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Functional Microgels and Microgel Systems Published as part of the Accounts of Chemical Research special issue “Stimuli-Responsive Hydrogels”. Felix A. Plamper† and Walter Richtering*,†,‡ †
Institute of Physical Chemistry, RWTH Aachen University, Landoltweg 2, 52056 Aachen, Germany DWI-Leibniz-Institute for Interactive Materials, 52074 Aachen, Germany
‡
CONSPECTUS: Microgels are macromolecular networks swollen by the solvent in which they are dissolved. They are unique systems that are distinctly different from common colloids, such as, e.g., rigid nanoparticles, flexible macromolecules, micelles, or vesicles. The size of the microgel networks is in the range of several micrometers down to nanometers (then sometimes called “nanogels”). In a collapsed state, they might resemble hard colloids but they can still contain significant amounts of solvent. When swollen, they are soft and have a fuzzy surface with dangling chains. The presence of cross-links provides structural integrity, in contrast to linear and (hyper)branched polymers. Obviously, the cross-linker content will allow control of whether microgels behave more “colloidal” or “macromolecular”. The combination of being soft and porous while still having a stable structure through the cross-linked network allows for designing microgels that have the same total chemical composition, but different properties due to a different architecture. Microgels based, e.g., on two monomers but have either statistical spatial distribution, or a core−shell or hollowtwo-shell morphology will display very different properties. Microgels provide the possibility to introduce chemical functionality at different positions. Combining architectural diversity and compartmentalization of reactive groups enables thus short-range coexistence of otherwise instable combinations of chemical reactivity. The open microgel structure is beneficial for uptake-release purposes of active substances. In addition, the openness allows site-selective integration of active functionalities like reactive groups, charges, or markers by postmodification processes. The unique ability of microgels to retain their colloidal stability and swelling degree both in water and in many organic solvents allows use of different chemistries for the modification of microgel structure. The capability of microgels to adjust both their shape and volume in response to external stimuli (e.g., temperature, ionic strength and composition, pH, electrochemical stimulus, pressure, light) provides the opportunity to reversibly tune their physicochemical properties. From a physics point of view, microgels are particularly intriguing and challenging, since their intraparticle properties are intimately linked to their interparticle behavior. Microgels, which reveal interface activity without necessarily being amphiphilic, develop even more complex behavior when located at fluid or solid interfaces: the sensitivity of microgels to various stimuli allows, e.g., the modulation of emulsion stability, adhesion, sensing, and filtration. Hence, we envision an ever-increasing relevance of microgels in these fields including biomedicine and process technology. In sum, microgels unite properties of very different classes of materials. Microgels can be based on very different (bio)macromolecules such as, e.g., polysaccharides, peptides, or DNA, as well as on synthetic polymers. This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general, fundamental features of microgels are independent of the chemical nature of the building moieties. Microgels allow combining features of chemical functionality, structural integrity, macromolecular architecture, adaptivity, permeability, and deformability in a unique way to include the “best” of the colloidal, polymeric, and surfactant worlds. This will open the door for novel applications in very different fields such as, e.g., in sensors, catalysis, and separation technology.
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INTRODUCTION
we focus on submicrometer-sized microgels, which are often prepared by precipitation polymerization). When collapsed, microgels can behave as hard colloids, while still containing solvent. In contrast, they are soft with a fuzzy surface and dangling chains when they are swollen. Most essential, the
There are three major classes of colloids: rigid particles, flexible macromolecules, and micellar aggregates based on surfactants. Microgels being macromolecular networks of colloidal size and swollen by the solvent, however, do not directly fit into only one of these categories, as illustrated in Figure 1.1 The microgel’s architecture is determined by its chemical connectivity within the finite-size network (within this Account, © XXXX American Chemical Society
Received: October 31, 2016
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Figure 1. Diversity of the colloidal realm: microgels (center) unite properties of fundamental classes of colloids, i.e., rigid particles, flexible macromolecules, and surfactants.
Figure 2. Schematic illustration of penetrable core−shell microgels with different chemical functionalities (indicated by different symbols) in core and shell, respectively; the interstitial transport plays an additional role, especially when microgels of different types are assembled into a device.
presence and the amount of cross-links determines their “colloidal” or “macromolecular” character.2 In addition, microgels exhibit extraordinary interfacial properties, though they do not necessarily possess an amphiphilic nature (which is in contrast to surfactants). Due to solvent inside the microgels, they are soft objects where the term “soft” applies twofold: (i) microgels can have a soft interaction potential as it is known from other colloidal systems; (ii) the microgel itself is soft and deformable, while still retaining its structural integrity. The swelling results in an open structure with high mobility of solvent and solute molecules, chain segments as well as of the entire microgel. Therefore, mass exchange with the surroundings is fundamentally different from other colloids: there is no sharp boundary between inside and outside, and the exchange of solvent and solutes between microgel and environment can alter size and shape of the microgel itself. In other words, microgels are sensitive to their environment; they interact with it through adaptation of their size, shape, and properties. Microgels can even combine different modes of mass transport, i.e., solely by diffusion inside the microgel structure next to diffusive or fielddriven displacement of the microgel itself. These unique conceptual combinations of structure with chemical and physical properties are illustrated in Figure 2. These unique properties of polymer microgels need to be programmed at the synthesis stage where selection of the building blocks, reaction sequence, and reaction conditions will determine such important parameters as size, shape, swelling degree and chemical as well as topological composition. Consequently, the advanced chemical design of microgels has inspired in recent years both fundamental research of microgel properties, application potential in materials science, and chemical processes. In all cases, porosity and deformability are beneficial features, which will be discussed below in more detail. Further, microgels are capable to respond to external stimuli such as, e.g., temperature, ionic strength, pH, electrochemical stimulus, pressure, and light. The subsequent adjustment of both their shape and volume provides the opportunity to reversibly tune their physicochemical properties. Then, their intraparticle properties are closely linked to their interparticle interactions. This includes their equilibrium and nonequilibrium phase behavior, as well as transport properties. Microgels both in bulk and at interfaces exhibit macromolecular or polyelectrolyte properties on a length scale comparable to the
mesh size, polymer network features on scales comparable to the size of an individual microgel, and (soft) colloidal behavior on a scale comparable to the mean interparticle distance.3 In other words, microgels exhibit combined properties of very different classes of materials, uniting the “best” of the colloidal, polymeric, and surfactant world. In the following, we will address specific examples for the key properties of microgels (functionality, architectural versatility, permeability, deformability), enabling applications in a technological or biomedical context. This Account focuses on synthetic microgels (mainly based on acrylamides); however, the general fundamental features can also be achieved by microgels based on biopolymers such as, e.g., polysaccharides, peptides, or DNA.
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FUNCTIONALITY Functional chemical groups or anchoring groups for chemical functionality are often introduced during the microgel synthesis. Precipitation polymerization allows preparing microgels with variable size and low dispersity in size.4 Hereby, monomers turn into polymers, which are eventually insoluble in the solvent under the polymerization conditions.5 After an initial nucleation period, which determines the number of particles, freshly polymerized polymer adds onto the preformed nuclei leading to a continuous growth with conversion. By help of a cross-linker (like N,N′-methylene-bis(acrylamide) or even degradable ones6), the assembled polymer chains remain positioned within the network, which can then swell under appropriate conditions. As an example, the polymerization of N-isopropylacrylamide NIPAM at high temperatures leads to colloidal particles, which soak up water upon cooling due to the thermosensitivity of the PNIPAM scaffold. In addition, PNIPAM microgels show sensitivity toward hydrostatic pressure7 and solvent composition.8 PNIPAM-based microgels are readily available, allowing the incorporation of considerable amounts of functional comonomers (see Scheme 1). The same is true for other scaffolds like poly(N-vinylcaprolactam) PVCl, poly(N,N-diethylacrylamide) PDEAAM, or poly(N-isopropylmethacrylamide) PNIPMAM. Generally, hydrophilic comonomers can be randomly distributed within the network as long as B
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Accounts of Chemical Research Scheme 1. Exemplary Monomers Used for Functional Microgels
and even (magnetic16/plasmonic17) nanoparticles get absorbed into or adsorbed onto the microgel (see below). This supramolecular assembly approach can be also extended to hydrogen bonding or hydrophobic cavities (like cyclodextrins)18 as coupling motifs (see Figure 3). Further, decoration of the network with crown ethers allows the complex formation with ions, making the microgels reversible polyelectrolytes.19 Apart from such a supramolecular modular assembly, functional groups can be covalently attached to the microgel network. This was demonstrated for, e.g., redox-active units.20,21 Lightsensitivity can be introduced via monomers (like azobenzene compounds,22 spyropyran derivatives or photo-cross-linkers23) or surfactants24 and allow even a variation of the thermoresponsive properties by illumination.
the overall copolymer is still solvophobic enough during the preparation conditions. In need of highly charged microgels, however, a different route via an emulsion polymerization of protected monomers is available.9 The functional comonomers comprise anionic or cationic moieties (like acrylic acid or N-(3-aminopropyl) methacrylamide, respectively), giving yield to polyelectrolyte microgels with10 and without a pH-dependent degree of ionization (the latter can be achieved by quaternization of the amino groups).11,12 These ionic groups often lead to a considerable swelling of the microgels in water dispersion and they can act as anchor points toward other entities, complexing with the charged units. Small multivalent counterions,13 oppositely charged polyelectrolytes,14 proteins and enzymes,15 C
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Figure 3. Pathway to supramolecularly cross-linked microgels (Reproduced with permission from ref 18. Copyright 2016 The Royal Society of Chemistry).
Figure 4. Thermoinduced collapse of hollow core−shell−shell microgels with different transition temperatures for the shells (Adapted with permission from ref 39. Copyright 2016 Macmillan Publishers Ltd.).
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ARCHITECTURE Many microgels do not have a homogeneous segment density within their swollen structure. This is mainly due to different reactivities of monomer and cross-linker, which when being consumed faster, leads to higher segment densities in the interior, while a fuzzy surface with dangling chains constitutes the outer part.25 Still, (inverse) miniemulsion methods can be used to approach constant segment densities also in the swollen state.26 These examples already indicate that homopolymer microgels (including additional cross-linker) can have different architectures and internal structures. Recent improvements in synthesis provide access to ultralow cross-linked microgels,27−29 hollowish microgels with lower segment density in the center,30,31 up to hollow microgels.32 Here, cross-linking procedures after particle formation were introduced as well as the use of sacrificial cores, which can be dissolved after microgel synthesis. It was shown for the latter example that higher crosslinking densities of the microgel shell prevent (back-)swelling of the shell into the interior upon core removal.33 Besides these structural diversity in homopolymer microgels, there is much more variability when taking different compartments inside copolymer microgels.34 As one of the first examples, core−shell microgels were established by seeded
growth precipitation polymerizations onto preformed core particles.35,36 As one option, thermoresponsive polymers with different volume phase transition temperatures (VPTTs) were united, while the sequence of polymer shells and the respective VPTTs of each component influence the total swelling behavior of the microgel. A corset effect was observed,37 when a polymer shell with lower VPTT was used, while the core (with higher VPTT) is already ready for water uptake.38 As an extension of this approach, hollow microgels that consist of two network shells with different sensitivity, e.g., to temperature, were developed (see Figure 4).39 This allows controlling colloidal stability and permeability independently. Not only a distinct core−shell(−shell) architecture is easily available, but also a rather random placement of smaller hydrophobic domains40 within the microgels are possible (dirty snowball structure).41 Besides the interplay of regions with different phase transition temperatures and hydrophilicity, the combination of pH-sensitive, (oppositely)42 charged and uncharged35,43 regions leads to microgels the swelling of which depends strongly on their morphology. Core−shell-type structures reveal distinctly different pH-dependent swellling in contrast to polyampholytic microgels (which include also zwitterionic microgels)44 with random distribution of cationic and anionic D
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substantial complexation between these entities and the microgel is observed.55 Even more, the microgel selectively incorporates one type of the redox-couple, especially in the heat, where the collapsed microgel acts like an insulated parcel for ferricyanide (hexacyanoferrate(III)). After using the thermotriggered change in charge density for the study on the electrochemical behavior of redox-active entities in porous colloidal dispersions, we could also introduce electrochemistry as a novel stimulus56 to modify the size of microgels (at constant temperature).13 By electrolysis, the size can be reversibly switched, which is accompanied by an electrotriggered uptake and release of hexacyanoferrates (see Figure 6).56 Within the microgel network, the hexacyanofer-
moieties. The latter provide a pronounced collapse close to the isoelectric point.45 Though hardly the focus now, we envision that anisotropic microgels will add additional architectural freedom to these systems, especially when expanding the above-mentioned variability toward the anisotropic structures.19 In this direction, surface-bound microgel strings have been produced, which could be used as templates for the generation of aligned, conductive gold leads with diameters in the 300 nm range.46
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PERMEABILITY Swollen microgels are permeated by solvent, allowing the diffusion of smaller entities into the interior of the microgel. Taking advantage of the above-mentioned compartmentalization, microgels are on the verge to act as housing and/or reaction site for multistep chemical transformations (“microfactories”; see also Figure 5). The transport of molecules can be
Figure 5. Illustration of the different localizations of enzymes of various sizes after ab-/adsorption into and on microgels (Reproduced with permission from ref 52. Copyright 2015 American Chemical Society).
even stimulated by action of the stimuli-sensitive swelling/ collapse. A sponge-like uptake of biomaterial facilitates the microgel loading: the swelling “sucks” the surrounding molecules into the interior of the particles.47,48 In case of more hydrophobic enzymes, collapsed microgels show enhanced uptake.15 At the same time, the microgels can be used as phase-transfer shuttles for enzymes and nanoparticles from aqueous to organic solvent and vice versa.49 In general, the relative size of the interacting entity and the microgel mesh size is decisive,50,51 whether the interior of the microgel is accessible (an intramolecular size exclusion). Absorption is mainly encountered when the guest size is smaller than the microgel mesh size, while in the opposite case mainly adsorption onto the outer regions of the microgels is observed.43 A similar principle was observed for enzyme uptake, as larger enzymes are located at the outside, while smaller enzymes penetrate into the interior of the microgel.52 The latter bienzymatic systems with different locations of the enzymes can be regarded as one of the first microgel factories, as catalytic cascade reactions are possible within one colloidal entity (see Figure 5).52,53 The availability of complexing guest entities toward surface reactions was studied, namely, toward electrochemical conversions.54 It is expected that center-bound redox-active entities cannot directly participate in the electrochemical conversion due to the large distance to the electrode, which is kept by the overall microgel dimensions. By exchange (in the case of freely moving entities) or by an electrohopping mechanism, still a considerable part of the redox-active units can be electrochemically addressed. In the time scale of the electrochemical experiments, the main electron pathway constitutes the electron transfer to/from freely diffusing electroactive entities, though a
Figure 6. Switching the size of microgels by electrochemical stimulation: simplified schematic illustration (top) and reversible size changes (bottom; adapted with permission from ref 13. Copyright 2015 American Chemical Society).
rates lead then to some additional physical cross-linking.57 As other approaches to electroactive microgel systems, incorporation of polyaniline into the microgel,58 ferrocene units in the backbone,59 and ruthenium complexes as pendent groups20 were suggested.
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DEFORMABILITY An intriguing feature of microgels is their adaptivity: they can deform and adapt their shape to their surroundings. This is already seen when incorporating swollen microgels with different sizes into colloidal crystals. A minor microgel component of larger size deswells to fit into the lattice of the major microgel component of smaller size.60 At the same time, microgels can translocate pores, which are considerably smaller than their actual size (swollen state).61 Due to their deformability, they tend to stick to solid interfaces in a pancake-like conformation,62,63 leading to a substantial deformation (expansion parallel to surface; compression in direction perpendicular to surface) compared to the unperturbed state in suspension (see Figure 7).64 The degree of cross-linking is of great relevance for the shape of adsorbed microgels:2,30 a transition from spherical shape to a flat adlayer is observed and the stresses that occur during the E
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Figure 8. Simulation snapshot of a hollow microgel adsorbed at an oil−water interface (Adapted with permission from ref 77. Copyright 2015 American Chemical Society).
Figure 7. Deformation of adsorbed microgels shown by a scanning force microscopy height image (Adapted with permission from ref 2. Copyright 2016 American Chemical Society).
adsorption can even lead to bond breakage. Physically crosslinked microgels can even form ultrathin films.65 Often, the mode of interaction with surfaces can be of electrostatic nature.13 In case of platinum surfaces, there is only limited adsorption, as seen by electrochemical impedance data.55 However, hydrophobic graphite surfaces provide a rather irreversible way of microgel attachment, though the ionic microgel can then be largely swollen after adsorption. Hence, the hydrophobic contacts of PNIPAM-based microgel and the surface are less detrimental than the water−graphite interface. Further, higher microgel coverage can be reached if the adsorption takes place in the collapsed state.47 Such microgel layers were used for thermo-switchable cell-adhesion66 or gates for polymer adsorption onto multilayers.67 When going to a liquid−liquid interface, the structure of the microgel is again altered, as part of the microgel protrudes into the oil phase, which is a nonsolvent for the polymer used. Polymers are known to adsorb to interfaces even without being amphiphilic, such as, e.g., poly(ethylene oxide)68 or PNIPAM.69,70 Here the notion amphilicity is understood as the capability of undergoing segregational self-assembly, i.e., the formation of micelles. Microgels that reveal no self-assembly in bulk solution can adsorb to interfaces and again, strong deformation is observed parallel to the interface in order to cover as much interface as possible.71−77 Hereby detrimental oil/water contacts are prevented, Figure 8. Perpendicular to the interface, a swollen “hemisphere” is connected to a smaller collapsed hemispherical domain. This unique structure is also responsible for exceptional properties of microgel-stabilized emulsions, sometimes called mickering emulsions, Figure 9.79,78 Such microgel-stabilized emulsions can be broken upon applying a trigger and are in contrast to particle-stabilized Pickering emulsions, which lack the action of deformation. As mentioned above, introducing charged moieties into microgels strongly affects their swelling in the aqueous bulk phase.12 At oil−water interfaces, the influence of electrostatic interaction is still poorly understood. The packing of microgels
Figure 9. Optical micrograph of an oil-in-water emulsion consisting of heptane droplets stabilized with cationic (blue) and anionic microgels (yellow), showing noncoalescence (Adapted with permission from ref 79. Copyright 2012 National Academy of Sciences).
at the interface is hardly affected by the charges80,81 however, compression80 and shear moduli are affected,82 indicating that viscoelastic properties of the microgel-covered interface are relevant for emulsion stability.83
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APPLICATIONS The above-mentioned properties of microgels make them interesting as easily available entities for a number of applications and in the following we will mention a few. Of industrial importance is the on-demand stabilization84 and breakage of emulsions.85,86 Here, the switchable emulsion stability was utilized for biocatalytic systems, where a waterbased enzyme transforms an oil-soluble substrate. Due to the large interface in case of the emulsion, facilitated transfer and subsequent conversion of the reactants is achieved. After accelerated reaction, the product can be easily separated from the enzyme upon triggered emulsion breakage, while the microgel and enzyme can be used for another reactor cycle.87,88 When further discussing microgel/enzyme systems, microgels can be employed to immobilize and protect enzymes in organic solvents.89 Furthermore, surface-attached microgels can be perfect templates for the deposition of these biocatalysts. This is due to the fact that swollen microgels consist mainly of water and easily preserve the structure of the enzymes,90 even for capricious examples.52 When using electrode surfaces for microgel and enzyme deposition, biosensors for, e.g., phenol F
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Finally, we want to mention, without discussing details, that medical applications are envisioned that exploit the specific properties of microgels.99−103
could be constructed, as the product of the enzymatic oxidation (quinone) is detected electrochemically.47 As another approach, surface-bound ordered microgel layers (etalons) were developed for the optical readout of analytical signals, as the analyte-dependent swelling leads to a shift in the Bragg peaks of the photonic materials.91 By uniting microgels with nanoparticles, these constructs can be used also for analytical purposes in terms of surfaceenhanced Raman scattering, making again use of the sizeselective detection due to the size-exclusion effect of the microgel.92 Nanoparticle possess also catalytic properties. Hence, it was demonstrated that the thermoresponsive properties of microgel/nanoparticle hybrids allows modulating the catalytic conversion with temperature,93 while the change in hydrophobicity even endows a modulated catalytic selectivity (switchable preferential conversion of one of the reactants).94 Due to their unique chemical functionality, physical properties, and in particular their interfacial behavior, microgels represent a new platform for soft matter materials as discussed above. The functional microgels are then part of a larger system, where the microgel contributes a vital property to the application system. The new desired functionality causes two challenges in chemical engineering unit operations: microgel functionalities have to be engineered for the desired application (product design) and the fabrication process has to be tailored to achieve the desired functionality (process design). A bottleneck in industry-scale microgel production is their purification, as ultracentrifugal separation, which is often used on lab scale, is hardly applicable on large scale. Hence, ultrafiltration has been proposed as a possible workup, which however can suffer from filter cake formation. This filter cake formation has been studied by microfluidic approaches.95 At the same time, conditions have been identified, which allow the purification of microgels with ultrafiltration procedures.96 The blocking of membranes with microgels can be also turned into an advantage: microgels were used for their infiltration into hollow-fiber membranes, which lead to an easy preparation of thermoresponsive membranes with temperature-dependent permeability (Figure 10).97,98 This is also an example of how microgels bring function to a composite material.
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CONCLUSIONS AND PROSPECTS Microgels are on the verge of their extensive implementation in applications because of their unique combination of special features: structural integrity, compartmentalization, orthogonal functionalization, softness, deformability, permeability, and adaptivity. The grand challenge of microgel research is to combine in a modular approach (i) the curiosity-driven research on new functional microgels with (ii) their application-driven assembly to functional systems and finally (iii) a product-process design that considers the desired properties of the microgel, the microgel system as well as the processes during synthesis, assembly, and application (see Figure 11). We anticipate that microgels will attract even more
Figure 11. Illustration of the interplay between product design and process design to transfer the chemical functionality into applications.
researchers in the future and the development of more and more products based on this very peculiar class of colloids is soon to come.
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected]. ORCID
Felix A. Plamper: 0000-0002-0762-6095 Walter Richtering: 0000-0003-4592-8171 Notes
The authors declare no competing financial interest. Biographies Felix A. Plamper studied chemistry at the University of Bayreuth, Germany, and at the Lund University, Sweden. After his Ph.D. under the supervision of Axel Müller (Bayreuth), he joined in 2007 the group of Heikki Tenhu for a postdoctoral stay at the University of Helsinki, Finland. He completed his habilitation at the RWTH Aachen
Figure 10. Scanning electron micrograph of a microgel-modified polymer membrane (like shown in ref 97; microgels are seen as submicrometer-sized spheres on top and inside the pores). G
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University, Germany, becoming a docent in 2015. His main interest is in complexation phenomena in polymeric systems. He was awarded several scholarships and prizes (like the Young Scientist Prize of the German Chemical Society - GDCh-Fachgruppe Makromolekulare Chemie). Walter Richtering studied chemistry at the universities of Bochum and Freiburg and obtained his Ph.D. with Prof. Burchard at the University of Freiburg. Afterward, he joined the University of Massachusetts as Feodor-Lynen Fellow of the Alexander von Humboldt Foundation. He was appointed Professor for Physical Chemistry at Kiel University in 2000 and to the chair of Physical Chemistry at RWTH Aachen University in 2003. In 2016 he was appointed as associated leading scientist at the DWI-Leibniz-Institute for Interactive Materials. He is coordinator of the collaborative research centre 985 “Functional Microgels and Microgel Systems”.
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ACKNOWLEDGMENTS We acknowledge the financial support of the Deutsche Forschungsgemeinschaft within the SFB 985 Functional Microgels and Microgel Systems.
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