pubs.acs.org/Langmuir © 2009 American Chemical Society
Retrospective on the Future of Polyelectrolyte Multilayers† Joseph B. Schlenoff* Department of Chemistry and Biochemistry, The Florida State University, Tallahassee, Florida 32306 Received June 1, 2009. Revised Manuscript Received June 27, 2009 The layer-by-layer, or multilayer, method of thin film growth has evolved into a widely-used enabling technology. Starting in the mid 1990’s, an exponentially increasing number of publications on the topic, many appearing in this Journal, have shown how multilayers may be adapted to passive and active coatings, devices and architectures. Looking forward, this Perspective briefly summarizes some of the most promising emerging ideas and applications.
With roots in an extraordinarily prescient publication by Iler1 in 1966, the modern age of polyelectrolyte multilayering was initiated at the beginning of the 1990s.2 A volume on the topic, published in 2003,3 along with other review articles4-6 documents the rapidly expanding interest in, and potential uses for, these versatile thin films. Much of the groundbreaking research has been reported in the pages of Langmuir. Rather than laying out a comprehensive list of potential applications, this Perspective will attempt to highlight the most promising emerging areas of practical and fundamental importance in polyelectrolyte multilayers (PEMUs, an acronym that describes the material) or layerby-layer assembled films (LbL films, where the acronym is for the process). A preliminary survey of the exponentially growing body of literature might suggest that the field is mushrooming rather than maturing. The theme that “anything nano” is a potential building block for multilayers was appreciated early (perhaps as far back as Iler’s work): polymers, dendrimers, colloids, clay minerals, carbon nanotubes, and viruses. However, several basic principles, many recently established, have been developed such that the tool kit of starting materials is now matched by a tool kit of ideas. What might the future hold?
New Approaches to Multilayering Using the traditional alternating dipping method, d-LbL, the multilayering process itself is slow, even if it is automated. Methods for preparing multilayers have evolved to accelerate the coating process and to bring the technique out of the smallscale laboratory environment. If the substrate is spun while immersed, then enhanced mass transport by convection speeds up the deposition by an order of magnitude. The resulting films are also more uniform and smoother. We have been employing † Part of the “Langmuir 25th Year: Self-assembled polyelectrolyte multilayers: structure and function” special issue.
(1) Iler, R. K. J. Colloid Interface Sci. 1966, 21, 569–594. (2) Decher, G. Science 1997, 277, 1232–1237. (3) Decher, G.; Schlenoff, J. B. Multilayer Thin Films: Sequential Assembly of Nanocomposite Materials; Wiley-VCH: Weinheim, Germany, 2003. (4) Bertrand, P.; Jonas, A.; Laschewsky, A.; Legras, R. Macromol. Rapid Commun. 2000, 21, 319–348. (5) Hammond, P. T. Adv. Mater. 2004, 16, 1271–1293. (6) Sukhishvili, S. A.; Kharlampieva, E.; Izumrudov, V. Macromolecules 2006, 39, 8873–8881. (7) Dubas, S. T.; Schlenoff, J. B. Macromolecules 1999, 32, 8153–8160.
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such hydrodynamic LbL (h-LbL) deposition for about a decade.7 Hydrodynamic methods are also effective for coating the internal surfaces of tubes and channels, such as microfluidic systems. Spin assembly, sa-LbL, marries traditional rapid spin coating of polymers on substrates with the self-limiting aspects of adsorption.8-10 Sprayed films, sp-LbL, can be prepared quickly over large areas.11-13 Films grown in the exponential regime, e-LbL14-16 adsorb larger amounts of material, requiring fewer layers, and preformed complexes are another avenue for speeding up deposition.17 Perhaps we will soon see hyphenated deposition, such as sp-e-LbL, rapidly providing films of adequate thickness.
Passive Coatings A few layers are often sufficient to control the surface or interfacial properties of an article. There has been much excitement over superhydrophobic18 and superhydrophilic LbL coatings. These often involve both polymers and particles as well as roughness to minimize contact angle hysteresis. Key issues with such coatings are speed of application and durability. For the simple control of wetting, the LbL method competes with a one-pass dip or spray coating. The multifunctionality of a multilayer might provide added value/ properties. We are likely to see further biomimetic multilayer coatings.19 Electroosmosis is another phenomenon influenced by just a layer or two. Polyelectrolytes are well suited to establishing a reproducible surface charge essential for electroosmotic flow, (8) Cho, J.; Char, K.; Hong, J. D.; Lee, K. B. Adv. Mater. 2001, 13, 1076–1078. (9) Chiarelli, P. A.; Johal, M. S.; Casson, J. L.; Roberts, J. B.; Robinson, J. M.; Wang, H. L. Adv. Mater. 2001, 13, 1167–1171. (10) Lee, S.-S.; Hong, J.-D.; Kim, C. H.; Kim, K.; Koo, J. P.; Lee, K.-B. Macromolecules 2001, 34, 5358–5360. (11) Schlenoff, J. B.; Dubas, S. T.; Farhat, T. Langmuir 2000, 16, 9968–9969. (12) Kolasinska, M.; Krastev, R.; Gutberlet, T.; Warszynski, P. Langmuir 2009, 25, 1224–1232. (13) Izquierdo, A.; Ono, S. S.; Voegel, J. C.; Schaaf, P.; Decher, G. Langmuir 2005, 21, 7558–7567. (14) Elbert, D. L.; Herbert, C. B.; Hubbell, J. A. Langmuir 1999, 15, 5355–5362. (15) Porcel, C.; Lavalle, P.; Ball, V.; Decher, G.; Senger, B.; Voegel, J. C.; Schaaf, P. Langmuir 2006, 22, 4376–4383. (16) Picart, C.; Mutterer, J.; Richert, L.; Luo, Y.; Prestwich, G. D.; Schaaf, P.; Voegel, J. C.; Lavalle, P. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 12531–12535. (17) Guo, Y.; Geng, W.; Sun, J. Langmuir 2009, 25, 1004–1010. (18) Zhai, L.; Cebeci, F. C.; Cohen, R. E.; Rubner, M. F. Nano Lett. 2004, 4, 1349–1353. (19) Zhai, L.; Berg, M. C.; Cebeci, F. C.; Kim, Y.; Milwid, J. M.; Rubner, M. F.; Cohen, R. E. Nano Lett. 2006, 6, 1213–1217.
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which is widely used to steer liquids in microfluidic or lab-on-achip devices. Although the utility and advantages of multilayers have been clearly demonstrated in microfluidics,20-22 the technique has not yet been widely adopted. Composites often benefit from a thin film that enhances the interfacial contact between disparate materials. Micro- and nanoparticles coated with polyelectrolytes are suited to highperformance composites. For example, carbon nanotubes and other minerals assembled into multilayers yield materials with exceptional mechanical properties.23
Active Coatings Smart (or at least obedient) coatings are figuring strongly in the future of multilayers, particularly at the biointerface where the fragility of films made from hydrated polyelectrolytes is less of an issue. Furthermore, the advantages of the LbL method may be more fully realized and appreciated by producing films with gradient properties. Because most multilayers are well hydrated, they are suited to the biological interface. Good compatibility of multilayer materials properties with the in vivo environment has been put to use in preparing biocompatible coatings for implantable biomedical devices, such as stents.24-26 Given the current disappointment with the first generation of active, drug-eluting stents (for example, problems with late stent thrombosis27) and their prevalence, we are likely to see a significant use of multilayers in this area. Both one-shot25,28,29 and a programmed, series30 delivery of genetic material within LbL films have been demonstrated. The latter again showcases the advantages of the LbL method in preparing gradient-composition ultrathin films, as does the sequential delivery of drugs31 from multilayers. Matching cells to multilayers is a more recent activity that has revealed some of the most promising properties of multilayers, where hydrophobicity,32,33 composition,14,34 and stiffness35 may be tuned by the components, conditions, and sequence of layering. The adhesion, proliferation, and differentiation of cells are directed to a large extent by the multilayer. It is possible to layer nutrients, ligands, and genetic material, as mentioned above, during LbL assembly. Beyond simple cell culture, multilayers have been shown to promote wound healing (20) Graul, T. W.; Schlenoff, J. B. Anal. Chem. 1999, 71, 4007–4013. (21) Barker, S. L. R.; Tarlov, M. J.; Canavan, H.; Hickman, J. J.; Locascio, L. E. Anal. Chem. 2000, 72, 4899–4903. (22) Katayama, H.; Ishihama, Y.; Asakawa, N. Anal. Chem. 1998, 70, 5272– 5277. (23) Srivastava, S.; Kotov, N. A. Acc. Chem. Res. 2008, 41, 1831–1841. (24) Thierry, B.; Winnik, F. M.; Merhi, Y.; Silver, J.; Tabrizian, M. Biomacromolecules 2003, 4, 1564–1571. (25) Jewell, C. M.; Zhang, J.; Fredin, N. J.; Wolff, M. R.; Hacker, T. A.; Lynn, D. M. Biomacromolecules 2006, 7, 2483–2491. (26) Kim, T. G.; Lee, H.; Jang, Y.; Park, T. G. Biomacromolecules 2009, 10, 1532–1539. (27) Joner, M.; Finn, A. V.; Farb, A.; Mont, E. K.; Kolodgie, D. D.; Ladich, E.; Kutys, R.; Skorija, K.; Gold, H. K.; Viramani, R. J. Am. Coll. Cardiol. 2006, 28, 193–202. (28) Zhang, J.; Chua, L. S.; Lynn, D. M. Langmuir 2004, 20, 8015–8021. (29) Elbakry, A.; Zaky, A.; Liebl, R.; Rachel, R.; Goepferich, A.; Breunig, M. Nano Lett. 2009, 9, 2059–2064. (30) Jessel, N.; Oulad-Abdeighani, M.; Meyer, F.; Lavalle, P.; Haikel, Y.; Schaaf, P.; Voegel, J. C. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 8618–8621. (31) Wood, K. C.; Chuang, H. F.; Batten, R. D.; Lynn, D. M.; Hammond, P. T. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 10207–10212. (32) Mendelsohn, J. D.; Yang, S. Y.; Hiller, J. A.; Hochbaum, A. I.; Rubner, M. F. Biomacromolecules 2003, 4, 96–106. (33) Salloum, D. S.; Olenych, S. G.; Keller, T. C. S.; Schlenoff, J. B. Biomacromolecules 2005, 6, 161–167. (34) Richert, L.; Lavalle, P.; Vautier, D.; Senger, B.; Stoltz, J. F.; Schaaf, P.; Voegel, J. C.; Picart, C. Biomacromolecules 2002, 3, 1170–1178. (35) Schneider, A.; Francius, G.; Obeid, R.; Schwinte, P.; Hemmerle, J.; Frisch, B.; Schaaf, P.; Voegel, J.-C.; Senger, B.; Picart, C. Langmuir 2006, 22, 1193–1200.
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in arteries.36 Much of the patent activity is at the biological interface.
Passive Devices Multilayers have much to offer as elements with designed properties that go beyond the interfacial regime. Competition from other well-established methods for making optical components suggests that multilayers as passive antireflective coatings37 may not progress much beyond the proof of principle. Similarly, whereas LbL films with periodic fluctuations in refractive index yield optical devices such as Bragg reflectors,38 the requirement for the deposition of hundreds of layers is a challenge for scale up. Multilayers have shown impressive numbers for separating species when deployed as membranes. LbL deposition usually proceeds on the surface39,40 or within the pores41 of a supporting passive membrane. Membrane-separations techniques such as pervaporation and ultrafiltration are already in widespread use, and the modification of existing media with LbL films offers an apparently simple add-on technology that may provide significant improvements.42 Our laboratory has developed chiral multilayers for membrane or chromatographic separations of optically active compounds.43 More recent multilayers are optimized for proton transport in fuel cell membranes.44,45 There is much competition in fuel cell membranes and electrodes, but the fact that particles, including catalysts, are kinetically trapped during LbL probably helps disperse them better in a multilayer than if they were simply mixed in with other components.46 Since they were first reported,47-49 much attention has been paid to refining capsules made, and particles coated, via LbL methods for drug delivery. Again, the potential technologies are in strong competition this time with myriad other methods for rapidly synthesizing micrometer-sized biocompatible carriers for drugs. A further level of sophistication is probably needed to set multilayer-coated particles apart.50,51
Active Devices In active devices, the architecture or physical properties of the multilayer lead to specific responsive properties. The definition of devices could include single-use systems programmed to degrade or disrupt in response to an external stimulus. Ideally, a drugloaded capsule might decompose on reaching its target,52 or such a capsule might be disrupted by irradiation53,54 (36) Thierry, B.; Winnik, F. M.; Merhi, Y.; Tabrizian, M. J. Am. Chem. Soc. 2003, 125, 7494–7495. (37) Hiller, J.; Mendelsohn, J. D.; Rubner, M. F. Nat. Mat. 2002, 1, 59–63. (38) Zhai, L.; Nolte, A. J.; Cohen, R. E.; Rubner, M. F. Macromolecules 2004, 37, 6113–6123. (39) Krasemann, L.; Tieke, B. J. Membr. Sci. 1998, 150, 23–30. (40) Harris, J. J.; Stair, J. L.; Bruening, M. L. Chem. Mater. 2000, 12, 1941–1946. (41) Hollman, A. M.; Bhattacharyya, D. Langmuir 2004, 20, 5418–5424. (42) Malaisamy, R.; Bruening, M. L. Langmuir 2005, 21, 10587–10592. (43) Rmaile, H. H.; Schlenoff, J. B. J. Am. Chem. Soc. 2003, 125, 6602–6603. (44) Argun, A. A.; Ashcraft, J. N.; Hammond, P. T. Adv. Mater. 2008, 20, 1539– 1543. (45) Daiko, Y.; Katagiri, K.; Matsuda, A. Chem. Mater. 2008, 20, 6405–6409. (46) Farhat, T. R.; Hammond, P. T. Adv. Funct. Mat. 2006, 16, 433–444. (47) Pommersheim, R.; Schrezenmeir, J.; Vogt, W. Macromol. Chem. Phys. 1994, 195, 1557–1567. (48) Peyratout, C. S.; D€ahne, L. Angew. Chem., Int. Ed. 2004, 43, 3762–3783. (49) Caruso, F.; M€ohwald, H. J. Am. Chem. Soc. 1999, 121, 6039–6046. (50) Wiemann, L. O.; Buthe, A.; Klein, M.; van den Wittenboer, A.; D€ahne, L.; Ansorge-Schumacher, M. B. Langmuir 2009, 25, 618–623. (51) Jain, P.; Jain, S.; Prasad, K. N.; Jain, S. K.; Vyas, S. P. Mol. Pharm. 2009, 6, 593–603. (52) Zelikin, A. N.; Quinn, J. F.; Caruso, F. Biomacromolecules 2006, 7, 27–30. (53) Mu~noz Javier, A.; del Pino, P.; Bedard, M. F.; Ho, D.; Skirtach, A. G.; Sukhorukov, G. B.; Plank, C.; Parak, W. J. Langmuir 2008, 24, 12517–12520. (54) Angelatos, A. S.; Radt, B.; Caruso, F. J. Phys. Chem. B 2005, 109, 3071– 3076.
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Many of the devices in the “passive” category become “active” if surface or internal charge is controlled.38 Surface charge, and therefore flow rate, in microfluidics is controlled by pH, for example.55 The flow rate through multilayer-coated pores is constricted when the LbL films swell as a result of an increase in extrinsic charge caused by pH cycles.56 In the arena of sensors, freestanding ultrathin LbL membranes are exquisitely sensitive to small changes in pressure.57,58 The LbL technique would appear to be highly suited to the fabrication of thin film sensors, especially those that respond to species dissolved in aqueous environments. The many publications that followed early indications59 of this promise have not converged on a set of guidelines for when the LbL technique provides a superior means for immobilizing responsive components in sensors. This is perhaps because most sensors are highly tailored to what they are trying to measure. Researchers attempting to include LbL methods into sensor development should be encouraged to do so, taking advantage of the spatial resolution available60 and also the ease of preparing conformal coatings.61 There is significant uncharted territory in the use of multilayers in devices that control ion flow. These are not simply membranes with predetermined ion permeabilities;ion flux is under active and reversible control. They are elements in an ion logic circuit. Examples of rectifying and “transistor”-like behavior in multilayers have been demonstrated.62
Fundamentals Fundamental science and understanding of multilayers have advanced substantially but still lack in key areas. More is known of LbL films made from two polyelectrolyte components, as opposed to polyelectrolyte/particle combinations. Unfortunately, many of the firmly entrenched ideas regarding how multilayers are formed and what drives them are wrong. The extensive theory developed for monolayer adsorption of polymers at hard interfaces63 cannot be extended to multilayers. For most multilayers (those that grow “linearly”), the amounts of polyelectrolyte are not adsorbed in their thermodynamic limit. A discussion of “loops” versus “trains” versus “tails” adapted from polymer adsorption continues, despite early recognition of the fact that limited adsorption kinetics leads to “fuzzy” layering.2 We have emphasized the connection between the extrinsic (counterion) charge content and polyelectrolyte mobility and the fact that invading polyelectrolyte chains grind to a halt when they run into regions of low extrinsic charge.64 Experiments on some highly hydrated systems show that at least one of the polyelectrolytes can access the entire film and LbL growth proceeds exponentially.14-16 Linear and exponential growth represent different ends of a continuous spectrum of diffusion mobility. Theoretically, any combination of LbL components can be grown under conditions of linear or exponential growth. A linear system transitions to an (55) Sui, Z. J.; Schlenoff, J. B. Langmuir 2003, 19, 7829–7831. (56) Lee, D.; Nolte, A. J.; Kunz, A. L.; Rubner, M. F.; Cohen, R. E. J. Am. Chem. Soc. 2006, 128, 8521–8529. (57) Jiang, C.; Markutsya, S.; Pikus, Y.; Tsukruk, V. Nat. Mater. 2004, 3, 721–728. (58) Markutsya, S.; Jiang, C.; Pikus, Y.; Tsukruk, V. Adv. Funct. Mater. 2005, 15, 771–780. (59) Decher, G.; Lehr, B.; Lowack, K.; Lvov, Y.; Schmitt, J. Biosens. Bioelectron. 1994, 9, 677–684. (60) Lutkenhaus, J. L.; Hammond, P. T. Soft Matter 2007, 3, 804–816. (61) Ali, M.; Yameen, B.; Neumann, R.; Ensinger, W.; Knoll, W.; Azzaroni, O. J. Am. Chem. Soc. 2008, 130, 16351–16357. (62) Salloum, D. S.; Schlenoff, J. B. Electrochem. Solid-State Lett. 2004, 7, E45– E47. (63) Fleer, G. J.; Cohen Stuart, M. A.; Scheutjens, J. M. H. M.; Cosgrove, T.; Vincent, B. Polymers at Interfaces; Chapman & Hall: London, 1993. (64) Jomaa, H. W.; Schlenoff, J. B. Macromolecules 2005, 38, 8473–8480.
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exponential one if the LbL conditions are such that intermolecular interactions are sufficiently weak.64 Some recent findings have been hard to accept. For example, it has long been assumed that the “driving force” for polyelectrolyte association is electrostatics. The driving force is, in fact, mainly entropic, driven by the release of counterions and waters of hydration as polyelectrolyte complexes.65 The term “ion pairing” as the mechanism and the driving force is more appropriate. The energy of association is simply proportional to the number of water molecules released.66 An understanding of what leads to polyelectrolyte overcompensation, even for exponential systems, which approach the thermodynamic limit, is still prominently missing from the theory. Whereas the structure of LbL films is well established, mostly from neutron reflectivity,64,67,68 the dynamics of their polymer or inorganic constituents is not. More dynamics studies, such as those available from NMR,69 are needed. In comparison, the theory of ion transport through multilayers is relatively well developed.70,71 Most interesting is the reversible nonlinear dependence of ion transport on the concentration of extrinsic charge.71 The amorphous complexes formed by polyelectrolyte multilayers are ideal for those interested in transport through soft condensed matter.
Conclusions Many “potential” LbL applications were showcased after the field was initiated in 1991/1992. So where are the products? Clearly, the marketplace damped the initial euphoria surrounding this new technology, as it has done/will do repeatedly. The rest of this Perspective will attempt to predict what persistent applications might emerge. Because multilayers are tedious to apply if one goes beyond the first few layers, the applications will need to be of high value. Most multilayers deposited from aqueous solutions and not subjected to a toughening step (sintering, cross-linking) need to be in quasiprotected environments, where the films will be sheltered from physical abuse. Early applications are envisaged for multilayers in contact with aqueous environments, particularly those in sensors and microfluidics, where a few layers of material provide high added value/performance. Sensitive, selective, fast nonfouling multilayer biosensors of proprietary composition will likely appear in the marketplace. Membranes and other separations are also simple to implement, and all applications can benefit from the combination of selectivity and surface nonfouling properties in certain LbL systems. Particles, including nanoparticles, nanorods, and nanoplates, are effectively stabilized by multilayers when dispersions are required. Coated particles are then useful for nanocomposites. Optimum dispersion and orientation of particles within thin composite films are promoted by the LbL technique. Longer-term applications are clearly indicated for the biointerface. Multilayers are likely to play a significant role in cell culture and tissue engineering. Because of regulatory requirements, it will take some time for biomedical applications to emerge, (65) Bucur, C. B.; Sui, Z.; Schlenoff, J. B. J. Am. Chem. Soc. 2006, 128, 13690– 13691. (66) Schlenoff, J. B.; Rmaile, A. H.; Bucur, C. B. J. Am. Chem. Soc. 2008, 130, 13589–13597. (67) Kharlampieva, E.; Kozlovskaya, V.; Ankner, J. F.; Sukhishvili, S. A. Langmuir 2008, 24, 11346–11349. (68) L€osche, M.; Schmitt, J.; Decher, G.; Bouwman, W. G.; Kjaer, K. Macromolecules 1998, 31, 8893–8906. (69) Fortier-McGill, B.; Reven, L. Macromolecules 2009, 42, 247–254. (70) Farhat, T. R.; Schlenoff, J. B. Langmuir 2001, 17, 1184–1192. (71) Farhat, T. R.; Schlenoff, J. B. J. Am. Chem. Soc. 2003, 125, 4627–4636.
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particularly those in vivo, but the potential payback could be significant for drug delivery, implant (catheters, stents, electrodes, valves) compatibilization, gene therapy, and other biomaterials. Because biopolymers are included in the vast palette of components for LbL assembly, customizing multilayers for personalized medicine is rather straightforward. Multifunctional materials will be key to creating niches. In the area of fundamental science, there is still much to learn about these fascinating materials. Indicators are pointing to a
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converging set of rules for understanding multilayers, provided some inappropriate ideas can be jettisoned. Note Added after Issue Publication. Because of a production error, references 1-6 were inadvertently omitted from the originally published PDF version of this perspective. The correct version was published on the Web on June 18, 2010, and an Addition and Correction appears in the July 20, 2010 issue.
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