Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
ORGANIC BIOELECTRONICS Electrochemical Devices based on Conjugated Polymers Joakim Isaksson Norrköping, 2007 Organic Bioelectronics Electrochemical Devices based on Conjugated Polymers Joakim Isaksson Linköping Studies in Science and Technology. Dissertations, No. 1128 Copyright ©, 2007, Joakim Isaksson, unless otherwise noted Printed by LiU-Tryck, Linköping, Sweden, 2007 ISBN: 978-91-85831-03-6 ISSN: 0345-7524 Cover by Joakim Isaksson: Ion Pump with Cell (front) and Wettability Switch (back) “It’s a one-day experiment… …OK, OK, maybe two days…” Professor Magnus Berggren ABSTRACT Since the Nobel Prize awarded discovery that some polymers or “plastics” can be made electronically conducting, the scientific field of organic electronics has arisen. The use of conducting polymers in electronic devices is appealing, because the materials can be processed from a liquid phase or from a solution, much like ordinary non-conducting plastics. This gives the opportunity to utilize printing technologies and to manufacture electronics “roll-to-roll” on flexible substrates, ultimately at very low costs. Even more intriguing are the possibilities to achieve completely novel functionalities in combination with the inherent compatibility of these materials with biological species. Therefore, organic electronics can merge with biology and medicine to create organic bioelectronics, i.e. organic electronic devices that interact directly with biological samples or are used for other biological applications. This thesis aims at giving a background to the field of organic bioelectronics and focuses on how electrochemical devices may be utilized in biological applications. An organic electronic wettability switch that can be used for lab-on-a-chip applications and control of cell growth as well as an electrochemical ion pump, which can regulate cell communication and serve as an efficient drug delivery device, are introduced. Furthermore, the underlying electrochemical structures that are the basis for the above mentioned devices, electrochemical display pixels etc. are discussed in detail. In summary, the work contributes to the understanding of electrochemical polymer electronics and, by presenting new bioelectronic inventions, builds a foundation for future projects and discoveries. I POPULÄRVETENSKAPLIG SAMMANFATTNING Efter upptäckten 1977, vilken år 2000 belönades med Nobelpriset i Kemi, att vissa polymerer eller ”plaster” kan göras elektriskt ledande, har forskningsområdet organisk elektronik vuxit fram. Organisk elektronik handlar om att använda ledande organiska polymerer för att bygga elektroniska komponenter, vilket är lockande eftersom materialen i regel kan hanteras i flytande form ungefär som vanliga plaster. Detta innebär att elektronik kan tillverkas från rulle till rulle med tryckteknologier på plastfolie eller papper till väldigt låga kostnader. Ännu mer intressant är möjligheten att med ledande polymerer få helt nya funktioner som inte är tänkbara med klassisk elektronik och dessutom uppvisar många ledande polymersystem väldigt god kompatibilitet med biologiska material. Sammantaget innebär detta att organisk elektronik kan integreras med biologi och medicin för att skapa organisk bioelektronik, dvs. organiska elektronikkomponenter som direkt interagerar med biologiska material eller mer generellt används för biologiska applikationer. Målet med avhandlingen är att ge en bakgrund till forskningsområdet organisk bioelektronik, med fokus på elektrokemiska komponenter. Här introduceras en organisk elektronisk ”vätbarhetsswitch” med tillämpningar på analyschip och för kontroll av celltillväxt samt en elektrokemisk ”jonpump” för elektroniskt styrd cellkommunikation och administrering av biologiska substanser. Vidare diskuteras de grundläggande elektrokemiska strukturer som är basen för ovan nämnda komponenter, elektrokemiska displaypixlar, etc. Sammanfattningsvis bidrar arbetet till förståelsen för elektrokemisk polymerelektronik och bygger med de nya bioelektroniska komponenterna en grund för framtida forskningsprojekt och upptäckter. II FOREWORD AND ACKNOWLEDGEMENTS With a recent degree in engineering biology, directed towards biomaterials, and an additional semester in the biomedical research school, the field of organic electronics was a new and exciting challenge for me. Although it took some time to really get to know the world of polarons, cleanroom practices and cut-and-paste electronics, the enthusiasm and drive of the Organic Electronics group immediately swept me away. I quickly realized that (when you learn to prioritize) it is very stimulating to work in a group where the time required for new project ideas is always more than the available man-hours and where out-of-the-box thinking is highly valued. During the course of my Ph D studies, the focus slowly shifted from printed organic electronics towards organic bioelectronics. Actually, one of the main intentions with the engineering biology study program is to educate people in physics and math, as well as in chemistry and biology, in order to function as a link between the engineering and medical communities. Therefore it was very satisfying to take part in the initiation of the ion pump project, in close cooperation with cell biologists at Karolinska Institutet. The project has been the perfect example of truly multidisciplinary research, where the initial hurdles can be quite large but the final results and the road to get there are very rewarding. I am pleased to see that the results of the research efforts, summarized in this thesis, have generated new projects and opportunities for the future, and I will always take pride in my tiny contribution to the development of organic bioelectronics. I hope that the reader of this thesis will find the contents interesting and inspiring, regardless of whether he or she is working with research on related topics or is someone who simply wants to have a glance at what I have been up to for five years. With that said, I could of course not have done the work on my own and there are several people who have my sincere gratitude and deserve credit for the thesis becoming a reality. I would therefore like to thank all of you, who have helped me, with large or small things, at work or in private, during my time at LiU Norrköping. More specifically, I would like acknowledge the following people: III Min handledare, Professor Magnus Berggren, som har gett mig chansen att arbeta i gruppen Organisk Elektronik och varit en outtömlig källa av inspiration och idéer. En obotlig optimist och en cynisk skeptiker matchar varandra ganska bra! Tack för att du har gett mig förtroende och ansvar samtidigt som du har stöttat när det behövts. My co-supervisor, Nate Robinson, who always had the time to help and never was afraid to ask the difficult questions. Thanks for everything that you taught me, from scientific experimental designs to “secret” management skills. We do not always agree, but I usually count on you being right. Agneta Richter-Dahlfors, som tillsammans med Magnus har gjort det möjligt för mig att få medverka i integrationen mellan biologi och organisk elektronik. Tack för ett väldigt givande samarbete (jag vet nu bättre än någonsin att ett cellexperiment inte är något man ”snyter ur näsan”). Min motsvarighet på ”andra sidan”, Peter Kjäll, som ihärdigt har odlat celler på alla komponenter som jag skickat upp och trollat fram fantastiska resultat. Tack för många trevliga dagar på MTC, även de tillfällen när alla experiment har gått åt *******. Att hålla skärpan efter lunch i ett mörkt mikroskoprum med en DeLuxeBurgare i magen är en utmaning utöver det vanliga... David Nilsson, min mentor och jonpumpskamrat. Jag har för länge sedan tappat räkningen på alla prover vi analyserade, men jag saknar våra AAS-dagar. Sophie Lindesvik, som har koll på allt och lite till om allt och lite till som rör universitetet. Tack för just allt och lite till, inklusive att den här avhandlingen finns. Payman Tehrani, min ständigt glada labpartner i displayprojektet. Tack för trevliga timmar i labbet och för att du (oftast) höll reda på alla WM-polymerer. Övriga medförfattare, inte minst XPS-perfektionisten Calle Tengstedt och yrvädret Linda Robinson. Klas Tybrandt, min ”efterträdare” som direkt blev självgående och drivande i jonpumpsprojektet och därmed gav mig tid att skriva den här avhandlingen. IV Daniel Simon and Xavier Crispin, for valuable comments on the contents of this thesis The entire group of Organic Electronics. Thanks all of you for personal friendships, scientific team-spirit, long coffee breaks and stimulating discussions. Acreo, för tillhandahållande av material, hjälp i labbet (Anurak med flera), patentering etc. Familj och vänner som har hjälpt mig glömma jobbet och därmed ladda batterierna emellanåt: Oscar, som har blivit en god vän på jobbet och tillsammans med Anna, Oliver och Alva förgyllt och förenklat tiden utanför detsamma. Tack för värme, generositet, middagar, barnpassning (dygnet runt) och vänskap i allmänhet. Johan och Jenny. Tack för midsommar, nyår, schackspel, Lagavulin och annat som helt enkelt gör livet lite bättre. Mamma och Pappa, som har onyanserat höga tankar om mig men som ständigt finns där. Storasyster, för att du alltid har varit just Storasyster. Sist, kanske minst, men också utan konkurrens viktigast i mitt liv och därmed en stor anledning till att jag är där och den jag är idag; min lilla familj. Johanna, min älskling och bäste vän, som tar hand om mig, alltid tror på mig och betyder mer än vad jag kan sätta ord på. Tack för allt. Moa och Viktor, som sätter färg på min vardag och ger perspektiv på andra utmaningar i livet. Tack för att ni finns. Joakim Isaksson, Norrköping 2007-08-30 The work was funded by The Swedish Foundation for Strategic Research, The Royal Swedish Academy of Sciences and The Swedish Research Council. V LIST OF INCLUDED PAPERS Paper 1 A Solid-state Organic Electronic Wettability Switch Joakim Isaksson, Carl Tengstedt, Mats Fahlman, Nathaniel D. Robinson and Magnus Berggren Advanced Materials 16, 316-320 (2004). Contribution: All experimental work, except the photoelectron spectroscopy. Wrote the first draft of the manuscript and was involved in the final editing and submission of the manuscript in cooperation with the co-authors. Paper 2 Electronic Modulation of an Electrochemically Induced Wettability Gradient to Control Water Movement on a Polyaniline Surface Joakim Isaksson, Nathaniel D. Robinson and Magnus Berggren Thin Solid Films 515, 2003-2008 (2006) Contribution: All experimental work. Wrote most of the manuscript and coordinated the final editing and submission of the manuscript in cooperation with the co-authors. Paper 3 Electrochemical Control of Surface Wettability of poly(3-alkylthiophenes) Linda Robinson, Joakim Isaksson, Nathaniel D. Robinson and Magnus Berggren Surface Science 600, L148-L152 (2006) Contribution: Small part of the experimental work. Coordinated the final editing and submission of the manuscript in cooperation with the co-authors. VI Paper 4 Evaluation of Active Materials Designed for use in Printable Electrochromic Polymer Displays Payman Tehrani, Joakim Isaksson, Wendimagegn Mammo, Mats R. Andersson, Nathaniel D. Robinson and Magnus Berggren Thin Solid Films 515, 2485-2492 (2006) Contribution: All the experimental work (not including polymer synthesis) together with P. Tehrani. Was involved in the final editing of the manuscript in cooperation with the co-authors Paper 5 Electronic Control of Ca2+ Signaling in Neuronal Cells using an Organic Electronic Ion Pump Joakim Isaksson#, Peter Kjäll#, David Nilsson, Nathaniel D. Robinson, Magnus Berggren and Agneta Richter-Dahlfors Nature Materials 6, 673-679 (2007) Contribution: Significant part of the experimental work. Wrote a large part of the manuscript draft (not including the biology sections) and coordinated the final editing and submission of the manuscript in cooperation with the co-authors. # Shared authorship Paper 6 Electronically Controlled pH Gradients and Proton Oscillations Joakim Isaksson, David Nilsson, Peter Kjäll, Nathaniel D. Robinson, Agneta Richter-Dahlfors and Magnus Berggren Submitted Contribution: All the experimental work. Wrote most of the manuscript and coordinated the final editing and submission of the manuscript in cooperation with the co-authors. VII RELATED WORK NOT INCLUDED IN THE THESIS Electrochemical Wettability Switches Gate Aqueous Liquids in Microfluidic Systems Linda Robinson, Anders Hentzell, Nathaniel D. Robinson, Joakim Isaksson and Magnus Berggren Lab on a Chip 6, 1277-1278 (2006) The results from the paper above where acknowledged as a “Research Highlight” in Nature (2 November 2006) with the following paragraphs: MICROFLUIDICS Go with the flow Lab Chip 6, 1277–1278 (2006) The controlled flow of liquids in microscopic channels on ‘microfluidic’ chips could permit chemical analysis of tiny samples as well as more efficient industrial chemical synthesis. But how can the fluid traffic be directed down the right channels? Microscopic valves and gates are cumbersome, so Nathaniel Robinson and his colleagues at Linköping University in Sweden propose to do away with all moving parts. They made channels with floors whose wettability can be controlled electrically, using conducting polymers that have different surface properties when electrochemically oxidized or reduced. Water injected into such a system flows preferentially along the oxidized channels (pictured right). Patents Wettability Switch (WO/2005/053836) Electrically Controlled Ion Transport Device (Patent pending) VIII TABLE OF CONTENTS 1. INTRODUCTION 1 2. CONDUCTING POLYMERS 5 2.1 Conjugated polymers 5 2.2 Doping of conjugated polymers 8 2.3 Optical properties of conjugated polymers 12 2.4 Examples of commonly used conjugated polymers 15 2.5 Ionic conduction in polymer films 20 3. BASIC ELECTROCHEMICAL STRUCTURES 21 3.1 Reduction and oxidation of conducting polymers 21 3.2 “Structure 1” 24 3.3 “Structure 2” 25 3.4 “Structure 3” 27 4. SURFACE ENERGY – WETTABILITY 29 4.1 Surface tension in theory 30 4.2 Contact angle measurements 31 4.3 Other techniques to study surface tension 36 5. CELL COMMUNICATION 39 5.1 Communication between and inside cells 39 5.2 Calcium signaling 42 6. ORGANIC BIOELECTRONICS 47 6.1 Sensors 47 6.2 Microfluidics 49 6.3 Actuators 52 6.4 Delivery systems 53 7. ELECTROCHEMICAL DEVICES IN PAPERS 1-6 7.1 Electrochemical wettability switch 55 55 7.2 PEDOT:PSS displays with improved optical contrast 64 7.3 Organic electrochemical ion pump 67 8. CONCLUDING DISCUSSION 77 REFERENCES 79 PAPERS 1-6 NOMENCLATURE β Parameter for determination of pendant drop shape φ Hanging drop turning angle (rad) γ Surface energy, surface tension (N/m) γd Dispersive part or surface energy (N/m) γp Polar part of surface energy (N/m) γlv Liquid-vapor surface tension (N/m) γsl Solid-liquid interfacial energy (N/m) γsv Solid-vapor surface energy (N/m) λ π-bond Wavelength (m) Bond between overlapping p-orbitals θ True contact angle (degrees) θ’ Measured contact angle (degrees) ∆ρ σ-bond Difference in density (kg/m3) A Area (m2) Bond between overlapping s-orbitals A- Anion, here with the charge -1 A, B, C, D Electrode labels a. u. Arbitrary units AB Electrolyte that covers electrodes A and B C+ Cation, here with charge +1 D Drain contact DBSA Dodecylbenzene sulfonic acid dH2O de-ionized water E Energy (eV) e- Electron Eox Oxidation potential (V) F Force (N) FURA-2 AM Intracellular fluorescent probe for Ca2+ detection g Gravitational constant (m/s2) G Gate contact HCN-2 Neuronal cell line HOMO Highest Occupied Molecular Orbital IBC Current between electrodes B and C [K+] Concentration (M), in this case of potassium ions l Length (m) ∆L* LUMO Change in luminance (lightness), optical contrast M+ Cation, here with charge +1 n Number of replicates OTFT Organic Thin Film Transistor Ox Oxidized P- n-doped polymer, here with charge -1 P+ p-doped polymer, here with charge +1 P0 Neutral polymer P3AT poly(3-alkyl thiophene) P3BT poly(3-butyl thiophene) P3HT poly(3-hexyl thiophene) P3OT poly(3-octyl thiophene) Lowest Unoccupied Molecular Orbital PANI Polyaniline PBFI Fluorescent probe for detection of K+ PEDOT poly(3,4-ethylene dioxythiophene) PSS poly(styrene sulfonate) r Surface roughness R0 Radius of curvature at the apex of a pendant drop (m) Red Reduced s Dimensionless curvature length of a pendant drop S Source contact V Potential (V) VAB Potential between electrodes A and B (V) VOCCs Voltage Operated Calcium Channels w Width (m) W Work (Nm) Generic variables, like x, y and z are used in different contexts throughout the text. CHAPTER 1 1. INTRODUCTION In the year 2000, the Nobel Prize in chemistry was awarded to Alan J. Heeger, Alan G. MacDiarmid and Hideki Shirakawa for “the discovery and development of electrically conductive polymers”.1 23 years earlier, these three gentlemen had discovered that polymers, what we generally call plastics, could not only be used as insulating materials but also be made electronically conducting.2 Until their surprising breakthrough, polymers were considered as important materials because they are easy to process from solution and their mechanical properties can be tailor-made during synthesis, but intrinsically conducting polymers sounded like something of a paradox. Some polymers were already known to have semiconducting properties but Heeger, MacDiarmid and Shirakawa found that the materials can be “doped” to achieve metallic conduction. The idea of making electronic devices with the same process, flexibility and, perhaps more importantly, at the same cost as e.g. a plastic bag is of course very appealing and the discovery has opened up a completely new field of science. Since the polymers have a carbon base, in equivalence to the materials in living organisms, the use of intrinsically conducting polymers in electronic devices is often called organic electronics. 1 Chapter 1: Introduction Since it is generally possible to dissolve or emulsify polymers in water or organic solvents and thereby handle the materials as liquids, common printing techniques can be used for manufacturing of electronic components.3-5 Instead of printing different colors, several conducting polymers can be used as inks in the printing press. There are of course a number of practical issues to deal with but roll-to-roll printing of electronics on flexible substrates such as paper or insulating plastic foil is already a reality. The speed and performance of such printed devices is not comparable to what is achieved in the traditional silicon industry but since a printing press can process up to several 100 meters per minute, the cost for each device is close to nothing. This, in combination with the environmental hazards of tedious silicon processing and the fact that many conducting polymers are biocompatible,6,7 make organic electronics even more interesting. Examples of organic electronic applications include light emitting diodes,8-10 solar cells,11-13 thin film transistors,14,15 electrochemical transistors and logic circuits16-18 and sensors.19-21 Apart from the electronic conductivity itself, conducting polymers have a number of other exceptional properties, as compared to inorganic materials, which make it possible to create completely new types of devices. One way of using the unique properties of conjugated materials and to achieve novel functionalities is to focus the attention towards biology. The application of organic electronics on biology and medicine is called organic bioelectronics, which is the topic of this thesis. The aim of the thesis is to briefly describe the scientific background of organic bioelectronics, followed by a more detailed explanation of the functionality and characteristics of newly developed devices. To start off, the upcoming chapter gives an introduction to the physics and chemistry of conjugated polymers, exemplified by a few polymer systems as well as some of their applications. Thereafter, fundamental electrochemical structures that utilize these materials are described. Two chapters are dedicated to give a brief background on the topics of surface science and cell communication, which are vital to understanding the bioelectronic devices presented at the end of the thesis. A review chapter on the field of organic bioelectronics aims at showing the 2 Chapter 1: Introduction importance and potential of this research area, as well as the almost perfect match between organic electronics and life sciences. This puts the electrochemical bioelectronic devices in a context and also pinpoints some of the challenges that remain to be solved. The thesis is concluded with a detailed description of the electrochemical bioelectronic inventions that comprise the base for the accompanying papers, followed by a concluding discussion and a glance towards future bioelectronic projects and applications. Papers 1-3 describe the organic electronic wettability switch, which gives the possibility to electronically control the wettability of a surface, create surface energy gradients etc. The device is interesting for bioelectronic applications like microfluidic channels and control of cell-growth but could also have novel uses in e.g. printing technologies. Paper 4 discusses printable organic electrochromic displays with a contrast-enhancing layer. Papers 5 & 6 present the organic electronic ion pump, used for cell communication studies and potentially also for drug delivery applications. The ion pump utilizes the ion conductivity of a conjugated polymer-polyelectrolyte system to electrophoretically transport ionic species from a source electrolyte and deliver them to cells that live on the surface of the polymer in a second electrolyte. The work is based on the development of all-organic, electrochemical and presumably printable devices with very similar structures and materials but completely different applications. The papers and the new devices comprise a small, but hopefully important, contribution to the scientific fields of organic electronics in general and, with the exception of the electrochromic display, organic bioelectronics in particular. 3 4 CHAPTER 2 2. CONDUCTING POLYMERS A polymer (poly = many in Greek) is a material that consists of many repeated units, called monomers (mono = one). Natural polymers are for instance DNA, proteins, cellulose etc., but polymeric materials can also be synthesized. Since the number of possible polymer designs is close to infinite, the chemical and physical properties can more or less be tailor-made for a specific application. Most polymers or their monomers are soluble in water or organic solvents. This means that the material can be handled and processed as a liquid and therefore simple manufacturing techniques such as moulding, casting, spin coating, screen printing etc. can be used to create structures and shapes before or after polymerisation. The class of polymers that can conduct electricity is referred to as (intrinsically) conducting polymers. 2.1 Conjugated polymers What is the difference between the polymer in a plastic bag and one that can conduct electricity like metals? A common material in regular plastic bags is polyethylene, which is a very good insulator. In polyethylene, each carbon binds to two other carbons and to two hydrogen atoms (Figure 1a). The physical chemist would say that the carbon is sp3-hybridized, i.e. hybridization between the s-, px-, py and pz-orbitals yields four equivalent hybrid orbitals, and forms four σ(sigma)-bonds to the surrounding atoms. Every carbon valence electron is 5 Chapter 2: Conducting Polymers then localized in such a bonding molecular orbital and can therefore not transport current. Polyacetylene (Figure 1b) has a very similar chemical structure but in this case each carbon only binds to three other atoms. The carbon is now sp2-hybridized and forms three σ-bonds. However, since carbon has four valence electrons, each carbon atom has one electron left in a non-hybridized p-orbital. These atomic p-orbitals are oriented perpendicular to the polymer backbone, and overlap in a delocalized electron cloud along the polymer chain to form molecular π(pi)-bonds. The result is a conjugated molecular structure with alternating single and double bonds between carbon atoms. Figure 1. Chemical structures of a. Polyethylene and b. Polyacetylene with shorthand notations below. The most stable form of polyacetylene (trans-polyacetylene), drawn in Figure 2 with shorthand notation, where each vertex represents a carbon atom with hydrogen atoms, has a so-called degenerate ground state. I.e. there is no difference in energy if the positions of the double bonds and the single bonds are interchanged. This means that the electrons in the π-bonds can be found between any two carbon atoms and thus move along the polymer chain. The longer the molecule, the smaller is the energy gap and for very long molecules, energy bands are formed. 6 Chapter 2: Conducting Polymers If all bond lengths between carbon atoms were the same, polyacetylene would behave like a one-dimensional metal. However, this is not the case, because of so-called Peierls distortion, i.e. it is more energetically favorable for the molecule to have an alternating bond configuration. Therefore, an energy gap appears in the band structure, like for inorganic semiconductors. The highest occupied molecular orbital (HOMO) defines the high energy edge of the valence band and the lowest unoccupied molecular orbital (LUMO) is the bottom of the conduction band. Figure 2. Polyacetylene has a degenerate ground state, i.e. the two single-double bond alternation schemes have the same total energy. The presence of a band gap means that energy has to be given to the system in order to excite electrons from the valence band to the conduction band and pure polyacetylene therefore has semiconducting properties instead of metal behavior. Due to the conjugation (delocalization of π-electrons), the bandgap is still very small (1.5 eV) compared to polyethylene (>8 eV), which is an insulator. Most other conjugated polymers (e.g. polythiophene, see 2.4.1) have a nondegenerate structure, i.e. there is only one energy ground state. In this case the single and double bonds cannot be interchanged without a cost in energy, due to distortion of the molecular structure, and the band gap of a polymer with a nondegenerate ground state is slightly larger than in a degenerate conjugated molecule. Once again, thanks to the conjugation, the band gap is small enough to yield semiconducting properties. 7 Chapter 2: Conducting Polymers 2.2 Doping of conjugated polymers Pure polyacetylene is a semiconducting material, but the number of thermally excited charge carriers and their mobilities are limited. Therefore, although the conductivity is higher than in polyethylene, it is far from that of a metal. Heeger, MacDiarmid and Shirakawa discovered that charge carriers can be introduced in polyacetylene by chemical doping of the material, which results in a conductivity increase by several orders of magnitude. This discovery earned them the Nobel Prize in chemistry and revolutionized the field of conjugated polymers. A comparison of conductivities for different organic and inorganic materials is shown in Figure 3 (from Ref. 22). Figure 3. Conductivity of a few organic and inorganic materials. Adapted from Ref. 22. Positive doping of a conjugated polymer means that an electron is removed from the valence band (addition of a positively charged “hole”) and negative doping denotes when an electron is added to the conduction band. Although the 8 Chapter 2: Conducting Polymers physics is different, this way to create mobile charge carriers in an organic semiconductor can be compared to p- and n-doping, respectively, in inorganic semiconductors like Si. However, a high percentage of dopant is needed to increase the conductivity in the polymer compared to only a few ppm in Si. Conjugated polymers can be doped in a number of different ways, such as chemical and electrochemical doping, charge injection doping, photo doping and acid-base doping.22,23 For degenerate systems, like trans-polyacetylene, a geometrical defect in the polymer chain can create a modification of the bond length alternation pattern, as shown in Figure 4. The domain “wall” between the two types of bond length alternation is called a soliton and is characterized by a new energy state in the middle of the band gap. The “extra” charge resides in this state, which is localized over a relatively short distance (X = 10 to 20 C-C bonds in Figure 4). If the bond order is shifted without the addition of an external charge, a neutral soliton with spin = ½ is created, as shown in Figure 4a. Solitons are present in trans-polyacetylene because of defects or simply on chains containing an odd number of carbon atoms. Although they have no charge, the solitons can be detected experimentally because of their spin. When an electron is added to the polymer chain through n-doping, existing solitons are energetically favorable to charge and a negative soliton with no spin appears (Figure 4b). If an electron is instead subtracted from the polymer, a positive soliton without spin is created as seen in Figure 4c.24,25 The energy states described above refer to the idealized case of an isolated polymer chain. In reality, interactions between chains must be considered and if the charged states stem from chemical or electrochemical doping, a counter ion will be ionically coupled to the polymer chain in order to maintain charge neutrality (see also 3.1). This ion will contribute to the geometrical distortion of the molecule and localize the soliton. Most conjugated polymers are, however, not degenerate, i.e. they have one unique energy ground state. When a non-degenerate conjugated polymer is doped, the geometric distortion induces a state of higher energy. The structure 9 Chapter 2: Conducting Polymers distortion coupled to the introduced charge is called a polaron, which can move along the polymer chain and thereby participate in the electronic conductivity of the material.26,27 Polarons can also be created in non-degenerate systems, such as trans-polyacetylene, but only at higher doping levels when all solitons have been charged. Figure 4. Solitons in trans-polyacetylene. a. Neutral. b. Negative. c. Positive. X denotes the localization of the soliton One example of a simple non-degenerate conjugated polymer is poly(paraphenylvinylene) (PPV). Doping of this polymer changes the bond alternation and creates a geometrically distorted region with quinoid structure instead of the regular aromatic, as shown in Figure 5. This also leads to the appearance of new energy levels inside the band gap. Upon further doping, it is sometimes energetically favorable to form bipolarons, which are doubly charged and spinless, instead of two separate polarons. In a simplified picture, the charges in 10 Chapter 2: Conducting Polymers the bipolaron repel each other because of Coulomb forces but, at the same time, the separation of two polarons costs elastic energy since the quinoid configuration is a higher energy state than the aromatic. This situation can be compared to the equilibrium state of a spring and the bipolaron will therefore be localized over few rings, as shown in Figure 5. Figure 5. Formation of a negative polaron and bipolaron in poly(paraphenylvinylene). 11 Chapter 2: Conducting Polymers The energy levels of the polarons and bipolarons are, to a large extent, correlated to the HOMO and LUMO of the neutral quinoid form and the energy difference between these levels is smaller than in the aromatic case. The new levels formed inside the bandgap upon doping create new allowed optical transitions at lower energies (see also 2.3). As in the soliton case, the formation of polarons and bipolarons described above is idealized and correspond to one isolated molecular chain, without charge neutralizing counter ions that localize the polaronic charge carriers. 2.3 Optical properties of conjugated polymers Conjugated polymers have small optical bandgaps and many of the materials therefore absorb light in the visible region (wavelengths, λ = 400-800 nm; or energy, E = 1.5-3 eV). Consequently, conducting polymers are often colorful materials, which also means that if the electronic structure and associated allowed optical transitions are modified, e.g. upon doping, we can follow the color transition with our eyes when the absorption of light changes. 2.3.1 Absorption and emission A material can absorb a photon, i.e. a quantum of light, if the photon energy matches the difference between the energy of the excited state and the ground state (Figure 6). If that is the case, the molecule receives the photon energy and is excited to a higher energy state, with increased atomic separation. From this state the molecule can return to the energy ground state via radiative or nonradiative processes. In a radiative decay, a new photon is created and light is thereby emitted (spontaneous emission). The light emission is quenched if a non-radiative decay allows the molecule to come back to the ground state by donating the excitation energy to surrounding molecules via collisions (phonons) or energy transfer. Since some of the energy is always lost in vibrations, the energy of the emitted light is lower than that of the absorbed light (red-shifted wavelength), as shown schematically in Figure 6. 12 Chapter 2: Conducting Polymers Figure 6. Absorption and emission. a. Schematic energy diagram showing two electronic states with vibrational levels. The energy “wells” show the relationship between energy and the reaction coordinate. The incoming photon is absorbed by the molecule, which is then excited. After vibrational relaxation, the molecule can return to the electronic ground state by emission of a new photon with lower energy. b. Sketch of absorption and emission spectrum with visible vibrational peaks. The emitted light has a lower energy and the wavelength is thereby higher (red-shifted). 13 Chapter 2: Conducting Polymers Organic light emitting diodes also utilize the radiative decay of an excited state to emit light, but in this case, excited electron-hole pairs, referred to as excitons, are created by injection of charges with an applied electric field. Organic solar cells work the other way around. Incoming photons excite the molecules and, when the excited charges are separated, power can be collected at the electrodes. 2.3.2 Electrochromism in conjugated polymers Since optical absorption corresponds to differences in energy states, the absorbance spectrum of a material is a signature of the electronic and vibrational levels (Figure 6). When a conjugated polymer is doped, new energy levels are created inside the band gap (as seen in Figure 5) and new optical transitions are thereby possible. Many conjugated polymers can be electrochemically doped, with a resulting change not only in conductivity but also in color. Such a material, which alters color upon electrochemical switching, is called electrochromic.28-30 Examples of applications for organic electrochromic materials are flexible thin electrochemical displays,16 autodimming windows31 etc. The use of organic materials for electrochromic applications has several advantages, besides the previously mentioned ease of manufacturing. Addition of side chains to conjugated polymers or modification of the effective conjugation length alters the energy level configuration and thereby the color of the material.32,33 It is therefore possible, to some extent, to design materials with the right color absorption to match the demand of a specific application. Since electrochemical switching of conjugated polymers also alters the electronic conduction properties, organic electrochromic pixels may be integrated with electrochemical transistors17 and logic18 to build truly all-organic matrixaddressed displays.16 Examples of common electrochromic polymers are given below and simple organic electrochemical structures are described in more detail in 3.2-3.4. 14 Chapter 2: Conducting Polymers 2.4 Examples of commonly used conjugated polymers The research field of conjugated polymers has accelerated rapidly since the discovery of doped polyacetylene, and a number of different polymers and their derivatives have been synthesized in order to achieve materials with tailor-made properties. Polyacetylene itself is of course the ”original” conducting polymer but difficulties with processing and poor stability in ambient atmosphere limits the use of the material in real applications. Other groups of polymers are therefore today utilized much more frequently in organic electronics. A few materials of interest for the work in this thesis will be presented below. 2.4.1 Polythiophenes Polythiophene and derivatives thereof have become popular conjugated polymers for applications such as light emitting diodes,8,10,34 field-effect transistors,14,35,36 solar cells,37,38 memory applications39,40 and capacitors.41 The first synthesis of a material similar to polythiophene was reported already at the end of the 19th century but it was not until the 1980s that the well-defined polymeric material was presented.42 Figure 7. a. polythiophene. b. poly(3-alkylthiophene), R denotes an alkyl chain. c. Example of the regioregular configuration, which preserves the conjugation in the material. Polythiophenes (Figure 7a) are insoluble in organic solvents due to the rigid polymer backbone and side-chains have therefore been added to the material. 15 Chapter 2: Conducting Polymers Common polythiophene derivatives are molecules with an alkyl chain on the 3position of the thiophene ring as shown in Figure 7b. Poly(3-hexylthiophene) (six carbons in the alkyl side chain) has proven to be a material with both good solubility in organic solvents and nice film-forming properties. Today, pure and highly regioregular head-to-tail poly(alkylthiophenes) (Figure 7c) are commercially available and can be used to form conjugated and well ordered semiconducting thin layers by e.g. spin casting. Poly(3-alkylthiophenes) can be utilized as the active materials in the electrochemical wettability switch, described in 7.1 and Papers 1-3. 2.4.2 PEDOT:PSS One polythiophene derivative has become especially important in organic electronics, particularly for electrochemical devices. During the late 1980s, Bayer AG in Germany developed poly(3,4- ethylene dioxythiophene) or PEDOT (Figure 8a). This p-doped polymer in combination with the charge balancing counter-ion poly(styrene sulfonate) (PSS-) (Figure 8b) forms a water soluble (emulsion) polymer-polyelectrolyte system (PEDOT:PSS) with nice filmforming properties, high conductivity and tremendous stability in the p-doped (oxidized) state.32 Figure 8. a. poly(3,4-ethylene dioxythiophene) (PEDOT). b. poly(styrene sulfonate) (PSS) 16 Chapter 2: Conducting Polymers Applications incorporating PEDOT:PSS range from solid state devices like light emitting diodes43,44 and solar cells,45,46 where the polymer works as the anode or hole injecting electrochromic sensors,21,47,48 layer, to displays,16,31 electrochemically electrochemical bio-electrodes49,50 active structures, transistors and such as logics,17,18 etc. The mechanical and chemical stability of PEDOT:PSS films in combination with good electrochromic properties and high conductivity make the material an excellent base for all-organic electrochemical devices. A film of PEDOT:PSS can be reversibly switched between the oxidized and neutral state several times. PEDOT:PSS is almost transparent in the oxidized doped state and dark blue in the neutral semiconducting state, as seen from the absorbance spectrum in Figure 9. Electrochromic displays with PEDOT:PSS on paper and plastic are discussed in detail in 7.2 and Paper 4. The PEDOT:PSS electrochemical ion pump is presented in 7.3 and Papers 5 & 6 Figure 9. Absorbance spectrum of PEDOT:PSS film in the neutral and oxidized (p-doped) state. 2.4.3 Polyaniline Another essential conjugated polymer is polyaniline (PANI). The first samples of polyaniline, also called aniline black, were prepared in the early 19th century but the material was usually an unwanted deposit on the anode during electrolysis with aniline. In 1910, Green and Woodhead51 managed to control the 17 Chapter 2: Conducting Polymers synthesis of PANI and also started to characterize the polymer. Due to the cheap raw material, stable conducting forms, strong electrochromism and ease of processing, PANI has since then become a popular material in both industry and science.42,52 PANI is a complex conjugated polymer, since the material has a number of intrinsic oxidation states and several routes of doping. Fully reduced PANI is transparent and called leucoemeraldine, with a chemical structure as shown in Figure 10a. The dark blue semi-oxidized (~50%) state is named emeraldine base (Figure 10b) and the violet blue fully oxidized material is termed pernigraniline base (Figure 10c). Contrary to most other polyaromatics, none of these states are electronically conducting, not even the fully oxidized pernigraniline form. Instead, PANI becomes conducting when the semi-oxidized state is protonated and a green emeraldine salt is formed. This highly conducting doped form, shown in Figure 10d, can actually be reached through two completely different pathways. If the emeraldine base is treated with e.g. hydrochloric acid, protonic acid doping occurs as protonation of the imine nitrogen atoms (⎯N==) creates positively charged protonated imines (⎯NH+⎯), balanced by negative ions from the acid. This is so called non-redox doping, but in another route, chemical or electrochemical doping of the reduced leucoemeraldine base can also be utilized to obtain the very same conducting salt.22,42,52-54 The nonconductive emeraldine base is soluble in N-methyl-pyrrolidone but the conducting salt, protonated with hydrochloric acid, is practically insoluble in organic solvents. One way to achieve a soluble (emulsion) conducting PANI salt, without incorporating covalent side chains, is to dope the material with surfactant alkyl sulfonic acids that donate protons to the polymer.55,56 This way of preparing the p-doped material also results in a slightly different chemical composition. Apart from the larger surfactant counter ions, which of course affect solubility and film formation, protonated amine units (⎯NH2+⎯) have also been detected along with the imine dittos in these systems.52,57,58 The effect of the surfactant counter ion on the surface properties of such a system is a key element in the wettability switch, described in 7.1 and Papers 1-3 18 Chapter 2: Conducting Polymers Figure 10. Polyaniline (PANI) oxidation states. a. Leucoemeraldine. b. Emeraldine base. c. Pernigraniline. d. Protonated emeraldine salt (charge balancing counter ions not shown). The dots represent unpaired electrons (radicals). The electrochromic properties of PANI makes it a suitable candidate for multicolor electrochromic displays.28 Other areas of application include antistatic coatings and corrosion protection,59,60 biomaterials,61,62 light emitting diodes,63,64 sensors,65,66 field effect transistors67 and batteries.68 19 Chapter 2: Conducting Polymers 2.5 Ionic conduction in polymer films A very useful property of many conjugated polymer systems is the ability to conduct not only electrons but also ions, e.g. when electrochemical doping or undoping of the polymer is accompanied by mass transport of ions in or out of the material. This provides the possibility to electrochemically switch the entire bulk of a conjugated polymer film, but the ionic movement per se and the effect that it has on the volume and conductivity of the polymer can also be directly used in applications such as artificial muscles,69-71 sensors47,48 and drug release devices.72-74 Polymer-polyelectrolyte systems with a surplus of counter ions in the film can have ion conductivities that are equal to or even larger than that of aqueous solutions.75,76 PEDOT:PSS is an example of such a porous, phase separated material, with electronically conducting conjugated polymer islands surrounded by insulating PSS.75-78 Ions from an aqueous solution enter the polymer film hydrated and the ion conductivity in the material will therefore increase, once it is swelled with water. The transport mechanism of ions in the film can be either electromigration or diffusion, depending on the ion gradient and electric field that act on the species.79 In this case, the ion conduction primarily occurs in the (hygroscopic) PSS phase and is thus effectively independent of the oxidation state of the PEDOT. There are, however, examples of conjugated polymer coated membranes with electrochemically switchable ion conductivity80,81 and even protein transport properties.82 From a bioelectronics perspective, the fact that conjugated polymers can conduct ions and work as ion-to-electron transducers48 (and vice versa) is of course very intriguing and can be used in e.g. organic neural electrodes.83,84 In biological systems, local potentials across membranes are created and sustained by differences in ionic concentrations and ions like Ca2+ are versatile cell signaling substances that govern many important processes in our bodies (Chapter 5).85-87 Electronically controlled transport of such ions through the polymer film and communication with cells on top of the polymer layer is the principle of the organic electronic ion pump, described in 7.3 and Papers 5 & 6. 20 CHAPTER 3 3. BASIC ELECTROCHEMICAL STRUCTURES Since many conjugated polymers can be doped and undoped by electrochemical reactions and thereby change their intrinsic properties, such as color, conductivity and wettability, these materials are well suited as the working material in different electrochemical devices. The devices presented in this thesis, and many devices before that,16,17,21,88,89 all originate from similar simple electrochemical structures that can be easily manufactured on flexible substrates with “printable” materials. The work towards achieving such all-printed electrochemical devices is an outcome of the collaboration between the group of Organic Electronics90 and Acreo AB.91 The function of these fundamental base structures will therefore be described in this chapter. 3.1 Reduction and oxidation of conducting polymers An electrochemical reaction means that a chemical phenomena is associated with charge separation of some sort, often in the form of charge transfer.92 Two or more half-reactions have to take place, one oxidation and one reduction reaction. In a simple two-electrode electrochemical cell (Figure 11), the electrodes are separated in space but linked by two conducting paths. The electrolyte between the electrodes can transport ionic charges and the conducting wires of course conduct electrons. The electrodes may either work as inert sources and sinks for electrons transferred to and from species in solution, 21 Chapter 3: Basic Electrochemical Structures or take part in the electrochemical reaction itself. If the sum of the free energy changes at both electrodes is negative, energy is released and the cell works as a battery. If it is positive, a bias voltage can be applied to drive the electrochemical reaction, as illustrated in Figure 11. Figure 11. Sketch of a simple electrochemical cell. The anions (A-) are electrostatically drawn towards the anode (+) and the cations (M+) towards the cathode (-). Many conducting polymers can be either n-doped by reduction (addition of electrons to the polymer) or p-doped by oxidation (withdrawal of electrons from the polymer), as shown in reaction (1) and (2), respectively. P denotes the polymer, Mx+ means one or many cations (positively charged) and Ay- stands for one or many anions (negatively charged). P 0 + xe− + M x + → P x − M x + (1) P 0 + A y − → P y + A y − + ye − (2) n-doped conjugated polymers are often not as chemically stable as p-doped polymers, if oxygen or water are present, and the polymer systems used in electrochemical devices are therefore often switched between a neutral (undoped) and an oxidized (p-doped) state. As an example, commercially available PEDOT:PSS (2.4.2) is originally (as received) conducting and partially 22 Chapter 3: Basic Electrochemical Structures oxidized. From here the material can either be further oxidized to a more conducting state or reduced to the semi-conducting neutral polymer. The reactions are reversible in both directions, which makes the polymer system suitable for electrochemical devices. The reduction (left to right) and oxidation (right to left) of PEDOT:PSS can be written as: PEDOT + : PSS − + e− + M + ↔ PEDOT 0 + PSS − M + (3) An electrochemical technique such as voltammetry, i.e. the applied potential is swept and the current measured, is a common way to characterize conducting polymers. This technique yields the oxidation potential, i.e. a measure of how much energy is needed to withdraw electrons from the polymer HOMO level, and the reduction potential, a similar characteristic (addition of electrons) of the LUMO. The measurement is performed with a potentiostat and a threeelectrode system.92 The reaction to be studied occurs at the working electrode. A reference electrode, such as Ag/AgCl, with a well-defined electrochemical potential is used to keep the working electrode at a constant absolute potential. To maintain the potential as stable as possible, a third auxiliary electrode (counter electrode) is used to pass the current. The counter electrode is often made of Pt and should have a large active area. The potentiostat can also be used to synthesize polymeric materials on the working electrode by electropolymerization.93,94 The monomer is then present in the electrolyte and when a potential is applied, oxidation or reduction of the monomer can create reactive radicals. Several radicals can connect to form polymeric chains and since the reaction takes place at the working electrode, the polymeric film will cover that surface. Organic electrochemical devices should preferably be self-supporting structures that contain relatively few layers and, in the best case, are printable. Therefore, the design of a typical organic electrochemical cell is somewhat different from that shown in Figure 11. The electrolyte is generally solid or gel-like instead of a liquid. Conducting polymer materials work as one or several electrochemical electrodes, where reduction and oxidation takes place, but may also function as electronic and ionic conductors. The polymers can e.g. be spin-coated on the 23 Chapter 3: Basic Electrochemical Structures substrate but are, as in the case of PEDOT:PSS, sometimes commercially available in rolls of pre-coated films on plastic foil or paper. The devices often have a lateral configuration, i.e. the electrodes are situated in the same plane with the electrolyte on top or underneath. Patterning of these polymer films is generally done by simply cutting non-conducting lines or by over-oxidation of the PEDOT, i.e. electrochemically or chemically destroying the conductivity of the material.3 In order to achieve smaller features, photolithographic techniques may also be used to manufacture the devices. 3.2 “Structure 1” If an electrolyte is cast to cover a stripe of polymer film, made from a conducting polymer-counter ion system like PEDOT:PSS, the resulting device configuration is referred to as “Structure 1”. If a voltage is applied along the polymer film, as shown in Figure 12, a gradient in oxidation state and color will appear. There are two parallel paths for charge transfer between the electrodes in the system. The polymer film is electronically conducting, which means that electrons can move through the material, which then works as a resistor. Since the polymer is not a perfect electronic conductor, there is always a potential difference between the two sides of the polymer stripe when a voltage is applied. Therefore, with the electrolyte on top, the positive side of the polymer will start to be oxidized and the negative side reduced. As long as the electrochemical reaction occurs in the polymer film, charges can be transported as ions through the electrolyte. Reduction of the polymer film drastically increases the impedance locally and thereby makes it more difficult for current to pass straight through the “resistor”. More reduction and oxidation will then take place as the oxidation gradient builds up. This behavior of the “Structure 1” is responsible for the saturation of drain-source current in the electrochemical transistor by Nilsson et al.17,95 If the applied potential goes to zero (open-circuit) the internal potential difference in the polymer will even out and the gradient disappear. 24 Chapter 3: Basic Electrochemical Structures Figure 12. Structure 1. a. Side view with electronic and ionic conduction paths. b. Top view. 3.3 “Structure 2” If the polymer film of Structure 1 is instead divided into two electrodes by a nonconducting line, “Structure 2” has been created, as shown in Figure 13. Electrochemically, Structure 2 is a direct equivalent to the electrochemical cell shown in Figure 11. The two electrodes are electronically isolated and ionic transfer is the only path for charge transport between them. When a bias voltage is applied, the negative electrode will start to be reduced and the positive electrode becomes oxidized. The loss or gain of charges inside the polymer film is balanced out by migration of ions in the electrolyte and across the electrolytepolymer interface. The electronic current in the wires and the ionic current in the electrolyte will flow as long as electrochemistry can take place at the polymer electrodes. If the voltage supply is removed, there is no closed circuit 25 Chapter 3: Basic Electrochemical Structures for the electrons to spontaneously go back and the electrodes will therefore keep their respective oxidation states, until chemically affected by e.g. oxygen in the atmosphere. With electrochromic materials such as PEDOT:PSS or polyaniline:dodecylbenzene sulfonic acid (PANI:DBSA), Structure 2 works as a very simple display pixel and several such structures can, in combination with electrochemical transistors, build up all-organic matrix-addressable displays.16 Improvement of optical contrast in PEDOT:PSS paper display pixels is discussed in 7.2 and Paper 4. Structure 2 also represents the basic configuration of the electrochemical wettability switch (7.1 and Papers 1-3), the electrochemical ion pump (7.3 and Papers 5 & 6) and works as the gate in the electrochemical transistor.17 Figure 13. Structure 2. a. Side view with electronic and ionic conduction paths. b. Top view. 26 Chapter 3: Basic Electrochemical Structures 3.4 “Structure 3” The device called “Structure 3” is slightly more complicated than the previously described configurations. In this case, the polymer film is divided into three separate pieces by non-conducting lines, as shown in Figure 14, but only the outer two segments work as charge donating/accepting electrodes. When a voltage is applied between the two electronic contacts, there are several paths for charge transport. Because of the bias voltage, the two outer electrodes are oxidized and reduced respectively, and ions are transported between them, in the same way as seen for Structure 2 (Figure 13). Figure 14. Structure 3. a. Side view with electronic and ionic conduction paths. b. Top view. 27 Chapter 3: Basic Electrochemical Structures Parallel to this charge transport, the middle segment of conjugated polymer is also capable of conducting electrons if ion to electron transduction can take place through oxidation on one side and reduction on the other. Therefore, an electrochemical gradient will be induced in the middle polymer piece of Structure 3 when the outer electrodes are biased. This electrochemical gradient only exists as long as electrochemistry occurs at the two electrodes. If the voltage is disconnected or the electrode material is consumed, the outer pieces of polymer will stay oxidized and reduced, but the gradient in the middle will disappear, in the same way as with Structure 1. The induced oxidation gradient is a result of the local electric field in the electrolyte and can therefore, as cleverly shown by Said and co-workers,89 be used to map and visualize electric fields in the electrolyte. When PANI:DBSA is used as the conducting polymer, the oxidation gradient also serves as a wettability gradient, which can be used to control the spreading of water droplets on the polymer surface (7.1 and Papers 1 & 2). 28 CHAPTER 4 4. SURFACE ENERGY – WETTABILITY The formation and characteristics of interfaces between liquids and solids depend on the surface properties of the involved materials. Wetting behavior can therefore provide valuable information in a number of scientific and industrial areas. For small volumes, surface effects are even more pronounced and surface science is therefore a crucial part of micro- and nanotechnology. Examples of application areas depending on (and utilizing) wettability are e.g.: Microfluidics – How do small volumes of a liquid move on a surface or in a channel? Control of surface treatments and cleaning steps – Is the surface clean? Anti-fouling surfaces – Why are the leaves of the lotus plant always dry? Biomaterials – How will the biomaterial interact with human tissue? Pharmaceuticals – How will the drug particles dissolve and be absorbed in the body? Composites – How will the reinforcement material adhere to the matrix? Printing technologies – How will the ink adhere and spread on the paper coating? 29 Chapter 4: Surface Energy - Wettability 4.1 Surface tension in theory The molecules at the surface of a liquid or a solid behave differently from their counterparts in the bulk, since they lack neighbors in one direction. The surface therefore has “free energy” along the interface exposed towards the surrounding media and it is, neglecting other forces, energetically favorable to decrease the surface area as much as possible. This is why liquids form spherical (lowest area/volume ratio) droplets in e.g. air. The surface energy, γ, is characteristic for a solid or liquid material in the interface towards a specified gas phase, such as air (with vapor). The surface energy determines the energy needed to increase the area of the surface, i.e. high surface energy means strong attraction between the surface molecules of a material. For liquid-gas interfaces, the surface energy is generally referred to as the surface tension or interfacial tension. A common example of surface tension and surface energy is that of a thin rectangular frame of width l, pulled through a liquid-gas interface, e.g. water-air, as drawn schematically in Figure 15 (from Ref. 96). Figure 15. Creation of a thin liquid film by pulling a wire frame through an air-water interface. Adapted from Ref. 96 30 Chapter 4: Surface Energy - Wettability A thin film of the liquid may be formed in the frame and a certain force is then needed to lift the rectangle and thereby increase the surface area (the weight of the frame and film are not considered here). If γ is the force per unit length to create the new interface, i.e. the interfacial tension, the force needed to move the frame and thereby create two new interfaces, one on each side of the liquid film, can be written as: F = 2γ l (4) If the frame is moved a short distance, dx, the amount of work done is given by: dW = 2γ ldx (5) If the area, A, of the liquid film is considered instead, γ has the units of energy per unit area (surface energy) and equation (5) can be written as (once again the factor 2 comes from the two sides of the film): dW = 2γ dA (6) This shows that γ can be thought of as either an interfacial tension or as a surface energy, the quantities are identical. The SI unit for surface energy / surface tension is Nm/m2 = N/m. The surface tension can be divided into polar (permanent dipoles) and dispersive (induced dipoles) parts. Polar materials, like water, typically have strong bonds between the molecules and therefore show high surface tensions in air. 4.2 Contact angle measurements When a small volume of liquid is placed on a solid surface in e.g. air, the equilibrium state between the two materials and the surrounding vapor determines the shape of the liquid droplet. In a simplified picture, the free energy of the solid surface can be seen as a force that will tend to spread the liquid droplet in order to decrease the solid-vapor interface. On the other hand, there is a cost in energy to form a new liquid-solid interface and therefore the 31 Chapter 4: Surface Energy - Wettability interfacial energy between the liquid and solid works as a force in the opposite direction. Finally, the surface tension of the liquid tries to contract the droplet in order to decrease the liquid-vapor interfacial area and is therefore a third force, parallel to the tangent of the droplet. The shape of the droplet can be seen as the equilibrium between these forces as shown in Figure 16. The solid surface energy in the surrounding vapor is denoted γsv, the liquid-vapor surface tension γlv and the solid-liquid interfacial energy γsl.96,97 Figure 16. Surface tensions (γ) and contact angle (θ) when a liquid droplet is placed on a solid surface in the vapor atmosphere. The angle between the solid surface and the droplet tangent is called the contact angle, θ, and is a direct measure of how a liquid wets a solid surface (Figure 16). The relationship between the surface tensions and the contact angle is expressed in the Young-Dupré equation, which simply reflects the trigonometric relationship between the three forces.96,97 cos θ = γ sv − γ sl γ lv (7) Contact angle measurements are fairly simple in practice, but since the technique is very surface sensitive, cleanliness is extremely important. The most common instrument used to determine contact angles is the goniometer. It usually consists of a sample table, a syringe for dispensing of the liquid and a microscope lens or a camera to record the contact angles (Figure 17). If the 32 Chapter 4: Surface Energy - Wettability system has a camera connected to a computer, several images can of course be recorded over time and contact angle values are then generated from the acquired images by software. When the liquid drop is created at the tip of the syringe, which is then lowered down until the drop contacts the solid surface, the measured contact angle is “static”. If nothing else is stated, contact angle values refer to static measurements. Figure 17. Photograph of a goniometer setup. Liquid droplets for contact angle measurements are applied to the solid surface with the syringe. The camera takes pictures of the droplets and computer software can then evaluate the images. If the volume of the liquid droplet is increased while in contact with the surface, the tangent line moves away from the syringe and the measured angle is referred to as the “advancing” contact angle. If the volume is instead decreased in a similar fashion, the contact angle is “receding”. In many cases, there is a hysteresis between the advancing and receding contact angle values. The 33 Chapter 4: Surface Energy - Wettability advancing angle is always equal to or larger than the receding and the difference could originate from e.g. relaxation from contaminated surfaces or liquids, surface roughness or surface immobility.97 One example of obvious hysteresis is a water droplet sliding down a dirty windowpane. The front of the droplet is slightly pinned to the window and therefore forms a large advancing contact angle as gravity drags the water down. Similarly, if the back of the droplet is stuck, it will form a small receding angle against the glass. In many cases, water is used as the standard liquid when measuring contact angles. A surface that water wets (low contact angle) is called hydrophilic, while materials with high water contact angles are labelled hydrophobic. From Figure 16 and equation 7, one can see that a high solid surface energy will generally result in low water contact angles, since γsv is then high and γlv is likely low, and vice versa. The absolute value of the solid surface energy cannot be measured directly, because the interfacial tension is also unknown, but it is possible to estimate with contact angles from several liquids. A series of homologous liquids, such as alkanes of different length, can be used to create a so-called Zisman plot. The cosines of the contact angles are plotted versus the surface tensions of the liquids and give a linear relationship. The “critical surface tension” corresponding to cos θ = 1 (γsv = γlv) can be extrapolated from the plot and this value gives a good estimation of the surface energy of the material studied.96,97 Another approach to estimate the surface energy of a solid surface is to measure contact angles with two or more liquids, of which one should be mainly polar and the other non-polar. The intermolecular energy is the sum of the polar and dispersive component and this relationship also holds for the surface tensions. The polar and dispersive part of the solid surface energy can therefore be evaluated by e.g. the geometric mean equation (γp denotes the polar and γd the dispersive parts of the interfacial tensions): d d γ SL = γ SV + γ LV − 2 ⎡ ( γ LV γ SV )+ ⎣⎢ (γ p LV Equation (7) and (8) give equation (9): 34 γ SVp ) ⎤ ⎦⎥ (8) Chapter 4: Surface Energy - Wettability d d γ LV (1 + cos θ ) = 2 ⎡ ( γ LV γ SV )+ ⎣⎢ (γ p LV γ SVp ) ⎤ ⎦⎥ (9) If the contact angles have been measured with at least two liquids, with known polar and dispersive liquid-vapor interfacial tensions, equation (9) can be used to calculate the values of the solid surface energy components (two liquids give two equations for two unknowns).98 Apart from the surface energy of the solid material, the surface topography can also affect the wetting behavior. A structured surface with high roughness will decrease the water contact angles compared to a smooth material if the original contact angle is less than about 90°. The topography of the surface then forms small capillaries for the water. The liquid can penetrate the micro cavities and will therefore quickly wet the surface. If the angle is slightly larger than 90°, the uneven surface will instead result in much higher angles. In this case the water cannot enter the capillaries and has to form larger angles to the available solid surface. The effect of surface roughness on contact angle measurements can be estimated with the simple Wensel equation (10), where r denotes the surface roughness, defined as the ratio of the true area of the solid to the apparent area, θ ’ is the measured contact angle and θ is the “true” contact angle.96,97,99 r= cos θ ' cos θ (10) If the surface is very hydrophobic or very rough, air trapping underneath the drop has to be considered (the Cassie regime) but this state is generally only meta-stable for water.99 The creation of rough surfaces is a common technique to achieve superhydrophilic and superhydrophobic surfaces, artificially as well as in nature. Sun and co-workers100 have e.g. achieved reversible thermal switching of water contact angles between ~0° and 150°. A famous example of a superhydrophobic surface in nature is the leaf of the lotus plant (Figure 18). This ingenious structure barely gets wet when it rains and is also self-cleaning, since the water forms large contact angles and simply rolls off the rough waxy surface of the leaves, which have several levels of texture.101,102 35 Chapter 4: Surface Energy - Wettability Figure 18. Lotus leaf and raindrop. Used with permission from Victoriaadventure 103 and the photographer Byoung Sup Ghill (Copyright ©) 4.3 Other techniques to study surface tension 4.3.1 Pendant drop The surface tension of a liquid (in e.g. air) or the interfacial tension between liquids can be calculated directly from the shape of a drop, which hangs from the syringe in the surrounding media. The shape of the drop (Figure 19) is mathematically described by three first order differential equations (11-13).104,105 dx = cos φ ds (11) dz = sin φ ds (12) dφ sin φ = 2+ βz − ds x (13) β= 36 ∆ρ gR02 γ (14) Chapter 4: Surface Energy - Wettability x and z are coordinates of a point on the drop profile divided by R0, the radius of curvature at the apex, which makes them dimensionless. φ is the turning angle at that point and s is the dimensionless curvature length from apex to the same point. The shape of the droplet is characterized by β, which is defined in equation (14), where ∆ρ is the difference in density between the phases and g is the gravitational constant.104,105 Figure 19. The pendant drop coordinate system. From a digital image of the droplet, acquired with e.g. a goniometer, computer software can quickly solve the system of differential equations numerically to best fit the droplet shape, with the same methods as when analyzing contact angles. If the liquid and gas densities are known, the surface tension can then be extracted. The pendant drop method has the advantage of being independent of the liquid contact angle to the solid support, as oppose to tensiometry that is described below, and gives quick accurate values of surface tensions. Evaluating 37 Chapter 4: Surface Energy - Wettability the surface tension of a liquid before using it for contact angle measurements is a good way to check for possible contamination. 4.3.2 Tensiometry A classical technique to measure surface tension and interfacial interactions is tensiometry.106,107 The principle of tensiometry is the same as in the example with the rectangular frame described in 4.1, i.e. the force exerted when a solid probe interacts with a surface or interface is a measure of the involved interfacial tensions. Apart from the surface tension of the analyzed liquid, the forces will depend on the size and shape of the probe as well as the contact angle between the liquid and the probe. Different shapes and types of probes can be used, but the most common ones are rings and plates. The results from tensiometric measurements are often very accurate and objective, but the technique requires a fair amount of the liquid to be analyzed and if the solid is studied, it has to be of a regular shape with the same surface on all areas that contact the liquid. 38 CHAPTER 5 5. CELL COMMUNICATION Cells, in all organisms, need to be able to sense and interact with their environment in order to survive. In multicellular organisms, like ourselves, all the cells have to function together at the same time and a complex system of inter- and intracellular signaling pathways have therefore evolved. The scientific field of cell signaling is naturally huge and to accurately describe even a few of the most important pathways and signaling molecules is far beyond the scope of this thesis. Therefore, this chapter only briefly illustrates the basic aspects of cell communication in general terms and exemplifies with one incredibly important, yet very simple, signaling entity; the calcium ion. 5.1 Communication between and inside cells Cells can communicate with each other in a number of different ways, as outlined in Figure 20. Cells that are not in direct contact communicate by the release of signaling molecules, which are detected by receptors on (sometimes inside) the target cells (Figure 20a). Such molecules that bind specifically to protein receptors are generally referred to as ligands. If the ligands, e.g. hormones, travel long distances in the organism through the blood stream, often to another tissue, the signaling is called endocrine. If the signaling molecules are instead rapidly detected and have their effect in close proximity to 39 Chapter 5: Cell Communication the signaling cell, the communication is denoted paracrine. If the signaling cell and the target cell are one and the same, the signaling is called autocrine.108,109 Figure 20. Cell communication methods. a. Release of ligands, detected by receptors on the target cell. b. Molecules at the surface of the signaling cell are detected by membrane receptors along the target cell surface. c. Direct transport of intracellular signaling molecules through gap junctions. d. Synaptic signaling via transport of an action potential along the axon, followed by electric or chemical communication with the target cell. Adapted from Ref. 108 & 109. Cells that are in direct contact with each other can of course communicate rapidly and easily by either receptor-ligand signaling (Figure 20b) or directly through gap junctions (Figure 20c). In the first case, the signaling cell has ligand molecules in the plasma membrane, which recognize and bind to specific 40 Chapter 5: Cell Communication surface markers on the target cell. Gap junctions, on the other hand, are protein tubes that are formed between the plasma membranes of adjacent cells. They literarily work as hundreds of pipes that let small signaling molecules pass directly from one cell to the other. The passage can, however, be closed at any time by a conformational change of the gap proteins, e.g. as a response to high ionic concentrations or if the neighboring cell dies.108,109 The signaling mechanism in our nervous system is synaptic signaling (Figure 20d), which means that the signal is propagated as changes in the electrical membrane potential along the axon of the neuronal cell. A stimulus, which locally shifts the membrane potential (depolarization), activates voltage-gated Na+ channels that allow Na+ to enter the cell. The influx of positive charges further depolarizes the membrane, which has a resting potential of about –70 mV, and causes new channels to open. When the membrane potential reaches an equilibrium value of +50 mV, the Na+ channels are temporarily inactivated and the potential returns to its resting value. This decrease in potential is also speeded up by a simultaneous flux of K+ out from the cell, through voltageactivated K+ channels. At the same time, the neighboring part of the membrane is triggered and the wave of self-amplifying depolarization (action potential) spreads along the membrane. The inactivation of the Na+ channels lasts for a few ms after reaching the resting potential, which prevents the signal from propagating backwards. Since the cells are very long (up to 1 m) the signal can be transported fast (up to 100 m/s) over extensive distances. The transfer of the signal between cells (synapse) can be either electrical, i.e. an ion current travels directly between cells through gap junctions, or chemical via opening of voltageoperated calcium channels (VOCCs, see 5.2), activated by membrane depolarization, and subsequent release of neurotransmitters that are detected by receptors on the neighboring target cell.108-110 The propagation of an action potential, where one stimulus triggers a sequence of events, is one example of how the signals are amplified in cellular communication. Amplification also takes place inside the cells through so called second messengers. The extracellular signaling molecule, the first messenger, starts the production or release of small intracellular molecules, i.e. second 41 Chapter 5: Cell Communication messengers. Each such second messenger in turn activates new molecules in a cell signaling cascade, which not only amplifies the signal to create an effective end result in the target cell, but also allows for improved control of the response through possible inhibitory feedback loops. Furthermore, signaling molecules in one cascade can activate other pathways, which may work in parallel to induce the same end result or diverge into new or even counter-acting cellular responses. The fact that two completely different signals can use the same second messenger, highlights the complex nature of cell signaling and the difficulty in scientifically studying cell communication, e.g. by inhibition of specific receptors or second messengers. For instance, how can the cell know which signal that originally activated a specific second messenger if it is active in several pathways? One example of how this is actually solved in nature is the use of oscillating signals, which carry information not only in the molecular species in themselves, but also in both their frequency and amplitude.111,112 This has in recent years proven to be the case with Ca2+ signaling, which is discussed in the section below. 5.2 Calcium signaling One of the most versatile intracellular signaling molecules in our body is the calcium ion, which in a sense controls almost everything that we do. Our muscle movement, brain activity and every single heart beat involves Ca2+ signaling. In addition, this very simple ionic species is involved in fertilization, cell development and differentiation as well as programmed cell death.86 The key to such an enormous span of regulated cellular processes from a single signaling molecule is resolution in time and space. The actual location of concentration changes inside the cell as well as the frequency and amplitude of Ca2+ oscillations provide the necessary triggering and addressing of the signaling cascades. The wide dynamic range can be exemplified by neurotransmitter exocytosis, which is activated within microseconds and, at the other end of the scale, cell proliferation and fertilization with periodicities of several hours (see Figure 21).86,87 42 Chapter 5: Cell Communication Figure 21. Intracellular Ca2+ signaling. Ca2+ pulses are, via second messengers, triggered by a stimulus and generated from the balance between ON and OFF reactions. Calcium ions can enter or leave the cell via specific transporting pathways through the cell membrane and be released from or stored in intracellular compartments. Organelles like the mitochondria are involved in changing the dynamics of the signaling process. Examples of oscillation period times corresponding to cellular responses are shown at the bottom of the figure. Adapted from Ref. 87. 43 Chapter 5: Cell Communication As shown schematically in Figure 21, the intracellular Ca2+ level is constantly determined by a balance between ON reactions, which introduce calcium into the cell, and OFF reactions that removes the signal. Controlled variations in these ON and OFF signals, as a response to an external stimulus, create the necessary Ca2+ pulses to trigger specific signaling systems.87 During the ON reactions, most of the intracellular Ca2+ ions have been transported from outside the cell, through the plasma membrane. The extracellular Ca2+ concentration is much higher than the intracellular one, which creates an electrochemical gradient across the cell membrane that is not permeable to the ions. If Ca2+-specific entry channels (shown as generic uniporters in Figure 21) are opened in the plasma membrane, the gradient drives Ca2+ into the cell, thereby increasing the intracellular concentration. A commonly studied type of transport channels are the VOCCs (see also 5.1) that exist in excitable cells, such as muscle cells, glandular epithelial cells and neurons. VOCCs can generate very rapid actions in e.g. muscle contraction and synaptic exocytosis but may also be involved in slower events like inflammatory responses.87,113 Other types of membrane Ca2+ channels include receptoroperated channels and second-messenger-operated channels. A second important source of Ca2+ is the intracellular stores, primarily in the endoplasmatic reticulum (or the muscle cell equivalent, sarcoplasmatic reticulum). Release from these stores is regulated with second messengers, as a response to external stimuli and, indirectly, by Ca2+ itself. To fine-tune the calcium signal, in time and space, buffers in the cell are loaded with Ca2+ during the ON reaction and unloaded during the OFF reaction. At the same time, other Ca2+-binding proteins work as effectors that activate different calcium responsive cellular processes.87 In order to create Ca2+ pulses or oscillations with specific frequencies, OFF reactions must balance out the ON reactions and decrease the intracellular calcium concentration. Calcium ions are removed from the cytoplasm by various pumps and exchangers, such as Ca2+-ATPase pumps, Na+/Ca2+ exchangers and mitochondrial uniporters, which transports the ions out from the cell or into the internal stores, as shown in Figure 21. These tools are not only important for the 44 Chapter 5: Cell Communication cell in the event of a signaling cascade, but also to remain homeostasis with a stable resting level of Ca2+ in the cytosol.87,114 As shown in Figure 21, mitochondria have an active role in the OFF reaction. Already at low concentration changes, as a response to the character of the intracellular calcium signal, mitochondria can rapidly take up Ca2+ through uniporters to quickly clear the cytosol from the ion. The calcium ions are then released in a much slower fashion and can subsequently be permanently removed from the cell by pumps and exchangers.87,114 Apart from variations of the Ca2+ concentration in time, spatial resolution is crucial for calcium signaling, especially in rapid responses.87,115 As an example, the individual dendritic spines on neurons work as independent signaling units, thereby increasing the computational capacity of the cell. Also, calcium signals localized on one cell can spread from cell to cell and even between different cell types.87 The knowledge of calcium signaling reveals that it is necessary to consider not just the signaling entity per se but also the spatial and temporal properties of the signal, when communicating with cells or studying cell communication. This is an aspect that makes cell signaling even more complex and a strong motivation, whether thought of as a scientific tool for cell studies or a delivery device for future therapeutic purposes, for the organic electronic ion pump, presented in 7.3 and Papers 5 & 6. 45 46 CHAPTER 6 6. ORGANIC BIOELECTRONICS Compared to metals and inorganic semiconductors, organic materials such as conjugated polymers are softer and chemically much more similar to the materials in our body. This is reflected in the fact that many polymer systems are highly biocompatible,6,7 i.e. living cells can easily adhere and proliferate on the material surface. Also, the potential use of flexible transparent substrates, the formation of porous layers with large effective surfaces, high electronic and ionic conductivity, electronic switching of various physical properties etc. make conjugated polymer devices very promising candidates for future bioelectronic applications. 6.1 Sensors The use of conjugated polymers in different biological and chemical sensors has recently attracted a lot of attention.116,117 One approach is to simply include different biomolecules in conducting polymer electrodes, which localizes and controls the spatial resolution of the biologically active molecule and acts as a transducer, by converting the biochemical signal into an electronic ditto.117,118 Similarly, changes in the color or conductivity of the polymer itself, e.g. as a response to the chemical nature of the environment, can be used as the transducer mechanism in chemical sensors.48,65 47 Chapter 6: Organic Bioelectronics In the search for sensors that are inexpensive and can be miniaturized and integrated with other electronic components on portable high sensitivity devices for immediate retrieval of data, organic thin film transistors (OTFTs) are very attractive alternatives.116,119-121 These devices provide electronic output with in situ amplification of the signal, as well as compatibility with standard microelectronic manufacturing techniques. The OTFT sensors can generally be divided into two types of devices, as depicted in Figure 22. The first category describes sensors based on organic or polymeric field effect transistors (Figure 22a), i.e. the conductivity of the transistor channel is modulated by controlling the charge carrier density in an organic semiconducting film with an applied electric field across an insulating layer. The detection principle can here be due to direct analyte-semiconductor interactions or indirect via specific receptor molecules on the device surface. The sensor response variables can be changes in the bulk and field-induced conductivity, threshold voltage or field-effect mobility.20,116,119,122 Examples of such sensors are chemical gas sensors19,20,120 as well as ionic and biomolecular sensors.123,124 The second category of OTFT sensors is represented by the electrochemical transistor, as exemplified in Figure 22b. In this case the modulation of the channel conductivity is due to electrochemical doping/dedoping of the organic semiconductor, charge balanced by ions from a solid or liquid electrolyte. The electrochemical transistor is generally slower than its field effect counterpart but, on the other hand, requires very low voltages (~ 1 V) and is easily integrated with liquid analytes. Also, these devices are not built up from structures including any critical dimensions, such as very thin films, and should therefore be easier to integrate in a roll-to-roll manufacturing process.125 All-organic lateral transistors17,18 and sensors21 on plastic or paper can be realized by combining “Structure 1” (channel) and “Structure 2” (gate), described in Chapter 3. Recent examples of novel sensor concepts utilizing the electrochemical transistor is a glucose sensor126,127 and an ion-selective sensor that uses ion channels in a bilayer lipid membrane.128 The response variable in these cases is the level of modulation from the gate potential. 48 Chapter 6: Organic Bioelectronics Figure 22. Examples of typical organic thin film transistor sensors. a. Field-effect transistor for sensing of vapors.19 The gate (G) is a conductor underneath an insulating oxide. The source (S) and drain (D) are evaporated gold contacts. Exposure of the semiconducting channel to different vapors is detected as changes in the source-drain current. b. Electrochemical transistor for glucose sensing.126,127 The source (S), drain (D) and active channel are in the same layer of PEDOT:PSS. The gate (G) is in this case a platinum wire. The analyte solution contains the sample and the enzyme (here glucose oxidase) for the specific analysis. The modulation of source-drain current by the gate is determined by the concentration of analyte in the solution. 6.2 Microfluidics In order to realize cheap, fast and high sensitivity analysis of e.g. blood or saliva, for use at home or close to the patient (bed-side) at the hospital, it is necessary to combine the different sensor concepts with systems that handle small volumes of liquid. The “lab-on-a-chip” approach aims at having the entire analysis system on easy-handled miniature single-use chips, but the delivery of fluid and control of fluid motion is still a major problem, and in many cases such techniques require large external instrumentation. To be able to create an independent analysis lab on the microscale, the driving force to control fluid 49 Chapter 6: Organic Bioelectronics motion must originate from within the integrated device and not from external pumping equipment.129,130 One way to guide and regulate liquid flow in microfluidic applications is to create transitions from wetting to non-wetting regions on the surfaces in contact with the fluid. A liquid on a solid surface will find it energetically favorable to move from an area with lower wettability (high contact angle) towards higher wettability (decreased contact angle).131,132 Therefore, several publications on how to switch the contact angle of a surface have been presented in the last few years. The external stimuli can be e.g. temperature,133 light,134 electric fields135 or electrochemistry.136 Also, a number of cleverly integrated systems, using e.g. pressure driven flow of bubbles,137 microheater arrays138 and electrophoretic manipulation of drops,139 have been realized and in some cases also commercialized. The use of conjugated polymers to regulate wetting in all-organic electrochemical devices is presented in 7.1 and Papers 1-3. Such an approach is intriguing, because the devices switch at very low voltages (~ 1 V) and numerous polymer systems can be used.58,140-143 Taken together, this gives the potential to integrate these devices with organic electronic sensors and transistors to create very cheap single-use lab-on-a-chip structures on paper or plastic foils. As a first proof of concept, the organic electronic wettability switch has been used to guide water in microfluidic bifurcations.144 Liquid flow in a microfluidic channel assembled on top of the organic device is shown in Figure 23a and a conceptual image of an integrated system, where the response from sensor-transistors in the channel guide the liquid downstream, is presented in Figure 23b. Causley and co-workers also further developed the concept of the organic electronic wettability switch for microfluidic applications, but they used the liquid within the channel as electrolyte instead of having a solid electrolyte layer underneath.143 The prime target of that particular work was to induce sample reagent mixing and fluid movement on a microfluidic chip, using very low addressing power. In another work aiming at creating low power fluid management systems for integrated microfluidics, the same group utilized 50 Chapter 6: Organic Bioelectronics conjugated polymer actuators, described in the section below, to develop an organic microfluidic pump.145 Figure 23. Organic microfluidics. a. Green colored water in a microfluidic channel on top of an organic wettability switch.144 The right side has been electrochemically switched to a more hydrophilic state and consequently the water prefers that path. Top: Picture before water has entered the channel. Bottom: Picture of water in the channel, where the path that most of the water takes is indicated with an arrow. b. Conceptual image of an organic microfluidic system containing transistor-sensors integrated with wettability switches. This gives the possibility to analyze the sample with the sensors and also guide different samples in different paths, depending on the outcome of the sensing. 51 Chapter 6: Organic Bioelectronics 6.3 Actuators When a conjugated polymer film is electrochemically oxidized or reduced, as discussed in Chapter 3, the electronic current is accompanied by mass transport of charge balancing counter ions into or out from the material. These ions, especially when carrying solvent molecules such as water, can have a relatively large total volume and thereby significantly alter the volume of the polymer film, as shown in Figure 24. If part of the film is fixated to an electromechanically inert material, such as gold, the swelling of the polymer will cause the entire structure to bend or extend in a certain direction. This is the principle behind one kind of conjugated polymer actuators; micromuscles.6971,145-147 By using microfabrication techniques, it is possible to create electronically addressable micro-robots that can manipulate objects on the size of a single cell.69,146 Also, since the electrochemical devices are biocompatible,6,7 operate at low voltages and run in liquid solutions, such as cell media or body fluids, micromuscles are highly interesting for biomedical applications like cell clinics, blood vessel connectors or drug delivery systems (see section below).70,148 Figure 24. Conjugated polymer actuator. In the simple case illustrated here, the neutral polymer film contains no ions (left). When a voltage is applied between the electrodes (right), the polymer is oxidized (positively charged) and counter ions enter into the film, thereby changing the volume of the material. 52 Chapter 6: Organic Bioelectronics 6.4 Delivery systems When a drug is administered as a single dose, e.g. when we take a pill, the time that the concentration of the active substance in our body is actually within the therapeutic range is highly limited. The only way to extend this time frame, during which the concentration is above the minimum effective level, is to increase the initial dose and, as illustrated in Figure 25, thereby risk toxic effects from the temporarily very high concentration of drug in the body. If the drug could instead be released slowly in a controlled fashion (dotted line in Figure 25), the time that a certain amount of substance is effective in the body could be drastically prolonged. This not only improves the therapeutic effect but is also a competitive and cost effective advantage on the huge pharmaceutical market. Examples of drug delivery systems existing today include diffusion controlled and chemically controlled systems.149 Figure 25. Drug concentration in the body for single dose administration and controlled release (adapted from Ref. 149). The therapeutic range is between the minimum effective level and the toxic level. Instead of only having a constant concentration of the drug in the optimum range over a long period of time, one step further would be a system capable of responding quickly to the varying needs of the patient (dash-dotted line in Figure 25). This gives the possibility to, at any time, adjust the concentration of 53 Chapter 6: Organic Bioelectronics the drug in the body, e.g. as a response to an integrated or external sensor output in a feedback system. Once again, when searching for biocompatible, cheap and flexible electro-responsive devices, organic electronics is one appealing choice and several electronically regulated drug delivery systems using conjugated polymers have been presented during the last few years. Examples of such organic bioelectronic delivery systems include PEDOT:PSS coated nanotubes,150 mechanical systems using polymer actuator valves70,148,151 as well as conjugated polymer films, in which the drug is the counter ion, temporarily coupled to the doped polymer and released when the doping level is changed electronically.72-74 The two latter types are the most common choices and are associated with slightly different advantages and disadvantages. The use of actuators as mechanical valves makes it possible to release large or small, charged or neutral molecules but requires relatively complex structures with moving parts that may be expensive to manufacture and sensitive to mechanical failures. The delivery systems based on polymer films loaded with the drug as counter ions are, on the other hand, much simpler devices. They are, however, intrinsically limited to charged drugs and often have the problem of undesired leakage through ion exchange with the surrounding electrolytes. Although currently designed as an in vitro tool to study cell communication, by delivering ionic species, the ion pump described in 7.3 and Papers 5 & 6 can also be considered as an electronically controlled drug delivery system, for future in vivo use. This device has comparably low leakage and can locally deliver high doses of the specific chemical, with a very good on/off ratio, but is currently limited to delivering relatively small charged species. 54 CHAPTER 7 7. ELECTROCHEMICAL DEVICES IN PAPERS 1-6 The unique properties of conjugated polymers give possibilities for devices with completely new functionalities that would not be possible to achieve with inorganic metals or semiconductors. Three electrochemical devices, with very similar structures but completely different features and applications, are presented in this chapter. The electrochemical wettability switch and the ion pump are novel devices for primarily biological applications, while the electrochromic display with an additional polymer layer is an improvement to already existing technology with potential utilization in scientific and industrial areas related to displays. The chapter is also a summary of the published work that comprises this thesis and further details about the devices can therefore be found in Papers 1-6. 7.1 Electrochemical wettability switch As mentioned in Chapter 4, many physical processes are governed by surface interactions and it is therefore crucial to have control of the surface properties in numerous applications. When a conjugated polymer is oxidized or reduced, the bulk properties, such as color and conductivity, change as a result of the chemical reorganization in the material, but what happens at the surface? It turns out that the wettability or water contact angle of the polymer surface will in fact often be modified along with the oxidation state (see also Papers 1-3).142 55 Chapter 7: Electrochemical Devices in Papers 1-6 In undoped or neutral polymer systems, e.g. polyalkylthiophenes, doping will induce dipoles at the surface and thereby generally increase the surface tension of the material (polar materials have high surface tension / low water contact angles). More complex systems, such as PANI pre-doped with DBSA (Figure 26), where the charge-balancing counter-ion is a surfactant, i.e. a molecule with one hydrophobic and one hydrophilic end, can actually work the other way around. 7.1.1 PANI:DBSA wettability switch When PANI is in the fully reduced leucoemeraldine state, the DBSA molecules are not bound to the polymer chain and can show their water-loving parts at the surface when water is placed on top. This means that the material will be hydrophilic and give low water contact angles. If, on the other hand, PANI is oxidized to the doped pernigraniline state, the hydrophilic sulfonic acid groups of DBSA bind ionically to the polymer backbone and the hydrophobic alkyl chains are instead exposed at the surface. Therefore the oxidized polymer film shows a more hydrophobic behavior, see Figure 26 and 27. Figure 26. Polyaniline salt doped with dodecylbenzene sulfonic acid (PANI:DBSA). a. PANI:DBSA with x undoped amine groups, y protonated imines and z protonated amines. b. DBSA chemical structure with the hydrophilic sulfonic acid group and the hydrophobic 12-carbon alkyl chain. 56 Chapter 7: Electrochemical Devices in Papers 1-6 Figure 27. The structure 2 electrochemical wettability switch. a. PANI:DBSA wettability switch. b. Water droplets and associated contact angles on oxidized and reduced PANI:DBSA. The electrochemical wettability switch utilizes the control of the oxidation state of a polymer film via an applied potential. If the oxidation state of the material also determines the surface wettability, it is thereby possible to electronically control the latter. The simplest wettability switch is Structure 2 with PANI:DBSA as the polymer film (Figure 27a). The difference compared to the Structure 2 in Figure 13 is that, in this case, the electrolyte has instead been placed underneath the polymer film in order to expose the active surface to the surrounding environment. When a bias voltage is applied, the negatively addressed PANI:DBSA electrode will switch to the yellow reduced state and the positively biased electrode to the dark blue oxidized state. Since both states of the polymer are conducting enough, the switch is reversible. If water contact angles are measured on each of the surfaces, it is clear that the applied voltage has modified the surface wettability (see contact angles in Figure 27b). Since the 57 Chapter 7: Electrochemical Devices in Papers 1-6 oxidation state of the polymer system also changes the color of the material, it is possible to couple the electrochromic state to the water contact angle of the surface. The relationship between water contact angle, absolute oxidation potential, versus a Ag/AgCl reference electrode, and optical absorbance at 700 nm, where the difference in absorbance between oxidation states is large, for a PANI:DBSA electrochemical wettability switch is shown in Figure 28. 45 grees) Contact Angle (de 40 35 30 25 20 15 10 5 0 -0.2 0.0 E ox ( V 0.2 vs. Ag /Ag Cl ) 1.0 0.8 ) nm 00 7 0.4 e( nc 0.2 ba r 0.0 so Ab 0.6 0.4 Figure 28. PANI:DBSA contact angle versus oxidation potential and absorbance at 700nm. 7.1.2 P3AT wettability switch Similarly to the device structure with PANI:DBSA, it is also possible to make electrochemical wettability switches that include undoped polyalkylthiophenes (P3AT) as the active material. As mentioned in the beginning of this chapter, electrochemical doping of the material creates dipoles, i.e. positive polarons charge-neutralized by counter ions, in the polymer film, thereby changing the wettability of the surface. Since the P3AT is initially neutral (pristine) and cannot easily be reduced, silver paste was used as the negatively addressed 58 Chapter 7: Electrochemical Devices in Papers 1-6 counter electrode, underneath the electrolyte, as shown schematically in Figure 29a. Figure 29. P3AT wettability switch. a. Device architecture. When the potential is applied, the positively addressed P3AT is oxidized and the negatively biased silver is reduced. b. Three different P3ATs with different side groups (O is octyl, H is hexyl and B is butyl). Three different P3ATs with varying side-chain lengths, as shown in Figure 29b, have been tested. The alkyl side-chains have a hydrophobic character and thereby increase the water contact angle of the neutral polymer film, as compared to the non-substituted polythiophene. As seen in Figure 30, the longer the side-chain, the more hydrophobic is the neutral P3AT film. When the 59 Chapter 7: Electrochemical Devices in Papers 1-6 polymer is oxidized, the surface becomes more polar and the water contact angle decreases. However, the alkyl side-chains also shield the water from the polar polymer backbone to some extent and the switching effect therefore depends on the number of carbons in the alkyl group (Figure 30). Shorter sidechains provide less shielding and thereby increase the wettability switching effect. Figure 30. P3AT contact angles. a. Static water contact angles of P3OT, P3HT and P3BT in the pristine (neutral) and electrochemically oxidized state. b. Difference in contact angle between neutral and oxidized states of the P3ATs. 60 Chapter 7: Electrochemical Devices in Papers 1-6 Since the initial contact angle and the corresponding wettability switch depends on the chemical nature of the side groups, it is possible to fine tune the system to get the desired properties, simply by the choice of substitution chemistry. As an example, the use of surface morphology to increase the net surface energy switch effect and create superhydrophobic to superhydrophilic transitions depends on the contact angle of the smooth surface. Theoretically, in order to achieve a switch from superhydrophobic to superhydrophilic, the change in contact angle should occur around 90°.99,100 Thus, in this case, P3HT (102° to 89°) would probably be the best candidate for such an electronic switch. 7.1.3 Electronic modulation of wettability gradients In equivalence to the device described in 7.1.1, it is also possible to make a PANI:DBSA Structure 3 wettability switch. When the outer electrodes are biased, an oxidation, color and wettability (water contact angle) gradient is induced in the middle polymer section. If a drop of water is placed on the wettability gradient, it will automatically move or spread towards the reduced, more hydrophilic side. Hence, it is possible to guide the droplet in the direction of the electric field, without the use of a microfluid channel or hundreds of volts. Figure 31. 4-terminal electrochemical wettability switch. Electrodes A and D form structure 2, while B, C and D constitute Structure 3. The bistable voltage Vad will modulate the oxidation state, color and wettability in D, while Vbc controls the gradient. 61 Chapter 7: Electrochemical Devices in Papers 1-6 If the polymer film is divided into four electrodes, i.e. a 4-terminal electrochemical wettability switch, it is possible to modulate the level of an induced wettability gradient via a bi-stable Structure 2 voltage. As seen in Figure 31, electrodes A and D form Structure 2, while B, D and C combine to Structure 3. D is thus common for both substructures and this is where the gradient will be formed. When a bias voltage, Vad (~3 V), is applied between A and D, the electrode chosen to be positive will be oxidized and the negative electrode will thereby be reduced. If Vad is disconnected and another potential, Vbc (~15 V), is subsequently applied between B and C (along “Structure 3”), a gradient in oxidation, color and wettability will be induced along electrode D. Since the A-D structure is bi-stable, the initially applied Vad voltage will determine the average level of oxidation in electrode D, even after that the gradient has been created. The gradient will therefore exhibit different absolute levels, depending on Vad, for the same Vbc. (Figure 32) Figure 32. Color gradient at electrode D of a 4-terminal electrochemical wettability switch, modulated with different Vad. Approximate corresponding water contact angles are shown on the right-hand side yaxis. Vbc = 15 V 62 Chapter 7: Electrochemical Devices in Papers 1-6 Figure 33. Droplet movement on the surface of electrode D in a 4terminal electrochemical wettability switch, modulated with different Vad. Vbc = 15 V a. Droplet movement for three Vad (three devices). b. Photographs of droplet movement. 63 Chapter 7: Electrochemical Devices in Papers 1-6 The wettability characteristics along D is thus also determined by Vad, which means that spreading and motion of water on the polymer surface can be modulated by the small bi-stable voltage (Figure 33). If D is initially oxidized (positive Vad), water droplets placed in the center of the induced gradient will hardly move at all, but for negative Vad, the water droplet spreads quickly towards the reduced side and make a net transport of almost 1 mm. 7.2 PEDOT:PSS displays with improved optical contrast Electrochromic pixels consisting of PEDOT:PSS, as the color-switching material, on plastic foil or paper are very promising for all-organic printed displays. Pixel elements (Structure 2, see 3.3) can be combined with electrochemical transistors to build up active matrix-addressed displays or simply be individually addressed, such as in a 7-segment device (Figure 34a). Figure 34. Printable displays. a. Two lateral seven segment displays on paper, patterned on the same piece of PEDOT:PSS. b. Printing press for organic electronics with printed test pattern. Both photos copyright © Niclas Kindahl, Fotofabriken and Acreo AB.91 64 Chapter 7: Electrochemical Devices in Papers 1-6 PEDOT:PSS is a suitable base-material for simple organic printable displays, since the pre-coated polymer films are relatively environmentally stable and can be patterned through various manufacturing processes (see e.g. Ref. 3). It is also possible to process the polymer material in the form of a solution (emulsion), which gives additional flexibility when transfering the manufacturing to a real printing press (Figure 34b). PEDOT:PSS exhibits fast and reversible electrochromic switching but, as can be seen from Figure 9, the absorption of the colored reduced state does not cover the entire visible spectrum (400-800 nm). The lack of absorption around and below 550 nm, where our eyes are very sensitive, gives a relatively low perceived optical contrast as compared to many other electrochromic systems. One possible solution to this problem is to add another polymer film directly on top of PEDOT:PSS in Structure 2. Apart from proper processability, mechanical stability and good adhesion to the PEDOT:PSS layer, such a second polymer needs the following properties in order to improve the function of the displays: The polymer should absorb light between 400 and 550 nm in the reduced (neutral) state and be transparent when oxidized. The polymer film needs good ionic conductivity to promote fast switching of the display. Electronic conductivity is not as crucial, since that is well provided by PEDOT:PSS in the lateral direction. The oxidation potential has to be sufficiently low, in combination with printable water-based electrolytes, to enable oxidation without risking over-oxidation (irreversible loss of conductivity in the material). Several conjugated polymers, synthesized by the group of Mats Andersson at Chalmers University of Technology in Gothenburg, have been explored as candidates for the contrast-enhancing layer. The chemical structures are outlined in Figure 35. From spectroscopic and electrochemical characterizations (details in Paper 3), two main design criteria for the second polymer layer can be suggested. First, 65 Chapter 7: Electrochemical Devices in Papers 1-6 oligo(ethylene oxide) side chains seem to increase the ionic conductivity of the polymer layer. This is expected, since oligo(ethylene oxide) prevents crystallization of the polymer molecules and is therefore commonly used in solid polymer electrolytes.152 Second, polymers with ethylenedioxythiophene (EDOT, as in the PEDOT monomer, Figure 8a) moieties show lower oxidation potentials and can consequently be reversibly switched in the water-based electrolyte without over-oxidation. Polymers III and IV fulfill these criteria and become transparent when oxidized, which means that they are well-suited for use in the contrastenhancing layers. O O O O O O S O O n S O I n S S n II O O III O O O O O O O O O n O O O O n V O O O O S S O O O O VII O S VIII S n O O O O N VI O n S S IV O N S S O O O O S S O O O n O S S N S N IX Figure 35. Conjugated polymers for a contrast-enhancing layer on PEDOT:PSS displays. 66 n Chapter 7: Electrochemical Devices in Papers 1-6 Organic flexible displays with polymer III and IV, respectively, deposited on PEDOT:PSS have been manufactured and characterized with spectrophotometry. As shown in Figure 36, the optical contrast defined as the change in luminance ∆L* (details in Paper 3), is almost doubled by the addition of a second polymer layer. Figure 36. Optical absorbance, measured in transmittance mode, of flexible organic PEDOT:PSS displays with and without contrastenhancement layer. ∆L* denotes the optical contrast. a. Only PEDOT:PSS. b. PEDOT:PSS plus polymer III. c. PEDOT:PSS plus polymer IV. 7.3 Organic electrochemical ion pump Due to their organic chemical composition and relatively soft mechanical properties, conjugated polymers generally work well as biocompatible materials (see Chapter 6). In many cases, our living cells use ionic species, such as potassium and calcium, in the signaling cascade when communicating internally and with each other. The internal ionic concentrations often oscillate at specific frequencies, as a response to external stimuli, and thereby induce several activities, e.g. gene expression, in the cell (Chapter 5). If the ion transport to and from the cell could be controlled electronically, with spatial and temporal resolution, it would be possible not only to study in detail how cells interact with each other and the surrounding environment but also to stimulate specific responses. 67 Chapter 7: Electrochemical Devices in Papers 1-6 Figure 37. The ion pump. a. The architecture of the ion pump shown as separated layers. The four PEDOT:PSS electrodes are labelled A to D. PEDOT:PSS in the over-oxidised region (pink colour) between B and C conducts ions but not electrons. b. Schematic top view of the device with voltages applied. x = 7 mm, y = 12 mm, z = 4 mm or 50 µm and w = 2 mm. c. Schematic cross-section of the B and C electrodes. P denotes PEDOT. M+ and C+ are cations. 68 Chapter 7: Electrochemical Devices in Papers 1-6 The goal with the organic electrochemical ion pump project has been to do just that, i.e. use the properties of conjugated polymers to, in a controlled fashion, deliver ions to cells that grow on the polymer surface. An electrophoretic ion pump including PEDOT:PSS as the active material has therefore been developed and studied (details in Papers 5 & 6). In the device, electronic addressing signals control and drive an ionic current, which enables transfer of ions from a source electrolyte to a receiving electrolyte separated by a thin film polymer channel. The four electrodes denoted A-D in Figure 37, are biased with three voltages (VAB, VBC and VCD). This configuration results in transport on/off ratios of above 300, delivery of large amounts of ions and exact electronic control of the released dose. The left electrolyte (AB) in Figure 37 is a reservoir containing a relatively high concentration of the ion to be transported into the right electrolyte (CD). The CD electrolyte contains another cation or can be a more complex solution such as cell medium. The two electrodes labeled B and C are separated by a watersaturated polymer electrolyte (over-oxidised3 PEDOT:PSS), which conducts ions but not electrons. This is equivalent to the simple Structure 2, but with a much “slower” electrolyte that prevents the ions in the liquid electrolytes, whose areas are defined with the hydrophobic photoresist SU-8, from diffusing and mixing spontaneously. When applying the potential VBC, which oxidizes B and reduces C, the cations in the reservoir electrolyte (and hence in the polymer film B) are transported in the electric field through the polymer electrolyte to the target electrolyte. As soon as the ions reach the edge of the CD electrolyte, they rapidly diffuse away from the 200 nm thin polymer film and enter the liquid. Electrode A and B form yet another Structure 2, biased with VAB, which allows B to be continuously regenerated. Similarly, electrode D, via VCD, prevents electrode C from being completely reduced. The following paragraphs describe the characteristics of the ion pump when transporting potassium ions (K+). The name of the device implies that it should be possible to pump ions against a concentration gradient. Figure 38a shows that this is indeed the case. In this measurement, both the reservoir and the target electrolyte contained 2 mM potassium acetate, i.e. no additional ions were added to the target electrolyte. 69 Chapter 7: Electrochemical Devices in Papers 1-6 Initially, there is an ion exchange between the electrolytes and the PEDOT:PSS, which can be seen as a decrease in the potassium concentration after leaving the solution on the polymer film for 25 min. If potentials are instead applied for the same length of time, the final concentration of K+ is significantly higher in the CD electrolyte as compared to the concentration in AB. Figure 38. K+ transport with the ion pump. a. Comparison of [K+] in AB and CD when starting with identical electrolyte solutions in both. OFF indicates that no voltages were applied between any of the electrodes and ON means VAB = 1 V, VBC = 10 V, VCD = 1 V. Standard deviations are shown as error bars (n = 4). b. Time resolved transport of K+ between the electrolytes and of electrons between B and C. (VAB = 1 V, VBC = 10 V, VCD = 1 V). c. Current measured between B and C for three different VBC (VAB = 1 V, VCD = 1 V). d. Corresponding relationship between transported K+ and total B-C charge after 10 min. The red line shows the linear fit and the outer blue lines represent the 95% confidence interval. In b-d, the AB electrolyte was 0.1 M KCl, and CD was 0.1 M Ca(C2H3O2)2 (calcium acetate). 70 Chapter 7: Electrochemical Devices in Papers 1-6 Figure 38b shows the transport of total charge (integrated B-C current) and K+ between B and C in a device operated for 30 min. The transport rates are relatively constant during the first 8-10 min of operation, while at later stages, the current and consequently the ion transport rate decreases rapidly. The electric field along the polymer electrolyte channel only exists provided that electrochemical reactions occur in B and C. When the limiting electrode, in this case A, is consumed, electrode B quickly runs out of oxidation sites and the electric field disappears. It is evident from Figure 38b that when the current drops, the ionic transport rate is slightly higher than the measured B-C charge transport rate. This results from K+ that electromigrate partly through the polymer electrolyte as long as the electric field is maintained and subsequently diffuse into the target electrolyte. Locally, however, the concentration will rapidly saturate or decrease when no electromigration occurs, since diffusion in the electrolyte removes ions from the line of delivery (see Figure 39a and 41). The current characteristics for three different VBC is shown in Figure 38c, and the correlation between the total charge and the amount of transported ions after 10 min of operation is displayed in Figure 38d. There is a linear relationship between the amount of K+ transported and the total charge transfered between B and C after 10 min. It is possible to control the transport of ions by the choice of applied potentials and, perhaps more importantly, count the number of delivered ions simply by integrating the B-C current. If no voltages are applied, the diffusion-mediated leakage of K+ from the reservoir electrolyte to the target electrolyte is very small, as experiments show that less than 10 nmol K+ is found in the target electrolyte after 4 h. The relatively low optical absorbance of PEDOT:PSS thin films in combination with its biocompatible surface properties (Paper 5) make the material highly suitable for microscopy-based cell studies. Therefore, we† have tested to grow neuronal cells on the C (and D) electrodes of the ion pump devices and to locally open VOCCs (Chapter 5) in the cell membrane, by electronically delivering high concentrations of K+. If the CD electrolyte with the cells is Ca2+-containing cell medium, a calcium response will be triggered in the cells when the potentials are applied. By loading the cells with the fluorescent marker FURA-2 AM, which †All experiments with cells were performed by Peter Kjäll in the group of Agneta Richter-Dahlfors at Karolinska Institutet. 71 Chapter 7: Electrochemical Devices in Papers 1-6 is only active when it resides inside the cells, changes in the intracellular calcium level can be detected with a fluorescent microscope in real-time. The results of such microscope measurements are summarized in Figure 39. 72 Chapter 7: Electrochemical Devices in Papers 1-6 Figure 39. Microscopy recordings of electronically induced ion fluxes in electrolyte and cells. a. Time-lapse microscopy of ion pump-mediated K+ transport from AB (0.1 M KCl) to CD electrolytes (0.1 M Ca2+ acetate containing the K+-sensitive probe PBFI) at VBC = 10 V (continuous line). Dotted line = dH2O as AB electrolyte, where increased fluorescence at 60 min results from manual addition of 50 mM KCl directly to the CD electrolyte. Dashed line = activation of the ion pump for 15 min, followed by a switch to the OFF state causes the fluorescence increase to stop. Reactivation of the pump 10 min later causes the [K+] increase to continue. b. Intracellular Ca2+ fluxes in FURA-2 AM-loaded HCN-2 cells in cell culturing medium on the CD electrode resulting from ion pump delivery of K+ from the AB electrolyte. Continuous line = intracellular Ca2+ response when only VBC = 10 V is applied. Dotted line = increased K+ transport rate (VBC = 10 V, VAB and VCD = 1 V) causes a pronounced Ca2+ response in cells. Dashed line = inactive ion pump causes no cellular response (OFF state), while increased fluorescence at 30 min results from manual addition of 50 mM KCl to CD electrolyte. Dashed-dotted line = dH2O as AB electrolyte causes no Ca2+ response in HCN-2 cells. c. Intracellular Ca2+ fluxes result from K+-mediated depolarization of the cell membrane. Dashed line = Ca2+ response in FURA-2 AM-loaded cells on the CD electrode results from K+ transported from AB to CD electrolyte (VBC = 10 V, VAB and VCD = 1 V). Continuous line = experiment in the presence of GdCl3 in the CD electrolyte. Dotted line = experiment in the presence of nifedipin in the CD electrolyte. d. Visualization of the pH gradient formed in the CD electrolyte during pumping of protons (VAB=1 V, VBC = 10 V, VCD = 1 V). Deep red colour indicates pH ~ 2 and clear yellow is pH ~ 5. e, f. The ion pump provides spatial control of cellular responses: e. Continuous line = time-lapse microscopy of intracellular [Ca2+] in FURA-2 AM-loaded HCN2 cells located adjacent to the 4 mm wide barrier. Dotted line = cells located 1 mm and 2 mm (dashed line) from the barrier. f. Time-lapse microscopy of intracellular [Ca2+] in FURA-2 AM-loaded HCN-2 cells located on the 50 µm wide microchannel (continuous line) and cells located 500 µm from the microchannel (dotted line). 73 Chapter 7: Electrochemical Devices in Papers 1-6 To show that it is really the VOCCs that are activated by the elevated potassium concentration, these calcium channels can be selectively blocked with Gd3+ or nifedipin.153,154 If either of these chemicals is present in the CD-electrolyte, no response is detected when K+ is transported to the cells (Figure 39c). To be able to target and stimulate single cells or even parts of cells, devices that provide spatial control of ion fluxes are necessary. The ion pump delivers ions to the target electrolyte through the polymer electrolyte channel between B and C. When reaching the edge of the CD electrolyte, ions immediately diffuse from the 200 nm thin film into the solution. During operation of the device, the concentration of ions becomes very high at the distribution point, while it decays with increasing distance, because diffusion cannot evenly redistribute the ions as fast as they are supplied. This effect is qualitatively visualized using H+ (AB electrolyte = HCl, pH 1; CD electrolyte = KCl, pH 5). The color change of a pH-sensitive indicator paper placed on top of electrode C in the CD electrolyte indicates delivery of protons (Figure 39d and 40). A continuous increase of [H+] close to the delivery line occurs, while diffusion creates a pH gradient along electrode C. To investigate whether this also is reflected in the ability of K+ to induce Ca2+ fluxes in cells, Ca2+ imaging of FURA-2 AM loaded cells located at different distances from the barrier was performed. Cells located in the immediate vicinity of the barrier respond as expected with increased intracellular Ca2+ while cells located 1 mm and 2 mm away from the barrier are unresponsive (Figure 39e). To further increase the spatial resolution and stimulate individual cells, devices with 50 µm wide (a size that corresponds to many eukaryotic cell types) B-C channels were manufactured (z = 50 µm in Figure 37). Figure 39f demonstrates the induced Ca2+ response in a cell located on such a microchannel, while distantly located cells, approximately 500 µm away from the delivery point, were unresponsive. The experiments above show that the ion pump has temporal resolution in the sense that it can be turned ON and OFF but, as discussed in Chapter 5, many cellular signals are not static with one level for OFF and another for ON. Instead, they have an oscillating character, carrying information in both the 74 Chapter 7: Electrochemical Devices in Papers 1-6 amplitude and the frequency. To evaluate the possibility of creating such oscillating signals with the ion pump, protons were pumped with the device and detected with pH paper in the CD-electrolyte. By applying short square-wave pulses and rely on diffusion in the electrolyte to remove protons from the delivery line during the time between pulses, it is possible to create oscillating ion signals, as shown in Figure 41 (details in Paper 6). Figure 40. pH gradient along electrode C. a. Change in pH at constantly applied potentials (VAB = VCD = 1 V, VBC = 5 V). Protons are delivered faster than the rate with which they diffuse away from the delivery line. The pH close to the release line therefore continuously drops at the same time as a gradient is created along electrode C. b. Examples of photographs of pH paper at different time scales with the same potentials as above applied. 75 Chapter 7: Electrochemical Devices in Papers 1-6 Figure 41. Electronically controlled oscillating ion signals. Short pulses can be used to create oscillations in the CD electrolyte close to the release line. VAB = VCD = 1 V during the pulses, otherwise 0 V. a. 15 s pulses with VBC = 10 V. b. 10 s pulses with VBC = 5 V. 76 CHAPTER 8 8. CONCLUDING DISCUSSION The work with the bioelectronic devices presented in this thesis is of course not ending here, since many opportunities, and hopefully rewards, remain. The organic electrochemical wettability switch has the potential to be used in more complex bioelectronic microfluidic devices and corresponding applications. Also, since cell adhesion (or protein adhesion) and proliferation on a surface can be highly dependent on the wetting properties, the wettability switch can be utilized to electronically control where and when cells are present on a surface. The organic electronic ion pump has already been integrated with cells and a future focus in that project is instead to pump larger and more specific molecules, preferably with improved resolution in both time and space. Another route to go with the device is to incorporate it with tissue or even living animals, as a first step towards true drug delivery applications. A general take-home-message from the seven preceding chapters is that conjugated polymers are far more than just electronically conducting plastics. By using the materials in electrochemical or electronic devices, it is possible to control physical properties, like e.g. resistivity, shape, surface wettability and color, by applying a voltage. The number of applications where such organic electronics can be incorporated is naturally enormous and one important part of the conjugated polymer evolution is integration with biology and medicine. Whether used in artificial muscles, neural prosthetics, sensors, drug release 77 Chapter 8: Concluding Discussion systems or complete lab-on-a-chip solutions, organic electronics has the potential to further bridge the gap between man-made electronics and living species from nature. As stated several times in this thesis, there is a very good match between organic electronics and biological materials but that is of course only worth something if people and resources are devoted to utilize the technology. The scientific communities of physics/chemistry and biology/medicine are getting closer and closer to each other, as more and more groups see the rewards of common multidisciplinary efforts and shared knowledge. With such powerful joint forces, the relatively young scientific field of organic bioelectronics can continue to grow and be an important part of life science research. The potential to create considerable scientific and commercial value is huge, both when it comes to increasing the understanding of fundamental biologic questions as well as to incorporate organic bioelectronics in the diagnostic and therapeutic health-care tools of the future. There are, needless to say, still several general issues regarding e.g. life-time, stability and operational speed of organic devices, which have to be solved before any products can enter the market in volume. These are, however, not specific problems to organic bioelectronics but rather a part of the ongoing organic electronics development. Therefore, the entire conjugated polymer community continuously works at finding new ways to improve the performance and stability of organic electronic devices, and repeatedly succeeds. Furthermore, the necessary specifications for bioelectronic applications are in many cases comparably modest. As an example, sensors and lab-on-a-chip solutions are often meant to be cheap, single-use devices for bedside utilization close to the patient. In this case, the requirements on speed and life-time are generally low or moderate and can be met by organic electronics. No doubt, organic bioelectronics is one of the research fields where organic electronics is not simply a cheaper alternative to existing technologies but instead leads the way towards new breakthroughs. 78 REFERENCES REFERENCES 1. Official Nobel Prize Webpage. (2007). http://nobelprize.org 2. Chiang, C.K. et al. Electrical conductivity in doped polyacetylene. Phys. Rev. Lett. 39, 1098-1101 (1977). 3. Tehrani, P. et al. Patterning polythiophene films using electrochemical over-oxidation. Smart Mater. Struct. 14, 21-25 (2005). 4. Sirringhaus, H. et al. High-resolution inkjet printing of all-polymer transistor circuits. Science 290, 2123-2126 (2000). 5. Blancheta, G.B., Loo, Y.-L., Rogers, J.A., Gao, F. & Fincher, C.R. Large area, high resolution, dry printing of conducting polymers for organic electronics. Appl. Phys. Lett. 82, 463-465 (2003). 6. George, P.M. et al. Fabrication and biocompatibility of polypyrrole implants suitable for neural prosthetics. Biomaterials 26, 3511-3519 (2005). 7. Wang, X. et al. Evaluation of biocompatibility of polypyrrole in vitro and in vivo. J. Biomed. Mater. Res. A 68, 411-422 (2004). 8. Berggren, M. et al. Light-emitting diodes with variable colours from polymer blends. Nature 372, 444-446 (1994). 9. Burroughes, J.H. et al. Light-emitting diodes based on conjugated polymers. Nature 347, 539-541 (1990). 10. Inganas, O. et al. Thiophene polymers in light emitting diodes: making multicolour devices. Synth. Met. 71, 2121-2124 (1995). 11. Brabec, C.J., Padinger, F., Hummelen, J.C., Janssen, R.A.J. & Sariciftci, N.S. Realization of large area flexible fullerene - conjugated polymer photocells: a route to plastic solar cells. Synth. Met. 102, 861-864 (1999). 79 References 12. Alam, M.M. & Jenekhe, S.A. Efficient solar cells from layered nanostructures of donor and acceptor conjugated polymers. Chem. Mater. 16, 4647-4656 (2004). 13. Brabec, C.J., Sariciftci, N.S. & Hummelen, J.C. Plastic solar cells. Adv. Funct. Mater. 11, 15-26 (2001). 14. Sirringhaus, H., Tessler, N. & Friend, R.H. Integrated optoelectronic devices based on conjugated polymers. Science 280, 1741-1744 (1998). 15. Stutzmann, N., Friend, R.H. & Sirringhaus, H. Self-aligned, verticalchannel, polymer field-effect transistors. Science 299, 1881-1884 (2003). 16. Andersson, P. et al. Active matrix displays based on all-organic electrochemical smart pixels printed on paper. Adv. Mater. 14, 14601464 (2002). 17. Nilsson, D. et al. Bi-stable and dynamic current modulation in electrochemical organic transistors. Adv. Mater. 14, 51-54 (2002). 18. Nilsson, D., Robinson, N., Berggren, M. & Forchheimer, Electrochemical logic circuits. Adv. Mater. 17, 353-358 (2005). 19. Crone, B. et al. Electronic sensing of vapors with organic transistors. Appl. Phys. Lett. 78, 2229 (2001). 20. Torsi, L., Dodabalapur, A., Sabbatini, L. & Zambonin, P.G. Multiparameter gas sensors based on organic thin-film-transistors. Sens. Actuators, B 67, 312-316 (2000). 21. Nilsson, D., Kugler, T., Svensson, P.O. & Berggren, M. An all-organic sensor-transistor based on a novel electrochemical transducer concept printed electrochemical sensors on paper. Sens. Actuators, B B86, 193197 (2002). 22. MacDiarmid, A.G. Synthetic metals: a novel role for organic polymers. Synth. Met. 125, 11-22 (2001). 23. Heeger, A.J. Semiconducting and metallic polymers: the fourth generation of polymeric materials. Synth. Met. 125, 23-42 (2001). 24. Su, W.P., Schreiffer, J.R. & Heeger, A.J. Solitons in Polyacetylene. Phys. Rev. Lett. 42, 1698-1701 (1979). 25. Su, W.P., Schreiffer, J.R. & Heeger, A.J. Soliton Excitations in Polyacetylene. Phys. Rev. B: Condens. Matter 22, 2099-2111 (1980). 26. Salaneck, W.R., Friend, R.H. & Bredas, J.L. Electronic structure of conjugated polymers: consequences of electron-lattice coupling. Phys. Rep. 319, 231-251 (1999). 80 R. References 27. Moliton, A. & Hiorns, R.C. Review of electronic and optical properties of semiconducting π-conjugated polymers: Applications in optoelectronics. Polym. Int. 53, 1397-1412 (2004). 28. Somani, P.R. & Radhakrishnan, S. Electrochromic materials and devices: Present and future. Mater. Chem. Phys. 77, 117-133 (2002). 29. Carpi, F. & De Rossi, D. Colours from electroactive polymers: Electrochromic, electroluminescent and laser devices based on organic materials. Optics Laser Techn. 38, 292-305 (2006). 30. Mortimer, R.J. Organic electrochromic materials. Electrochim. Acta 44, 2971-2981 (1999). 31. Heuer, H.W., Wehrmann, R. & Kirchmeyer, S. Electrochromic window based on conducting poly(3,4-ethylenedioxythiophene)- poly(styrene sulfonate). Adv. Funct. Mater. 12, 89-94 (2002). 32. Groenendaal, B.L., Jonas, F., Freitag, D., Pielartzik, H. & Reynolds, J.R. Poly(3,4-ethylenedioxythiophene) and its derivatives: Past, present, and future. Adv. Mater. 12, 481-494 (2000). 33. Reynolds, J.R. et al. Unique variable-gap polyheterocycles for highcontrast dual polymer electrochromic devices. Synth. Met. 85, 1295-1298 (1997). 34. Barta, P., Sanetra, J. & Zagorska, M. Efficient electroluminescence in regioregular polyalkylthiophene light-emitting diodes. Synth. Met. 94, 119-121 (1998). 35. Bao, Z., Dodabalapur, A. & Lovinger, A.J. Soluble and processable regioregular poly(3-hexylthiophene) for thin film field-effect transistor applications with high mobility. Appl. Phys. Lett. 69, 4108-4110 (1996). 36. Ong, B., Wu, Y., Jiang, L., Liu, P. & Murti, K. Polythiophene-based fieldeffect transistors with enhanced air stability. Synth. Met. 142, 49-52 (2004). 37. Sicot, L. et al. Improvement of the photovoltaic properties of polythiophene-based cells. Sol. Energy Mater. Sol. Cells 63, 49-60 (2000). 38. Too, C.O. et al. Photovoltaic devices based on polythiophenes and substituted polythiophenes. Synth. Met. 123, 53-60 (2001). 39. Majumdar, H.S., Bolognesi, A. & Pal, A.J. Switching and memory devices based on a polythiophene derivative for data-storage applications. Synth. Met. 140, 203-206 (2004). 81 References 40. Majumdar, H.S., Bolognesi, A. & Pal, A.J. Memory applications of a thiophene-based conjugated polymer: Capacitance measurements. J. Phys. D: Appl. Phys. 36, 211-215 (2003). 41. Mastragostino, M., Paraventi, R. & Zanelli, A. Supercapacitors based on composite polymer electrodes. J. Electrochem. Soc. 147, 3167-3170 (2000). 42. Feast, W.J., Tsibouklis, J., Pouwer, K.L., Groenendaal, L. & Meijer, E.W. Synthesis, processing and material properties of conjugated polymers. Polymer 37, 5017-5047 (1996). 43. Elschner, A. et al. PEDT/PSS for efficient hole-injection in hybrid organic light-emitting diodes. Synth. Met. 111, 139-143 (2000). 44. Fichet, G. et al. Self-organized photonic structures in polymer lightemitting diodes. Adv. Mater. 16, 1908-1912 (2004). 45. Song, M.Y., Kim, K.-J. & Kim, D.Y. Enhancement of photovoltaic characteristics using a PEDOT interlayer in TiO2/MEHPPV heterojunction devices. Sol. Energy Mater. Sol. Cells 85, 31-39 (2005). 46. Zhang, F., Johansson, M., Andersson, M.R., Hummelen, J.C. & Inganas, O. Polymer photovoltaic cells with conducting polymer anodes. Adv. Mater. 14, 662-665 (2002). 47. Bobacka, J. Potential Stability of All-Solid-State Ion-Selective Electrodes Using Conducting Polymers as Ion-to-Electron Transducers. Anal. Chem. 71, 4932-4937 (1999). 48. Vazquez, M., Danielsson, P., Bobacka, J., Lewenstam, A. & Ivaska, A. Solution-cast films of poly(3,4-ethylenedioxythiophene) as ion-toelectron transducers in all-solid-state ion-selective electrodes. Sens. Actuators, B B97, 182-189 (2004). 49. Asberg, P. & Inganas, O. Hydrogels of a conducting conjugated polymer as 3-D enzyme electrode. Biosens. Bioelectron. 19, 199-207 (2003). 50. Cui, X. & Martin, D.C. Electrochemical deposition and characterization of poly(3,4-ethylenedioxythiophene) on neural microelectrode arrays. Sens. Actuators, B 89, 92-102 (2003). 51. Green, A.G. & Woodhead, A.E. Aniline-black and allied compounds. Part I. J. Chem. Soc. 97, 2388 - 2403 (1910). 52. Kang, E.T., Neoh, K.G. & Tan, K.L. in Progress in Polymer Science (Oxford), Vol. 23 277-324 (Elsevier Sci Ltd,Exeter,Engl, 1998). 82 References 53. Epstein, A.J. & MacDiarmid, A.G. Polyanilines: From solitons to polymer metal, from chemical curiosity to technology. Synth. Met. 69, 179-182 (1995). 54. Jozefowicz, M.E. et al. Multiple Lattice Phases and Polaron-Lattice Spinless-Defect Competition in Polyaniline. Phys. Rev. B: Condens. Matter 39, 12958-12961 (1989). 55. Ahlskog, M. et al. Heat-induced transition to the conducting state in polyaniline/dodecylbenzenesulfonic acid complex. Synth. Met. 69, 213214 (1995). 56. Ikkala, O.T. et al. Counter-ion induced processibility of polyaniline: Conducting melt processible polymer blends. Synth. Met. 69, 97-100 (1995). 57. Barra, G.M.O., Leyva, M.E., Gorelova, M.M., Soares, B.G. & Sens, M. Xray photoelectron spectroscopy and electrical conductivity of polyaniline doped with dodecylbenzenesulfonic acid as a function of the synthetic method. J. Appl. Polym. Sci. 80, 556-565 (2001). 58. Isaksson, J., Tengstedt, C., Fahlman, M., Robinson, N. & Berggren, M. A Solid-state Organic Electronic Wettability Switch. Adv. Mater. 16, 316320 (2004). 59. Panipol Oy webpage. (2007). http://www.panipol.com 60. Konagaya, S., Abe, K. & Ishihara, H. Conductive polymer composite PET film with excellent antistatic properties. Plast., Rubber Compos. 31, 201204 (2002). 61. Kamalesh, S. et al. in Journal of Biomedical Materials Research, Vol. 52 467-478 (John Wiley and Sons Inc.,New York,NY,USA, 2000). 62. Zhang, F., Kang, E.T., Neoh, K.G., Wang, P. & Tan, K.L. Reactive coupling of poly(ethylene glycol) on electroactive polyaniline films for reduction in protein adsorption and platelet adhesion. Biomaterials 23, 787-795 (2002). 63. Chung, J., Choi, B. & Lee, H.H. Polyaniline and poly(N-vinylcarbazole) blends as anode for blue light-emitting diodes. Appl. Phys. Lett. 74, 3645-3647 (1999). 64. Lee, H.-M., Lee, T.-W., Park, O.O. & Zyung, T. Polymer light-emitting diode prepared with an ionomer and polyaniline. Adv. Mater. 10, 17-23 (2000). 65. Xie, D. et al. Fabrication and characterization of polyaniline-based gas sensor by ultra-thin film technology. Sens. Actuators, B 81, 158-164 (2001). 83 References 66. Dhawan, S.K., Kumar, D., Ram, M.K., Chandra, S. & Trivedi, D.C. Application of conducting polyaniline as sensor material for ammonia. Sens. Actuators, B 40, 99-103 (1997). 67. Pinto, N.J. et al. Electrospun polyaniline/polyethylene oxide nanofiber field-effect transistor. Appl. Phys. Lett. 83, 4244-4246 (2003). 68. Cai, Z., Geng, M. & Tang, Z. Novel battery using conducting polymers: Polyindole and polyaniline as active materials. J. Mater. Sci. 39, 40014003 (2004). 69. Jager, E.W.H., Smela, E. & Inganas, O. Microfabricating conjugated polymer actuators. Science 290, 1540-1545 (2000). 70. Smela, E. Conjugated polymer actuators for biomedical applications. Adv. Mater. 15, 481-494 (2003). 71. Smela, E., Inganas, O. & Lundstrom, I. Controlled Folding of Micrometer-Size Structures. Science 268, 1735-1738 (1995). 72. George, P.M. et al. Electrically controlled drug delivery from biotindoped conductive polypyrrole. Adv. Mater. 18, 577-581 (2006). 73. Kontturi, K., Pentti, P. & Sundholm, G. Polypyrrole as a model membrane for drug delivery. J. Electroanal. Chem. 453, 231-238 (1998). 74. Wadhwa, R., Lagenaur, C.F. & Cui, X.T. Electrochemically controlled release of dexamethasone from conducting polymer polypyrrole coated electrode. J. Controlled Release 110, 531-541 (2006). 75. Bobacka, J., Lewenstam, A. & Ivaska, A. Electrochemical impedance spectroscopy of oxidized poly(3,4-ethylenedioxythiophene) film electrodes in aqueous solutions. J. Electroanal. Chem. 489, 17-27 (2000). 76. Lisowska-Oleksiak, A. & Kupniewska, A. Transport of alkali metal cations in poly(3,4-ethylenethiophene) films. Solid State Ionics 157, 241-248 (2003). 77. Greczynski, G. et al. Photoelectron spectroscopy of thin films of PEDOTPSS conjugated polymer blend: a mini-review and some new results. J. Electron Spectrosc. Relat. Phenom. 121, 1-17 (2001). 78. Greczynski, G., Kugler, T. & Salaneck, W.R. Characterization of the PEDOT-PSS system by means of X-ray and ultraviolet photoelectron spectroscopy. Thin Solid Films 354, 129-135 (1999). 79. Wang, X., Shapiro, B. & Smela, E. Visualizing ion currents in conjugated polymers. Adv. Mater. 16, 1605-1609 (2004). 84 References 80. Burgmayer, P. & Murray, R.W. Ion gate electrodes. Polypyrrole as a switchable ion conductor membrane. J. Phys. Chem. 88, 2515-2521 (1984). 81. Ren, X. & Pickup, P.G. Ion transport in polypyrrole and a polypyrrole/polyanion composite. J. Phys. Chem. 97, 5356-5362 (1993). 82. Zhou, D., Too, C.O., Wallace, G.G., Hodges, A.M. & Mau, A.W.H. Protein transport and separation using polypyrrole coated, platinised polyvinylidene fluoride membranes. React. Funct. Polym. 45, 217-226 (2000). 83. Nyberg, T., Inganäs, O. & Jerregård, H. Polymer hydrogel microelectrodes for neural communication. Biomed. Microdev. 4, 43-52 (2002). 84. Nyberg, T., Shimada, A. & Torimitsu, K. Ion conducting polymer microelectrodes for interfacing with neural networks. J. Neurosc. Meth. 160, 16-25 (2007). 85. Berridge, M.J. Calcium oscillations. J. Biol. Chem. 265, 9583-9586 (1990). 86. Berridge, M.J., Bootman, M.D. & Lipp, P. Molecular biology: Calcium - a life and death signal. Nature 395, 645 (1998). 87. Berridge, M.J., Bootman, M.D. & Roderick, H.L. Calcium signalling: dynamics, homeostasis and remodelling. Nat. Rev. Mol. Cell Biol. 4, 517529 (2003). 88. Chen, M., Nilsson, D., Kugler, T., Berggren, M. & Remonen, T. Electric current rectification by an all-organic electrochemical device. Appl. Phys. Lett. 81, 2011-2013 (2002). 89. Said, E., Robinson, N.D., Nilsson, D., Svensson, P.-O. & Berggren, M. Visualizing the electric field in electrolytes using electrochromism from a conjugated polymer. Electrochem. Solid-State Lett. 8, 12-16 (2005). 90. Organic Electronics webpage. (2007). http://www.orgel.itn.liu.se 91. Acreo AB official webpage. (2007). http://www.acreo.se 92. Brett, C.M.A. & Brett, A.M.O. Electrochemistry: principles, methods and applications. (Oxford University Press, Oxford; 1993). 93. Baba, A. et al. Electropolymerization and doping/dedoping properties of polyaniline thin films as studied by electrochemical-surface plasmon spectroscopy and by the quartz crystal microbalance. J. Electroanal. Chem. 562, 95-103 (2004). 85 References 94. Kabasakaloglu, M., Kiyak, T., Toprak, H. & Aksu, M.L. Electrochemical properties of polythiophene depending on preparation conditions. Appl. Surf. Sci. 152, 115-125 (1999). 95. Robinson, N.D., Svensson, P.O., Nilsson, D. & Berggren, M. On the current saturation observed in electrochemical polymer transistors. J. Electrochem. Soc. 153, H39-H44 (2006). 96. MacRitchie, F. Chemistry At Interfaces, Edn. 5th. (Academic Press, San Diego, CA; 1990). 97. Adamson, A.W. Physical Chemistry of Surfaces, Edn. Fifth. (John Wiley and Sons, Inc, New York, NY; 1990). 98. Shimizu, R.N. & Demarquette, N.R. Evaluation of surface energy of solid polymers using different models. J. Appl. Polym. Sci. 76, 1831-1845 (2000). 99. Lafuma, A. & Quere, D. Superhydrophobic states. Nat. Mater. 2, 457-460 (2003). 100. Sun, T. et al. Reversible Switching between Superhydrophilicity and Superhydrophobicity. Angew. Chem. 43, 357-360 (2004). 101. Feng, L. et al. Super-hydrophobic surfaces: From natural to artificial. Adv. Mater. 14, 1857-1860 (2002). 102. The lotus effect website. (2007). http://www.lotus-effekt.de 103. Victoria Adventure. (2007). http://www.victoria-adventure.org/ 104. Jennings, J.W.J. & Pallas, N.R. An Efficient Method for the Determination of Interfacial Tensions from Drop Profiles. Langmuir 4, 959-967 (1988). 105. Touhami, Y., Neale, G.H., Hornof, V. & Khalfalah, H. Modified pendant drop method for transient and dynamic interfacial tension measurement. Colloids Surf., A 112, 31-41 (1996). 106. Harkins, W.D., Young, T.F. & Cheng, L.H. The Ring Method for the Detemination of Surface Tension. Science 64, 333-336 (1926). 107. Francis, C.K. & Bennet, H.T. The Surface Tension of Petrolium. Ind. eng. chem. 14, 626-627 (1922). 108. Alberts, B. et al. Molecular biology of the cell, Edn. Three. (Garland Publishing, Inc., New York; 1994). 109. Hancock, J.T. Cell signalling. (Pearson Education Limited, Essex; 1997). 86 References 110. Tortora, G.J. & Grabowski, S.R. Principles of anatomy and physiology. (John Wiley & Sons, New York; 2000). 111. Berridge, M.J. The AM and FM of calcium signalling. Nature 386, 759760 (1997). 112. Dolmetsch, R.E., Lewis, R.S., Goodnow, C.C. & Healy, J.I. Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature 386, 855-858 (1997). 113. Uhlen, P. et al. alpha-Haemolysin of uropathogenic E-coli induces Ca2+ oscillations in renal epithelial cells. Nature 405, 694-697 (2000). 114. Collins, T.J., Lipp, P., Berridge, M.J. & Bootman, M.D. Mitochondrial Ca2+ Uptake Depends on the Spatial and Temporal Profile of Cytosolic Ca2+ Signals. J. Biol. Chem. 276, 26411-26420 (2001). 115. Tour, O. et al. Calcium Green FlAsH as a genetically targeted smallmolecule calcium indicator. Nat. Chem. Biol. 3, 423-431 (2007). 116. Mabeck, J. & Malliaras, G. Chemical and biological sensors based on organic thin-film transistors. Anal. Bioanal. Chem. 384, 343-353 (2006). 117. Malhotra, B.D., Chaubey, A. & Singh, S.P. Prospects of conducting polymers in biosensors. Anal. Chim. Acta 578, 59-74 (2006). 118. Darain, F., Park, S.-U. & Shim, Y.-B. Disposable amperometric immunosensor system for rabbit IgG using a conducting polymer modified screen-printed electrode. Biosens. Bioelectron. 18, 773-780 (2003). 119. Torsi, L. & Dodabalapur, A. Organic thin-film transistors as plastic analytical sensors. Anal. Chem. 77, 380-387 (2005). 120. Wang, L., Fine, D. & Dodabalapur, A. Nanoscale chemical sensor based on organic thin-film transistors. Appl. Phys. Lett. 85, 6386-6388 (2004). 121. Someya, T., Dodabalapur, A., Gelperin, A., Katz, H.E. & Bao, Z. Integration and response of organic electronics with aqueous microfluidics. Langmuir 18, 5299-5302 (2002). 122. Wang, L., Fine, D., Sharma, D., Torsi, L. & Dodabalapur, A. Nanoscale organic and polymeric field-effect transistors as chemical sensors. Anal. Bioanal. Chem. 384, 310-321 (2006). 123. Bartic, C., Campitelli, A. & Borghs, S. Field-effect detection of chemical species with hybrid organic/inorganic transistors. Appl. Phys. Lett. 82, 475-477 (2003). 87 References 124. Bartic, C., Palan, B., Campitelli, A. & Borghs, G. Monitoring pH with organic-based field-effect transistors. Sens. Actuators, B 83, 115-122 (2002). 125. Berggren, M., Nilsson, D. & Robinson, N.D. Organic materials for printed electronics. Nat. Mater. 6, 3-5 (2007). 126. Zhu, Z.T. et al. A simple poly(3,4-ethylene dioxythiophene)/poly(styrene sulfonic acid) transistor for glucose sensing at neutral pH. Chem. Comm. 13, 1556-1557 (2004). 127. Macaya, D.J. et al. Simple glucose sensors with micromolar sensitivity based on organic electrochemical transistors. Sens. Actuators, B 123, 374-378 (2007). 128. Bernards, D.A., Malliaras, G.G., Toombes, G.E.S. & Gruner, S.M. Gating of an organic transistor through a bilayer lipid membrane with ion channels. Appl. Phys. Lett. 89, - (2006). 129. Moorthy, J. & Beebe, D.J. Organic and biomimetic designs for microfluidic systems - New strategies offer a flexible approach to designing microscale devices. Anal. Chem. 75, 292a-301a (2003). 130. Erickson, D. & Li, D. Integrated microfluidic devices. Anal. Chim. Acta 507, 11-26 (2004). 131. Suda, H. & Yamada, S. Force measurements for the movement of a water drop on a surface with a surface tension gradient. Langmuir 19, 529-531 (2003). 132. Daniel, S. & Chaudhury, M.K. Rectified motion of liquid drops on gradient surfaces induced by vibration. Langmuir 18, 3404-3407 (2002). 133. Liang, L. et al. Surfaces with reversible hydrophilic/hydrophobic characteristics on cross-linked poly(N-isopropylacrylamide) hydrogels. Langmuir 16, 8016-8023 (2000). 134. Ichimura, K., Oh, S.-K. & Nakagawa, M. Light-Driven Motion of Liquids on a Photoresponsive Surface. Science 288, 1624-1626 (2000). 135. Prins, M.W.J., Welters, W.J.J. & Weekamp, J.W. Fluid Control in Multichannel Structures by Electrocapillary Pressure. Science 291, 277280 (2001). 136. Gallardo, B.S. et al. Electrochemical Principles for Active Control of Liquids on Submillimeter Scales. Science 283, 57-60 (1999). 137. Prakash, M. & Gershenfeld, N. Microfluidic bubble logic. Science 315, 832-835 (2007). 88 References 138. Darhuber, A.A., Valentino, J.P., Davis, J.M., Troian, S.M. & Wagner, S. Microfluidic actuation by modulation of surface stresses. Appl. Phys. Lett. 82, 657-659 (2003). 139. Link, D.R. et al. Electric control of droplets in microfluidic devices. Angew. Chem. 45, 2556-2560 (2006). 140. Isaksson, J., Robinson, N.D. & Berggren, M. Electronic modulation of an electrochemically induced wettability gradient to control water movement on a polyaniline surface. Thin Solid Films 515, 2003-2008 (2006). 141. Robinson, L., Isaksson, J., Robinson, N.D. & Berggren, M. Electrochemical control of surface wettability of poly(3-alkylthiophenes). Surf. Sci. 600, L148-L152 (2006). 142. Wang, X., Ederth, T. & Inganas, O. In situ wilhelmy balance surface energy determination of poly(3-hexylthiophene) and poly(3,4ethylenedioxythiophene) during electrochemical doping-dedoping. Langmuir 22, 9287-9294 (2006). 143. Causley, J., Stitzel, S., Brady, S., Diamond, D. & Wallace, G. Electrochemically-induced fluid movement using polypyrrole. Synth. Met. 151, 60-64 (2005). 144. Robinson, L., Hentzell, A., Robinson, N.D., Isaksson, J. & Berggren, M. Electrochemical wettability switches gate aqueous liquids in microfluidic systems. Lab Chip 6, 1277-1278 (2006). 145. Wu, Y. et al. TITAN: A conducting polymer based microfluidic pump. Smart Mater. Struct. 14, 1511-1516 (2005). 146. Jager, E.W.H., Inganas, O. & Lundstrom, I. Microrobots for micrometersize objects in aqueous media: Potential tools for single-cell manipulation. Science 288, 2335-2338 (2000). 147. Lu, W., Smela, E., Adams, P., Zuccarello, G. & Mattes, B.R. Development of Solid-in-Hollow Electrochemical Linear Actuators Using Highly Conductive Polyaniline. Chem. Mater. 16, 1615-1621 (2004). 148. Xu, H., Wang, C., Wang, C.L., Zoval, J. & Madou, M. Polymer actuator valves toward controlled drug delivery application. Biosens. Bioelectron. 21, 2094-2099 (2006). 149. Ratner, B.D., Hoffman, A.S., Schoen, F.J. & Lemons, J.E. (eds.) Biomaterials Science: an introduction to materials in medicine. (Academic Press, London; 1996). 150. Abidian, M.R., Kim, D.H. & Martin, D.C. Conducting-Polymer Nanotubes for Controlled Drug Release. Adv. Mater. 18, 405-409 (2006). 89 References 151. Low, L.M., Seetharaman, S., He, K.Q. & Madou, M.J. Microactuators toward microvalves for responsive controlled drug delivery. Sens. Actuators, B 67, 149-160 (2000). 152. Murata, K., Izuchi, S. & Yoshihisa, Y. An overview of the research and development of solid polymer electrolyte batteries. Electrochim. Acta 45, 1501-1508 (2000). 153. Flemming, R., Xu, S.Z. & Beech, D.J. Pharmacological profile of storeoperated channels in cerebral arteriolar smooth muscle cells. Br. J. Pharmacol. 139, 955-965 (2003). 154. Miller, R.J. Multiple calcium channels and neuronal function. Science 235, 46-52 (1987). 90