi-compartment compartment micelle in aqueous media based on the self-assembly micelles.62–68 For example, in 2005 Laschewsky and coworkers of the amphiphilic triblock copolymer, polybutadiene-b-poly-

prepared multicompartment micelles with a structure that was (2-vinyl pyridine)-b-poly(methacrylic acid) (PB800-b-P2VP190- compared to a doughnut with a raspberry filling based on the b-PMAA550) and its quaternized analogue PB-b-poly(N-methyl- 71 self-assembly of a poly(4-methyl-4-(4-vinylbenzyl)morpholin- 2-vinylpyridinium)-b-PMAA (PB800-b-P2VPq190-b-PMAA550). 4-ium chloride)-b-polystyrene-b-poly(pentafluorophenyl 4-vinyl- At high pH, the PB800-b-P2VP190-b-PMAA550 triblock copolymer benzyl ether) ABC triblock copolymer in water. This triblock forms core–shell–corona micelles (B200 nm) with a continuous P2VP shell. However, at pH 4, a patchy, collapsed shell was

Downloaded by Tsinghua University on 20 April 2011 is composed of three incompatible segments namely a hydrophilic block with morpholinium units, a hydrophobic found due to partial intramicellar interpolyelectrolyte complex 69 Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J hydrocarbon block, and a hydrophobic fluorocarbon-rich block. formation between P2VP and PMAA. This was further

Then in 2009, Laschewsky and coworkers further reported an confirmed for the quaternized analogue, PB800-b-P2VPq190- ABC triblock copolymer (EHA)120-(OEGA)50-(FDA)40 con- b-PMAA550 triblock copolymer, which forms aggregates of sisting of three mutually incompatible segments, namely a similar size, also exhibiting a non-continuous, patchy shell. lipophilic, a hydrophilic and a fluorophilic block (Fig. 7). This The difference between these two systems is that the partial copolymer forms multicompartment micelles in aqueous intramicellar interpolyelectrolyte complexes of the positively solution, with a size which is large enough to employ cryogenic charged P2VPq and the partially negatively charged PMAA electron tomography (cryo-ET) as a technique to reveal the are present over the whole investigated pH range (4–10). These compartmentalized micellar core.70 micelles are dynamic and their corona length and the aggrega- To date, multicompartment micelles/particles are mainly tion are able to respond to changes in pH or salinity. based on hydrocarbon–fluorocarbon hybrid systems due to Usually multicompartment micelles are made in aqueous the unique properties of fluorocarbons such as extraordinary solution however in 2009, Mueller and coworkers reported the thermal, chemical and biological inertness, low surface tension, formation of multicompartment micelles in acetone, as shown high hydrophobicity, fluidity, rigidity, and high gas dissolving in Fig. 8.64 The polymers used for self-assembly were ABC capacities caused by their strong intramolecular and weak triblock copolymers, polybutadiene-b-poly(2-vinyl pyridine)- intermolecular interactions. However, in 2009, Walther and b-poly(tert-butyl methacrylate) (BVT), which were synthesized coworkers synthesized a new non-fluorinated amphiphilic via living sequential anionic polymerization in THF. Cross- block terpolymer, poly((sulfamate-carboxylate)isoprene)-b-poly- linking of the polybutadiene compartment was carried out

styrene-b-poly(ethylene oxide), PISC230-PS52-PEO151, which either via ‘‘cold vulcanization’’ or photopolymerization after is capable of forming a multicomponent micelle. In acidic the addition of a multifunctional acrylate. In both cases, the solutions, the terpolymers self-assemble into kinetically multicompartmental character of the micellar core was fully trapped multicompartment micelles, with the core consisting preserved, and the micelles could be transformed into multi- of discrete PS and PISC domains and the PEO block forming component core-stabilized completely organic nanoparticles. the shell. In basic pH, the multicompartment micelles undergo In 2007, Kim and Taton reported a novel method for an irreversible transition (due to the change in hydrophobicity preparing water-soluble organic/inorganic multifunctional

2406 Chem. Soc. Rev., 2011, 40, 2402–2416 This journal is c The Royal Society of Chemistry 2011 中国科技论文在线 http://www.paper.edu.cnView Online

Fig. 8 Multicompartment micelles by self-assembly of triblock copolymers in organic media.64

Fig. 10 Overview of approaches for the preparation of Janus particles. Fig. 9 Preparation of multifunctional hybrid nanostructures by (a) Two-dimensional technique involving shading of one particle side co-encapsulation of multiple types of nanoparticles (A and B) within after immobilization. (b) Ellipsoidal complex core coacervate micelle a cross-linkable block copolymer micelle.72 with an interpolyelectrolyte complex core. (c) Pickering emulsion route. (d) Janus particles with two inorganic compartments, snowman-, acorn-, dumbbell-like nanoparticles (top to bottom). (e) Microfluidic photo- and multicompartment nanoparticles by the co-encapsulation polymerization system. (f) Electrospinning using a bi-phasic nozzle.43 of different magnetic (g-Fe2O3 and Fe3O4), semiconductor (CdSe/ZnS), and metal (Au) nanoparticles in shell cross-linked In 2009, Wurm and Kilbinger published a mini-review focusing block copolymer micelles.72 As shown in Fig. 9, these hybrid on Janus particles through the self-assembly of polymers in nanostructures could be spontaneously assembled from solution solution and in bulk.44 Dendukuri and Doyle summarized the by simultaneous desolvation of the nanoparticles and amphiphilic preparation of Janus microparticles by microfluidics in 2009.25 block copolymer components. Given the ease of synthesis and Instead this review will focus on the rapid growth in interest in robust nature of this method, this approach has been proposed to Janus particles in the last two years. be a general protocol for the preparation of multifunctional Recently, a number of new methods have been developed nanostructures without the need for explicit multimaterial

Downloaded by Tsinghua University on 20 April 2011 for the preparation of Janus particles. For example, in 2010, synthesis or surface functionalization of the nanoparticles. Okubo and coworkers reported a versatile two-step approach Other non-spherical multicompartment micelles have been Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J for the preparation of micrometer-sized, monodisperse, prepared using self-assembly techniques. For example, in 2007 ‘‘mushroom-like’’ Janus polymer particles in aqueous dispersed Cui et al. reported the synthesis of a kinetically controlled systems.73 As shown in Fig. 11, the first step is the preparation multi-compartment polymer cylinder.50 In this work the authors of spherical poly(methyl methacrylate) (PMMA)/poly(styrene- dissolved a poly(acrylic acid)-b-poly(methyl acrylate)-b-poly- 2-(2-bromoisobutyryloxy)ethyl methacrylate) (P(S-BIEM)) styrene (PAA-b-PMA-b-PS) triblock copolymer in tetrahydro- Janus particles based on the internal phase separation induced furan (THF), then added water to trigger the self-assembly. by slow solvent evaporation of toluene from the homogeneous After adding 2,20-(ethylenedioxy)diethylamine (EDDA), multi- PMMA/P(S-BIEM)/toluene droplet dispersed in the aqueous compartment cylinders were formed due to the complexation medium. The second step is the surface-initiated atom transfer of PAA with the diamine, EDDA. This technique relies on radical polymerization (ATRP) of 2-(dimethylamino)ethyl divalent organic counter ions and solvent mixtures to drive methacrylate (DM) using the Janus particles from the ATRP the organization of the block copolymers towards a specific initiator groups located at one side of the surface. As a con- pathway to form complex one-dimensional structures. sequence, mushroom-like PMMA/P(S-BIEM)-graft-poly(DM) Janus particles were prepared, which had pH-responsive 2.3 Janus particles properties. As mentioned in the introduction, many techniques have been developed for the fabrication of Janus particles. However, as the focus of this article is to review the recent progress in the preparation of patchy, multi-compartment and Janus particles, we are not going to detail all the methods mentioned above. Instead, details of these methods can be found in several recent excellent reviews covering the preparation of Janus particles. For example, in 2008, Walther and Mueller summarized several Fig. 11 Schematic representation for the preparation of ‘‘mushroom- pathways of Janus particle preparation, including block like’’ PMMA/P(S-BIEM)-g-PDM Janus particles by site selective copolymer self-assembly and the methods shown in Fig. 10.43 surface-initiated ATRP of DM in the aqueous medium.73

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Furthermore, the above mushroom-like Janus particles were (o100 nm) with inorganic materials presents a great challenge applied as particulate surfactants.74 The PDM functionality to materials scientists.75 Silica is a widely used material for grafted on one side of the Janus particle reversibly exhibited a building concentric core–shell structures with cores such as volume phase transition in response to pH and temperature in metallic or magnetic nanoparticles or quantum dots, however an aqueous medium; that is to say, the surface properties it is challenging to fabricate Janus nanoparticles with partial of the Janus particles comprising both PDM and PMMA silica shells.75 This is due to the amorphous nature of silica, reversibly changed between amphiphilic and hydrophobic hence it is often difficult to fine-tune the surface tension or based on the responsive nature of the PDM segment. As a lattice mismatch between silica and these core materials. In result, 1-octanol-in-water emulsion droplets stabilized by the 2010, Chen and coworkers developed a new and elegant amphiphilic Janus particles coalesced at alkaline pH and also approach to control silica deposition spatially on the surface at 60 1C around neutral pH, due to desorption of the hydro- of Au nanospheres (Fig. 12). Selective deposition of the phobized Janus particles from the interface to the oil phase. polymers was driven by the partitioned surface functionalities This work highlights the potential for the design of responsive on the Au nanospheres through competitive ligand coordina- and functional anisotropic materials, for advanced applica- tion (Fig. 13). The formation of partial silica shells around tions, using well-established chemistries. the Au reduced the symmetry of the Au nanospheres while In 2009, Zhao and coworkers reported a one-step approach keeping the cores available for further modification. Using this for the synthesis of amphiphilic Janus silica particles by approach, Ag nanospheres or Ag nanorods could be grown on

surface-initiated free radical polymerization at the liquid– the exposed Au surface, generating ternary Ag–Au–SiO2 liquid interface.33 However, these Janus particles are not bimetallic structures and further reducing the symmetry of strictly biphasic particles based on the presented TEM images the nanostructures.75 but instead are perhaps better described as patchy particles. In 2010, Patnaik et al. reported the one-pot hemimicellar Later the same year, this group reported the synthesis of Janus synthesis of oriented, amphiphilic, and fluorescent Janus gold silica particles decorated with biotin molecules and poly- clusters, establishing the Janus character in terms of ligand (ethylene oxide) (PEO) chains on two hemispheres based on asymmetry and distribution.76 The method was based on the a two-step click reaction.34 As shown in Fig. 12, polystyrene efficient Langmuir strategy, where the in situ two-dimensional (PS) particles coated with azide modified silica particles were (2D) reduction of Au3+ in a sprayed micellar electrostatic + used as templates. On the PS surface one hemisphere of a silica complex, TOA –AuCl4 , was accomplished by subphase particle was exposed to the solvent and the other one was tryptophan that acted as the hydrophilic protecting ligand embedded in the PS domain. The alkynated biotin molecules on one hemisphere of the spherical gold cluster. In contrast to were grafted onto the exposed side of the silica particle using previously reported micelle-assisted Janus cluster formation, Cu(I) catalyzed click reactions. After removal of PS, the their cluster growth occurred inside the surface pressure driven embedded part of the silica particle was released, and alkynated hemi-micelles, which rapidly formed 2D cluster arrays without

Downloaded by Tsinghua University on 20 April 2011 PEO chains were grafted to the particle through a further any interfacial reorientation. The Janus structure of the Cu(I) click reaction. As a result of this biofunctionalization the

Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J resultant Janus particles showed a strong and selective inter- action with avidin. It is proposed that these Janus particles could find potential applications in fields such as targeted drug delivery, as sensors or in biodetection. In the future this templated fabrication approach could be readily extended to further biomolecules or materials functionality and also extended to different functional polymer chains. The majority of Janus particles reported are micrometre in size, as the fabrication of small Janus nanoparticles

Fig. 13 (a) Schematic illustration of the ligand competition that led

to the formation of Janus Au–SiO2 particles; (b) TEM of Janus Au–SiO2; inset, a digital photo showing the product of a scaled-up Fig. 12 Scheme for the preparation of bioconjugated Janus particles.34 synthesis (72 mL).75

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resultant particles was validated using angle dependent polarized Fourier Transform Infrared Reflection-Absorption Spectroscopy (FT-IRRAS), where orientation dependent vibrational changes in the adsorbed ligand functionalities were detected. Electrochemical impedance measurements of the transferred Janus layers onto hydrophobized ITO revealed that the heterogeneous electron transfer rate constant showed a clear orientational odd–even parity effect with the odd layers showing much higher rates of transfer. Isobaric area relaxa- tion investigations provided further evidence of a hemisphe- rical instantaneous nucleation with an edge growth mechanism for the nanoclusters formed at the tryptophan subphase. Surface pressure as a thermodynamic variable effectively controlled the interparticle separation. Furthermore, intercluster electron coupling exhibited an insulator–metal transition in the Janus cluster monolayers through scanning electrochemical Fig. 15 Selective disassembly of macro-Janus droplet assemblies. microscopy (SEM) investigations. (a–e) Trigger 1: pH-induced disassembly at 5 s intervals. (f) Thermally In 2010, Korgel et al. reported that hybrids of hydrophobic trapped hemisphere at pH 9 and 20 1C. (g–j) Trigger 2: thermally sub-2 nm-diameter dodecanethiol-coated Au nanoparticles induced disassembly of 1-dodecanol hemisphere on heating at 7 s 81 could be incorporated into the hemisphere of phosphatidyl- intervals. Scale bars: 1 mm. choline (PC) lipid vesicles by mixing preformed vesicles with detergent-stabilized nanoparticles followed by extrusion or a However, in this work the particles were observed to be a mixture dialysis process. The latter approach led to vesicles only partially of patchy, multicompartment and Janus micelles. Overall, the loaded with nanoparticles that segregated into hemispherical synthesis of exclusively Janus micelles is still difficult to achieve domains, forming a Janus vesicle– hybrid struc- using only the self-assembly of block copolymers. 77 In 2009, Weaver and coworkers reported a very elegant example ture, as shown in Fig. 14. These results provided evidence 81 that membrane-bound species, such as small proteins and of engineered emulsions composed of macro-Janus particles. other molecules, might interact much more strongly with the As shown in Fig. 15, reversible assembly/disassembly between hydrophobic membrane than previously anticipated, which the stable functional emulsion droplets and robust liquid may have implications in delivery applications.78 structures can be conveniently achieved. This reversible Besides spherical Janus particles, ellipsoidal,31 disc-like,79 process is driven solely by interactions on the droplet surface, and cylindrical80 Janus particles have been reported by the which can be controlled by subtle variation of the branched copolymer surfactant composition.

Downloaded by Tsinghua University on 20 April 2011 Cohen Stuart and Mueller groups, respectively. Although these Janus particles were characterized by many techniques such as In 2010 Yan et al. performed mesoscale simulations to explore the self-assembly of Janus nanoparticles with widely Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J dynamic light scattering (DLS), small-angle neutron scattering varying architectures using diblock copolymers, as shown in (SANS), and cryogenic transmission electron microscopy 82 (cryo-TEM), the direct observation of biphasic Janus character Fig. 16. They demonstrated that the coassembly of these of polymer-based Janus particles by TEM is challenging. A amphiphilic building blocks forms novel and tunable structures recent advance was reported in 2010 by Du and Armes who at the interface of the block copolymers, and consequently directly observed by TEM the biphasic nature of Janus influences the interface stabilization and structural evolution micelles made from a triblock copolymer in pure water.52 kinetics of the nanostructures. Their simulations suggested that Janus nanoparticle self-assembly occurs at block copolymer interfaces and this allows for considerable control over the creation of polymer nanocomposites with improved shear behavior. In this context, this approach is a viable strategy for creating functional materials with enhanced and tunable processing properties.

2.4 Complex nanoparticles with patchy, multicompartment and Janus character Recently, significant interest has emerged in the synthesis of complex patchy, multicompartment Janus nanoparticles, Fig. 14 Two methods used to form nanoparticle-vesicle hybrids: partially due to the difficulty in making perfectly biphasic (top) lipids and nanoparticles were combined and coextruded; (bottom) Janus particles. Compared with biphasic Janus particles, vesicles were formed first by extrusion and then dialyzed in the presence of Au nanoparticles dispersed with detergent. The lipid bilayer is complex nanoparticles with patchy, multicompartment and represented in green for the hydrophobic tails and blue for the hydro- Janus character have enhanced chemical surface variation philic head groups; dodecanethiol-passivated Au nanoparticles are and an increased number of available assembly mechanisms 14 tan spheres, and octylglucoside is represented by the red head group and morphologies. Given that metal nanoparticles have and a purple hydrophobic tail.77 dimensionally dependent surface plasmon resonances that

This journal is c The Royal Society of Chemistry 2011 Chem. Soc. Rev., 2011, 40, 2402–2416 2409 中国科技论文在线 http://www.paper.edu.cnView Online

single self-assembly method. Based on their previous results that amine-modified silica nanoparticles can be covalently attached to styrene-acrylic acid random copolymer films,83 the reaction solvent swells the polymer substrates as the reaction progresses, causing the silica particles to sink into the films, while the polymer chains wet up the sides of the particles. The authors utilized this spontaneous process to protect the bottom regions of 106, 230, and 460 nm diameter silica particles. Gold nanoparticles were then electrostatically assembled on the top surfaces of the amine-modified silica particles. On the 230 and 460 nm silica particles, the gold nanoparticles form a closely packed network. This packing density is dependent on the dimensions of the underlying silica particles and results in a red shift of the gold nano- Fig. 16 Model building blocks studied in this work. (a) Homo- particles optical absorption peak, relative to their absorption geneous sphere with radius Rs =2rc (HS). (b–f) Janus nanoparticles in solution. with various architectures. (g) Symmetric diblock copolymer. Each In principle, selective binding of multivalent ligands within a block consists of 10 beads and blocks A and B are shown by red and mixture of polyvalent amphiphiles provides a simple mecha- blue beads. The red and blue beads in the block copolymer have affinities to the pink and green beads in the nanoparticles, respectively.82 nism for driving domain formation in self-assemblies. This has been used to great effect in 2009, by Discher et al. who absorb radiation in the visible region of the spectrum, the reported spotted vesicles, striped micelles and Janus vesicles 84 formation of gold nanoshells around different core materials induced by ligand binding. Divalent cations crossbridge has garnered much attention in recent years. Furthermore, polyanionic amphiphiles, which thereby demix from neutral these hierarchical Au structures allow for the plasmon resonance amphiphiles and form spots or rafts within the vesicle structures to be tuned into the near-IR wavelength, which is an ideal as well as stripes within cylindrical micelles. Calcium- and trigger for controlled release if used as a drug delivery carrier. copper-crossbridged domains of synthetic block copolymers Thus, Janus particles that incorporate optically active species or natural lipids (phosphatidylinositol-4,5-bisphosphate) possess such as gold are attractive for many applications, including tunable sizes, shapes and/or spacings and can maintain their delivery vehicles and sensors. phase separated structure for years. Lateral segregation in For example, in 2010, McConnell et al. developed a new these ‘ligand-responsive Janus assemblies’ couples weakly to approach for the creation of self-assembled, optically tunable, curvature and proves to be restricted within the phase diagram multi-region and patchy gold-on-silica Janus particles with to narrow regimes of pH and cation concentration that are

Downloaded by Tsinghua University on 20 April 2011 tunable optical properties via a hierarchical self-assembly centred near the characteristic binding constants for the process, as shown in Fig. 17.14 Gold nanoparticles (ca.15nm) polyacid interactions. Remixing at high pH was observed Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J were electrostatically assembled on the top surfaces of nano- and was somewhat surprising, but the theory for strong lateral and sub-micrometre amino modified silica particles, which segregation shows that counterion entropy dominates electro- were selectively protected on their bottom surfaces by covalent static crossbridges, thus providing valuable insights into ligand- attachment to a copolymer PS-r-PAA film. The morphologies induced pattern formation within self-assemblies. of the gold particle layer, and the resulting optical properties To assess the coarsening and perhaps gain control over the of the Janus particles, could be readily tuned by changing the domain size, the authors extended the hydration time for surface energy between the silica and gold particles, followed vesicle formation. As shown in Fig. 18, by making polymersomes 1 by annealing. by the overnight hydration of polymer films heated to 60 C, In this work the authors reported the synthesis of multi- these longer hydration times gave larger domains that coarsen B 2 region particles with gold caps on the top surface, gold patches until there is only 1 domain per 15 mm vesicle after roughly around the particle equator and silica bottoms, and Janus 40 h. The total area fraction of domains per vesicle remains particles with tunable gold patch sizes that can be synthesized constant and is based on the initial mixing ratio and is on the nanometre and submicrometre scales. The multi-region independent of the hydration time, indicating that the phase and patchy Janus particles can both be synthesized from a separation is always complete. Furthermore, calcium-responsive Janus vesicles controllably form on a timescales of days and prove stable for much longer. In 2009, Mueller and coworkers reported dynamic core– shell–shell–corona patchy multicompartment micelles formed by two oppositely charged block copolymer systems, negatively charged polybutadiene-b-poly(N-methyl-2-vinylpyridinium)- b-poly(methacrylic acid) (PB-P2VPq-PMAA) and positively charged poly(N-methyl-2-vinylpyridinium)-b-poly(ethylene oxide) (P2VPq-PEO) diblock copolymers.63 The preformed Fig. 17 Schematic representation of the self-assembled formation of PB-P2VPq-PMAA triblock copolymer micelles have a soft patchy and multi-region Janus particles.14 polybutadiene core, an interpolyelectrolyte complex (IPEC)

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Fig. 20 A triblock copolymer (a) with two outer hydrophilic blocks that can self-assemble into mixed micelles (b), partly demixed or multicompartment micelles (c) or completely demixed, biphasic Janus Fig. 18 Controlled coarsening yields Janus-like polymer vesicles. micelles (d). The amphiphilicity upon triggering the hydrophilic- (a) Mixed films of 33 : 67 PAA-PBD : PEO-PBD were hydrated and to-hydrophobic transition may result in superstructure formation.85 vesicles were imaged at each time point (insets) to measure the domains per area. The coarsening of domains is shown to saturate 52 by B40 h, but the ‘% area’ occupied by domains remains relatively another terpolymer in water. They attribute this lack of constant throughout. (b) Most polymer vesicles showed fully segregated complete segregation to the energetic penalties in the core and domains after two or more days. Scale bars: 2 mm.84 the very minor energetic differences between multicompartment and Janus micelles inside the corona, which cannot counter- shell consisting of poly(N-methyl-2-vinylpyridinium) and poly- balance the entropic penalty of complete segregation. The ability (methacrylic acid). The negatively charged PMAA coronas of micelles to organize into superstructures or to be potentially were mixed in different ratios at high pH with positively used as interfacial stabilizers depends on the ratio of the two charged P2VPq-PEO diblock copolymers. Under these con- corona-forming blocks. As long as the PEO chains are longer ditions, mixing results in the formation of a second IPEC or of similar length as the thermoresponsive block, a sufficient shell in the PB-P2VPq-PMAA precursor micelles, which was shielding of the complete micelle occurs and aggregation is surrounded by a PEO corona. The resulting multicompartment prevented. This is even the case when PEO is the overall minor IPECs exhibit dynamic behavior, highlighted by a structural weight fraction. This systematic study, together with results on relaxation within a period of 10 days (Fig. 19). After a short different copolymer systems, highlights that truly self-assembled mixing time of ca. 1 h, the IPECs exhibit a star-shaped structure, Janus micelles based on block terpolymers or mixtures of whereas after 10 days, spherical core–shell–shell–corona objects diblock copolymers are currently extremely difficult to achieve. could be observed by TEM analysis (Fig. 19). These systems In these systems it is more likely that only a certain fraction of could be interesting candidates for utilization in catalytic applica- the individual system can be converted to completely biphasic tion or delivery carriers for sensitive substances through the particles. Until these issues can be resolved, materials and Downloaded by Tsinghua University on 20 April 2011 protective PEO corona.63 bioscience will have to rely on some of the more complex

Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J In 2010, Mueller et al. systematically studied the influence of methods to generate the attractive properties of Janus particles the length of a thermoresponsive block on the behavior and in a very defined way. phase segregation of micelles based on bis-hydrophilic block In 2010, Liu et al. reported an ABC triblock copolymer with terpolymers with two different outer hydrophilic blocks, as a carboxyl-containing terminal C block and a photocrosslinkable shown in Fig. 20.85 The lower critical solution temperature middle B block.86 In the presence of a diamine, ()-sparteine, (LCST) behavior of the PNiPAAm segment was used to which complexed with the C block and made it insoluble, the artificially increase the incompatibility within the corona-forming triblock copolymer self-assembled into hamburger-like micellar blocks. Phase separation of the corona can be triggered by the aggregates and segmented cylinders in a poor solvent for the B collapse of the PNiPAAm blocks via a thermally induced block. In these structures the B block forms the ‘‘buns’’ in a hydrophilic to hydrophobic transition. The extent of phase ‘‘hamburger’’ and the complexed C block forms the filling. separation can be increased by repeating the heating cycles, The soluble A chains stretched out from the bun surface into however, regardless of the length of the thermoresponsive the solvent phase. The main body of the segmented cylinders block, a full transition to Janus micelles could not be induced. was constructed through stacking alternating B and C stubs. This is consistent with recent results from the self-assembly of The cylinders were dispersed in solvent by the A chains

Fig. 19 Dynamic core–shell–shell–corona patchy multicompartment micelles.63

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stretching out from the surfaces of the B stubs. The buns of the hamburgers can be separated to yield Janus particles after the photocrosslinking of the buns of the hamburgers and the removal of ()-sparteine by dialysis.

3. Applications As mentioned before, anisotropic particles have many potential applications given their unique properties. For example, multi- compartment and patchy Janus particles have shown optical activity.14 Furthermore, Janus particles have a strict 50 : 50 distinct coverage in shape, composition, chemistry, polarity, functionality, electrical and other properties, making them suitable for application as switchable display devices,9 inter- face stabilizers,87 self-motile micro-particles,11 controllable pores in lipid membranes,12 smart nanomaterials such as bio- logical sensors, nanomotors, antireflection coatings,88 optical sensors,14 and anisotropic building blocks for complex structures.15 Recently, remote control of cellular behaviour with magnetic nanoparticles has become possible.89 To manipulate and control cell function through the magnetic actuation of nano- particles bound to the cell surface, it is important to have magnetic nanoparticles with suitable properties. In 2009, Yellen et al. developed a new method for the controlled Fig. 21 (a) Chain reaction of the three coupled enzymes with synthesis of ‘dot Janus’ particles which only have a metallic fluorogenic substrates for the first and third enzymes. (b) Fabrication coating covering 20% of their surface area (in contrast, half 7 o scheme of multi-compartment particles and coupled enzyme reaction. Janus has 50% coverage of metallic coating). The dot Janus particles have sufficiently small surface coverage of a cobalt 90 The multi-compartment particles were obtained when multiple film to allow compatibility with an optical trap. The near coprecipitation steps and one or several cross-linking procedures holonomic control over these spherical Janus particles opens were applied, as shown in Fig. 21. Each of the resulting up a new realm of advanced manipulation strategies that concentric compartments could be independently loaded with

Downloaded by Tsinghua University on 20 April 2011 will have important ramifications in nanoengineering. The selective biomolecules. Three coupled enzymes, b-glucosidase controlled manipulation of dot Janus particles affords new (b-Glu), GOX, and HRP were incorporated stepwise into such Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J degrees of freedom in the measurement of the mechanical particles. Each of these enzymes was located in a separate properties of molecules such as DNA, and other biomolecules. compartment, in a desired sequence, and at a defined position. Smoukov et al. reported that magnetic Janus particles can The distance between the enzyme containing compartments be assembled into staggered chain structures under the action was also varied, including spacing compartments consisting of of magnetic and electric fields. This magnetic assembly of bovine serum albumin (BSA).7 When fluorogenic substrates particles could result in permanent structures, which can be 91 for b-Glu and HPR were used, the start and the end of the disassembled as required by remote demagnetization. This coupled enzyme reaction were visualized and recorded inside allows for the reversible and responsive selective assembly of individual particles, using confocal laser scanning microscopy. magnetic particles which may find applications in circuits or as A strong influence of the spacing on the reaction kinetics of the sensors. last enzyme was observed, suggesting an impaired diffusion Compartmentalization plays an indispensable role in the of the intermediate products of the chain reaction through biological cell where an enormous number of reactions and 7 the spacing compartments made of BSA. Importantly, this transport processes are executed in parallel. The study shown work demonstrated the influence of the spacing between in Fig. 21 was motivated by the need for a deeper under- compartments containing different enzymes on the reaction standing of the influence of compartmentalization on the kinetics on the microscopic scale within one microparticle. multiple functionalities and coupled reactions inside one particle. This study provides key information towards the design and In 2010, Baeumler et al. fabricated a spherical multicompartment application of multicomponent nanostructured systems. biopolymer particle by coprecipitation with calcium carbonate, followed by cross-linking of the macromolecules and dissolution of the inorganic support.7 These particles consisted of B80% horseradish peroxidase (HRP) and glucose oxidase (GOX) and 4. Challenges the enzyme activities were confirmed using standard assay 4.1 Scale up techniques. The enzyme particles were reusable at least six times, with a remaining activity between 30 and 50% from the initial In recent years there have been rapid developments in the experiment. research area of anisotropic particles. However, one of the

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challenges still remaining is how to make anisotropic particles in large quantities. In 2007, Chen and coworkers reported an efficient one-pot method for the preparation of amphiphilic polymeric Janus nanoparticles, as shown in Fig. 22.92 The desymmetrization tool is the water-dispersible hybrid nanotubes composed of an Fig. 23 Janus PAN/PS colloids are prepared by seeded emulsion inorganic nanotube surrounded by a hydrophobic polymer polymerization on cross-linked PAN hollow seed spheres.94 layer with water-soluble polymer chains grafted on the outer surface of the hydrophobic polymer layer. In aqueous suspension, a hydrophobic divinyl cross-linker and a hydrophobic free- radical initiator were solubilized in the hydrophobic polymer layer, and a hydrophilic monomer remained in the aqueous phase. During the polymerization of the hydrophobic cross- linker, the hydrophobic spheres composed of the resulting polymer were formed and grew in the hydrophobic polymer layer. One side of a sphere was exposed to the water phase when the diameter was larger than the thickness of the hydrophobic polymer layer. The water-soluble monomer was then initiated by the polymeric free radicals at the hydrophobic- sphere/water interface; the other side of the hydrophobic sphere was embedded in and protected by the hydrophobic polymer layer. This process led to the formation of amphiphilic Janus particles in which water-soluble polymer chains are grafted on Fig. 24 Schematic illustration of the procedure for generating one side of a hydrophobic sphere. Also, the Janus particles can asymmetric Au–PS colloidal particles.95 self-assemble in water into supermicelles, which can dissociate into individual nanosized Janus particles under some conditions. preparing these particles is to introduce Au or Ag colloids The preparation efficiency of this method is relatively high as a 2 min after (rather than before) starting the polymerization. result of the large area of the curved water/ hydrophobic polymer The hybrid particles formed were uniform in size, and each layer interface. one of them only contained one Au (or Ag) nanoparticle on its In 2009, Ravaine and coworkers produced Janus silica surface. Due to the simplicity of this procedure, it is possible nanoparticles on the gram scale, which were as small as 100 nm, that these methods be used for large scale production of based on a Pickering emulsion process, which is proposed to anisotropic particles. Given the uniform size and anisotropic 93

Downloaded by Tsinghua University on 20 April 2011 be readily scalable for industrial production. Then in 2010, composition, these hybrid particles are expected to find uses as Yang et al. reported the large-scale preparation of submicrometre building blocks to fabricate new types of structures and

Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J sized anisotropic Janus polymer colloids by seeded emulsion devices. In 2009 Wang and coworkers reported the protrusion polymerization, as shown in Fig. 23.94 Polymerization induced of polystyrene from polyelectrolyte multilayer encapulsation phase separation and was responsible for the growth of the to afford anisotropic polymer particles with snowman-like Janus colloids. Furthermore, the slow feeding of the monomer shapes. This approach is simple and also readily scalable for dropwise was important to ensure that the small anisotropic the production of anisotropic particles.96 colloids were formed and sufficient cross-linking of the formed In 2010, Tsukruk et al. reported titania/silica Janus micro- polymer was achieved to facilitate a more complete phase particles with controlled surface coverage by plasma polymeri- separation. However, in the above systems, it may be more zation, which are expected to be scalable for massive production.97 appropriate to describe the particles as ‘patchy’ due to the They used a masking technique reported previously by Yang poor biphasic nature of these ‘Janus’ particles. and coworkers.98 Initially, a sacrificial PS layer on a clean In 2009, Xia et al. reported a simple approach to prepare silicon substrate was spin-coated to a desired thickness close to asymmetric and hybrid patchy colloidal particles by precipita- the diameter of the microparticles (ca.3mm), which can be tion polymerization, as shown in Fig. 24.95 The key step in varied from 0.2 to 3.0 mm depending on the embedding level targeted. By varying the thickness of the PS layer, the masked areas of the spheres can be tailored to cover varying portions of the particles surface (Fig. 25). After the silica and titanium dioxide microparticles were embedded in the PS layer, selected materials could be effectively plasma polymerized on the open surface areas. The residual plasma enhanced chemical vapor deposition film can be removed by rinsing and sonication since the free-standing film is not tethered to a surface. Furthermore as the film is thin, the particles can easily break from the Fig. 22 Diagram illustrating the formation of water-dispersible free-standing film after the sacrificial layer is dissolved. hybrid nanotubes, the synthesis of Janus particles, their self-assembly These selective plasma polymerized coatings remained into a supermicelle and the dissociation of a supermicelle.92 firmly attached to the particles as the sacrificial polystyrene

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artifacts may be introduced during the staining process. Cryo-TEM has also been used for the characterization of anisotropic particles. This is a very powerful technique for imaging particles in their native state.55 However, unfortunately it is not suitable for big particles and artefacts can also be observed. In contrast, 2D NOESY NMR may provide indirect evidence of a phase separated nature within a particle based on whether different domains are in close contact or not. However, using this technique it is not possible to distinguish which kind of anisotropic particles have been prepared. Overall, a combination of the above techniques is required as well as the development of new methods to provide con- vincing evidence for the formation and characterization of anisotropic particles.

Fig. 25 (A) SEM image of 3 mm silica particles half embedded in a PS layer. (B) Embedded particles at typical depth in the PS layer. (C–E) 5. Conclusions Janus particles with controlled coating coverage: 3/4, 1/2, and 1/4.97 This review highlights the recent advances in the preparation and application of three common anisotropic particles: patchy, layer was dissolved and the Janus particles were released multicompartment and Janus particles. Due to the structural (Fig. 25). The coverage areas of the particles with the polymerized similarity of these three particles, these terms are sometimes coatings can vary over a wide range: from a high ratio of up to misused to incorrectly describe particles in the literature. It is 75% of the area coated (Fig. 25C) to an equal ratio with perhaps more appropriate to recognise that patchy, multi- approximately 50% coated area (Fig. 25D), and to very low compartment and Janus particles are different categories of ratio, down to 25% coated (Fig. 25E). The protect-and-release particles although there is sometimes overlap between their method proves to be a critical step and perhaps could be structures. In fact in reality, patchy Janus, patchy multi- applied in a number of different fabrication scenarios. Embedding compartment, Janus–Janus, Janus multicompartment particles, the microparticles into an easily removable sacrificial layer etc. have been observed. A key focus of this review has been facilitates the protection of the embedded portion while allowing to identify these different morphologies and compare their for further modification of the exposed portion. This leaves the properties and applications. This is especially important as in protected portion of the particle clean for further modification the last 2 to 3 years there has been increasing interest and later. By utilizing dissolvable polymer layers of different thick- growth in the study of such anisotropic colloidal particles. nesses, the microparticles can be easily coated to a controlled Hence in this review we have highlighted these recent advances Downloaded by Tsinghua University on 20 April 2011 degree of surface coverage through toposelective modification for the preparation of Janus, patchy and multicompartment before final release of the modified particles through dissolution Published on 08 March 2011 http://pubs.rsc.org | doi:10.1039/C0CS00216J particles and discussed some of the outstanding challenges and of the masking layer. potential advances in the field. 4.2 Characterization of anisotropic particles Acknowledgements Although many techniques such as conventional TEM (sometimes upon selective staining), cryo-TEM, SEM, SAXS, JD is supported by the program for professor of special and 2D NOESY NMR have been employed to reveal the exact appointment (Eastern Scholar) at Shanghai institutions of structure of anisotropic particles such as Janus, multicompartment higher learning, Pujiang project of science and technology and patchy particles, it is still difficult to fully determine the commission of Shanghai municipality (10PJ140900), the key structure of the particle. Often TEM is used to provide direct project of innovative scientific research of education commission evidence for anisotropic particle formation. However, for of Shanghai municipality (11ZZ31), and National Natural samples with poor electron density contrast under TEM, it is Science Foundation of China (NSFC, 21074095). EPSRC is often very difficult to reveal the phase separated nature of the acknowledged for the award of a fellowship to R.K.O. and the anisotropic particles by conventional TEM. Thus, selective Leverhulme Trust, Royal Society and University of Warwick staining of different domains of particles is a useful way to is acknowledged for funding. enhance the contrast. For example, Mueller et al. reported multicompartment micelles based on a poly(4-tert-butoxy- Notes and references styrene)-b-polybutadiene-b-poly(tert-butyl methacrylate) triblock copolymer, where poly(4-tert-butoxystyrene) can be selectively 1 M. Oeggerli, http://ngm.nationalgeographic.com/2009/12/pollen/ oeggerli-photography, 2009. stained by RuO4 and can be clearly viewed by traditional 2 T. L. Poulos, Nat. Prod. Rep., 2007, 24, 504–510. 51 TEM. In another example, selective staining of one hemisphere 3 A. Paananen, K. Laurikainen, E. Vuorimaa, H. Lemmetyinen, of Janus micelles by tetramethylorthosilicate was successfully J. Peltonen and M. B. Linder, Biochemistry, 2007, 46, 2345–2354. achieved and the resultant biphasic particles could be viewed 4 H. J. Hektor and K. Scholtmeijer, Curr. Opin. Biotechnol., 2005, 52 16, 434–439. by conventional TEM. Although TEM is an important 5 J. R. Whiteford and P. D. Spanu, Mol. Plant Pathol., 2002, 3, technique to confirm the anisotropic nature of particles, 391–400.

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2416 Chem. Soc. Rev., 2011, 40, 2402–2416 This journal is c The Royal Society of Chemistry 2011