Chapter 1: Soft, Nanoscale Janus Particles by Macromolecular Engineering and Molecular Self-assembly

Macromolecular engineering has evolved into a powerful toolbox for the preparation of complex polymer topologies with remarkable control over both the architecture and the distribution of monomer sequences into, e.g., block-type structures or well-defined branched macromolecules. The rapid advances in controlled/living polymerization techniques during the last two decades have greatly facilitated this development. In the context of Janus particles, macromolecular engineering is interesting not only for the direct synthesis of phase-segregated unimolecular objects, but also for harnessing the self-assembly capabilities of tailor-made polymers owing to mutually incompatible polymer blocks, solvophobic effects or specific molecular interactions. Indeed, self-assembly of block copolymers has proven to be a remarkably elegant strategy to generate polymer-based nano-objects, where we have seen progress to increasingly sophisticated soft nanoparticles, from simple diblock copolymer micelles and vesicles, to multicompartment micelles (MCMs) with increasingly complex geometries.^1–4  Still, directly breaking the symmetry into biphasic Janus (Figure 1.1) particles or micelles has remained a considerable challenge.

Polymer-based Janus particles formed by direct synthesis or self-assembly of block copolymers are unique among this class of non-centrosymmetric colloids. First, truly nanoscale dimensions (i.e. <100 nm) can be approached that are very difficult to tackle by, e.g., common desymmetrization reactions at interfaces or phase separation processes in emulsions, microfluidics or electrohydrodynamic jetting. Second, smart polymer segments, able to respond to environmental changes by phase transitions, impart a large-scale responsiveness to trigger superstructure formation or create strongly amphiphilic particles relevant for surface nanostructuring and the stabilization of interfaces. These properties render them a key building block for switchable materials. As a third criterion, polymers are also the crucial soft materials to communicate with the environment and to mediate interactions with cells, proteins and other living matter when approaching the biological interface with synthetic materials. Consequently, they are a valuable material class in the multitude of Janus particles available nowadays.

In this chapter, we review and discuss recent developments towards polymeric Janus particles. We place an emphasis on strategies specifically involving advanced polymer synthesis to create unimolecular objects and on methodologies utilizing self-assembly as well as post-transformations of self-assembled structures to create biphasic particles. Thereby, we focus on the small size regime and discuss particle architectures with different dimensionalities, in which at least one dimension is truly nanoscale (i.e. <100 nm). It may be noted that there are other approaches towards polymer-based Janus particles on the (sub)micron scale, such as phase separation in emulsion droplets, lithographic approaches in microfluidic channels and electrohydrodynamic co-jetting, which are, however, beyond the focus of this contribution and are discussed in other chapters. This chapter is grouped into four topics. The first three are (a) Janus particles via direct macromolecular engineering, (b) Janus particles via direct self-assembly and/or transformations in solution and (c) Janus particles via transformation of self-assembled triblock terpolymer bulk structures. We finally discuss (d) self-assembly properties of the synthesized Janus particles and highlight some potential applications that have already been realized.

The rapid advances in synthetic tools available to polymer chemists have triggered significant interest in the preparation of Janus particles. One of the earliest strategies involved the attachment or growth of different polymer chains to/from a single focal point or to/from a focal line with the aim of preparing spherical or cylindrical Janus particles, also known as heterografted star-shaped and cylindrical brush polymers. The resulting structures are outlined in Figure 1.2, which also highlights one of the major challenges for such nanoscale objects with high dynamics of the polymer chains. Phase separation of the chemically different polymer arms is required to realize a true Janus particle character in solution. However, phase separation for polymer arms emanating from a single focal point or from a dynamic micellar core – as will be discussed later – is not self-evident. It is governed by the interplay between entropy, favoring mixing of the polymer chains, and the enthalpic force of polymer chains to phase separate.^5,6  In solution, the latter is drastically reduced compared with the bulk state and it has proven a challenging task to design systems that allow a freely occurring phase separation. In this context, it is also important to point to another major obstacle, namely the difficulty of providing solid in situ proof for corona segregation of polymer nano-objects in solution. The nanoscale dimensions and the often weak natural contrast of different organic parts for imaging are the main complications. This challenge can be best met by 2D ¹H–¹H NOESY NMR (NOE  =  nuclear Overhauser effect), an NMR technique probing intermolecular distances via through-space coupling, or by direct (cryogenic) transmission electron microscope (TEM) imaging using suitable staining methods to augment the natural contrast.

Some of the first evidence that a phase separation in heteroarm star polymers can indeed occur was delivered by Kiriy et al.⁷  In their atomic force microscopy (AFM) investigations on a system of heteroarm star polymers composed of seven arms of polystyrene (PS) and seven arms of poly(2-vinylpyridine) (PS₇–P2VP₇), it was observed that different topologies of the molecules result upon deposition from different solvents on to mica (Figure 1.3). Chloroform (CHCl₃) led to a hat-shaped appearance, whereas tetrahydrofuran (THF) yielded a more globular shape. The dissimilar shapes were attributed to the adsorption of Janus-type conformations in the case of CHCl₃, whereas a mixed conformation was suggested for the molecules deposited from THF. These observations were supported by calculations of the solubility parameters, which confirmed that CHCl₃ is a more selective solvent for P2VP and thus can enforce intramolecular phase segregation and a Janus-type conformation in solution. One uncertainty related to the imaging of deposited molecules of dynamic species always lies in the unclear effect of the surface properties on the adsorption behavior, i.e. selective adsorption due to preferred adhesion – a problem hard to come by with ex situ techniques.

An improved focal point design was suggested by Ge et al., who reported the synthesis and stimuli-responsive self-assembly of double-hydrophilic Janus-type A₇B₁₄ heteroarm star copolymers with two types of water-soluble polymer arms, poly(N-isopropylacrylamide) (PNIPAAm) and poly(2-(diethylamino)ethyl methacrylate) (PDEAMA), emanating from the two opposing sides of a rigid toroidal β-cyclodextrin (β-CD) core.⁸  Owing to the pre-encoded phase separation within the focal point, an enhanced tendency for phase separation of the two arms can be expected. The authors found an interesting schizophrenic self-assembly behavior. Depending on the conditions for triggering the solubility to insolubility phase transitions of the two polymer arms, which are high temperature for PNIPAAm and high pH for PDEAMA, it was possible to switch between two vesicle states by inverting the membrane structure. Such a vesicle inversion procedure is a highly unlikely scenario for simple coil–coil diblock copolymers and can serve as indirect evidence for the Janus character of these stars.

Zhu and co-workers described a facile and large-scale synthesis of possibly the smallest unimolecular Janus nanoparticles by intramolecular crosslinking of the inner P2VP block of a polystyrene-block-poly(2-vinylpyridine)-block-poly(ethylene oxide) (PS-b-P2VP-b-PEO or SVEO) triblock terpolymer (Figure 1.4).⁹  Simple addition of an α,ω-dibromoalkane in a common solvent, dimethylformamide (DMF), resulted in nanoscale Janus particles with exactly one polymer arm of each end block attached to the central core. Interestingly, these Janus particles showed a concentration-dependent self-assembly behavior into supermicelles upon reaching a critical aggregation concentration, cac, of ∼2 mg mL⁻¹. Strikingly, this aggregation also took place in a good solvent (DMF) for both end blocks, PS and PEO, which is a first example of the unusual and intuitively unexpected self-assembly behavior of polymeric Janus particles in good solvents for both corona hemispheres.

Moving from these 3D systems with overall spherical character to 2D systems with cylindrical architectures, one can identify various synthetic efforts targeting different types of copolymer bottle brushes. Various groups have reported cylindrical copolymer brushes of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly(ε-caprolactone) (PCL), PS and polylactide (PLA) or PS and PEO with a statistical distribution of side-chains along the backbone (Figure 1.2b).^10–12  Although these molecules showed clustering into some irregular aggregates upon exposure to selective solvents, there are no conclusive data and discussion on the potential Janus character of such structures. Simulations by de Jong and ten Brinke demonstrated that complete phase separation may only occur at very high incompatibilities of the two grafted polymers (similar to hetero-arm star-shaped polymers), as expressed by a large Flory–Huggins parameter, χ.¹³  It was further suggested that a well-defined Janus cylinder may only be reached at theta conditions for both blocks and for rigid backbones (Figure 1.5). For good solvents and highly flexible backbones, common to most synthetic comb-shaped polymers, the extent of phase separation is reduced and the molecules undergo bending into different shapes.

Schmidt and co-workers found differently bent shapes for cylindrical brushes composed of P2VP and poly(methyl methacrylate) (PMMA), when imaged with AFM after deposition from different solvents.¹⁴  After quaternization of parts of the P2VP segments and deposition from CHCl₃ and H₂O, strongly bent horseshoe and multiply bent, spiral/meander-type conformations were observed. The strong bending within the horseshoe structures was attributed to a basically quantitative phase separation along the main axis, whereas a patchy structure was ascribed to the meander-type patterns. Ishizu and co-workers reported imaging data on the side-by-side aggregation of cylindrical brushes obtained by polymerization of PS and PEO macromonomers during a very slow evaporation process of 1 week, starting from a THF–water solution.¹⁵  These observations indicated that a reorientation can occur and that a biphasic character can develop if the correct solvent conditions (selectivity to drive self-assembly), concentration regime, and time scale are provided. These experimental systems and simulations, however, point to some limitations of this strategy when aiming at robustly phase-segregated two-dimensional cylindrical Janus brushes with corona segregation along the main axis. Further below, we will describe how to create similar Janus cylinders with very high precision using the controlled crosslinking of triblock terpolymer bulk phases.

Advances in polymer synthesis, however, have allowed the synthesis of a different type of cylindrical Janus particles. These are characterized by a phase separation perpendicular to the main axis into a cylindrical AB-type diblock brush.^16–22  Such structures are typically obtained by consecutive block polymerization of macromonomers or by the polymerization of AB diblock copolymers with orthogonally reactive moieties in both blocks permitting side-by-side polymer-analogous attachment of preformed polymer chains (grafting to) or the growth of polymers via (parallel) grafting from reactions. A variety of AB-type Janus cylinders have been reported with widely different physical properties. For instance, Rzyaev et al. described in great depth the synthesis and structure formation of PLA_comb-b-PS_comb AB-type Janus brushes with total molecular weights exceeding 1 MDa.^21,22  Since the dimensions of the resulting lamellar bulk phases of the stiff AB cylinders approached the wavelength of visible light, a photonic bandgap behavior and an opalescent appearance could be observed for solid samples. Direct visualization by AFM was reported by Matyjaszweski and Sheiko and co-workers for their poly(n-butyl acrylate)_comb-block-PCL_comb (PnBA_comb-b-PCL_comb) AB diblock brushes (Figure 1.6) with amorphous and crystalline side-chains.²³ 

In addition, Deffieux et al. employed a multi-step reaction scheme to create PS_comb-block-polyisoprene_comb (PS_comb-b-PI_comb) with glassy and liquid-like side-chains, thus further broadening the property range.¹⁶  Exposure to selective solvents such as heptane induced self-assembly into homogeneous and nearly spherical micelles. Similar self-assembly behavior was also reported for AB diblock brushes composed of PS and poly(acrylic acid) (PAA) side-chains.²⁴ 

In addition to the stepwise synthesis of unimolecular polymer objects via classical polymer chemistry, the desymmetrization of particles at interfaces has also reached the field of polymer-based nanoscale Janus particles. In general, toposelective modifications of immobilized particles are widely used to break the symmetry of inorganic particles and have greatly impacted the synthesis of Janus objects.

In the context of soft nano-objects, Chen and co-workers reported a simple one-pot process, in which they used PEO-b-P4VP-stabilized yttrium hydroxide nanotubes (YNTs, diameter ∼200 nm and length 3–4 μm) as the interface for symmetry breaking. After initial formation of the polymer-coated YNT rods due to the adsorption of P4VP segments on the YNT surfaces via hydrogen bonding, a mixture of a radical initiator [azobisisobutyronitrile (AIBN)] in divinylbenzene (DVB) and additional NIPAAm was added to the dispersion (Figure 1.7).²⁵  Because of the solubility characteristics of the various compounds, AIBN and DVB accumulated in the P4VP phase, whereas NIPAAm remained dissolved in the continuous phase. Subsequent heating induced polymerization of the DVB in the confined space on the YNTs and nanoscopic, crosslinked polydivinylbenzene (PDVB) beads were formed due to the increased incompatibility of P4VP and PDVB polymers developing during the DVB polymerization. The radicals reaching the outer surface also initiated the NIPAAm polymerization, which led to the side-selective growth of PNIPAAm grafts, equaling an in situ desymmetrization. The collapsed state of the PNIPAAm during the thermal polymerization prevented the dissolution of the modified PDVB beads from the YNTs. After resting at room temperature, the PNIPAAm/PDVB Janus particles separated from the polymer-coated inorganic rods. Dynamic light scattering (DLS) and TEM revealed flower-like aggregates of the strongly amphiphilic Janus particles with a hydrodynamic radius <R_h>_z  =  320 nm, which could be dissociated by the addition of excess surfactant to yield isolated Janus particles with an average radius of 80 nm. Interestingly, the process might be suitable for different monomers and could potentially be cycled using the same polymer-coated YNTs.

Solution-based self-assembly of block copolymers into micellar aggregates has rapidly developed throughout recent decades. It originally appeared fairly straightforward to design systems capable of leading to a Janus-type conformation of micellar coronas. Systems conceived for that purpose involve ABC triblock terpolymers with an inner solvophobic block as micellar core and the A and C end blocks forming the corona. Additionally, a mixture of two diblock copolymers of the AB and BC type was expected to lead to feasible situations for Janus-type separation of the A/C corona and a common B core. Similar considerations for the phase separation of the polymer arms as discussed above for hetero-grafted polymers also apply. High incompatibility of the two A/C corona blocks and suitable solvent conditions are required (Figure 1.8a). Interestingly, however, Halperin calculated that a mixture of AB and BC will only lead to co-micellization into mixed micelles for low incompatibility of the two end blocks.²⁶  It was predicted that high incompatibility of both corona blocks would in fact lead to a set of two homogeneous populations of AB and CB micelles. Therefore, forced co-micellization of AB and CD diblock copolymers, carrying attractive interactions between the B and C blocks, was thought to be a viable alternative. The problem of uncertain co-micellization can be fully overcome for ABC triblock terpolymers possessing a chemical connectivity between the two corona blocks A and C.

A theoretical treatment of the corona segregation was presented by Charlaganov et al., who used 2D self-consistent field theory (SCF) for an ABC triblock terpolymer system to calculate that corona phase segregation between A and C starts to occur at χ_AC ≈ 0.5 and leads to fully biphasic A/C coronas at χ_AC ≈ 1.⁶  Such a high degree of incompatibility between the two corona-forming blocks is yet difficult to achieve in the case of dissolved polymer segments in solution.

A number of groups, including ourselves, devoted significant effort to understanding and eventually mastering the challenge of fully phase-separating coronas within micellar systems. For instance, Hu and Liu²⁷  demonstrated that introducing adenine and thymine into the PCEMA segments of two diblock copolymers, poly(tert-butyl acrylate)-block-poly{(2-cinnamoyloxyethyl methacrylate)-ran-[2-(1-thyminylacetoxyethyl methacrylate)]}, PtBA-P(CEMA-T) and PS-block-PCEMA-ran-[2-(1-adeninylacetoxyethyl methacrylate)]}, PS-P(CEMA-A), leads to enhanced mixing of both chains in micelles due to H-bonding of the nucleic acid pairs. The observation of better mixing due to secondary interactions between both solvophobic blocks points to their significant incompatibility, as predicted by theory. However, despite the existing repulsion of both corona blocks, full segregation could not be obtained and different populations of patchy multicompartment micelles (MCMs) were found. Similar results were obtained by Zheng et al.²⁸  for a system of two diblock copolymers, PCEMA-block-poly(glyceryl methacrylate) and PCEMA-block-PSGMA (PSGMA  =  succinated PGMA), with PCEMA forming the solvophobic core, and by Ma and co-workers^29,30  and Kim et al.³¹  for a system using PNIPAm-block-P4VP and PEO-block-P4VP with a protonated P4VP as insoluble block or using stereo-complex formation of PNIPAAm-block-PLLA and PEO-block-PDLA, respectively.

Fang et al., in detailed TEM investigations, looked at the corona structure of micelles formed by ABC triblock terpolymers carrying a solvophobic semifluorinated middle block B and two corona blocks of poly[4-(tert-butoxy)styrene] (A, PtBS) and poly(tert-butyl methacrylate) (C, PtBMA).³²  A distribution of MCMs with few patches in the corona was found and the MCMs underwent supramicellar polymerization into extended, branched, mesoscale polymers upon exposure to a selective solvent inducing the precipitation of PtBS. This indicates a majority fraction of two opposing patches. Selective staining and subsequent imaging allowed the various building blocks and their patchiness to be resolved (Figure 1.8d, e).

In a refined system, Walther and co-workers investigated a range of bis-hydrophilic PEO-b-PnBA-b-PNIPAAm triblock terpolymers with respect to their thermo-reversible aggregation in water.^33,34  After micellization in water (PnBuA as cores), various heating cycles were used to induce the collapse of the PNIPAAm corona chains and to study its effect on the superstructure formation (Figure 1.8a). The expulsion of the solvent was used as means to raise artificially the χ-parameter in this system. Indeed, the formation of larger worm-like superstructures was seen with increasing heating cycles. This indicated a restructuring of the corona from a mixed to a phase-segregated morphology, thereby leading to larger sticky patches and enforced aggregation. A complete phase separation into Janus micelles was again not observed, as their supramicellar aggregation would have led to isolated clusters. Two to three corona patches of one block were the dominant corona configurations as judged by the cryo-TEM images obtained at high temperatures. Similar observations of patchy multicompartment micelles based on triblock terpolymers were also reported by Du and Armes for a PEO-block-poly(ε-caprolactone)-block-poly(2-aminoethyl methacrylate) triblock terpolymer in water, with PCL blocks forming the micelle cores (Figure 1.8b).³⁵ 

Using a different driving force for self-assembly, Schmalz and co-workers reported on the thermo-reversible formation of worm-like micelles from a PS-block-polyethylene-block-PMMA (SEM) triblock terpolymer with a crystallizable middle block in organic media.^36,37  TEM investigations revealed a core–corona structure for the worm-like micelles, in which the core was formed by crystalline polyethylene (PE) domains and the soluble corona exhibited a patched structure composed of microphase-separated PS and PMMA chains (Figure 1.8c), as proven by 2D ¹H–¹H NOESY NMR and TEM investigations of selectively stained samples. A fully biphasic corona could not yet be obtained.

Consequently, some generalities derive among the systems. Despite greatly different chemistries and also driving forces to generate the self-assembled, near solvent-free cores, it can be realized that success towards freely self-assembling Janus micelles is limited. This can be explained by considering that the gain in enthalpy by reducing the interface between a few patches is small compared with the accompanying loss of the entropy of the system due to full confinement and positional order of both sets of corona chains.

A breakthrough for self-assembled Janus micelles was reported by Voets and co-workers, who published very comprehensive studies on slightly anisometric Janus micelles using the forced co-assembly of two oppositely charged diblock copolymers (AB + CD) into a complex-core coacervate micelle with PEO and polyacrylamide (PAAm) as coronal blocks.^38–42  This system is different from the aforementioned approaches using solvophobic blocks or crystallization (solid cores) as it yields a hydrogel-like swollen core formed by an interpolyelectrolyte complex of B [poly(2-methylvinylpyrrolidinium iodide) (P2MVP) and C (PAA). In particular, the unique, slightly asymmetric shape, the absence of cross peaks in the 2D ¹H–¹H NOESY NMR spectra and additional self-consistent field modeling support the phase-separation into Janus micelles. Detailed NOESY NMR studies confirmed cross peaks for poly(glycidyl methacrylate) (PGMA) instead of PAAm, thus proving a mixed corona of PEO and PGMA, but showed no cross peaks for the PAAm–PEO pair, thus indicating a demixed corona (Figure 1.8f–h). The segregation was found to be fairly robust as changes in the ratio and degrees of polymerization of the corona blocks, different temperatures and salt-induced modification of the association numbers did not lead to any indications of mixed coronas. So far, this system represents the most remarkable success for freely self-assembling Janus micelles.

Although the commonly observed formation of MCMs (patchy micelles) with phase-segregated coronas and multiple patches in systems targeting Janus micelles may at first glance seem disappointing, Cheng et al., for instance, demonstrated how to use those MCMs as intermediate templates to generate Janus particles by transformation reactions in solution (Figure 1.9).⁴³  They started with MCMs with PEO–poly(2-vinylnaphthalene) (P2VN) corona patches surrounding a non-covalently crosslinked PAA–diamine core, as formed by the co-assembly of PEO-b-PAA and P2VN-b-PAA diblock copolymers. Dialysis from DMF against water of pH 7 was used to trigger the collapse of the P2VN patches and a subsequent decrease in the pH value to 3.1 favored hydrogen bonding between PAA and PEO blocks, leading to the formation of one P2VN and one PAA–PEO hemisphere. TEM images of the solutions at pH 3.1 display large submicron-sized tubular aggregates coexisting with Janus micelles. The tubular structures can unwind upon ultrasonication into trapezoidal and semicircular flat particles with similar extension. The thickness of the resulting trapezoids of ∼30 nm suggests an alternating bilayer of the amphiphilic Janus particles. The complicated nature of the system using mixtures of polymers, and also various complex formations and solvent and solubility changes, do not yet allow a full picture to emerge of the unusual self-assembly processes. However, it is yet another example of the complex and often surprising self-assembly behavior of Janus particles.

Furthermore, Wooley and co-workers reported on the desymmetrization of shell-crosslinked polymer nanoparticles via a cyclic strategy to produce nanoscopic Janus particles that bear two kinds of clickable surface functional groups (thiol and azide).⁴⁴  The polymer nanoparticles were prepared through self-assembly of amphiphilic PAA-b-PS diblock copolymers in water, followed by azide functionalization and intramicellar crosslinking. The desymmetrization process involved the click conjugation of these small polymer nanoparticles with their azide functionalities on to comparably larger gold nanoparticles modified with heterotelechelic α-alkyne-ω-thiol-oligo(ethylene oxide) units. After separation of excess polymer nanoparticles, addition of more heterotelechelic ligands was used to liberate the Janus particles, now carrying both alkyne groups on the unmodified sides and thiol groups on the modified sides. The ligand exchange reactions also recovered the gold nanoparticle for further desymmetrization reactions. To confirm the anisotropic distribution of thiol groups on the resultant Janus particles, the thiol-functionalized regions were labeled with 2 nm citrate-stabilized gold nanoparticles and TEM imaging confirmed the biphasic characterization. This conjugation approach can be considered an advanced staining method to visualize compartmentalization in soft polymeric nanoparticles with weak contrast in electron microscopy.

As discussed in the previous section, it has remained very challenging to create Janus micelles via direct self-assembly in solution. However, prior to most of these investigations, the self-assembly of triblock terpolymers into a variety of bulk structures was used to design Janus particles.^45,46  Triblock terpolymers are a fascinating class of materials as they are able to form a wide variety of complex and highly defined microphase-segregated bulk morphologies.⁴⁷  The structure-guiding factors therein are the volume fractions of all components and the polymer incompatibilities as expressed by the mutual Flory–Huggins χ-parameters or interfacial tensions. Importantly, slight changes in the chemical compositions that lead to different interfacial tensions among the block segments can drastically influence the stability areas of certain morphologies. Therefore, not every triblock terpolymer displays the same amount of morphologies. Furthermore, slight external influences, e.g. the nature of the film-casting solvent, the addition of swelling solvents or crosslinking, may also trigger changes in the structure. This can, however, be turned into an advantage, as solvent annealing or film casting from selective solvents can be used to tailor the microphase-segregated structure into a specific, desirable non-equilibrium morphology.

Polystyrene-block-polybutadiene-block-poly(methyl methacrylate) (PS-b-PB-b-PMMA; SBM) is the most deeply studied triblock terpolymer system and its phase diagram is exemplarily depicted in Figure 1.10 (left). The lamellar structures were identified as suitable precursor morphologies for the fabrication of non-centrosymmetric Janus colloids. For instance, spherical Janus micelles can be prepared based on the selective crosslinking of spherical PB domains located at the interface of two lamellar domains of PS and PMMA in the so-called lamella-sphere (ls) morphology of SBM triblock terpolymers.⁴⁶  This methodology has been broadly and successfully developed by us and extended to the generation of Janus cylinders and Janus discs or Janus sheets (Figure 1.10, right).^48–51  Recently, Janus ribbons that form by a longitudinal connection of two Janus cylinders have also been synthesized due to the trapping of a metastable state during a phase transition.⁵² 

The underlying principle is to tailor the polymer structure (and also crosslinking procedures) in such a way that the geometry of the central part, B, within the microphase-segregated morphology of an ABC triblock terpolymer can be controlled in its dimensionality from spherical to cylindrical and then to a lamellar domain. This is typically achieved by increasing the weight fraction of the inner block, while keeping the weight fractions of the outer blocks symmetrical. The symmetrical volume fractions of the outer blocks maintain the overall lamellar structures, while the increase in the volume fraction of the inner block induces the phase transitions from lamella-sphere (ls) to lamella-cylinder (lc) and to fully lamellar (ll) morphology.

After a specific microphase-segregated morphology has been obtained, the non-centrosymmetric orientation of the terminal blocks, A and C, can be preserved by crosslinking the inner block, B. Thereafter, liberation of the core-crosslinked particle can be achieved via simple dissolution (in the case of spherical Janus micelles) or using an ultrasound-assisted dispersion of the crosslinked bulk films, necessary to cut down extremely long cylinders and/or large discs. A large variety of different chemical crosslinking methods, such as radical crosslinking, thermally or photo-induced dimerization or chemical crosslinking with additives, can be performed in the bulk phase. The choice of crosslinkable polymer segments is similarly wide. Some of the most frequently used include polydienes, cinnamoyl groups, polyacids/bases or gelable groups based on alkoxysilane motifs. This versatility in terms of crosslinking together with the rapid developments in controlled/living polymerization techniques over the past decade has greatly simplified the targeting of suitable polymer structures.

During the last decade, this method has been established as an extremely viable large-scale route towards the generation of nanoscopic Janus particles of different architectures. Due to the very well-defined nature of the microphase-segregated bulk structures, the resulting Janus particles also exhibit precise, near monodisperse cross-sections. Since the long period of the bulk structures depends on the overall molecular weight of the block terpolymer, the resulting dimension of the cross-section of the Janus colloid, i.e. radius, diameter and thickness of Janus micelles, Janus cylinder and Janus discs, respectively, can thereby be tuned. The sizes typically accessible via reasonable efforts in terms of accessible molecular weights of the precursor terpolymers are between 10 and 50 nm for the cross-section of the resulting colloids. Nowadays this approach allows the preparation of different Janus particles on the multigram scale (up to 100 g) with reasonable synthetic effort (a few days). The precision engineering of the particle shape, the versatility of the chemical composition and the scalability of the synthesis have proven very valuable in studying hierarchical self-assembly and potential fields of applications, as will be discussed later.

After the development of the phase diagram and the discovery of the lamella-sphere morphology in triblock terpolymers, Ishizu and co-workers⁴⁵  and Müller and co-workers⁴⁶  concurrently designed triblock terpolymer systems suitable for the preparation of Janus micelles. Ishizu and co-workers used a polystyrene-block-poly(2-vinylpyridine)-block-poly(tert-butyl methacrylate) ((PS-b-P2VP-PtBMA); SVT) polymer, which could be forced into a lamella-sphere bulk structure upon casting from toluene, being a poor solvent for P2VP.⁴⁵  The crosslinking of the central P2VP domains with 1,4-diiodobutane led to spherical-type Janus micelles with PS and PtBMA hemispheres. Light scattering analysis of the core-crosslinked Janus micelles revealed a weight-average of 47 polymers crosslinked within one biphasic particle. The Janus micelles exhibited an intensity-weighted hydrodynamic radius, <R_h>_z, of 38 nm in a good solvent (THF) for both corona hemispheres. Müller and co-workers reported detailed investigations of the synthesis and self-assembly behavior of Janus micelles based on SBM triblock terpolymers.⁴⁶  The PB center block was crosslinked by either ‘cold vulcanization’ using S₂Cl₂ or radical polymerization via a co-cast radical initiator. The resulting SBM Janus micelles, obtained after simple dispersion in organic solvents, could be converted into strongly amphiphilic and water-soluble SBMAA Janus micelles via alkaline hydrolysis of the PMMA part into poly(methacrylic acid) (PMAA).⁵³  Both species showed remarkable hierarchical self-assembly behavior in solution, as discussed below. The dedicated manipulation of the triblock terpolymer bulk phases also permits access to particle shapes of lower dimensionality, such as 1D Janus cylinders and 2D Janus discs. Both types of particles can hardly be afforded with a similar combination of precise control in cross-section, nanoscale dimensions and scalable production by any other technique.

Concerning cylindrical Janus particles, we reported their successful preparation via the selective crosslinking and subsequent dispersion of suitable lamella-cylinder bulk phase of SBM block terpolymers (Figure 1.12).^48,51  The process resulted in Janus cylinders with PS and PMMA hemicylinders that can be several micrometers in length. Liu et al. reported that the diameter of these cylinders can be adjusted via the molecular weight and resulting long period of the block terpolymer.⁴⁸  Walther et al. demonstrated that a simple sonication treatment can be used as a convenient tool to shorten the cylinders to the nanometer scale. The length was a function of both the energy and the duration of the sonication treatment.⁵¹  Suitable staining of the corona hemicylinders also allowed the two corona compartments to be discerned in TEM imaging to give solid proof for the existence of corona segregation even after transfer of the crosslinked bulk structures in solution. In a recent extension of this concept, Wolf et al. synthesized the first fully water-soluble and pH-responsive Janus cylinders based on crosslinking and subsequent hydrolysis of a poly(tert-butoxystyrene)-block-polybutadiene-block-poly(tert-butyl methacrylate) triblock terpolymer forming a lamella-cylinder phase in the bulk.⁵²  After hydrolysis, the resulting Janus cylinders were composed of one hemicylinder of poly(4-hydroxystyrene) (PHS), which is soluble above pH 10, and a second hemicylinder of PMAA, soluble above pH 4. Detailed cryo-TEM investigations and the use of Cs counterions as staining agent for the charged PMAA side-chains allowed the Janus character to be directly visualized. This represents one of the most convincing, real space proofs of Janus particles in solution and may provide guidelines for the analysis of polymer-based Janus particles or other soft multicompartment polymer nano-objects in the future.

With respect to two-dimensional Janus discs, sheets or tiles, two different synthetic systems were used for the fabrication of planar Janus particles. We reported the preparation of Janus discs based on polystyrene-block-polybutadiene-block-poly(tert-butyl methacrylate) (SBT) block terpolymers (Figure 1.13).⁴⁹  The chemical composition and incompatibility of the various components therein facilitated the formation of a fully lamellar (ll) morphology even at very low contents of PB. Although a low content of PB complicates tight crosslinking, a thin lamella of crosslinked PB simplified the dissolution of the crosslinked template, as less energy is necessary to disintegrate the crosslinked polymer structure. Owing to the low content of PB, the system was very susceptible to morphological changes upon exposure to solvents or chemicals required for the crosslinking.⁵⁴  The changes in bulk morphologies upon exposure to different crosslinking conditions were investigated in detail and revealed that careful control is required to achieve sufficient stabilization of the PB phase while maintaining the desired bulk morphology. Optimization led to the use of highly efficient thiol–polyene free radical polymerization reactions to achieve tight crosslinking of the thin PB domain.⁵⁴  After crosslinking, sonication-assisted dispersion was used to liberate the Janus discs/platelets. Similarly to the case of Janus cylinders, the particle size decayed in an exponential fashion with fragmentation of large Janus platelets into significantly smaller ones in the beginning. The average sizes could be tuned from the micrometer level down to the nanometer scale. The flat, disc-shaped character of the Janus particles was confirmed both by cryo-TEM and AFM (Figure 1.13a). Interestingly, the particles displayed a rather round-shaped appearance. This was attributed to the introduced ultrasound shock waves that tend to cut off protrusions and fragment Janus platelets along major existing crack tips, hence leading to a more circular appearance.

Recently, Zhang et al. reported the preparation of Janus discs based on the gelation crosslinking of a poly(2-vinylpyridine)-block-poly[3-(triethoxysilyl)propyl methacrylate]-block-polystyrene triblock terpolymer containing siloxane moieties in the central block. Upon gelation into a silsesquioxane network, the terminal P2VP and PS blocks of the initial block terpolymer were compartmentalized on the two sides of the dispersed colloids, leading to hybrid Janus discs/platelets.⁵⁵ 

In terms of self-assembly of completely hydrophobic SBM Janus micelles, a combination of various analytical tools, such as fluorescence correlation spectroscopy (FCS), small-angle neutron scattering (SANS) and static and dynamic light scattering (SLS and DLS), in addition to AFM, indicated the existence of an equilibrium between molecularly dissolved Janus micelles (unimers) and aggregates (multimers), so-called supermicelles.⁴⁶  The cluster formation into supermicelles was even observed in good solvents for both blocks (THF) and a surprisingly low critical aggregation concentration (cac) of ∼7 mg L⁻¹ was found with FCS (Figure 1.11a). Note that a similarly unexpected aggregation was later also observed in the case of ultrasmall Janus particles with only one polymer arm of PS and PEO tethered to a crosslinked P2VP core in SVEO triblock terpolymers (see above, Figure 1.4).⁹  The individual SBM Janus micelles and their supermicelles had number-average hydrodynamic radii, <R_h>_n, of ∼10 and 53 nm, respectively, as determined by FCS. These FCS results were corroborated by SANS and DLS and further analysis pointed to an average aggregation number of ∼11 Janus micelle subunits within one supermicelle. When adsorbed on surfaces, AFM imaging revealed a height profile similar to a fried egg (Figure 1.11b, c). Well-ordered surface patterns could be observed due to the near monodisperse character of the Janus micelles and their supermicelles. The aggregates proved to be compact and stable and also did not show any tendency to open up into individual micelles when being spread as a Langmuir monolayer from CHCl₃ solution on to a water surface.⁵⁶  The number of Janus micelles that formed a domain in the spread monolayers was found to be similar to the number of Janus micelles associating into supermicelles in solution.

In contrast to the unexpected self-assembly of SBM Janus micelles in good solvents for both corona hemispheres, the SVT ones reported by Ishizu and co-workers required exposure to a selective solvent (acetone) to induce the collapse of the PS side and present a strongly solvophobic side to stimulate further aggregation.⁴⁵  Collapse of the PS side was accompanied by a diminished <R_h>_z of 24 nm of the individual Janus micelles, compared with 38 nm before the collapse, and the occurrence of a small fraction of larger self-assemblies at 83 nm.

After hydrolysis of the PMMA segments of the SBM Janus micelles to PMAA, giving strongly amphiphilic SBMAA Janus micelles, detailed investigations of the solution properties revealed hierarchical self-assembly on two levels.⁵³  Similarly as in organic solution for the non-hydrolyzed analogues, self-assembly of single Janus particles into defined clusters took place above a cac of 0.03 mg mL⁻¹ (Figure 1.11d). The resulting spherical supermicelles showed radii of 40–60 nm, which increased significantly upon ionization at higher pH values due to the stretching of the PMAA polyelectrolyte chains. About 30 SBMAA Janus micelles formed one supermicelle. In addition to these clusters, even larger aggregates, so-called giant micelles, with sizes up to 2 μm could be identified by imaging techniques (Figure 1.11e, f). Although the detailed structure of the very large giant micelles is unknown so far, it was suggested that the internal structure may be similar to that of multilamellar vesicles, albeit being composed of particles instead of surfactant molecules.

In contrast to spherical Janus micelles of the same chemical composition, the SBM Janus cylinders did not undergo supracolloidal aggregation in a good solvent for both hemicylinders.⁵¹  DLS, SANS and cryo-TEM (in organic solvents) supported the presence of non-aggregated Janus cylinders at concentrations up to 50 g L⁻¹ in THF (Figure 1.12a). Supracolloidal aggregation could be induced by transfer into selective solvents such as acetone (poor solvent for PS), which led to the observation of fiber-like aggregates, the length of which depended on the overall particle concentration (Figure 1.12b–e). The superstructured fibers were composed of 2–4 Janus cylinders at a given cross-section, that were toposelectively aggregated to shield the inner insoluble PS hemicylinder against the solvent. A cac of 0.2 g L⁻¹ was found below which unimolecularly dissolved Janus cylinders were identified as stable particles. Below this cac, stabilization occurred via an intramolecular mechanism, in which the collapsed PS side was sufficiently protected by the PMMA arms extending around large parts of the cylinder to minimize the contact between PS and solvent. Aggregation on a second hierarchical level could be triggered when depositing Janus cylinders on surfaces from more concentrated solutions. This induced network-like patterns, in which different pore sizes and different surface compositions could be achieved simply by changing the concentration and the solvent quality.

In the case of SBT Janus discs, we identified their partial self-assembly in good solvents (THF) for both sides, PS and PtBMA.⁴⁹  Direct imaging via cryo-TEM in THF turned out to be particularly valuable in visualizing back-to-back stacking of Janus discs into sandwich-type structures. The supracolloidal aggregation could be enhanced by dispersion in selective solvents (e.g. acetone for PS). The detailed multicompartment cross-section and the inherent Janus character of the colloids could be demonstrated via embedding the aggregates into a photo-crosslinkable silicone oil, followed by microtome slicing and imaging of the ultrathin cross-sections by TEM (Figure 1.13b).

These SBT Janus discs were subsequently rendered strongly amphiphilic via acidic hydrolysis of PtBMA into PMAA, leading to SBMAA Janus discs consisting of one PS and one PMAA side.⁵⁰  Significant differences in the solution behavior were identified for differently sized Janus discs. Small discs (diameter <200 nm) showed only a minor amount of superstructures as seen by AFM and cryo-TEM and were thus mostly not aggregated via back-to-back stacking. The long PMAA chains, protruding out from the other side, partly shielded and sufficiently stabilized the fully collapsed, hydrophobic PS sides of the Janus discs against water. Significantly larger Janus discs were unable, however, to protect fully the PS side by expanded PMAA chains and displayed strong crumbling and bending and protected the PS side mostly via an intraparticle mechanism, i.e. by flipping over one part of the structure. Owing to the intrinsic stiffness of the crosslinked layer, efficient bending is favored with increasing size of the particle. Interestingly, large-scale back-to-back stacking was mostly not observed for this system and the presence of large hydrophobic faces exposed to water remains an unexpected observation.

Binks and Fletcher’s first prediction of the enhanced interfacial adsorption capabilities of biphasic Janus particles spurred significant efforts to develop advanced particulate surfactants.⁵⁷  Janus particles uniquely combine amphiphilicity known from classical surfactants with the Pickering character that strongly holds solid particles at interfaces. Their calculations predicted an up to threefold stronger adsorption of Janus particles compared with particles of uniform wettability. This effect is most relevant for nanoscale particles, as the dynamics on this length scale are much higher than for micron-scale particles, whose adsorption strength is already very large simply due to the Pickering effect. Therefore, breaking the symmetry of nanoscale particles can lead to substantial and crucial improvements of the interfacial desorption energy compared with thermal energy. Moreover, since the engineering capabilities of particle synthesis nowadays allow precise tailoring of the particle architecture, it is also possible to nanostructure the interface laterally or impart additional properties, such as side-selective reflectivity or catalysis.

A first proof of principle for the enhanced interfacial activity of Janus nanoparticles was delivered by Glaser et al., who verified that bimetallic slightly amphiphilic Janus particles indeed induce a larger decrease in the quasi-equilibrium interfacial tension of liquid/liquid interfaces as compared with homogeneous particles.⁵⁸  Following this demonstration, we investigated the size-dependent effects of disc-shaped SBT⁴⁹  and cylindrical SBM Janus particles⁵⁹  on the interfacial tensions of liquid/liquid interfaces. In both cases, progressively enhanced adsorption was found for Janus particles when increasing their dimensions, i.e. Janus disc diameter and Janus cylinder length, respectively (Figure 1.14a, b). Nonetheless, one has to keep in mind that these results are expected based on simple considerations of the Pickering effect, which basically states that the maximum of the desorption energy of a solid homogeneous sphere located at a liquid/liquid interface is proportional to the square of its radius (E ∼ R²). However, more important were the observations that Janus discs are significantly more powerful in reducing the interfacial tension as compared with the linear, non-crosslinked terpolymer, serving as precursor polymer for the synthesis of the Janus particles. Moreover, a comparison of the effectiveness of Janus cylinders of a given length with that of a homogeneous cylinder (e.g. core–shell PB–PS) clearly demonstrated a significantly higher interfacial activity, thereby further justifying research on advanced Janus-type surfactant particles (Figure 1.14b). Additionally, Ruhland et al. also characterized the time-dependent evolution of the surface structures formed during the adsorption of Janus cylinders at interface.⁵⁹  Initially, only isolated cylinders were observed in ex situ TEM images of the deposited interfacial areas. After prolonged adsorption, an increasingly better order with a local mesoscale liquid crystalline arrangement of the cylinders could be found, indicating pathways towards nanostructuring of droplet interfaces (Figure 1.14c). Thereafter, loosely attached multilayers were observed near the quasi-equilibrium interfacial tension at which the interface was nearly completely covered.

In terms of real-life and industrially relevant applications, we employed amphiphilic SBMAA and SBM Janus micelles (diameter ∼20 nm) as stabilizer for emulsion polymerization⁶⁰  and compatibilizer for polymer blends,⁶¹  respectively.

Emulsion polymerizations of styrene and n-butyl acrylate could be conducted in a facile batch process and did not require additives or miniemulsion polymerization techniques, as do other Pickering emulsion polymerizations using non-amphiphilic particles. The resulting latex dispersions displayed very well-controlled particle sizes with extremely low polydispersities, typically below 1.02 (Figure 1.14d). The particle size was controlled by the amount of particulate stabilizer added to the system. A detailed analysis of the surface coverage of the latex particles revealed a loose coverage of the latex surface by the Janus particles, in which the surface area stabilized by one Janus particle exceeded its cross-section several times (Figure 1.14e). A comparison with block copolymer systems or standard Pickering particles known from the literature strongly indicates a superior performance of the Janus particles and thus renders this material and simple process highly interesting for further fundamental studies and also industrial applications.

In a second application study, we used SBM Janus particles on a multigram scale for the blend compatibilization of a PS–PMMA polymer blend system in a twin-screw mini-mixer.⁶¹  It was shown that the Janus particles locate exclusively at the interface of the two polymer phases despite the high temperature and shear conditions (Figure 1.14f). Constant decay of the domain size of the dispersed phase could be observed, independent of the blend composition used. The performance of the Janus particles in compatibilizing the polymer blend was found to be significantly superior to other state-of-the-art compatibilizers, such as linear triblock terpolymers of the same composition. Common problems such as micellization of the stabilizer and insufficient adsorption at the interface were absent to a major extent. The origin of the continuous decrease lies in the enhanced adsorption of the Janus particles at the interface, which is in turn caused by their biphasic particle character. In contrast to block copolymers or homogeneous particles, the Janus particles are located at the interface, even at high temperature and shear, because the desorption energy of a Janus particle from the interface under processing conditions was calculated to be almost as high as for a homogeneous particle at room temperature. In addition, the Janus particles exhibited an ordered arrangement at the polymer blend interface. Therefore, they provide efficient means for the nanoscopic engineering of polymer blend systems while matching macroscopic processing constraints.

The toolbox of polymer chemistry and the self-assembly capabilities of block copolymers provide powerful strategies for the preparation of nanoscopic, responsive and precisely structured Janus particles with a wide range of architectures. Although some limitations clearly remain to be overcome as in the case of the direct self-assembly and spontaneous symmetry breaking of block copolymers in solution, other approaches have evolved into large-scale synthetic routes for precisely engineered soft nano-objects. This has not only allowed the detailed study of the unusual self-assembly behavior of different Janus particles as a function of the architecture, but also permitted prototype application studies employing these particles as advanced particulate surfactants.

What could be some of the next challenges to master? There is still a need to develop even simpler, direct and large-scale access routes to soft nanoscopic Janus particles. Attracting further attention from industry requires finding solution-based strategies that are feasible at high concentrations during particle synthesis and allow easily tunable chemistry. Progress in this direction could push the developments in the direction of interfacial compatibilizers further from laboratory-scale models into technological processes for high-end applications.

On a more fundamental level, there is still a lot of unexplored territory with respect to controlled stimulus-responsive self-assembly, in which simple triggers achieve large rearrangements of structures and properties. Encoding the ability for programmable and on-demand structure formation based on such ‘intelligent’ Janus particles may be formulated as one of the ultimate goals. Furthermore, hardly any application studies have addressed fields beyond the stabilization of interfaces. Just to name one field of interest, such small compartmentalized particles with well-defined functionalities located inside polymer coronas are, for instance, ideal candidates for biomedical applications and the amphiphilic character may well lead to fundamentally different interactions with cell membranes and opens up possibilities for spatially separated biosensing/biotargeting and detection. Therefore, interfacing the progress on the side of macromolecular engineering and polymer self-assembly further with application specialists would span some crucial gaps and aid in the focused development of new generations of tailored and responsive soft Janus nano-objects.