Perspective pubs.acs.org/cm
The Rise of Organic Bioelectronics Jonathan Rivnay, Róisín M. Owens, and George G. Malliaras* Department of Bioelectronics, Ecole Nationale Supérieure des Mines, CMP-EMSE, MOC, 880 route de Mimet, 13541 Gardanne, France ABSTRACT: In this Perspective, we make the case that the biological applications of organic semiconductor devices are significant. Indeed, we argue that this is an arena where organic materials have an advantage compared to traditional electronic materials, such as silicon. By discussing the physical structure and morphology of conjugated polymers, we are able to emphasize the key properties that make organic materials ideal for bioelectronics applications. We highlight a few recent devices that show either unique features or exceptionally high performance. On the basis of these examples, we discuss the future trajectory of this emerging field, note areas where further research is needed, and suggest possible applications in the short term. KEYWORDS: organic electronics, bioelectronics, conducting polymers
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electrolyte and the electronic current that flows in the electrode. A state-of-the-art solution involves the use of conducting polymers coatings that have been shown not only to reduce impedance but also to enhance implant lifetime.4 In the last twenty years, the field of organic electronics has experienced tremendous growth, driven mainly by the development of organic light emitting diodes for display applications.5 This was followed by the development of organic thin film transistors for flexible circuitry6 and sensors,7 and of organic photovoltaics for solar energy harvesting.8 The field uses conjugated small molecules and polymers, which exhibit semiconductivity because of their delocalized π-electrons.9 These materials can be doped p-type or (less frequently) n-type to a highly conducting state by adding a chemical that either oxidizes or reduces the π-conjugated structure.10 A change in the doping state (also called redox status) can also be achieved when ions from an electrolyte enter an organic film, or vice versa. In this case the compensating electronic charge is supplied by a metal contact and the process is called “electrochemical doping”. The physics of these systems is very rich and continues to attract a great deal of attention. Organic electronic materials have been quietly entering the realm of bioelectronics in biosensors and neural implants. A classic example is the use of conducting polymer coatings on neural electrodes as mentioned above. In 2007, a seminal review by Magnus Berggren and Agneta Richter-Dahlfors coined the term “Organic Bioelectronics”.11 Today there are several dozen groups in Europe, the Americas, Asia and Australia that are active in the field, with multiple international symposia each year catering to this fast-growing community, and with traditional organic electronics meetings adding special
INTRODUCTION Bioelectronics is a field that dates back to the work of Luigi Galvani in the 18th century. In the now famous experiment, he made the detached legs of a frog twitch by applying a small voltage. Today there are a variety of bioelectronic devices available that offer improved healthcare, offer environmental protection, and accelerate the pace of scientific progress. These include biosensors such as glucose monitors for diabetics, pacemakers/defibrillators and cochlear implants for restoration of lost or damaged physiological functions, and biomedical instruments that provide a deeper understanding of the how cells communicate with each other and with their environment. Bioelectronics is in the news, especially since the launch of the EU Flagship Initiative called the “Human Brain Project” and the US equivalent “Brain Activity Map”. Bioelectronics permeates the popular media, where, for example, seemingly unwitting moviegoers are exposed to concepts of bioelectronic prosthetics, often cast in a negative light as part of a villain’s persona or power. Despite potential misconceptions that may arise through such publicity, it is hard not to get excited by a field that creates so many possibilities and so much hype. Bioelectronics is a field that is limited by the materials that transduce signals across the biotic/abiotic interface. One example is in glucose sensors, which utilize an enzyme that acquires electrons when it interacts with glucose. Getting these electrons to an electrode is the limiting process and various materials approaches have been employed to improve it.1 The current state-of-the-art in glucose sensing is the third generation biosensors which employ a molecular wire to shuttle these electrons from the enzyme to the electrode.2 Another example is neural interfaces, in which the impedance across the interface between the electrode and the cerebrospinal fluid is the key parameter that determines the fidelity/ efficiency of electrical recording/stimulation.3 For these applications, there is a great deal of interest in developing coatings that decrease impedance and hence improve the connection between the ionic current that flows in the © 2013 American Chemical Society
Special Issue: Celebrating Twenty-Five Years of Chemistry of Materials Received: July 4, 2013 Published: September 19, 2013 679
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Figure 1. Schematics of an inorganic semiconductor, silicon, and an organic semiconductor, PEDOT, at the interface with an electrolyte. The hydrated ion is meant to be the same in both schematics, defining the relative scale. The insets show the action of p-type dopants, boron in silicon, and PSS in PEDOT, respectively.
applications. In the case of organic bioelectronics, a comparison between organics and silicon, the champion material of electronics, is also instructive. Figure 1 shows schematics of silicon and of a conjugated polymer film, such as poly(3,4ethylenedioxythiophene) (PEDOT), in contact with an electrolyte solution. Both materials are shown to be doped p-type, silicon with boron and PEDOT with poly(styrene sulfonate) (PSS). A solvated ion is shown in the electrolyte to define a relative scale. Silicon is held together by a network of covalent bonds, where each atom shares valence electrons with four neighbors. In contrast, the organic material consists of (macro)molecular blocks within which atoms are covalently bonded to each other, however these blocks are held together by means of weak van der Waals interactions and, in the case of doped materials, electrostatic interactions as well. The prevalence of van der Waals interactions in the “soft” organic material defines the key difference with the “hard” silicon. Stemming from this bonding arrangement are the identifying characteristics of organics: First, organics offer facile chemical modif ication. The toolbox of organic chemistry can be used to modify the structure of the molecular blocks with near-infinite possibilities. One can engineer functionality by altering the π-conjugated backbone or the side groups, thus changing (opto-)electronic, mechanical or biologically relevant properties. Moreover, a wealth of structures that range from single crystals all the way to exotic forms such as disordered composites and hydrogels can often be produced from the same fundamental conjugated molecular block. Second, organics offer the possibility of low
sessions on biological applications. In a review we wrote a few years ago, we highlighted the fact that there seems to be a transition from using organic coatings to using organic devices, which we interpreted as a sign of the field maturing and taking a more sophisticated approach to interfacing with biology.12 Rather than focus on specific methods, materials or devices, in this perspective we take a different approach: We discuss the structure of organic materials and focus on their identifying characteristics. The latter are highlighted through a comparison with traditional inorganic semiconductors, such as silicon. We then discuss how these characteristics can be put to use in the field of bioelectronics. This perspective is meant as a personal, forward-looking view of the field of organic bioelectronics, and not as a literature review. The objective is not to produce a comprehensive list of references (the reader is referred to the reviews mentioned above and to recent literature13), but rather to use only a small number of examples that highlight the properties of interest in an informative manner. These examples are mostly from the work of our own groups, which simply reflects the fact that we practice what we preach. We tried to avoid the use of jargon and make this perspective accessible to a large audience, hopefully not at the expense of rigor.
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WHY ORGANICS? A beneficial exercise when considering new applications for a class of materials is to analyze their identifying characteristics and to find how they match the requirements of these 680
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proximity of the interface induces a flux of ions which changes this electric field and hence the output current; thus allowing neuronal activity to be detected by means of a transistor. In this format, the interaction between the electronic material and the biological media is limited by the presence of the insulator. The maximum change in the doping state of the silicon is determined by the maximum number of ions that can accumulate at the (2D) electrolyte/oxide interface. Let us imagine that we could remove the oxide, and allow the ions to penetrate the volume of the semiconductor. This device is called the organic electrochemical transistor (OECT), and was invented by Mark Wrighton and co-workers17 in 1984. An OECT uses an organic semiconductor layer as the channel, and takes advantage of the lack of an oxide at the interface with the electrolyte, and of the ability of the organic material to transport ions, in order to yield a 3D interaction with the biological milieu. In these devices, ions from the electrolyte penetrate the volume of the polymer film and change its conductance. We recently showed that OECTs outperform field-effect transistors in measuring small potential fluctuations in electrolytes.18 We took advantage of this feature to record brain activity in a rat model for epilepsy.19 We placed conformal OECT arrays on the surface of the brain and showed that brain activity could be measured with a record-breaking signal-to-noise ratio (Figure 2). This demonstrated that OECTs are able to detect low-level
temperature processing. The weak interactions that hold the molecular blocks together can be easily overcome by mild heating (mostly in small molecules) or a solvent (mostly in polymers), and a film can be deposited from vapor or solution on a wide variety of substrates. Third, organics allow for oxidef ree interfaces with aqueous electrolytes. In the sketch of Figure 1 we assume that the silicon crystal is cleaved and exposed to the atmosphere, which gives rise to the growth of an oxide layer. In contrast, the surface of the organic contains no broken covalent bonds and is oxide-free. Organics can therefore be in direct contact with the biological milieu, which, as we shall see, offers important opportunities in bioelectronics. Fourth, organics can support efficient ion transport at room temperature. The relatively large space between molecules, courtesy of the weak van der Waals interactions, allows ions to move efficiently in the film. Moreover, hydrophilic organic films can absorb water and swell, which further enhances ion transport (this is discussed later). Finally, in organics, excitations couple strongly to the structure of the molecule, and by extension, of the film. In silicon, the presence of electronic charge does not modify the lattice appreciably, as atoms are bonded with each other in a 3D manner. In contrast, removing an electron from a thiophene chain causes part of the chain to revert from an aromatic to a quinoid structure (see Figure 1). When doping is performed in an electrolyte solution, the corresponding uptake/ release of ions can cause large dimensional changes in the organic film. As a result, electrical doping not only affects the electrical properties of the film, but has a dramatic influence across the board. Changes in optical and mechanical properties upon doping, have been used to great advantage for making electrochromic displays14 and actuators for artificial muscles,15 respectively. In the discussion above, we painted a picture using a broad brush. There are other identifying characteristics that set apart organics from silicon such as their “soft” mechanical properties, but these are not as overarching for bioelectronics and need to be considered in the context of a specific application. We will now proceed to examine the ramifications of the identifying characteristics listed above.
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OXIDE-FREE INTERFACES, ION TRANSPORT These two characteristics, in our opinion, constitute the key advantage of organic electronic materials in bioelectronics. They allow exchange of ions between the biological milieu and the bulk of the electronic material. This means that the whole volume of the film, not just its surface, is involved in the interaction with the biological environment, a feature which can be exploited to yield powerful biosensors and bioactuators. We discuss this in the context of two devices, the organic electrochemical transistor (OECT) and the organic electronic ion pump (OEIP). One of the most inspiring applications of bioelectronics is the use of transistors to record the electrical activity of neurons, an application pioneered by Peter Fromherz and co-workers.16 To explain this briefly, let us look back at the piece of silicon shown in Figure 1. The oxide acts as a physical barrier between ions in the electrolyte and the silicon. Application of a potential between the electrolyte and the silicon leads to ion accumulation at the electrolyte/oxide interface. This creates an electric field, which changes the doping state of the silicon via the field-effect mechanism. In a transistor, we measure the current that flows in the silicon, which reflects the electric field at the interface with the electrolyte. A neuron firing in the
Figure 2. Optical micrograph of an array carrying OECTs and electrodes, placed over the somatosensory cortex (a) and detail of the transistor and electrode structures (b). Recordings from an OECT (pink) and an electrode (blue), showing the superior recording ability of the former (c).
activity that was poorly detectable with surface electrodes. These devices can, therefore, have important applications in the clinic, in particular in the field of epilepsy, where the identification of zones generating high-frequency oscillations or microseizures is critical for diagnosis. In an OECT, ions from the electrolyte enter the polymer film and change the magnitude of the hole current. The opposite is also possible, where the flow of a hole current in the polymer film causes the ejection of ions from the film to the electrolyte. This device is called the OEIP and was demonstrated recently by Magnus Berggren and co-workers.20 The device relies on electrophoretic transport of ions in the bulk of a PEDOT film, 681
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and hence requires an oxide-free interface and bulk ion transport (the ions are supplied from a reservoir to avoid depletion). OEIPs have been used in vivo to pump neurotransmitters thereby regulating hearing in an animal model.21 Such devices can have a great impact in medicine, as they are capable of delivering drugs with excellent spatiotemporal precision. As such, they can target a particular organ and deliver the drug only where and when needed.
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EXCITATIONS COUPLE TO STRUCTURE In the previous paragraphs, we discussed applications in which an organic electronic device records or stimulates biological events by exchanging ions with the biological milieu. At a higher level of sophistication, one can consider the changes that occur in the organic film itself as a result of this process. As implied by Figure 1, doping in organics is associated with a structural rearrangement along the π-conjugated backbone and this influences a range of properties including surface energy.22 An elegant demonstration of how this can be exploited to control cell behavior was reported by Robert Langer and coworkers.23 They took two conducting polymer films, one in its native oxidized state and a second that was electrochemically reduced, and seeded mammalian cells on them. They observed that the cells adhered and spread normally on the oxidized film, while they avoided contact with the reduced film. In addition to adhesion, the ability of the cells to synthesize DNA was also affected. More importantly, when the same experiment was repeated with indium tin oxide instead of a conducting polymer, there was no change in cell adhesion or function, indicating that the organic layer played a critical and active role in regulating these biological processes. The origin of this effect is not clear to date, but having an electrically triggered “velcro pad” for cells is a very interesting proposition for tissue engineering, a field that aims to control cell adhesion, differentiation, and assembly into tissues by providing the appropriate stimuli. Together with our colleagues at Cornell University, we recently looked at protein conformation on conducting polymer surfaces.24 We developed a PEDOT-based device that makes available a continuum of microenvironments each with a slightly different conducting polymer redox status. We incubated fibronectin, an important cell adhesion protein, on these devices and demonstrated that its conformation changes in a manner that reflects the underlying redox gradient (Figure 3). This permits the preparation of macroscopic surfaces onto which a desired protein conformation can be “dialed in” by applying the appropriate potential. This can have applications as a tool for biomedical research: A recent demonstration from Claudia Fischbach and co-workers, shows how this concept may be used to demonstrate that fibronectin conformation regulates the pro-angiogenic capability of tumor-associated cells.25
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Figure 3. Structure of a device that creates redox gradients in a PEDOT film, and resulting fibronectin conformation obtained by an optical imaging technique.
fibers.26 Moreover, it allows to maintain the functionality of biological moieties during device fabrication. One example is the work of Luisa Torsi and co-workers, who showed that organic layers can be deposited on top of sensitive biological layers without damaging them.27 This paves the way for a new paradigm in biosensor design, where the biological layer is not necessarily the last one to be deposited, but can be placed at a particular location inside a device to maximize transduction. The ability to chemically modify the active materials also allows tuning of biodegradability, which can be engineered by inserting the appropriate units along the backbone of a conjugated polymer.28
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A VISION OF THE FUTURE What will the next ten years bring for organic bioelectronics? There is certainly plenty of work to be done, both in understanding key fundamentals issues and in promoting the first applications. Starting with the fundamentals, the first area that should and will receive attention is ion transport in organic electronic materials, since this process is at the very heart of organic bioelectronics. The key challenge is the presence of both electronic and ionic carriers, which renders classical methods such as conductivity measurements and impedance spectroscopy very difficult to interpret. New techniques that provide complementary information on the same sample are needed in order to help decouple the contributions of electronic and ionic charges. To this end, we recently extended the so-called “moving front” experiment to measure mobilities of common ions injected into a PEDOT:PSS film from an aqueous electrolyte.29 This experiment ended up being very instructive, as the mobilities were found to be of a similar magnitude to those measured in water. This result was consistent with a very large swelling of the polymer film due to the uptake of water, and with the fact that cross-linking the film reduced the swelling and the ion mobility. These findings imply a new design rule for engineering materials for bioelectronics: maximize the uptake of water. It is interesting to note that the hole mobility in PEDOT does not seem to suffer much from the uptake of water, a fact that is not well understood. Work along these lines will not only bring about a better fundamental understanding of charge transport in organics, but will also lead to the development of materials that offer a better ability to interface with ionic fluxes in the
FACILE PROCESSING AND MODIFICATION
Low temperature processing and facile chemical modification are the “classical” characteristics of organics, much exploited in organic light emitting diodes and solar cells to endow features such as low-cost fabrication through roll-to-roll processing techniques, as well as and tunable optical absorption/emission spectra. These properties are also applicable in bioelectronics. Low-temperature processing allows the fabrication of devices with novel form factors, such as transistors integrated on woven 682
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yield better recordings.33 Printing conducting polymers MEAs on plastic would cost much less that 1 euro, offering to make these devices truly disposable. Opportunities also exist in vivo, on the short-term as tools for animal research and on a longer term in the clinic. At least one small company is promoting the use of conducting polymer electrodes for in vivo electrophysiology. Down the road, transistors, offering higher quality recordings, and biosensors, offering additional information, would yield superior products both in vitro and in vivo. Another example of in vitro diagnostics relates to the assessment of the barrier properties of cell monolayers and tissues, with potential applications in drug development, toxicology, and food safety. To this end, we recently reported the use of an OECT to read out paracellular transport of ions arising from the early stages of barrier disruption.34 Using a model of the gastrointestinal tract, we showed that the sensitivity of the OECT to small ions fluxes led to detection of breaches in barrier tissue that was better resolved than with commercially available instruments and has the potential to provide a time signature of the disruption that can not only detect adverse effects on barrier tissue, but also potentially elucidate a mechanism. Additional opportunities exist in developing tools for biomedical research, where dynamic control of the cell microenvironment offers new capabilities to biology. The device controlling fibronectin conformation, discussed above, is an example of such a tool. Finally, a host of biosensors is under intense development for applications ranging from medical diagnostics to safeguarding the environment.35 A word of caution is in order. Silicon is a formidable opponent, and backed by six decades of technological development, can gain new ground quickly. This is beautifully demonstrated by John Rogers and co-workers, who in the past few years showed that silicon-based bioelectronic devices can be mechanically flexible,36 compatible with skin contact,37 and even biodegradable.38 Still, the list of characteristics discussed above allows the fabrication of organic-based devices with either unique features (electrical control of cell adhesion/ function, OEIPs), or state-of-the-art performance (OECTs), that are currently beyond the reach of silicon. Nanocrystalline inorganic films can uptake ions from an electrolyte and change their doping level in a fashion similar to that in organic films.39 Their applications in bioelectronics have not yet been widely explored, but one would expect to see electrochemical devices with similar characteristics as organics. It will be interesting to see what will be the ultimate performance of such devices and how they may compare with organics. We do, however, expect organics to play a dominant role for biological applications given the complete set of characteristics they offer, which cannot be matched in any other materials class.
biological environment. This is open season for chemists: there has been relatively little work done on the synthetic side of organic bioelectronics compared to the more traditional organic electronic devices. Most materials used in bioelectronics have been around for one to two decades without much change, and are often used simply because they are commercially available. Such materials will also be useful for other applications, including batteries and fuel cells, devices that also require mixed ionic/electronic transport.30 A second area which is ripe for fundamental investigations, and is at the heart of materials science is the structure of the interface between organics and electrolytes. PEDOT:PSS, for example, is known to possess a PSS-rich top layer in the dry state,31 implying that the surface is very acidic. This, however, does not seem to bother a large variety of different cell types, which adhere and grow well on its surface. It is not clear how this surface looks when it takes up a large amount of electrolyte. Other unknown factors are the composition and structure of adsorbed extracellular matrix proteins, as well as the dimensions of the cleft between a cell and the surface of an organic material. The latter is important to control in electrical recording and stimulation devices. In addition to electronic properties and structure, a third area that will receive increased interest is the physics and engineering of devices that couple ionic and electronic currents. Both OECTs and OEIPs are relatively recent inventions and therefore their limits of operation have not yet been adequately explored. Devices that couple additional stimuli such as light to trigger biological activity offer enormous potential in optical prosthetics.32 In a similar vein, devices that convert electrical to mechanical actuation offer many opportunities in biology, for example, in drug delivery.15 Up until now the field of organic bioelectronics has focused on demonstrating “proof of principle” with a very wide variety of different applications in biology, ranging from individual molecules such as DNA to complex organs such as the brain. As the field matures however this somewhat scattered approach will be replaced by more in-depth applications using the truly unique toolbox of organic electronic devices and materials, to interact with biological systems, and to answer questions that remained hitherto unanswered. So, what will the first applications be? After all, without any applications the field is destined to deflate. A major opportunity lies in in vitro diagnostics, where organic electronic materials can endow better performance than existing technologies and also come with a potentially lower cost. Here, a perfect storm has been brewing for some time: On one hand there is the REACH regulation, which necessitates the assessment of toxicity of more than 30 000 chemical substances produced or imported into the EU above 1 ton per year. Since many diseases/disorders, including neurodegenerative ones, are suspected to also be caused by environmental toxins, there is a pressing need for the development of highthroughput screening techniques. On the other hand, there are directives to provide alternative approaches to animal testing, consistent with the 3Rs (refine, replace, reduce) principle. Cell culture- and tissue-based diagnostics will therefore be in great demand. One example is Au or Pt microelectrode arrays (MEAs) which monitor the firing of cells in cultures or tissues. MEAs sell for ∼100 euros/piece, which forces most users to try and reuse them. Conducting polymer electrodes have been shown to decrease the impedance at the interface with electrolytes and
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HOW TO EMBARK ON THIS FIELD We wish to close with some practical guidance, in which we try to distill our own experience on how to begin research in this field. The notion of interdisciplinary collaborations is not foreign to people working in organic electronics, a field that is defined by collaborations between chemists, physicists, materials scientists and engineers. Still, we often hear people say they are excited about organic bioelectronics but are concerned about their lack of knowledge in biology. In fact, two of the three authors of this perspective began with a layman’s knowledge of biology. What is important is to establish a good working relationship with a life sciences group. The absolute 683
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worst approach is to go at this alone, without input from the life sciences. Chances are, this approach will lead to work that is irrelevant: A physical scientist who develops a new technology for detecting DNA should not expect a clinician to do cartwheels given the number of DNA detection systems already installed in laboratories worldwide. Hardcore biologists and clinicians are notoriously intransigent about using novel technologies to study their systems of interest with a few rare and notable exceptions. This is understandable given the level of validation and benchmarking required for any novel device or technique, meaning that the benefits should be truly remarkable for it to be worthwhile. Biologists tend to have a different way of thinking about problems than physical scientists or engineers− rarely taking a systems view, but often reducing the focus to looking at individual interactions between proteins or molecules. Biologists also have to deal with innumerable parameters in any given experiment. To account for this, control experiments are carried out where every effort is made to maintain all conditions in order to study a single condition of interest. Physical scientists and engineers tend to take a very different approach: experiments generally contain a very well-defined and small number of parameters. This difference in experimental approach means that communication between disciplines can be challenging. Beyond the obvious problems of jargon and acronyms, there is a problem of knowledge base and experimental design. In our experience, it is very important that all parties are given equal footing not only in identifying ideas worth pursuing, but also in the design of the actual experiments. Having a good balance in team members coming from physical sciences/engineering and from life sciences is important and can ensure equal footing. After all, the students/postdocs are the glue that holds interdisciplinary projects together. The relatively new discipline of biomedical engineering has started to generate a new wave of students trained in physical and biological sciences, a true windfall for the field of organic bioelectronics. A broad diversity of scientists and engineers in a group generates its own built-in education database. We encourage tutorials, whereby anyone from a student to a faculty member can give a short talk on a relatively basic subject which can be vastly instructive to a newcomer to the field. In the same way, a variety of basic textbooks are available which, even if not strictly up to date on the latest developments, can provide a starting point to the scientist who needs first to understand the structure of a cell before deciphering a complex signaling pathway. We find that young researchers are extremely excited to work in this field and are willing to accommodate the sometimes slow pace of progress customary in life sciences research. It is important to understand and respect the different publishing cultures in physical sciences/engineering and in life sciences. The collaboration needs to accommodate the arduous process of running the multiple controls that are necessary to show statistical significance, while publishing the engineering advances in a timely manner. The latter are usually the objective of the first papers published by such collaborations, with subsequent more sophisticated papers being more heavy on the biology side.
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The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Notes
The authors declare no competing financial interest. Biographies Jonathan Rivnay received his B.Sc. in Materials Science from Cornell University in 2006 and his Ph.D. in Materials Science from Stanford University in 2011. His doctoral research focused on structure/ property relations and the role of defects and disorder on charge transport in organic semiconductors. Jonathan is currently a Marie Curie post-doctoral fellow in the Department of Bioelectronics at the Centre Microelectronique de Provence where he is developing organic electronic devices for electrophysiology and bio-interfacing applications. Róisı ́n Owens is an Associate Professor in the Department of Bioelectronics at the Centre Microélectronique de Provence. She received her BA at Trinity College Dublin, and PhD in at Southampton University, both in biochemistry. She did postdoctoral fellowships on tuberculosis and rhinovirus therapeutics at Cornell University. Her current research centers on the use of organic bioelectronics for in vitro diagnostics. She has received several awards including the European Research Council starting grant and a Marie Curie fellowship. Professor George Malliaras received a PhD in Mathematics and Physical Sciences from the University of Groningen, did a postdoc at the IBM Almaden Research Center, then joined the faculty of Materials Science and Engineering at Cornell University. He currently heads the Department of Bioelectronics at the Centre Microélectronique de Provence. He has received awards from the NY Academy of Sciences, the US National Science Foundation, and DuPont, and is a Fellow of the Royal Society of Chemistry.
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ACKNOWLEDGMENTS
This work was supported by the Agence Nationale de la Recherche (to G.G.M.), the European Research Council (to R.M.O.), and through additional grants from région PACA and CG13. J.R. was supported through a Marie CURIE Postdoctoral Fellowship.
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ABBREVIATIONS PEDOT:PSS poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate); OECT organic electrochemical transistor; OEIP organic electronic ion pump; MEA microelectrode array
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REFERENCES
(1) Ferri, S.; Kojima, K.; Sode, K. J. Diabetes Sci. Technol. 2011, 5 (5), 1068−1076. (2) Heller, A. J. Phys. Chem. 1992, 96 (9), 3579−3587. (3) Wallace, G. G.; Moulton, S. E.; Clark, G. M. Science 2009, 324 (5924), 185−186. (4) (a) Kim, D.-H.; Richardson-Burns, S.; Povlich, L.; Abidian, M. R.; Spanninga, S.; Hendricks, J.; Martin, D. C., Soft, Fuzzy, and Bioactive Conducting Polymers for Improving the Chronic Performance of Neural Prosthetic Devices. In Indwelling Neural Implants: Strategies for Contending with the In-Vivo Environment; Reichert, W. M., Ed.; CRC Press, Taylon and Francis: Boca Raton, FL, 2008; pp 165−207; (b) Asplund, M.; Nyberg, T.; Inganas, O. Polym. Chem. 2010, 1 (9), 1374−1391.
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(5) Arias, A. C.; MacKenzie, J. D.; McCulloch, I.; Rivnay, J.; Salleo, A. Chem. Rev. 2010, 110 (1), 3−24. (6) Gelinck, G.; Heremans, P.; Nomoto, K.; Anthopoulos, T. D. Adv. Mater. 2010, 22 (34), 3778−3798. (7) Someya, T.; Dodabalapur, A.; Huang, J.; See, K. C.; Katz, H. E. Adv. Mater. 2010, 22 (34), 3799−3811. (8) Kippelen, B.; Bredas, J.-L. Energy Environ. Sci. 2009, 2 (3), 251− 261. (9) Malliaras, G.; Friend, R. Phys. Today 2005, 58 (5), 53−58. (10) Skotheim, T. A.; Reynolds, J. R. Handbook of Conducting Polymers. Conjugated Polymers: Processing and Applications, 3rd ed.; CRC Press: Boca Raton, FL, 2007. (11) Berggren, M.; Richter-Dahlfors, A. Adv. Mater. 2007, 19 (20), 3201−3213. (12) Owens, R. M.; Malliaras, G. G. MRS Bull. 2010, 35, 449−456. (13) (a) Svennersten, K.; Larsson, K. C.; Berggren, M.; RichterDahlfors, A. Biochim. Biophys. Acta, Gen. Subj. 2011, 1810 (3), 276− 285. (b) Moulton, S. E.; Higgins, M. J.; Kapsa, R. M. I.; Wallace, G. G. Adv. Funct. Mater. 2012, 22 (10), 2003−2014. (c) Tarabella, G.; Mahvash Mohammadi, F.; Coppede, N.; Barbero, F.; Iannotta, S.; Santato, C.; Cicoira, F. Chem. Sci. 2013, 4 (4), 1395−1409. (d) Owens, R.; Kjall, P.; Richter-Dahlfors, A.; Cicoira, F. Biochim. Biophys. Acta, Gen. Subj. 2013, 1830 (9), 4283−4285. (14) Mortimer, R. J.; Dyer, A. L.; Reynolds, J. R. Displays 2006, 27 (1), 2−18. (15) Smela, E. MRS Bull. 2008, 33 (3), 197−204. (16) Fromherz, P., Neuroelectronic Interfacing: Semiconductor Chips with Ion Channels, Nerve Cells, and Brain. In Nanoelectronics and Information Technology; Waser, R., Ed.; Wiley-VCH Verlag: Berlin, 2003; pp 781−810. (17) Kittlesen, G. P.; White, H. S.; Wrighton, M. S. J. Am. Chem. Soc. 1984, 106 (24), 7389−7396. (18) Khodagholy, D.; Rivnay, J.; Sessolo, M.; Gurfinkel, M.; Leleux, P.; Jimison, L. H.; Stavrinidou, E.; Herve, T.; Sanaur, S.; Owens, R. M.; Malliaras, G. G. Nat. Commun. 2013, 4, 2133. (19) Khodagholy, D.; Doublet, T.; Quilichini, P.; Gurfinkel, M.; Leleux, P.; Ghestem, A.; Ismailova, E.; Hervé, T.; Sanaur, S.; Bernard, C.; Malliaras, G. G. Nat. Commun. 2013, 4, 1575. (20) Isaksson, J.; Kjall, P.; Nilsson, D.; Robinson, N. D.; Berggren, M.; Richter-Dahlfors, A. Nat. Mater. 2007, 6 (9), 673−679. (21) Simon, D. T.; Kurup, S.; Larsson, K. C.; Hori, R.; Tybrandt, K.; Goiny, M.; Jager, E. H.; Berggren, M.; Canlon, B.; Richter-Dahlfors, A. Nat. Mater. 2009, 8 (9), 742−746. (22) Isaksson, J.; Tengstedt, C.; Fahlman, M.; Robinson, N.; Berggren, M. Adv. Mater. 2004, 16 (4), 316−320. (23) Wong, J. Y.; Langer, R.; Ingber, D. E. Proc. Natl. Acad. Sci. U. S. A. 1994, 91 (8), 3201−3204. (24) Wan, A. M. D.; Schur, R. M.; Ober, C. K.; Fischbach, C.; Gourdon, D.; Malliaras, G. G. Adv. Mater. 2012, 24 (18), 2501−2505. (25) Wan, A. M. D.; Chandler, E. M.; Madhavan, M.; Infanger, D. W.; Ober, C. K.; Gourdon, D.; Malliaras, G. G.; Fischbach, C. Biochim. Biophys. Acta, Gen. Subj. 2013, 1830 (9), 4314−4320. (26) Hamedi, M.; Forchheimer, R.; Inganas, O. Nat. Mater. 2007, 6 (5), 357−362. (27) Angione, M. D.; Cotrone, S.; Magliulo, M.; Mallardi, A.; Altamura, D.; Giannini, C.; Cioffi, N.; Sabbatini, L.; Fratini, E.; Baglioni, P.; Scamarcio, G.; Palazzo, G.; Torsi, L. Proc. Natl. Acad. Sci. 2012, 109 (17), 6429−6434. (28) Rivers, T. J.; Hudson, T. W.; Schmidt, C. E. Adv. Funct. Mater. 2002, 12 (1), 33−37. (29) Stavrinidou, E.; Leleux, P.; Rajaona, H.; Khodagholy, D.; Rivnay, J.; Lindau, M.; Sanaur, S.; Malliaras, G. G. Adv. Mater. 2013, 25 (32), 4488−4493. (30) Abruna, H. D.; Kiya, Y.; Henderson, J. C. Phys. Today 2008, 61 (12), 43−47. (31) Greczynski, G.; Kugler, T.; Salaneck, W. R. Thin Solid Films 1999, 354 (1−2), 129−135.
(32) Ghezzi, D.; Antognazza, M. R.; Dal Maschio, M.; Lanzarini, E.; Benfenati, F.; Lanzani, G. Nat. Commun. 2011, 2, No. 166, DOI: 10.1038/ncomms1164. (33) Sessolo, M.; Khodagholy, D.; Rivnay, J.; Maddalena, F.; Gleyzes, M.; Steidl, E.; Buisson, B.; Malliaras, G. G. Adv. Mater. 2013, 25 (15), 2135−2139. (34) Jimison, L. H.; Tria, S. A.; Khodagholy, D.; Gurfinkel, M.; Lanzarini, E.; Hama, A.; Malliaras, G. G.; Owens, R. M. Adv. Mater. 2012, 24 (44), 5919−5923. (35) (a) Torsi, L. Anal. Bioanal. Chem. 2006, 384 (2), 309−309. (b) Lin, P.; Yan, F. Adv. Mater. 2012, 24 (1), 34−51. (36) Viventi, J.; Kim, D. H.; Vigeland, L.; Frechette, E. S.; Blanco, J. A.; Kim, Y. S.; Avrin, A. E.; Tiruvadi, V. R.; Hwang, S. W.; Vanleer, A. C.; Wulsin, D. F.; Davis, K.; Gelber, C. E.; Palmer, L.; Van der Spiegel, J.; Wu, J.; Xiao, J.; Huang, Y.; Contreras, D.; Rogers, J. A.; Litt, B. Nat. Neurosci. 2011, 14 (12), 1599−605. (37) Kim, D.-H.; Lu, N.; Ma, R.; Kim, Y.-S.; Kim, R.-H.; Wang, S.; Wu, J.; Won, S. M.; Tao, H.; Islam, A.; Yu, K. J.; Kim, T.-i.; Chowdhury, R.; Ying, M.; Xu, L.; Li, M.; Chung, H.-J.; Keum, H.; McCormick, M.; Liu, P.; Zhang, Y.-W.; Omenetto, F. G.; Huang, Y.; Coleman, T.; Rogers, J. A. Science 2011, 333 (6044), 838−843. (38) Hwang, S.-W.; Tao, H.; Kim, D.-H.; Cheng, H.; Song, J.-K.; Rill, E.; Brenckle, M. A.; Panilaitis, B.; Won, S. M.; Kim, Y.-S.; Song, Y. M.; Yu, K. J.; Ameen, A.; Li, R.; Su, Y.; Yang, M.; Kaplan, D. L.; Zakin, M. R.; Slepian, M. J.; Huang, Y.; Omenetto, F. G.; Rogers, J. A. Science 2012, 337 (6102), 1640−1644. (39) Norris, D. J.; Efros, A. L.; Erwin, S. C. Science 2008, 319 (5871), 1776−1779.
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dx.doi.org/10.1021/cm4022003 | Chem. Mater. 2014, 26, 679−685
