Designers and engineers have been dreaming for decades with motors sensing, by themselves, working and surrounding conditions, as biological muscles do originating proprioception. The evolution of the working potential, or that of the consumed electrical energy, of electrochemical artificial muscles based on electroactive materials (intrinsically conducting polymers, redox polymers, carbon nanotubes, fullerene derivatives, grapheme derivatives, porphyrines, phtalocyanines, among others) and driven by constant currents senses, while working, any variation of the mechanical (trailed mass, obstacles, pressure, strain or stress) thermal or chemical conditions of work. They are linear faradaic polymeric motors: currents control movement rates and charges control displacements. One physically uniform artificial muscle includes one chemically based polymeric motor and several sensors working simultaneously under the same driving reaction. Actuating (current and charge) and sensing (potential and energy) magnitudes are present, simultaneously, in the only two connecting wires and can be read by the computer at any time. From basic polymeric, mechanical and electrochemical principles a basic equation is attained. It includes and describes, simultaneously, the polymeric motor characteristics (rate of the muscle movement and muscle position) and the working variables (temperature, electrolyte concentration and mechanical conditions). By changing working conditions experimental results overlap theoretical predictions. The ensemble computer-generator-muscle-theoretical equation constitutes and describes artificial mechanical, thermal and chemical proprioception of the system. Proprioceptive tools and zoomorphic or anthropomorphic soft robots can be envisaged.
Acknowledgments: Authors acknowledge financial support from Spanish Government (MCI) Project MAT2011-24973, Jose G. Martinez acknowledges to the Spanish Education Ministry for a FPU grant (AP2010-3460).
References
[1] T. F. Otero and J. G. Martinez, Biomimetic intracellular matrix (ICM) materials, properties and functions. Full integration of actuators and sensors. J. Mater. Chem. B, 1, 26-38 (2013)
[1] T. F. Otero, J. J. Sanchez & J. G. Martinez, Biomimetic Dual Sensing-Actuators Based on Conducting Polymers. Galvanostatic Theoretical Model for Actuators Sensing Temperature. J. Phys. Chem. B 116, 5279-5290 (2012).
[2] J. G. Martinez & T. F. Otero, Biomimetic Dual Sensing-Actuators: Theoretical Description. Sensing Electrolyte Concentration and Driving Current. J. Phys. Chem. B, 116, 9223-9230 (2012).
[3] J. G. Martinez & T. F. Otero, Mechanical awareness from sensing artificial muscles: experiments and modeling. Sens. Actuators B-Chem. 195, 365-372 (2014)

We have created low-voltage ion-modulated transistors on paper using environmentally friendly electrolytes. Using a method of spontaneous vertical phase separation during application of a semiconductor/insulator blend we can create thin semiconductor layers on rough paper substrates. With this, drop casting or spin casting, technique we get a thin semiconductor layer on top of a polymer insulator. This fabrication method has several advantages, namely; the semiconductor is separated from the paper substrate that contains dopants that would penetrate and chemically dope the semiconductor, the amount of semiconductor needed in the blend in order to get working transistors can be as low as 0.5 wt% reducing both the cost and the amount of harmful semiconductor material needed, and finally making the semiconductor thin resulting in fast-switching devices. From a device performance standpoint the last point will be the most important one. We have found that ions from the electrolyte will always penetrate the semiconductor during operation. This is also the reason for the high currents observed in our ion-modulated transistors. During operation ions penetrate and dope the semiconductor resulting in a bulk transport through the semiconductor. A very disadvantageous side-effect of this is the reduced switching speed of the device (as a result of the slow ion motion in the semiconductor during the doping process). A thin semiconductor will effectively nullify this problem resulting in fast switching times. The semiconductor poly(3-hexylthiophene) (P3HT) and the insulator poly(L-lactic acid) (PLLA) is mixed together in chlorobenzene and drop casted onto the paper substrate. Due to the favorable surface energies and solvabilities involved, the PLLA will precipitate first and form a layer of insulator on the paper substrate leaving a P3HT-layer on top. The electrolyte is a mixture of choline chloride and different organic compounds, such as urea or glycol. When mixed together these form deep eutectic mixtures that are liquid or semi-liquid at room temperature. They are environmentally friendly and can be solution processable and thus compatible with roll-to-roll fabrication techniques. The best one of these mixtures is blended with a commercial binder to create a solid electrolyte that can be spin casted on top of the P3HT semiconductor. We demonstrate the usefulness of these type of devices by creating inverters and five-stage ring-oscillators that oscillate at 1 Hz. We further show how logic can be created using these environmentally friendly and disposable paper transistors by creating working SR-latches and flip-flops.

Additive fabrication techniques such as three-dimensional (3D) printing are receiving growing interest from a diverse range of fields due to their ability to quickly produce complex 3D objects. However, new applications of hydrogels such as soft robotics and cartilage tissue scaffolds require hydrogels with enhanced mechanical performance, which has stimulated an investigation into how hydrogels may be made electrically conducting, tougher and more enduring. Moreover, the parallel development of these materials and suitable 3D fabrication techniques has accelerated the advancement of many technologies including bionic implants, sensors, controlled release systems and soft robotics.
The understanding of how to marry these recent advances in materials (e.g. tough and/or electrically conducting hydrogels) with manufacturing (3D printing of hydrogels) for the purpose of building smart hydrogel materials is incomplete.
In this presentation I will describe our approach to 3D printing gels (consisting of the edible biopolymers gellan gum and gelatin) that is based on optimizing the rheological conditions for additive manufacturing with a 4^th generation 3D-Bioplotter. Gellan gum and gelatin are versatile ingredients in well-known food products such as the commercially available product Aeroplane Jelly. The crucial aspect to facilitate printing is that these gels can be prepared in a “one-pot” synthesis approach. The resulting gels based on a combination of ionically cross-linked gellan gum and covalently cross-linked gelatin networks exhibit suitable mechanically (1 MPa tensile stress at failure) and electrical (1 S/cm electrical conductivity) characteristics. The origin of the mechanical robust and electrical behavior will be discussed in detail. In addition, I will demonstrate that the gel&’s mechanical and electrical characteristics vary with the concentration of the charge carriers. Finally, I will present our results on 3D printed (electronic) hydrogel devices for future application in bionics and soft robotics.

The cost of healthcare is increasing at a pace that makes it impossible to continue in the way we've done so far. In the future, the patients must become more mobile and be able to carry out diagnostics and therapy on themselves. There is a strong need in the healthcare sector to find new innovative ways of communicating with the body and also to create autonomous systems for regulation of body functions. In this presentation we will give examples of strategies to realize this. The first example addresses the need for rapid, distributed diagnostics. We have developed an inexpensive disposable sensing system that can be produced in high volumes by means of printing. By combining the virtues of printed biosensors and paper-based diagnostics, we have introduced a new disposable instrument range exploiting the latest advances in printed electronics. This approach combines the sophistication of advanced electrochemical biosensors with a simple manufacturing technique to create a use-and-throw instrument. Performance of the overall system rivals that of current hand-held devices, but can be sold at a fraction of their cost. The second example addresses the need for highly localized and precise delivery of bio-active substances to the body. We have developed a platform for diffusive delivery in the absence of any fluid flow. This so called ion pump offers a unique possibility to translate electronic signaling to chemical signaling by using ions or neurotransmitters and applying an electric potential across the device. The device provide several sought-after features such as precise dosage control, minimally disruptive delivery due to the absence of #64258;uid #64258;ow, and precise on-off switching, far beyond what is possible using for instance micro-fluidics. The third example includes a novel way of using the body as a communication channel. We have developed a technology where simple messages can be transferred from a printed label, through the body to a mobile phone. All these examples illustrate different ways of communicating to, from and in the body which might be of significant importance in future healthcare systems.

Intensive research on stretchable electronics has led to the development of exciting applications such as stretchable sensors[1, 2] and stretchable displays[3]. This next generation electronics is expected to play a major role in biomedicine, as such wearable, implantable devices have the ability to conform to arbitrary shapes and follow our bodies movements. A highly conductive, easy-to-pattern elastic conductor is a key component to achieve reliable stretchable electronics. Here we report on the development of a printable elastic conductor with a stretchability of more than 200% and a conductivity of over 100 S/cm. We combine our printable conductor with organic transistors that are embedded it in silicone rubber to realize fully stretchable thin film transistors with a mobility of 1.6 cm²/Vs when operated at only 3V. Our devices show little performance change even when stretched up to 90% tensile. A gradual modulus transition from 9.1 GPa to 210 kPa at the interface between the non-stretchable platform hosting the organic transistor and the stretchable region containing the elastic conductor interconnects improves the mechanical robustness of the device by 50% and maximum stretchability of the printed elastic conductor by 100%. The elastic conductor was prepared by stirring silver flakes, fluorine rubber, 4-methyl-2-pentanone, and a fluorine surfactant - water solution for >12 h, followed by stencil printing of the mixed ink and subsequently drying of the solvents. Cross-sectional Scanning Electron Microscope (SEM) and Time of Flight Secondary Ion Mass Spectrometry (TOF-SIMS) images reveal the importance of the fluorine surfactant - water solution for the formation of the elastic conductor. We will discuss in detail the fabrication of the elastic conductors and our integration method to obtain fully stretchable organic transistors. The Authors are grateful to Daikin Inc. for providing the fluorine rubbers and N. Matsuhisa appreciates the support from ALPS.
[1] D.-H. Kim, et al., Science 333, 838-843 (2011).
[2] D. J. Lipomi, et al., Nature nanotechnology6, 788-792 (2011).
[3] T. Sekitani, et al., Nature Materials8, 494-499 (2009).

The field of semiconducting polymers is synonymous with “plastic electronics.” Not all organic semiconductors, however, embody the descriptor “plastic,” at least in the sense of deformability. Many of the best-performing conjugated polymers fracture at very small strains (le;2% on elastic substrates) and have tensile moduli similar to those of crosslinked epoxy resins (1-10 GPa). There is also a perceived competition between charge transport and mechanical compliance: large π-stacked crystallites permit unimpeded transport of charge, but confer stiffness in polymeric films with a semicrystalline microstructure. Commercial silicone elastomers (e.g., poly(dimethylsiloxane), PDMS) have tensile moduli in the range of 1 MPa, which is similar to that of the human epidermis. Subcutaneous tissue and internal organs, however, can be significantly more compliant (ge;10 kPa). Applying conjugated polymers to problems in biomedicine—to conform to curved biological surfaces without wrinkling and to rebound in response to deformation—is thus tantamount to lowering the tensile moduli of semiconducting polymers by several orders of magnitude. Our group has begun to understand the molecular parameters that influence the mechanical properties of high-mobility conjugated polymers. In particular, we have employed a technique based on the strain-induced buckling instability (surface wrinkling) to measure the tensile moduli of thin films that are difficult to assay using conventional means. We have supported our measurements by developing a semi-empirical theory that predicts the tensile moduli through analysis of the thermal properties and the chemical structure. Among our conclusions was that the length of the alkyl pendant group (installed for increased solubility) is a key determinant of the tensile modulus. Lengthening of the aliphatic side chain decreases the number of load-bearing, main-chain carbon atoms per cross sectional area and reduces the ability of the main chains to associate. Both effects reduce the tensile modulus and the mobility of charge carriers, and thus polythiophene bearing octyl side chains is not only ten times more compliant—but also a poorer semiconductor—than polythiophene bearing hexyl chains. The apparent competition between mechanical and charge-transport properties led us to synthesize block copolymers and “segmented” polymers whose blocks and segments permitted co-engineering of mechanical compliance and charge-carrier mobility. These studies provide the basis for our proposed method for increasing the elasticity further, toward that of biological tissue, for applications in stretchable solar cells and mechanical sensors for electronic skin.

Conjugated polymers such as poly(3,4-ethylenedioxythiphene) (PEDOT) are of interest for interfacing electronic biomedical devices with living tissue, however the mechanical properties of these materials are a concern for long-term applications. The quantitative analysis of the mechanical properties of PEDOT has received relatively little attention. This study examined the stiffness, strength and the adhesion of PEDOT films by the tensile testing of films electrochemically deposited on soft substrates (gold-coated paraffin) with lithium perchlorate as the counterion. The effective interfacial shear strength was estimated with a shear-lag model by measuring the crack spacing as a function of film thickness. The estimated Young&’s modulus of the PEDOT films was 2.5 ± 1.2 GPa, and the strain to failure was around 2%. The tensile strengths were 52 ± 25 MPa. The effective interfacial shear strengths were 0.6 ± 0.3 MPa. The addition of 5 mole% of a trifunctional EPh monomer caused the tensile strength of the PEDOT to increase to 283 ± 67 MPa, the strain to failure to remain about the same (2%) and the effective interfacial shear strength to increase to 2.4 ± 0.6 MPa.

In recent years, the bioelectronics field has seen the use of an increasing variety of conducting polymers because they promise to display tunable mechanical properties (flexibility) and the ability to form an intimate interface with living tissue - in strong contrast to their inorganic counterparts [1]. Even though transduction of ionic biosignals into electronic signals is thought to be the key mechanism for successful integration of electronic devices in biological systems, little insight has so far been gained that allows understanding the interplay of electronic and ionic conductivity in the currently employed materials [2]. Here we present a straight-forward and chemically inert materials science approach to this challenge that promises to control mixed ionic/electronic transport in ‘plastics&’ by blending organic semiconductors with insulating polymers. This assists in inducing a more polar nature to the resulting systems and introduces the capability of controlling the interdiffusion of biological media through the final structures. We will demonstrate that electronic transport can be maintained in such multicomponent systems upon blending with the insulating matrix. Moreover, initial studies show faster switching response in large-scale organic electrochemical transistors (OECT) when using blend systems compared to devices fabricated with a single-component conducting layer. This observation suggests our blend system shows efficient ionic conductivity. We tentatively relate this desirable behavior of the semiconductor:insulator blends to the more polar nature of the latter active layers, introduced through the insulating (commodity) polymers, in addition to the swelling of the blend in the aqueous electrolyte. We thus show that the use of conducting/insulating polymer blends has the potential to bring multifunctionality to the final material systems, including biological activity, biodegradation, topological cues, etc., which in turn promises to enable more specific interactions with biological systems.
[1] R. M. Owens et al., MRS Bulletin, 35, 449 (2010).
[2] S. Ghosh et al.,Electrochemical and Solid-State Letters, 3 (5), 213 (2000).

Organic field-effect transistors (OFETs) with a top-contact structure were fabricated by applying deoxyribonucleic acid (DNA) as a hole injection layer between organic semiconductor and electrousing a simple spray-coating process. Compared with that of the bare OFET, the OFET incorporated with a DNA hole injection layer exhibited a significant enhancement of field-effect mobility from 0.02 to 0.104 cm² V^minus;1 s^minus;1. By analyzing the electrical characteristics of these OFETs and the surface morphology of the pentacene film, the results showed that the dipole formation effect brought by the DNA interlayer effectively reduced the contact resistance between the gold electrodes and the pentacene film. Consequently, improved hole injection was obtained along with the enhanced electrical characteristics. Moreover, DNA is soluble in aqueous solvent only and compared to spin-coating process, spray-coating process is beneficial to film formation of DNA aqueous solution with high viscosity and thus make DNA interlayer well incorporated in OFET device. In order to confirm the performance enhancement effect brought by DNA interlayer, OFETs based on another p-type organic semiconductor of α-hexathiophene and the OFETs based on silver electrodes were also investigated. The results showed that the α-hexathiophene based OFETs also exhibited significant performance improvement and the large injection barrier between silver electrodes and the pentacene organic semiconductor was significantly reduced by DNA interlayer. In addition, among the four kinds of base-pairs in DNA molecule, the guanine base-pair exhibits the lowest oxidation potential owing to its peculiar sequence of H-bond donor or acceptor groups. Therefore, the guanine base-pair was selected to be further analyzed and the results confirmed the existence of the dipole formation effect in DNA molecule. Moreover, in the case of organic electronics, environmental stability is another crucial feature. The main discrepancy of pentacene film after exposure to air is the generation of the deep trap states. When the OFET is exposed to air, deep trap states which result from the absorption of H₂O and other molecules lead to a degradation in performance. When a DNA hole injection layer was introduced, the surface of pentacene film was protected from direct contact with ambient conditions and the degradation of the device was thus slowed down.

Mostly of the organic electronic devices are built from synthetic small molecules, conjugated polymers, oligomeric or blended semiconducting materials. Other straightforward approaches include self-organized columnar stacks of aromatic compounds like discotic liquid crystals (DLCs), bent-core molecules and polyaromatic dendrons. Besides the organic π-conjugated classes cited above a quite different alternative has been emerged in the recent years for device fabrication. Vladu, Sariciftci and Bauer called this new class as “exotic” materials and it comprehends biological or bioinspired materials like paper, leather, silk, gelatine, DNA and peptides. The motivation behind the use of such biodegradable materials as substrate, dielectrics or semiconductors is to generate more sustainable and eco-friendly electronics.
In this contribution, we report for the first time the preparation of a hybrid material having (L)-diphenylalanine (Phe-Phe or FF) as biological component and semiconducting polymers (SP) (e.g. P3HT, PFO or PCDTBT) as organic semiconductor. Conventionally, FF nanostructures have been obtained by simple mixing a small amount of highly concentrate (ca. 100 mg/mL) solution of FF in fluorinated solvent (e.g. hexafluoro isopropanol or hexafluoro ethanol) with deionized water (DI). By doing so, FF molecules self-assembly mostly into bundles of nanotubes. Our attempts using the conventional synthesis protocol were fruitless to produce FF nanostructures with SP. To enhance the incorporation of semiconducting polymer and also to get control over the shape and size distribution of FF structures we developed a procedure using ultrasound energy. In a brief, to a solution of FF in 1,1,1,3,3,3-hexafluoro-2-propanol (HFP) was added a stoichiometric amount of SP in 1,2-dichlorobenzene (DCB) and 100 mL of DI water. The process of self-organization initiated spontaneously by ultrasound tip giving rise to FF:P3HT hybrid material as a light-violet precipitated. The temperature was kept at 0-4 °C with an ice-water bath during all the process. After ceased the ultrasound energy application the material was allowed to stand for 8h. The crude product was washed and harvested with centrifugation-redispersion cycles (2265 g) using DCB as solvent. Then, the resulting solid was finally dried in vacuum oven at 60 °C for 24h. The hybrid materials as prepared were fully characterized by SEM, optical microscopy, dynamic light scattering (DLC), circular dichroism (CD), cyclic voltammetry (CV), FT-IR, XRD and thermal gravimetric analysis (TGA).
Those new bio-organic materials have the semiconducting properties of the conjugate polymers while keep the inherent self-organization of biological systems. Benefiting from such synergy high-performance organic electronic devices like OFETs can be envisioned.

Hydrogen-bonded pigments are very promising semiconducting materials because they combine performance with stability, low cost, and intrinsic biocompatibility. Herein we report progress with the epindolidione class of materials, structural isomers of the well-known natural dye indigo. We present the electrochemical and optical properties of epindolidione together with some of its derivatives, their crystalline structures, their applications in ambipolar organic field effect transistors and organic light emitting diodes. Stability studies of transistor and diode devices will be presented, wherein excellent stability is found in ambient as well as aqueous surroundings. Even very demanding aqueous environments in a pH range from 3 to 11 do not degrade operating devices. We have also fabricated sensors devices for operation in biologically-relevant aqueous environments, where the H-bonding functional groups lend themselves to easy functionalization to achieve selective biosensing.

We present the electrochemical reduction of CO₂ using biological and biochemical catalysts such as bacteria and dehydrogenase enzymes. The enzymatic reduction reactions of CO₂ using dehydrogenase enzymes is enabled by adding a sacrificial coenzyme as electron and hydrogen donor.^1,2 CO₂ is reduced to acids, aldehydes and finally alcohols in a three step reaction with each catalyzed by a different dehydrogenase and using the coenzyme Nicotinamideadenin dinucleotide (NADH) as the sacrificial electron and hydrogen donor. We show the immobilization of these enzymes in an alginate matrix on a carbon felt electrode suitable for a reproducible CO₂ reduction without any sacrificial mediator such as NADH needed.³ Reductions using dehydrogenase enzymes provide highly selective product generation. In another approach the application of microorganisms on such carbon felt electrodes gives the opportunity for a further selective CO₂ reduction.^4,5 Immobilized mixed cultures in an electrochemical system metabolize CO₂ to methane with high efficiencies. All electrochemical measurements were performed in two compartment cells using carbon felt electrodes with the immobilized enzymes or microorganisms respectively as working electrode. Cyclic voltammograms were recorded for electrochemical characterization. Results from CO₂ saturated samples are compared to N₂ purged setups to proof product generation from CO₂ reduction. Product generation was obtained by long-term electrolysis. Liquid and gaseous products were analyzed using capillary ion chromatography, gas chromatography and liquid injection gas chromatography.
The authors acknowledge the European Union and the county of Upper Austria for funding the Regio 13 project “REG-STORE”.
1. U. Ruschig, U. Müller, P. Willnow, T. Höpner, Eur. J. Biochem., 70, 325-330, (1976).
2. M. Aresta, A. Dibenedetto, Ref. Mol. Biotechnol., 90, 113-128(2002).
3. T. Reda, C. M. Plugge, N. J. Abram, J. Hirst, PNAS, 105, 10654-10658 (2008).
4. Y. Jiang, M. Su, Y. Zhang, G. Zhan, Y. Tao, D. Li, Int. J. Hydrogen Energy, 38, 3497-3502, (2013).
5. H. Li, P. H. Opgenorth, D. G. Wernick, S. Rogers, T-Y. Wu, W. Higashide, P. Malati, Y.-X. Huo, K. M. Cho, J. C. Liao, Science, 335, 1596, (2012).

Organic electronics has a remarkable potential for the development of electronic products that are non-toxic, environmentally friendly, and biodegradable. An ideal solution for the production of such devices involves the fabrication of electronics either from natural materials, or from materials that have been proved to be biodegradable or biocompatible. Natural or nature-inspired small molecules dielectrics and semiconductors have been recently successfully implemented in organic field effect transistors, and afforded performances on par with state-of-the-art synthetic organic materials. Among the materials we have exploited are naturally-occurring compounds like cellulose, shellac, various waxes and gums, nucleobases, sugars, carotenoids, indigoids, anthraquinone and acridone derivatives, to name a few.^{[i],[ii],[iii],[iv]} We have demonstrated fully-biodegradable devices and circuits featuring natural substrates, dielectric and semiconducting layers and showed that the success of implementing these novel class of ‘green&’ technologies to field effect transistors could be successfully extended to organic photovoltaic field.^[v]
[i]. Petritz, A. Wolfberger, A. Fian, A. Haase, A. Irimia-Vladu, M. Gold, H. Rothländer, T. Griesser, T.
Stadlober, B. Cellulose as Biodegradable High-k Dielectric Layer in Organic Complementary Inverters. Appl.
Phys. Lett.103, 153303 (2013).
[ii]. Irimia-Vladu, M. G#322;owacki, E.D. Schwabegger, G. Leonat, L. Akpinar, H.Z. Sitter, H. Bauer, S. Sariciftci,
N.S. Natural Resin Shellac as Substrate and Dielectric Layer for Organic Field-effect Transistors. Green
Chem. 15, 1473-1476 (2013).
[iii]. Irimia-Vladu, M. Glowacki, E.D. Troshin, P.A. Susarova, D.K. Krystal, O. Schwabegger, G. Ullah, M.
Kanbur, Y. Bodea, M.A. Razumov, V.F. Sitter, H. Bauer, S. Sariciftci, N.S. Indigo-a Natural Pigment for
High Performance Ambipolar Organic Field Effect Transistors and Circuits. Adv. Mater.24, 375-380 (2012).
[iv]. Glowacki, E.D. Leonat, L.N. Voss, G. Badea, M. Bozkurt, Z. Irimia-Vladu, M. Bauer, S. Sariciftci, N.S.
Ambipolar Organic Field Effect Transistors and Inverters with the Natural Material Tyrian Purple. AIP
Advances 1, 042132 (2011).
[v]. Glowacki, E.D. Leonat, L. Irimia-Vladu, M. Schwödiauer, R. Ullah, M. Sitter, H. Bauer, S.. Sariciftci, N.S
Intermolecular Hydrogen-bonded Organic Semiconductors: Quinacridone versus Pentacene. Appl.
Phys. Lett.101, 023305 (2012).

Charge transport (CT) through DNA has been extensively studied, and yet the mechanism of this process is still not yet fully understood. Besides the benefits of understanding charge transport through this fundamental molecule, further understanding of this process will elucidate the biological implications of DNA CT and advance sensing technology. Therefore, we have investigated the temperature and length dependence of DNA CT by measuring the electrochemical response of DNA monolayers modified with a redox-active probe. By using multiplexed electrodes, we are able to compare square wave voltammetry of distinct DNA sequences under identical experimental conditions. We vary the position of the probe, within a well matched DNA duplex, in order to investigate distance dependent kinetics. Through modeling analysis we are able to determine the charge transfer rates (k), transfer coefficients (α), and the redox active surface concentration (Γ*) of the DNA monolayer. The yield of transport is strongly connected to the stability of the duplex, linearly correlated to the melting temperature of the duplex. Additionally, the results show Arrhenius like behavior for multiple probe locations, with the transport rates following a 1/L length dependence, consistent with a hopping mechanism of transport. These results begin to clarify the significance of length and sequence on the stability of the duplex, which in turn, may be used to establish the guidelines for using DNA as a molecular wire in nanoscale electronics and sensing applications

One-dimensional organic nanowires have emerged as idealized model systems for the investigation of charge transport mechanisms at molecular length scales. However, there are significant difficulties associated with the synthesis and electrical characterization of well-defined organic nanowires. We have drawn inspiration from oligonucleotide synthesis to develop a facile strategy for the assembly of organic semiconductor building blocks in predetermined arrangements on a DNA-like backbone. The resulting constructs can be purified/processed under partially aqueous conditions via known biochemical techniques and feature many of the advantages of standard oligonucleotides, including a well-defined length, geometry, and sequence context. We have investigated the properties of self-assembled monolayers from our nanowires with electrochemical and synchrotron x-ray spectroscopy techniques. Our findings hold significance not only for fundamentally understanding nanoscale charge transport phenomena but also for the development of new types of biological and molecular electronic devices.

Natural electronics (bioelectronics) incorporate biological molecules in organic electronic devices as an inexpensive, performance-enhancing, and environmentally safe alternative to conventional materials. Devices such as the all-natural organic field-effect transistor (OFET)¹ and DNA-based electronics² demonstrate that renewable and sustainable materials can be applied to important device classes without sacrificing performance. Natural DNA, for example, has been shown to enhance device performance in organic light emitting diodes (OLED) by incorporating it as an electron blocking layer (EBL) to decrease power consumption, while still retaining performance equal (or superior) to that of conventional OLEDs³. While DNA has been an important molecule for bio-OLEDs, the path towards an all-natural OLED requires a more diverse set of biomolecules with optical and electrical properties that meet the rigorous requirements of OLED device design.
We report that the simpler and less costly nucleobases (adenine, guanine, cytosine, thymine, uracil) can replace the spin coated DNA layer and other conventional organic materials in the OLED structure and offer more diversity. The individual nucleobases (NBs) are small molecule constituents of the DNA polymer. They readily form thin films by by thermal evaporation with well-controlled thickness, high purity and film quality, all essential characteristics for OLED fabrication. In addition to fabrication advantages over DNA, using NBs eliminates variation of DNA properties (due to residual proteins and other contaminants, unknown base-pair sequences) and gives precise control over opto/electronic properties such as refractive index, dielectric constant, resistivity, and electron/hole transport. We report that OLEDs with NBs as an EBL have >2X the maximum efficiency (76 cd/A) and higher maximum luminance (132,000 cd/m²) than the baseline OLED (31 cd/A and 100,000 cd/m²) that uses non-biological EBL molecules. We demonstrate that NB properties have the potential to replace other synthetic organic compounds in the OLED structure. Examples include use of: (a) uracil as a hole blocking layer (HBL) to replace more costly conventional organic materials; adenine as a self-aligned layer on Au electrodes (a natural and non-toxic element) that is useful as a hole injection layer. Au electrodes are an attractive alternative to ITO electrodes as they are significantly more flexible without cracking. This is an important consideration for device fabrication on flexible plant-based cellulose substrates, a key goal towards an all-natural bio-OLED.
1 Irimia-Vladu, M. "Green" electronics: biodegradable and biocompatible materials and devices for sustainable future. Chemical Society Reviews, doi:10.1039/c3cs60235d (2014).
2 Steckl, A. J. DNA-a new material for photonics? Nature Photonics1, 3 (2007).
3 Steckl, A. J., Spaeth, H., You, H., Gomez, E. & Grote, J. DNA as an Optical Material. Opt. Photon. News22, 34-39 (2011).

The electrical properties of eumelanin, a ubiquitous natural pigment, have fascinated scientists since the late 1960&’s. For several decades, the hydration-dependent electrical properties of eumelanin have mainly been interpreted within the amorphous semiconductor model. Recent works undermined this paradigma leading to a change of perspective, from the amorphous semiconductor to the mixed ionic-electronic conductor, in eumelanin research.
We already reported on characterization of hydrated eumelanin in form of thin films, easily accessible to chemical and morphological characterization, by current-voltage measurements, transient current measurements with proton-transparent electrodes, and electrochemical impedance spectroscopy, complemented by X-ray photoelectron spectroscopy. We showed that the electrical response of hydrated eumelanin films is dominated by proton conduction (10^-4 S cm^-1 ) and electrochemical processes. [1,2]
To establish sound extended structure-property relationships in eumelanin thin films a deep knowledge of their chemistry is required. In this regard, a key role is played by the solvent, in our case DMSO, used to solution-process the films. Indeed, the solvent has to ensure eumelanin processability in thin film form without compromising the eumelanin chemical identity. We therefore characterized by means of TGA (Thermogravimetric Analisys) and DSC (Differential Scanning Calorimetry) the behaviour of the films. TGA shed light on the amount of bound water and residual DMSO as well as low weight components of eumelanin. DSC was used to investigate the macro- or supramolecular structural changes that can occur in the films varying the temperature. These studies set the basis for a solid knowledge of the chemical composition of the films and opened the possibility for important in depth analyses on the mechanism of proton conduction in eumelanin. Using a combined AFM and spatially resolved IR survey (Anasys nanoIR2) we explored the presence of water channels in eumelanin films. These new insights improve the current understanding of the charge transport properties of eumelanin opening the possibility to advance the knowledge on the functions of eumelanins in biology as well as to assess the potential of eumelanin for organic bioelectronic applications.
[1] J. Wünsche, F. Cicoira, C. F. O. Graeff, C. Santato, J. Mat. Chem. B, 2013, 1, 3836-3842.
[2] J. Wünsche, Y. Deng, P. Kumar, E. Di Mauro, J. Sayago, F. Cicoira, M. Rolandi, F. Soavi, A. Pezzella, and C. Santato, 2014, (submitted to Materials Horizons)

Organic compounds represent promising alternatives to inorganic materials for renewable and sustainable energy storage devices. Organic molecules can be processed into non-conventional form factors, are cost-effective, and exhibit reduced toxicity compared to other exotic inorganic materials. Carbonyls, carboxylates, amines are the attractive redox-active chemical signatures of organic compounds that could potentially be utilized as electrode materials by reversible binding of cations. While these redox-active organic compounds enable the novel pathway as charge storage devices, there are many persistent challenges that may limit the prospective utility of organic electrodes. Major challenges include low charge collection abilities and high solubility in electrolytes.
Here we introduce the use of biologically-derived eumelanin pigments as cathode materials in aqueous sodium-ion electrochemical storage devices. Eulemanin, a sub-class of melanin, exhibits redox-active signatures including pendant carboxylates, aromatic amines, and catechols that can support reversible cation binding. Eulemanins are ideal electrode materials because they are stable in aqueous electrolytes and are composed of nanostructured granules. Homogeneous microstructures overcome kinetic limitations of organic electrodes. Current collection in semiconducting melanins can be improved by incorporating conducting silver nanowire (AgNW) networks. Full cells are composed of sodium titanium phosphate (NaTi₂(PO₄)₃) anodes and eumelanin cathodes. Galvanostatic full cell discharge exhibits a stable working potential of 0.5 V. Specific capacities of full cells discharged at 0.05 Ag^-1 contain 49 and 78 mAhg^-1 for natural (NatMel) and synthetic melanin (SynMel) respectively. FT-IR and Raman spectra corroborate that Na⁺ associates with pendant carboxylates of eumelanins during discharge. Natural melanins exhibit unique potential plateaus during discharge that are not present in synthetic melanins. These data support the presence of porphyrin structures in natural melanins, which are largely absent in synthetic melanins. The details regarding the structure-property relationships will be discussed.
Taken together, eumelanin-based cathodes represent a material that is compatible with broader strategies of sustainable and renewable energy storage. Melanins are a class of organic molecules that exhibit suitable performance, cost-effectiveness, and limited processing to produce electrochemical storage devices.

The recent addition of transient biodegradable devices based on silicon nanomaterials and magnesium conductors to the field of bioelectronics shows considerable promise for implantable applications, due to a lack of need for device retrieval. To date, however, precise control over the degradation time of such devices has not been demonstrated. Extension beyond the 5 day survival time offered by direct magnesium oxide passivation has been shown with silk fibroin, but only in the capacity of a single directly-applied layer without degradation-modulating behavior. A more refined degree of control is clearly necessary for any future clinical applications of this technology to be feasible.
Here, we present a robust strategy for modulating device degradation though silk configured into nestable multilayer air pockets. The pockets are fabricated from cast silk fibroin films and sealed through a thermal-reflow-based welding method. Direct application of heat (~120^oC) and spatially controlled pressure (~50Psi) causes thermal reflow in non-beta-sheet crystallized silk, leading to a strong (~2 MPa) bond in the processed material, and is used to seal the edges between two films, trapping air and encapsulated devices inside. This process is applicable independent of the processing considerations inherent to the encapsulated device, and can be applied serially for additional passivation layers.
The mass transfer characteristics of the silk/air/device interfaces unique to this system are leveraged to control the degradation rate of encapsulated devices. This is studied from both a component and device perspective, and degradation control is demonstrated in proof-of-principle in vitro experiments, which show linear behavior with the addition of nested layers. Device degradation times are relatively short (2 hours), but future addition of magnesium oxide to the system could extend this precise control into week-long timescales. Additionally, the possibility of enhancement of function through release of efficacious bio-compounds from the pocket is established by leveraging the innate ability of silk fibroin to stabilize labile compounds. Devices are fabricated from silk films containing heat-labile antibiotics, and efficacy is maintained throughout device processing. Future addition of multiple dopants to nested pockets could lead to bi-functional devices with multiple controllable release and degradation rates.

For the emerging fields of biomedical diagnostics and environmental monitoring, where sensor platforms for in-situ sensing of ions and biological substances in appropriate aqueous media are required, electrolyte-gated organic field-effect transistors (EGOFETs) seem to be the transducers of choice. Due to the formation of an electric double layer at the electrolyte/organic semiconductor interface, they exhibit a very high capacitance allowing for low-voltage and water-stable operation. In combination with the outstanding properties of organic devices like biocompatibility, low-temperature processability on flexible substrates, as well as the possibility to tune the physical and chemical properties enhancing the selectivity and sensitivity, EGOFET-based sensors are a highly promising novel sensor technology.
Here the realization of the first ion-selective EGOFETs is discussed. In this context the device characteristics of poly(3-hexylthiophene) (P3HT) - based EGOFETs for various substrates using water with different concentrations of NaCl as an electrolyte and various gate electrode materials, are presented. In order to obtain a sensitive as well as selective response to sodium a commercial available ion selective membrane was introduced. This novel potentiometric sensor showed a sensitive linear response for a broad detection range between 10^-6 M and 10^-1 M Na⁺ and a selective as well as reversible response without a complex recovering process was achieved. Furthermore within this context, the basic characterization of these ion-selective membranes (ISMs) and the corresponding limiting factors for a proper combination with an EGOFET, will be discussed. Moreover besides presenting the general selective sensing mechanism of ISMs, the optimization as well as the fabrication of a new pH sensitive ISM will be presented. On the way to a pH-sensor for a broad detection range (pH 2 - pH 12) the challenges faced considering interfering ions and large membrane potential changes will be discussed.
K. Schmoltner, J. Kofler, A. Klug, E.J.W. List-Kratochvil, #8222;Electrolyte-gated field effect transistor for selective and reversible ion detection.“ Adv. Mater. 25 (47), 6895-6899 (2013).
J. Kofler, K. Schmoltner, A. Klug, E.J.W. List-Kratochvil, #8222;Hydrogen ion-selective electrolyte-gated organic field-effect transistor for pH sensing.“ Appl. Phys. Lett.104, 193305 (2014).

The energies involved in weak chiral interactions occurring between odorant binding proteins (OBPs) and carvone enantiomers are evaluated, down to a few KJ/mol, by means of a water-gated organic field-effect transistor (WGOFET) whose Au-gate is modified with a porcine-OBP (pOBP) self-assembled monolayer. The output current measured is dependent on the concentration of the analyte and pM concentrations can be detected. The binding curves also are significantly different between the two enantiomers. The modelling of the two curves allows the energies associated with the OBP-carvone complexes formation to be independently extracted, from the very same set of data. From the dissociation constants the standard free-energy the complex formation at the electrode is derived, while the threshold voltage shifts gives information on the electrostatic component. This approach, representing a unique tool to quantitatively investigate low-energy bio-chemical interactions, is rather general as it relies on the relative dielectric constants of the protein-SAMs and of the organic semiconductors being much lower than that of water. The role of the OBPs in the olfaction system is still under debate and the detection of neutral odorant species at the pM level by means of a WGOFET adds relevant pieces of information to the understanding of the odor perception mechanism at the molecular level.

The ever-growing demand for new biosensors has boosted the materials processing and synthesis in organic electronics. As a result, different layouts of organic field-effect transistors (OFETs) are now suitable to be operated in aqueous solution. Among them, electrolyte-gated organic field-effect transistors (EGOFETs) are the ultimate example [1]. In particular, these devices rely on an electrolytic solution, which acts as a gate dielectric bridging the gate electrode and the organic semiconductor thin-film. Different examples of biosensors have been successfully demonstrated in the past few years aiming at the detection of DNA, penicillin, streptavidin and dopamine [2].
Different factors are pivotal in order to achieve an electronic biosensor, such as the electrostatic screening, the pH of the aqueous environment and the density of the reactive sites assembled on the device [3]. An additional factor has to be taken into account for an immunological detection: the antibody (Ab) orientation once it is immobilized.
Here, it has been designed and fabricated an immunosensor towards interleukin-4 (IL4) and interlekin-6 (IL6). These two proteins belong to the cytokine family, which are known to be signalling mediators of the immune system. In particular, IL4 is an anti-inflammatory biomarker, whereas IL6 is a pro-inflammatory one.
The sensing core of this electronic device is the gate electrode (i.e. polycrystalline Au). The assessment of the role exerted by the Ab orientation has been pursued by comparing two different surface treatments: i) the use of an amine-terminated SAM activated by glutaraldehyde and ii) the exploitation of the recombinant protein G. Although the former protocol yields a covalent Ab grafting, it has a poor control on the orientation of the immobilized Ab. The latter leads to a highly oriented Ab on the gate electrode, making use of the biological functionality of recombinant protein G.
These two functionalization protocols have been characterized by DC/AC electrochemical measurements (viz. cyclic voltammetry and impedance spectroscopy). Furthermore, the bio-molecular recognition between antibody and antigen has been characterized by single force spectroscopy for both protocols. Many parameters have been successfully extracted, like (i) unbinding length and force, (ii) dissociation constant and (iii) reaction length. All these results point out how the protocol based on protein G leads to a more efficient bio-molecular recognition than the other one based on glutaraldehyde. As a result, the EGOFET shows sensitivity down to nM scale only for highly oriented Abs on the gate surface. In conclusion, electrical and nano-mechanical data have showed how the control of Abs orientation is crucial for IL4 and IL6 biosensing.
References
[1] L. Kergoat et al., Advanced Materials, 22, 2565-2569 (2010)
[2] S. Casalini et al., Organic Electronics, 14, 156-163 (2013)
[3] M. Hammock et al., ACS Nano, 7, 3970-3980 (2013)

Disorders of the nervous system effect hundreds of millions of people worldwide and the costs of these afflictions, both in terms of life lost and healthcare expenditure, are a heavy burden on us all. While some therapies have proven successful, treatments are still lacking for some of the most prevalent and debilitating forms of neurological impairments. Development of novel treatments will depend on precise interaction with the neurological pathways responsible for the disability. However, the complex circuitry of the nervous system has proven difficult to interface. While techniques ranging from pharmaceutics to electrophysiology have yielded insight into the function and dynamics of neural circuitry, better therapies demand new technological solutions.
The neuron itself is the most effective interface to other neurons. It is localized, it is highly selective, and it can transduce chemical signals into electrical signals and vice versa, without requiring liquid flow. A human-made device that could operate in such a chemical-electrical-chemical manner would enable its user one crucial addition to the biological neuron&’s set of capabilities: the ability to observe neural signaling electronically by connection to control hardware. This “artificial neuron” would thus become a key to studying, and eventually augmenting, neural signaling pathways with the ease and precision of modern electronics.
Organic electrochemical transistors (OECTs) have been successfully used for the detection of enzymatic reaction, mainly for glucose detection[1]. We recently developed an OECT, which could be used for the enzymatic detection of medically relevant concentrations of the neurotransmitter glutamate[2], which is one of the main excitatory neurotransmitter of the central nervous system. This sensor can be coupled to an organic electronic ion-pump[3], which can be used for a controlled delivery of neurotransmitters. When the intensity of the sensing signal reaches a defined threshold corresponding to a certain concentration in glutamate, the ion pump is triggered and the delivery of neurotransmitter starts, demonstrating the feasibility of mimicking the behavior of a neuron using organic electronic devices.
[1] Bernards et al. Journal of Materials Chemistry, 18 (2007)
[2] Kergoat et al. Advanced Materials, Early Views (2014)
[3] Tybrandt et al. Advanced Materials, 21 (2009)

The last years have witnessed a rapidly increased interest in the use of biomolecules as components of molecular bioelectronics devices. In most of the applications envisioned in the nano-biotechnology field, the biomolecule must be immobilized on the substrate. This can lead to a loss of the native functionality. Therefore, the design of strategies aiming at establishing a robust link between the surface and the biomolecule without affecting the activity of the latter is of paramount importance. The choice of the biomolecule should be based also on its stability in terms of temperature, pH and presence of organic solvent, as these experimental conditions can be extremely variable in the preparation of a bio-electronic device. Within this respect, electron transfer protein cytochrome c is an appealing candidate, displaying rather high stability and robustness. Nevertheless, this species lacks enzymatic activity which could be exploited in the design of biosensors.
We have designed, produced and characterized a set of yeast cytochrome c mutants, which endow the protein with novel peroxidase-like activity. These mutants can be adsorbed on gold electrodes functionalized with -COOH and/or -OH terminated Self Assembled Monolayers (SAMs) with retention of functionality. Both in solution and in the adsorbed phase, the investigated mutants are able to catalytically reduce O₂, H₂O₂ and nitrite anion.
The non native pseudo-peroxidase activity was provided by modifying the heme coordination by means of site-directed mutagenesis. In the M80A (namely methionine at position 80 replaced by an alanine) set of mutants, the axial binding Met80 was permanently substituted with a non-coordinating alanine M80A mutation (1,2). This mutation leads to a dramatic change in the reduction potential and, most importantly, endows the protein with non-native, pseudo-peroxidase activity. The K79H (lys-to-his) mutant instead reversibly interconverts between the native-like, His-Met heme-ligated form and a His-His-ligated conformer with remarkably different redox and enzymatic properties, which can be reversibly switched on/off by slight adjustment of the solution pH in proximity of neutral values (3,4).
Moreover, these mutants maintain their natural ability to efficiently transfer electrodes to/from a conducting substrate, thus ensuring electrical communication, and the higher stability with respect to natural peroxidases.
We envision the possibility to integrate these mutants in electrolyte-gated organic transistors, either upon adsorption on Au gate electrode or following incorporation into a room temperature ionic liquid to pattern the active area of the OECT. This would allow for the design of (implantable) biosensors towards reactive oxygen species (ROS).
References
1. Casalini et al., J.Phys.Chem. B, 2008, 112, 15555.
2. Casalini et al., J.Phys.Chem. B, 2010, 114, 1698.
3. Bortolotti et al., Chem. Sci., 2012, 3, 807.
4. Ranieri et al., Metallomics, 2014, 4, 874.

The ultimate goal for biodiagnostics is to provide a minimally invasive technology that combines rapid analysis and low cost fabrication. Label-free detection is an added advantage that decreases assay cost and operator time. One promising new technology that has the potential to respond to these specific requirements is the organic electrochemical transistor (OECT). We take advantage of the operating principle of the OECT to fabricate a sensor capable of continuously detecting low concentrations of a variety of physiologically relevant metabolites. During redox cycles, the metabolic analyte (glucose or lactate) and its corresponding enzyme (glucose oxidase or lactate oxidase) react, resulting in the transfer of an electron through a mediator (hydrogen peroxide) to the gate electrode. The electronic modification of the gate electrode induces a change in the transistor drain current that is proportional to analyte concentration. Incorporation of the biorecognition element directly into the device via functionalization can result in a one-step sensing platform. In this work, we incorporate functionalization sites within the conducting polymer (CP) PEDOT:PSS {poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate)} films by adding polymers with reactive sites while at the same time retaining conductive properties of the CP. Subsequently we fabricate planar OECTs with this functional conducting polymer serving as the transistor channel and gate. Enzymes are then immobilized within the transistor. We also show, as an alternative way of measuring mammalian cell integrity and viability for toxicology purposes, in vitro analyte detection, using these functionalized OECTs. The resulting device is capable of continuous, longterm measurement. Due to the inherent advantages of conducting polymers and the robust functionalization demonstrated, the sensing platform described here represents a significant step towards the realization of low-cost electronic-based sensors for biomarker detection.

Organic electrochemical transistors (OECTs), in recent years, have become the devices of choice for fabricating biosensors using semiconducting polymers. Although inorganic materials have long dominated the semiconductor market, organic semiconductors have been found to be much better candidates for interfacing with biological systems due to their high chemical variability, low elastic moduli and ability to perform both electronic and ionic transport. Because ionic species can penetrate the highly porous polymer film leading to large interfacial areas, OECT devices typically exhibit extremely large capacitances and display among the highest transconductance values in published literature. Of specific interest to us here is using OECTs to monitor and quantify ion transport across lipid bilayers and barrier tissues. Such devices would not only be useful as a sensitive diagnostic tool, but also represent a good potential candidate for building lipid-based biosensors.
To this date, the best performing OECTs are fabricated using the highly p-doped, conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). Due to its high conductivity and ability to readily uptake water and electrolytes, PEDOT:PSS devices have found their use in several medical applications. Previous studies have shown, for instance, that these devices can detect both the disruption of integral cell layers and lipid membranes as well as specific cation migrations across ion-transporting proteins. Although such experiments have been generally successful and a variety of biological membranes have been characterized, quantification of the impedances across these membranes has not been performed. The exact resistances and capacitances of the cell/lipid layers of interest and how they change upon introduction of toxins, for example, would be of great use for better understanding these physiological processes.
In this letter we present detailed circuit modeling of lipid-functionalized, PEDOT:PSS OECTs. Our results show firstly that both the lipid/cell membranes and the active channel can be simply modeled by two parallel RC circuits. The time and frequency responses of the OECT, which can be experimentally collected using transient current and impedance spectroscopy measurements, yield crucial information about the impedances of both the device and the membranes. By changing the membrane and device areas, it is possible to enhance the device sensitivity to lipid membranes. Finally we show that depending on the specific resistance of the membrane of interest, there is a maximum device size above which detection is not possible. Although we use electrical properties specific to that of spin cast PEDOT:PSS, our modeling results are general to all organic semiconductors and will be of great use to the bioorganic electronics community as we continue to work towards building better biosensors and more effective diagnostic tools.

Organic, charge-modulated Field Effect Transistors have been proposed since some time and have shown so far very interesting results in a variety of sensing tasks, both for chemical and physical variables, as well as, more recently, for the detection of the electrical activity of cells.
The core of the device is a floating gate organic transistor, capable to be operated at low voltages thanks to an ultra-thin, hybrid dielectric which can be fabricated over large areas at high yields. The sensitivity of the device is obtained by anchoring in a part of the floating gate a sensing layer (that, according to the application, may be, for instance, a probe molecular layer or an element dedicated to the transduction of a physical signal into an electrical charge as a piezoelectric layer) directly exposed to the measurement environment.
Apart from applying this measurement principle to a variety of applicative fields, an important issue is the possibility to have design rules for adapting the concept to the specifications imposed by the application. In this talk, this issue will be discussed and several examples of this approach will be given, including also multi-modal sensing, i.e. the ability to sense several parameters with an array of similar devices.

Stretchable electronics are expected to have important applications in mechanically robust consumer electronics, electronic skins for robotics, and advanced prosthetic devices. As the fundamental unit in many electronic circuits, stretchable transistors enable a large range of device applications, such as signal conditioning circuits for sensor networks and active addressing of stretchable displays. Implementing intrinsic stretchability could allow simplified processing methods, and could be compatible with lower-cost deposition methods. However, traditional electronic materials such as gold and silicon are not intrinsically stretchable. The success of intrinsically stretchable electronics relies on the development of materials with compatible mechanical and electrical properties. Good adhesion at the interfaces between materials is important for reliable operation during multiple strain cycles and mechanical stimulation. This work describes the materials selection considerations and the processing methods required for fabricating stretchable transistors. Our approach involves the use of solid elastomer dielectrics, which have highly elastic mechanical properties and reliable electrical characteristics. The source/drain electrodes are composed of 1D materials such as CNTs or silver nanowires that allow stretching to large strains while maintaining good conductivity. The effect of strain on each of the device components will be described, as well as the overall device characteristics with repeated strain cycles.

Phosphonium Ionic Liquid Electrolytes Based Organic Electrochemical Transistor
Ionic liquids (ILs) are binary salts consisting entirely of ions. ILs have captured the interest of the research community because of their unique physicochemical properties, such as high thermal and chemical stability, wide electrochemical windows, high ionic conductivity, optical transparency, low volatility and low toxicity. ILs can serve as “green” solvents for applications in organic synthesis, homogeneous and heterogeneous catalyst and act as “inert” media to store enzymes. Moreover ILs are promising as electrolytes in electrical and electrochemical devices, since they give access to a wide range of ionic conductivities and viscosities.
Organic electrochemical transistors (OECTs), which can be operated in aqueous solutions at low voltages (<1 V), have attracted great attention for applications in bioelectronics and sensing. OECTs have been used as sensors to monitor the formation of micelles, barrier tissue integrity and the attachment of cancer cells and fibroblasts cultured directly on the channel. OECTs have also been employed as sensors for hydrogen peroxide, glucose, lactate, dopamine, ions, and bacteria. OECTs are able to convert ionic currents in the electrolyte into electronic currents in the organic channel. With application of a small gate voltage, a large change in the current that flows in the channel can be observed. This phenomenon is originated from the fact that the electrolyte ions dedope the channel with the application of electric field. The current modulation in OECTs relies mainly on dedoping/doping process in the channel by electrolyte ions.
To further extend the applications of OECTs, we investigated the OECTs employing poly(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT:PSS) as the semiconductor, which is compatible with bioelectronics application owing to its cell adhesion and proliferation effect, and phosphonium ionic liquids with different viscosities as electrolytes. We found that the conductivity of the electrolyte is not the key factor of manipulating the IL OECT modulation, and the IL viscosity plays an important role in operating the IL OECTs. Our work sheds light on the role of the electrolyte viscosity on the operation of OECTs. Moreover ILs electrolytes are of interest for OECT based enzymatic sensors, as studies on enzymatic reactions have also revealed that, in ILs, some enzymes exhibit enhanced stability and excellent selectivity including substrate, regio- and enantioselectivity.

With the continuous improvement of organic electronics, future technology will be required for more environmentally friendly and better integration with green materials for sustainable organic electronics.Biomaterial and natural compound are especially environmentally friendly, can be mass produced inexpensively, and can contribute to sustainability in organic electronics. Therefore, it will become a trend that the conventional materials for use in electronic device will be replaced by more environmentally friendly and energy productive materials such as natural compounds and bio-inspired materials.
Here, we present that naturally occuring biomolecules of amino acids and peptides act as an ideal modifying material on metal oxide surfaces,such as indium tin oxide (ITO) and titanium dioxide(TiO₂). Work function of these modified surfaces shows an effective reduction to promote electron transfer at organic/metal oxide interfaces in organic or organic devices. These lead to a significant enhancement on performance for various organic based devices, including organic light-emitting diodes, solar cells and photodetectors.
References:
[1]Nie, R., Li A., Deng X.,J.Mater.Chem.A. 2014, 2, 6734.
[2]Li, A., Nie R., Deng, X., Wei, H., Zheng, S., Li, Y., Tang, J., Wong, K.-y., Appl.Phys.Lett. 2014,104, 123303.
[3]Deng, X., Nie R., Li A., Wei H., Zheng S., Huang W., Mo Y.,Su Y., Wang Q., Li Y., Tang J., Xu J.,Wong K.-y, Adv. Mater. Interfaces,2014, DOI: 10.1002/admi.201400215.

Organic thin film transistors are certainly attracting a big deal of attention in the scientific community due to the possibility of being fabricated at low costs over large areas and over highly flexible substrates, and most importantly because they could potentially be employed in a wide range of applications. In this work we introduce a highly flexible, and conformable, OTFTs architecture that can be operated at very low voltages, and that can be employed in wearable applications for monitoring bio-mechanical parameters. The core of a structure is an organic transistor fabricated using a combination of two ultrathin insulating materials, namely AlOx and Parylene C. Thanks to the high capacitance of the employed hybrid gate dielectric the devices can be operated at voltages as low as 2 V. All devices were fabricated using TIPS-Pentacene as organic semiconductor, deposited by drop casting, and showed mobilities up to 0.4 cm²/Vs with remarkably small leakage currents (50/100 pA). An accurate electromechanical characterization of the flexible devices demonstrated that they are very sensible to mechanical deformation and that their response is linear and reversible for induced surface strain up to 2%. Therefore, they can be successfully employed for the fabrication of wearable sensors for monitoring bio-mechanical parameters. Due to their high conformability, such devices, after being encapsulated with a 2 um thick Parylene C layer (in order to avoid undesired local damages on the device surface during mechanical deformation), have been transferred into elastic fabrics in order to obtain wearable sensing systems. Among several applications, we will show that such flexible and conformable structures can be sewn onto a glove and can be employed for a detailed monitoring of the fingers motions, but also of the wrist motion.
Moreover, mechanical stress tests demonstrated also that working within this range of deformations (surface strain between 0-2%) they can sustain continuous mechanical deformation (more than 3000 cycles) without changing their electrical performances, therefore they are suitable for practical applications.
The ease of fabrication and the high conformability of the developed structure represents a step forward towards the development of a wide range of applications within the smart wearable electronics field.

Organic Electrochemical Transistors (OECTs) all made of poly(3,4-ethylenedioxy-thiophene):poly(styrene sulfonate) (PEDOT:PSS) are devices based on a conductive channel and a gate contact which can exchange ions with an electrolytic solution. The working principle is based on the doping/de-doping process which can be modulated by means of the gate-to-source potential; because PEDOT:PSS behaves as a supercapacitor and both the gate and the channel are made of PEDOT:PSS, the device operates in a capacitive regime as demonstrated in [ref nostra]. Aiming at developing chemo or biochemical sensors, OECTs entirely made of PEDOT:PSS are very interesting devices because they are very easy to fabricate (for instance, by inkjet printing), can be operated at low voltage and finally are biocompatible. The fabrication process of OECTs modified with Ferrocene is reported in the present work. Ferrocene is an electron mediator able to catalyze the oxidation or reduction of many small molecules. The idea to modify PEDOT:PSS with Ferrocene is aimed at specializing the transistor in order to obtain a sensor for different analytes as, for instance, dopamine. Ferrocene immobilization is obtained through a two steps process: step one is based on the electrochemical polymerization of a thin layer of PEDOT-N₃ on the surface of the gate electrode thus introducing the azide (N₃) group on the surface; step two consists of the click reaction between alkyl ferrocene and N₃ group. As Ferrocene is able to undergo a faradaic reaction in the voltage range of the transistor operation, changes due to the Ferrocene immobilization in the operative regime of the device have been investigated. Finally, a few sensing applications obtained with devices containing a Ferrocene-clicked PEDOT:PSS electrode are presented.

We demonstrate the sensing of glucose through incorporation of the enzyme glucose oxidase into the gate of a bio-organic thin-film transistor (BioOTFT). The enzymatic oxidation of the glucose analyte, followed by the electrochemical breakdown of the liberated hydrogen peroxide, generates an addition of protons into the dielectric layer of the devices. We show that the electrical characteristics of the transistors is dependent on the ion concentration within their dielectric layer and thus consequently show a change in drain current which is related to concentration of glucose in a solution presented to their gate electrodes. The devices&’ response shows a systematic correlation with glucose concentration across 4 decades of analyte concentration encompassing both saliva and blood glucose concentration levels. The results are the first steps towards the development of a non-intrusive, saliva-based sensor for glucose and as a versatile platform for sensing based on enzymatically-catalysed reactions in general. We illustrate the potential of this method of enzymatic sensing from a printed BioOTFT platform.

Electrochemical storage materials that use aqueous electrolytes are amenable for applications ranging from grid-scale storage to biomedical devices. Hygroscopic ionomer electrolytes permit fine control over the transport of cations using various mechanisms. Smart polymers could enable spontaneous control of electrochemical discharge for use in the active control of battery operation. Here we present the design, fabrication, and characterization of pH-sensitive hydrogels as polymeric electrolytes that can control the discharge of aqueous sodium-ion batteries. Poly(acrylic acid)-based hydrogels are used as electrolytes in combination with activated carbon anodes and manganese oxide cathodes. pH-sensitive hydrogels exhibit mesh size transitions as the pH is adjusted from 1.5 to 7. Chemical control of hydrogel mesostructure permits selective discharge of the electrochemical cell in the “off” and “on” configuration, respectively. We report discharge times permitted in these two states while operating in galvanostatic conditions at 0.1C. pH-dependent discharge of electrochemical storage systems composed of biocompatible materials could serve as a passive control mechanism for battery operation in biomedical applications including ingestible electronic devices.

DNA is an attractive candidate for a biological nanowire due to its sequence specificity and self-assembling properties. Incorporating recent research on non-canonical base pairing, we design silver ion-mediated bonding in oligonucleotide sequences containing cytosine-cytosine mismatches with the potential to increase molecular conductivity. Using gel electrophoresis, fluorescent labeling, and thermal denaturation, we demonstrate the stability of DNA strands containing multiple C-Ag⁺-C bonds as well as a dependence upon the silver-to-mismatch molar ratio for effective duplexing. We successfully carry out end-ligation reactions with these duplexes which suggests an effective polymerization method and compatibility with enzymatic processes. Using ¹H-¹H COSY NMR, we detect cytosine-Ag⁺ intercalation, and further show the continued stability of this bond after exposure to precipitation and dialysis. Finally, we show first principle for the bio-integration of this nanowire system by constructing two functional genes for the PCR-assisted synthesis of both DNA- and RNA-based C-Ag⁺-C-mediated duplexes using the bacterial chassis E. coli. We posit that future studies may demonstrate the enhanced conductivity of these strands over native DNA. With enhanced stability, enzyme-compatibility, and a reliance on components naturally found in the environmental microbiome, we suggest that this system and a synthetic biology approach will enable a directed integration of biological systems into nanoscale engineering and ultimately expand the language of DNA nanotechnology.

Organic field-effect transistor (OFET)-based devices show great promise for chemical and biological sensing applications. OFET platforms have many advantages including high sensitivity, ultralow-cost, simple fabrication and flexible applications. In particular, transistor-based sensors with high sensitivity have been developed because they are expected to offer amplifying the electrical signals induced by analyte species with the presence of the gate (i.e., third) electrodes, compared with ion sensors that have two electrodes. Biological sensors for biomolecules using electrical signals have provided us with several important systems for targeted therapy. However, a large number of biosensors use high-cost enzyme immobilization methods because they offer great biological binding event or biological reaction. Here we report highly sensitive OFET-based biosensors functionalized with molecular sieves that can selectively detect critical ions related to delivery of neural stimulation. A cucurbit[6]uril derivative (CB[6]) was deposited as a molecular sieve layer onto p-channel semiconductor 5,5&’-bis-(7-dodecyl-9H-fluoren-2-yl)-2,2&’-bithiophene (DDFTTF) layer for the specific analyte binding events. Our approach demonstrates the possibilities for potential application of OFETs to biological sensors with high sensitivity and selectivity. Our results also suggest that the use of molecular sieves is a promising surface modification strategy for enhancing sensitivity and selectivity in biosensors.

Organic electrochemical transistors (OECTs) are able to operate in aqueous solutions at rather low voltages (< 1 V), thus providing an ideal interface between the worlds of biology and electronics. The inherent signal amplification of OECTs has the potential to yield sensors with low detection limits and high sensitivity. Moreover, the physical flexibility of PEDOT:PSS is particularly suitable for integration of OECTs in textiles for wearable sensors. However, to date, little attention has been dedicated to reveal the evolution of PEDOT: PSS in OECTs where PEDOT: PSS are in contact with electrolytes. The complex interactions between electrolytes and PEDOT: PSS films result in a variation of the film properties. Therefore, investigating on the evolution of PEDOT: PSS in OECTs is indispensable to further understand the OECTs behaviors and will be a significant reference for a better development of this potentially revolutionary device. In this work, the evolution of PEDOT: PSS films in OECTs is revealed by systemically investigating the influence of secondary dopants, surfactant, crosslinker, electrolytes as well as other related essential parameters on the conductivity, thickness and electrical- as well as mechanical- stability of PEDOT:PSS films. The evolution were explored through atom force microscope, X-ray photoelectron spectroscopic, Fourier transform infrared as well as long-term electrical characterizations. Research in organic bioelectronics has strongly increased during the last years, and this work sheds light on the underlying role of PEDOT: PSS films in OECTs, paving the way for the optimization of bioactive, flexible and printable organic bioelectronics devices.

Autonomous sensing of metal ions and biological species in remote environments with high reproducibility and sensitivity has the potential to enable many new applications. However, the large power draw of such devices limits their operational lifetime while prior demonstrations have typically incorporated the power source as an additional component, making the assembly bulky. We propose and demonstrate a sensing scheme in which the presence of ionic analytes disrupts (or triggers) the flow of electrical current between two electrodes, with the electromotive force provided by absorbed ambient light. This concept is implemented using the classical dye-sensitized solar cell structure consisting of cis-bis(isothiocyanato)bis(2,2prime;-bipyridyl-4,4prime;-dicarboxylato)-ruthenium (II) sensitizing dye (N3) and the iodide/triiodide redox shuttle. We demonstrate that the presence of Ag⁺ ions causes an appreciable change in the device characteristics, with a detection limit of 1 mu;M and provide an in-depth analysis of the underlying sensing mechanism. The ionic target species can also be generated using an auxiliary release mechanism so as to allow for indirect detection of biological analytes. This detection approach may enable a new class of highly miniature, low cost sensors for continuous, environmental and health monitoring.

Building artificial photosynthetic molecular machines capable of harvesting solar light for photocatalysis and energy production have attracted considerable interest over the last years. A possible approach to such systems consists in the assembly of hybrid architectures combining a synthetically tailored antenna for effective light harvesting with a natural photoconverter optimized by billion years of evolution. We have designed and synthesized hybrid complexes combining the photosynthetic reaction center (RC) of the bacterium Rhodobacter Sphaeroides R26 with tailored p-conjugated fluorophores which can act as antennas to extend the light harvesting capability of the natural RC in a wavelength range where the unmodified biological enzyme does not efficiently absorb [1]. The bio conjugation protocol developed enables to selectively functionalize the RC protein scaffold for efficient energy transfer. The resulting hybrid architectures outperform the natural system in light harvesting and conversion ability and in the photocatalytic reaction rate. Finally, the photosynthetic hybrids have been anchored on graphene layers or embedded into polymersomes aiming to integration of the photoactive units into electronic devices.
References
F. Milano, R.R. Tangorra, O. Hassan Omar, R. Ragni, A. Operamolla, A. Agostiano, G.M. Farinola, M. Trotta Angew. Chem. Int. Ed. 51, 11019 (2012)

Chip-like, field-portable sensing platforms with high sensitivity and biological specificity are of great interest to monitor changes in absorbance, luminescence, reflectance, refractive index, or other related optical properties of bio-chemical events. Organic electronics, specifically photodetectors (OPDs) and light emitting diodes (OLEDs), can be printed at low cost and offer the ability to tune optical and electrical properties specific to desired biological response to optical stimuli. These components can be readily integrated onto waveguide platforms and flexible substrates, eliminating the need for free space optics while maintaining high sensitivity of internal reflection platforms. A dual-beam, single chip-based refractive index sensor will be presented, consisting of an OLED light source and two OPDs. The sensor utilizes the considerable fraction of emitted light from conventional thin-film OLEDs that is coupled into the guided modes of an internal reflection element, instead of into the forward (display) direction. Noise due to mechanical vibrations is greatly reduced because the organic electronic components are fabricated directly onto the waveguide element (in-plane), eliminating the need for prism coupling and free space optics. The combination of OLED and OPDs provides an inexpensive sensor platform that can be easily produced and altered to fit numerous biological sensing needs. Specific criteria and opto-electronic design guidelines will also be discussed.

Photoplethysmogram (PPG) sensor is a device that combines an LED and a photodetector to optically probe arterial pulse waves. Wearable PPG sensors enable continuous and unobtrusive measurement of physiological parameters such as heart rate, heart rate variability and blood oxygen saturation. Currently the performance of wearable PPG sensors is largely limited by power consumption and motion artifacts during measurements. In this work, we show that these challenges can be addressed by introducing a high-sensitivity polymer bulk heterojunction phototransistor as the PPG detection unit. We explored a bulk heterojunction system consisting of a narrow bandgap polymer, poly(N-alkyl diketopyrrolo-pyrrole dithienylthieno[3,2-b]thiophene) (DPP-DTT), and [6,6]-phenyl-C61-butyric acid methylester (PCBM). The device exhibits ultrahigh responsivity (~ 5×10⁵ A W^-1) as well as wide tunability (>1×10⁴) of photoconductive gain. Such high responsivity is achieved through the combined effects of fast transport of holes in the polymer matrix and slow detrapping of electrons from the isolated PCBM domains. Meanwhile, the optical-tunable gate electrode enables wide gain tunability and very low noise current at room temperature. We integrated the phototransistor into a PPG sensor structure and realized continuous radial artery pulse wave monitoring at low power consumption. The ultrahigh sensitivity, together with the light weight and flexibility, make the phototransistor a very promising component for the next generation low-cost, wearable PPG devices for health monitoring and remote diagnostics.

Living cells, like HEK 293 o astrocytes can grow on top of an organic semiconductor films. This establishes a photonic interface for communication with the living system that has important application in electrophysiology and neuroscience. Upon polymer photoexcitation, the cell can be excited by modification of the membrane properties. The bio organic interface that is established is a thin cleft of ionic solution separating the polymer film from the cell membrane. Ions in the buffer solution are in chemical equilibrium with charge carriers in the polymer. The whole polymer thickness (few hundred nm) is contaminated by the liquid. A complete characterization of the hybrid solid/liquid interface will be presented [1], based on optical and electrical techniques. Experiments of cell stimulation by polymer photoexcitation will be described for both astrocytes [2] and HEK 293 cells. We will show that local photoinduced heating is responsible for HEKL 293 membrane excitation.
1. S. Bellani et al. The Journal of Physical Chemistry C 118(12), 6291-6299(2014) DOI: 10.1021/jp4119309
2. V. Benfenati et al. Photostimulation of Whole-Cell Conductance in Primary Rat Neocortical Astrocytes Mediated by Organic Semiconducting Thin Films” Adv. Health Care Mater. DOI: 10.1002/adhm.201300179

Pulse oximetry, a facile technique for noninvasively measuring pulse rate and arterial blood oxygenation, is a ubiquitous medical sensing method. However, rigid sensors and expensive optoelectronic components restrict the true potential of pulse oximetry by limiting sensing locations to finger tips or ear lobes. If an oximeter probe is realized in a flexible and wearable form-factor, the recent thrust towards wearable medical sensing can be advanced by putting oxygenation sensors on different parts of the body. In this work, we report an all-organic green light pulse oximeter - capable of measuring heart rate and arterial oxygen saturation. Green (532 nm) and red (626 nm) organic light emitting diodes (OLEDs) were used with an organic photodiode (OPD) sensitive at the mentioned wavelengths. We chose green light excitation because of the well-developed solution-processable green emitters, as opposed to the early development stage near-infrared emitter materials. The organic probe was compared to a commercially available oximeter, and we acquired pulse rate and oxygenation that lied within 1% and 2% error respectively during simultaneous measurements. To the extent of our knowledge, this is the first optoelectronic sensor fabricated using all-organic materials that works in conjunction with conventional electronics at 1KHz, and provides accurate pulse rate and blood oxygenation.

Organic semiconductors are important optoelectronic materials that are now of growing interest for sensing applications. They offer the potential for compact, light and flexible sensors that are simple to fabricate. Here we will present recent progress using organic light-emitting diodes and photodiodes for biophotonic applications with two examples. In the first example we will discuss a haemodynamic sensor using organic LEDs and photodiodes to measure changes in tissue oxygenation. The results of tissue oxygenation during a forearm ischemia experiment will be presented. In this experiment a tourniquet was used to restrict blood flow, and the resulting changes in oxygenation of forearm muscles were measured. In the second example we have made a flexible organic optoelectronic muscle contraction sensor that can distinguish between isotonic and isometric types of muscle contraction. We will also show the feasibility of this sensor for prosthetic actuation by actuating a robotic arm using the signal detected from a volunteer&’s real arm. These results provide another interesting direction for organic optoelectronics, and the possibility of measuring a range of important biomedical processes.

Combined systems of semiconducting polymers and aqueous electrolytes are emerging as the new frontier of organic electronics, with many promising applications in biology, neuroscience and medicine. A detailed characterization of polymer/water interfaces is thus urgently needed. In particular, the combined effect of contact with electrolytes and visible illumination should be taken into account, since many applications rely on exposure to light, or are meant to work in ambient room light conditions.
In this work, we first extensively characterize the chemical-physical processes occurring in thin films of poly(3-hexylthiophene) exposed to water saline solutions and visible light. Through combination of different spectroscopic techniques, we demonstrate that prolonged contact with saline solutions does not add further degree to photo-activated doping processes of the polymer; instead, it turns out that the reduced number of oxygen molecules present in water, compared to open air, acts as a limiting factor, thus fully validating the use of semiconducting polymers in contact with electrolytes.
In addition, we demonstrate that the recently demonstrated technique of cell stimulation by polymer photo-excitation (CSP) represents a versatile platform for full-optical control of cell excitation/inhibition. We report examples of functional interfaces between several combinations of conjugated polymers and different cell cultures (HeK cells, astrocytes, neuronal networks). A detailed model of the mechanisms occurring at the polymer/electrolyte interface and leading to cell photoexcitation, based on electrical and optical measurements, will be finally presented and critically discussed.

Contact lens becomes an increasingly attractive option for biosensing and drug delivery applications to ocular diseases. Here, we fabricated a smart contact lens composed of biosensor, drug delivery system, and power sources for the treatment of diabetes as a model disease. The biosensing and drug delivery systems were integrated together on a remotely powered contact lens. For the diagnosis of diabetes, tear glucose content was measured as a non-invasive alternative for the blood glucose content monitoring. The biosensor exhibited exceptional sensitivity and selectivity detection of glucose in physiological conditions. Current from the biosensor was proportional to nano molar level of glucose concentration and worked repeatedly in aqueous humor solution without contact lens corrosion. For the drug delivery system, we fabricated Au membrane coated flexible drug reservoirs on contact lens. Thin gold membrane was dissolved immediately by applying voltage in body fluid, and exhibited the pulsatile drug release to tear circulation with the clinical feasibility. Finally, electrical energy was provided by using WiTricity systems on smart contact lens to power the sensors, drug delivery systems, and wireless communication circuitry. Mounted receiver LED on the contact lens showed that the proper power was immediately transferred to contact lens from the distance of 7~20cm. This novel smart contact lens can be developed further as the futuristic nano clinic systems.

In the human brain, 10¹⁵ neuronal synaptic connections process 100 times more operations per second than the IBM Blue Gene supercomputer using as little power as a smartphone. Regulation of the synaptic signal strength from past synaptic events achieves memory and learning. With the recent physical demonstration of memristive-based devices two terminal devices with memory and learning functions have advanced electronic and neuromorphic computing. In these systems, typically slow moving ions are coupled with fast moving electrons. Ionic motion affords memory, with electronic current as the output signal. I will discuss fully ionic synaptic devices based on PdH_x contacts and a Nafion channel in which protons provide both memory and the output signal. These devices exhibit reversible short-term depression, short-term potentiation, and memory. Preliminary results on substrate driven biotic-abiotic protonic logic will be discussed.

Ionic direct currents (DC) are employed for electrokinetic transport of biomolecules in a variety of life science technologies. The generation of these currents is problematic as the requisite electrode reactions often create pH changes, gas formation, or toxic products. Here, we address these issues by introducing a microfabricated ionic four-diode bridge rectifier, based on bipolar membranes, capable of converting ionic alternating currents (AC) to ionic DC at high efficiency (86 %). Combined with conducting polymer electrodes, this structure allows for oscillatory electrode operation in the polarizable regime, thus avoiding electrolysis. When integrated into a simple drug delivery device, 11.4 nmol of the neurotransmitter acetylcholine could be delivered using only 1.2 nmol of net electronic charge, illustrating the decoupling of the delivery capacity from the limited electrode redox capacity. Taken together, the ionic rectifier is useful in a range of iontronic and electrochemical devices to extend the lifetime of the electrodes.

Active and dynamic delivery of biomolecules with high spatiotemporal resolution is of great significance within many life science applications. Our team has recently demonstrated such dynamic delivery of charged molecules with the ionic bipolar junction transistor (IBJT)^1,2. These IBJTs are three-terminal “iontronic” devices with emitter, collector and base terminals analogous to the source, drain, and gate of FETs. They are based on biocompatible polycations and polyanions, are fabricated with standard microfabrication techniques and represent fully ionic circuit components, with ions playing the role of charge carriers rather than electrons. The polyanions and polycations are connected at a neutral junction where injection and depletion of ions controls the ionic collector current. An anionic base can be used to amplify a cationic collector current (pnp-IBJT) or a cationic base can control an anionic collector current (npn-IBJT). While our previous reports showed good transistor behavior, they were not optimized regarding characteristics such as speed and gain. In this presentation, we focus on just such optimization. By decreasing the channel length in the neutral junction, a faster switching time can be reached. To increase ON/OFF ratio by preventing backflow of ions, polycations and polyanions with higher selectivity will be introduced. These optimized devices can be used for life science applications where high amplification, addressing and fast switching are required, and can also be incorporated in chemical circuits such as addressable delivery matrices.
¹ Tybrandt, K., Larsson, K. C., Richter-Dahlfors, A., & Berggren, M. (2010). Ion bipolar junction transistors. PNAS, 107(22), 9929-9932.
² Tybrandt, K., Gabrielsson, E. O., & Berggren, M. (2011). Toward Complementary Ionic Circuits: The npn-Ion Bipolar Junction Transistor. Journal of the American Chemical Society, 133(26), 10141-10145.

We are investigating the design, synthesis, and characterization of conjugated polymers such as poly(ethylene dioxythiophene) (PEDOT) and poly(propylene dioxythiophene (PProDOT) for interfacing a variety of electronically-active biomedical devices with living tissue. We have developed a variety of novel EDOT and ProDOT monomers with carboxylic acid, amine, and alkene functional groups. These new materials make it possible for us to systematically tailor the surface chemistry and promote specific interactions with solid inorganic substrates as well as living cells both in vitro and in vivo. We are also examining the polymerization of PEDOT and PProDOT into a variety of media including cell-laden hydrogels, ordered non-ionic surfactants, and living tissue. In this talk we will discuss the most recent results from these ongoing efforts, including characterization results from optical and electron microscopy; UV, visible and infared spectroscopy, and biological assays. We will also examine the mechanical properties of the resulting films, including their adhesion on solid substrates.

Damage to the peripheral nervous system by disease or trauma can have debilitating effects ranging from loss of sensation to paralysis. When such injuries occur, it is critical that they are treated quickly to reinnervate disconnected tissue before serious degradation occurs. Nerve guides are engineered structures designed to provide a channel that accelerates recovery by supporting and directing regenerating nerves, providing an alternative to autografts in clinical settings. In this work, we highlight new materials, testing platforms and fabrication processes being developed for electroactive nerve guides. The organic conductors PEDOT and graphene have been employed to deliver biphasic electrical pulses to neural modelling PC12 cells. Laser-cut electrodes in varying geometries allow for the distinct application of direct and field stimulation to cells in two and three dimensions. Fluorescence microscopy after staining against DAPI and szlig;-III tubulin identifies cell nuclei and extending neurites respectively, with differentiation rates and cell behaviour quantified using image analysis. For 3D culture, hydrogels based on the processable polysaccharide gellan gum have been investigated, coupling of this polymer to a short peptide containing the integrin binding RGD-sequence has been observed to significantly affect the attachment and differentiation behaviours of encapsulated cells. Additive fabrication processes that combine conductive and cell supporting elements as a single nerve guide structure will be discussed.

Neural signals play an important part in central nervous system physiology while their role is also essential in the understanding of neurological disorders. However, the recording of these signals can be a challenging task mostly due to the difficulties in the coupling between conventional electronics and biological systems. Lately, conducting polymers have emerged as one of the most promising candidates for the next generation devices in neural activity recording both in vitro and in vivo. Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT: PSS) ,in particular, has the unique ability to conduct both electronic and ionic carriers, offering a high performing platform for communication between biological systems and electronics. Furthermore, it demonstrates ease of processability and property tunability in contrast with its inorganic counterparts. Here, we demonstrate the use of PEDOT:PSS devices for in vitro measurements. Using PEDOT:PSS coated electrodes we were able to record neural activity ,such as local field potentials (LFPs) and action potentials (APs), both from hippocampal brain slices and from primary hippocampal cells. We also investigated the possibility to achieve similar recordings with Organic Electrochemical Transistors (OECTs).These devices, due to local amplification compared with electrodes, promise superior signal to noise ratio during the measurements. Our results demonstrate that PEDOT: PSS dramatically improves the resolution of electrophysiology and pave the way for the use of active devices such as OECTs in neural recordings. Furthermore, the PEDOT:PSS devices presented here provide a vehicle for fundamental research in the life sciences, facilitates the study of neural activity and opens new horizons in the understanding of the physiology and the neuropathology of the central nervous system.

Organic electrochemical transistors that utilize conducting polymer films as the channel have shown considerable promise as amplifying transducers for electrophysiology. Efficient local transduction of biological signals is of critical importance for applications in detection and mapping of brain activity in order to better understand both physiological and pathological states. The physics of organic electrochemical transistors, however, remains largely unexplored which subsequently prohibits their optimization and limits their utility. Here we show that the uptake of ionic charge from an electrolyte into a poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) film leads to a dependence of the effective capacitance on the entire volume of the film. We find that both the transconductance and the response time scale with channel geometry, and present a model that describes this scaling. Electrochemical transistors, therefore, present a new degree of freedom in addressing the tradeoff between gain and bandwidth, which allows the engineering of devices optimized for high frequency recordings of individual action potentials, as well as for low-frequency, network-level rhythms typical of electroencephalography. These devices show an exceptionally high transconductance of 3-10 mS and lead to high fidelity human brain recordings.

Transmission of electrochemical signals induced by the ionic flow among neurons is the key part of the nervous system. Therefore, monitoring or even regulating these signals is of great interest in understanding nervous-system physiology as well as diagnosis and therapy of neurological disorders. Recently, there has been a significant improvement in this field boosted by the usage of conducting polymers at the interface with biology. Particularly, Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT: PSS) offers great advantages in maintaining communication between electronics and biological systems due to its high electrical connectivity and ion permeability along with its bio-inert properties. Individual studies in the field span both electrical sensing to stimulation of neural activity. By using PEDOT:PSS coated electrodes, measurements of neural activity can be made ranging from local field potentials to unitary activity of neurons. In addition, electrophoretic delivery of neurotransmitters through a polymer film in a controlled and precise manner has previously been obtained both in vivo and in vitro by using organic electronic ion pumps. However, monitoring neural activity during ion pump stimulation has not yet been performed, which could supply valuable information about absolute effects of the delivery. Here, by combining the existing methods we aim to operate the above mentioned approaches simultaneously by using the same PEDOT:PSS contacts for both stimulation and recording. The subsequent aim is to monitor the brain activity in rat brain hippocampal-slices continuously, so that the effects of ions, i.e., Ca²⁺ or K⁺ as well as neurotransmitters, i.e., glutamate, acetylcholine can be precisely analyzed in the region of interest at the moment of delivery.

Implantable medical devices have to exhibit viscoelastic properties and surface chemistry matching those of the tissue/organ. The objective is to minimize invasiveness and immune reaction of the living system while retaining the functionality of the device performance. One strategy towards this aim is to use biodegradable materials, whose degradation rate in living conditions is tailored to the duration of the device application and can fulfil the requirement for minimal invasiveness. Organic Electronics devices as bioelectronic transducers allowing recording as well as stimulation have been demonstrated (T. Cramer et al., PCCP, 2013). Unification of this platform with the one of biodegradable materials, by means of a technology is highly desirable. Towards this aim, we explore an innovative technique to fabricate Organic Transistors on biodegradable and biocompatible substrates. As device architecture we target the electrolyte gated organic field effect transistor (EGOFET) and organic electrochemical transistor (OECT) that can be operated at low voltages in physiological liquids with fast switching speed and sensitivity. As a biocompatible device scaffold we chose poly(lactic-co-glycolic acid) (PLGA), a biodegradable, transparent and flexible copolymer also approved by Food and Drug Administration (FDA) for implantation. Fabrication of micro-structured gold electrodes on PLGA is achieved by means of a multifunction IR-laser beam marker and channel lengths down to 10 mu;m are obtained (A. Campana et al., Appl. Phys. Lett., 2013). Masks and solvents are not used. Small molecules as well as polymeric semiconductors are compared as active layer in the EGOFET or OECT devices. Structural integrity and electrical performances of the devices are investigated. Their high potentiometric sensitivity allows for recording of bioelectronic activity. As examples for recording and stimulation experiments we present transcutaneous electrocardiogram, ECG, recordings (A. Campana et al., Adv. Mater., 2014) and in-vitro experiments of neural progenitor cells cultured on the active surface of the device. Finally, a multifunctional, bioresorbable device with integrated microfluidics, which is currently tested in in-vivo experiments as implant at the lesion site of spinal cord injuries of a mouse model, is discussed.
This work has been financially supported by the EU 7th framework programme[FP7/2007-2013] under grant agreement n° 280772, project "I-ONE”.

A visible trend over the past few years involves the application of organic electronic devices to the interface with biology, with applications both in sensing and in actuation. Examples include biosensors, artificial muscles, and neural interface devices. The latter are of particular interest, as organic devices offer several distinct advantages compared to incumbent technologies, including mechanical flexibility, enhanced biocompatibility, and capability for drug delivery. Most importantly, high ionic mobilities in organic semiconductors enable the efficient interfacing between biological systems and electronics, as well as new modes of information processing. As such, organics promise to yield new tools for neuroscience and enhance our understanding on how the brain works. After a brief introduction, I will present a few examples of electrodes and transistors for applications in recording and stimulating brain activity. In vivo performance, electrical characteristics and properties such as mechanical flexibility and biocompatibility will be discussed.

Conventional electronics communicate with electronic signals, whereas living systems typically communicate with biomolecules and ionic fluxes. We are interested in creating an interface making communication between electronics and cells possible. Particularly, we want to translate an electronic signal into something that is understandable for the cells. To do this, an electron-to-biomolecule transducer is needed. We have previously reported on a device, the Organic Electronic Ion Pump (OEIP), which is capable of this transduction. The device, which is based on conducting polymers and polyelectrolytes, takes an electronic signal in the form of a current, and converts it into a delivery rate of a charged biomolecule. This is possible because of the Donnan exclusion of coions in the crosslinked polyelectrolyte, which makes up the delivery channel of the device. Thanks to the exclusion of coions, when a current is passed through the device only counterions - which are the biomolecules to be delivered - migrate through the material.
The OEIP has previously been used to achieve controlled substance delivery in vitro and in anesthetized animals. Here, however, we report on the development of a fully implantable version of the device designed specifically to alleviate pain in an animal model of neuropathic pain. We implanted the devices onto the spinal cord of rats, and two days after implantation, local delivery of the inhibitory neurotransmitter gamma-aminobutyric acid resulted in a significant decrease in pain responses. This represents, to our knowledge, the first demonstration of a therapeutic application of organic bioelectronics in awake, freely moving animals, and our hope is that it will pave the way for future implantable bioelectronic therapeutics.

In nerve and muscle regeneration applications, the incorporation of conducting elements into biocompatible materials has gained interest over the last few years, as it has been shown that electrical stimulation of some regenerating cells has a positive effect on their development. A variety of different materials, ranging from graphene to conducting polymers, have been incorporated into hydrogels and increased conductivities have been reported. However the majority of conductivity measurements are still performed in a dry state, even though material blends are proposed for applications in a wet in vivo environment. The focus of this work is to use polypyrrole nanoparticles to increase the wet-state conductivity of alginate, to produce a conducting, easily processable and cell-supporting blend. We have performed characterization and purification on the conducting polymer nanoparticle dispersions as well as electrochemical measurements to assess conductivity of the nanoparticles and hydrogel composites in the wet state, in order to determine whether filling an ionically - conducting hydrogel with electrically - conductive nanoparticles will actually enhance the conductivity. It was shown that the introduction of spherical nanoparticles in alginate does not increase, but rather slightly reduces, conductivity of the hydrogel in the wet state.

Organic conducting polyme such as polypyrrole or polythiophenes ( especially PeDOT) have proven to be effective in providing multimodal communications with living cells. The ability of one platform to provide electrical, mechanical and/or chemical stimulation through localised release is unprecedented.
The realisation of practical devices based on these materials depends on our ability to develop fabrication tools and protocols that enables them to be integrated into functional structures wherein bioactive entities and other structural components are spatially distributed in a way that provides optimal performance.
Bioactive entities can be introduced at the molecular level through the use of biopolymers, drugs or proteins as dopants. Alternatively conducting polymers can be grown thrughout a preformed polymer gel.
Structural integrity can be provided by combining more mechanically robust biopolymers such as alginates or chitosan with preformed organic conducting polymers. This can be achieved using printing technologies , including 3D printing or by knitting/ braiding preformed micron dimensional fibers.

Previous studies have clinically verified the use of polycaprolactone (PCL)-based macroporous scaffolds in bone tissue engineering applications, demonstrating their usefulness in promoting bone healing. In alternative studies conductive coating layers, used to provide electrical stimulation, were similarly shown to positively affect osteoblast proliferation and their long-term functions. Here we report the use of vapor phase polymerization as a straightforward technique for coating PCL macroporous scaffolds produced via fused deposition modeling (FDM) with poly(3,4-ethylenedioxythiophene):tosylate (PEDOT:tosylate). The surface and mechanical properties of the resulting conductive scaffolds have been investigated as these features are pivotal for their use in osteoinduction studies. The development of these organic electronically-functionalized scaffolds presents the opportunity to study the combined effects of electrical and topographical features in bone tissue engineering applications.

The organic electronic ion pump (OEIP) has recently attracted attention in the bioelectronics arena for its precise spatiotemporal resolution for in vivo delivery of biologically relevant ions. Owing to the abilities of OEIPs to exhibit a high degree of biocompatibility, a great flexibility in chosen device design parameters, and demonstrated precise electronic control of the delivered ions, OEIPs are a particularly promising tool for studies involving the complex chemical pathways and regulatory networks in biological systems. However, the development of such OEIP technologies is still in its infancy, and OEIP adoption across a wide variety of potential applications and fields of study is sorely lacking.
Here, we present anionic and cationic selective OEIP adapted for the delivery of biologically relevant ions to plant systems in vivo. Using OEIPs in conjunction with the model plant system Arabidopsis thaliana, we demonstrate for the first time in vivo delivery of ions and plant hormones targeted at the single-cell level in the proximity of plant root tips. In this multidisciplinary and collaborative effort, we utilize plant seedlings that have been genetically modified with green florescent protein that are sensitive to the presence or absence of specific molecules. By observing these seedlings with a horizontally mounted confocal macro/microscope, we are able to follow in real-time, delivery and transport of positively and negatively charged ions from the OEIP device to the targeted organelles and tissues of the plant root. Coupling the analytical techniques of both confocal imaging and the electronic control of OEIP devices, we demonstrate the potential of OEIPs as a powerful new tool for the dynamic manipulation and study of complex signaling in plant systems. Further, the OEIP devices and experimental techniques demonstrated may be readily generalized to a wide variety of biological systems.

Organic electrochemical transistor (OECT) offers the advantages of direct ion-to-electron converting, facile surface modification and compatibility of fabrication onto flexible substrates, which make it an ideal device for cell/tissue electrophysiology characterization. Previously, our group and others have used OECTs for recording biological signals from epithelial cells^[1] and brain.^[2] In this work, we report, to our knowledge, the first study of using OECT array to monitor cardiac action potentials and its application in cardiologic drug screening.
Rigid OECT array was fabricated on glass substrate with biocompatible conducting polymer poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonic acid) (PEDOT:PSS) as the active material. Detailed characterization showed that our OECT devices had large transconductances with the highest values in the range of several millisiemens, which were favorable for the signal transduction. Two kinds of cardiac muscle cells (i.e. HL-1 cell line and primary rat cardiomyocytes) were used and directly cultured on the surface of OECT array. The action potentials governing the contraction of cells were readily sensed by OECTs beneath. Thanks to the high transconductances, our OECT devices recorded action potential induced signals with signal to noise ratio (S/N) routinely larger than 4 and signals with S/N values larger than 10 were also frequently observed. Application of this system for cardiologic drug screening was then demonstrated. The stimulated frequency increase of action potential by positive chronotropic agent isoproterenol was successfully recorded by OECT in a quantitative way.
Flexible OECT array was also studied in this work by fabricating OECTs onto polyethylene terephthalate (PET) substrate. Characterization results revealed that the performance of flexible OECT array showed negligible change under different strains. And recorded action potential signals had same qualities of that from rigid devices.
In summary, for the first time, OECT array was implemented for detecting cardiac action potential signals and cardiologic drug screening. The excellent signal quality and plastic-compatible flexible device form brought by OECT open up the opportunities for low cost, disposable in vitro monitoring chips.
Acknowledgement: The authors thank the financial support from the Theme-based Research Scheme of Research Grants Council of Hong Kong SAR Government (Project Number: T13-706/11-2).
References
[1] C. Yao, C. Xie, P. Lin, F. Yan, P. Huang, I. M. Hsing, Adv. Mater.2013, 25, 6575.
[2] D. Khodagholy, T. Doublet, P. Quilichini, M. Gurfinkel, P. Leleux, A. Ghestem, E. Ismailova, T. Herve, S. Sanaur, C. Bernard, G. G. Malliaras, Nat. Commun.2013, 4, 1575.

We present the integration of an organic electrochemical transistor (OECT) with an epithelial cell monolayer to create a cell based sensor for barrier tissue integrity. Epithelial cell monolayers serve as functional barriers in the body, tightly controlling the flux of ions. Ion transport between cells is regulated by protein structures known as Tight Junctions (TJs). The ability to measure the function of TJs provides information about barrier tissue and is indicative of certain disease states. Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has the ability to conduct both electronic and ionic carriers, offering a unique platform for communication between biological systems and electronics.
Kidney MDCK-I cells were grown directly on the PEDOT:PSS film of the OECT. The transparency of the PEDOT:PSS allows optical observation of the cells. The recording of the barrier resistance - measured by the OECT - was performed simultaneously by taking optical images of this barrier. Red fluorescent protein was used to label the MDCK-I Actin proteins present in the tight junction. The introduction of pathogenic agents, such as green labelled Salmonella Typhimurium, to a healthy cell monolayer results in degradation of TJ proteins and can be monitored both electrically and optically throughout the time-course of infection. This measurement platform allows to precisely correlate the electrical changes of the biosensor - which corresponds to the trans epithelial resistance of the cell layer - to the optically labelled TJ proteins.
The biosensor presented here provides a vehicle for fundamental research in the life sciences, facilitating the study of barrier tissue and factors affecting its integrity and allows for the development of realistic in vitro cell models.

The different growth stages of cells and the formation of tissues, in vitro, are dependent on the cues expressed along the surface of the plates or scaffolds used to grow biological systems. There is a need to actively control the expression of both the chemical and physical properties of these artificial substrates, by the means of electronic addressing, which provides desired addressing and control at high spatiotemporal resolution.
Here, circuit surfaces and scaffolds are reported that include electronically switchable materials that enables precise control over the expression of various key-chemical components and physical parameters in order to dictate the growth and sorting properties of cell systems. Various electronically switchable materials have been explored and different system architectures have been manufactured to gain control over the various growth stages of cells systems, such as adhesion, proliferation, differentiation, cell sorting and also release of final cell systems ready for harvest.

In cell biology, active control over the parameters related to cultivation such as adhesion, proliferation and detachment of cells is desired. Today, detachment typically involves enzymatic treatments that can damage surface proteins on the cells. In areas such as tissue engineering there is therefore a need for alternative, less harmful methods. We have previously reported methods for electronic control of cell detachment through the use of the self-doped conducting polymer PEDOT-S. In those devices, the substrate layer that the cells grow on can be electroactively detached, leading to controlled cell release.
We here explore an alternative method for cell release, in which we utilize control of the surface charge of the cell culture area. By this method, we hope to further minimize the influence of external materials in the detached cell cultures while still minimizing the stress on the cells by avoiding enzymatic treatment.
As an initial test, fibroblasts have been detached using this method. The cells could be collected and re-seeded for further culturing after detachment. When re-seeded they assumed a normal morphology.
In this presentation, we will discuss the fabrication of these surfaces, the in vitro results and what implications they might have for e.g. tissue regeneration.

Cell membrane electrical noise is an intrinsic property of living cell membranes, caused by ion channel movements generating electrical current on the order of a few femto- to pico-amperes. Measurement of this electrical noise can reveal valuable knowledge of underlying biochemical, physiological and pathological processes as recently explored. A number of sophisticated devices have been proposed in the literature; these include transistors and cantilevers.
In this work we followed a simple approach and we studied how basic electrode arrays using organic semiconducting polymers can be used to probe cell cultures using electrical noise as a probing technique. The aim is to build a very simple platform for drug screening.
We report on microelectrode arrays based on semiconducting polymers such as inkjet printed PEDOT:PSS and electrodeposited doped poly3-methlythiophene. The electrical sensitivity of these polymer based electrodes is compared with conventional metal microelectrodes arrays based in gold and in platinum. As test bed we used rat glioma-derived C6 cell line and Neuro 2A (Mouse neuroblastoma). Glia cells display a form of excitability that is based on variations of the Ca²⁺ concentration and N2A cells can produce a variety of signals upon stimulation by neurotransmitters. Bursts of quasi-periodic signals generated by the cells with a frequency below 1 Hz were measured and are discussed.
We also report that the electrical-double layer at the interface cell/substrate plays a crucial role on the ability to detect minor electrical changes related with cell activity. The shape of the signals recorded is dependent on the electrode design (width and spacing). The time constant associated with the interface electrode/cell culture medium controls the shape of the signals recorded.
Signal drifts caused by chemical changes in the cell-culture medium, long term stability and reliability of polymer based electrodes is also addressed.
This wok is part of an ongoing EU project, “Implantable Organic Nanoelectronics” (I-ONE-FP7) which is aimed to the use of organic electronics in implantable devices for the treatment of the spinal cord injury.

We developed a temperature sensor based on polymer and conductive filler for biomedical application. Flexible temperature sensor is one of the key devices to realize the flexible bio-medical application without heat damage to bio cell and tissue. There are many kinds of temperature sensors; thermocouples [1] and resistive temperature detectors (RTDs) [2]. These sensors show very small change, this mean that we have to need highly accurate and complex electronic circuits to measure the change of temperature. And also, protection circuits are also needed to integrate these devices. To avoid these complex circuits, we fabricated the flexible temperature sensor based on polymer and conductive filler. A temperature sensor shows 6 orders of magnitude change in resistivity near the temperature of a human skin. Moreover, we can control the sensitive temperature range by changing the polymer.
A polymer was synthesized by UV polymerization of mixing two kinds of acrylic acid. Then, we mixed 25wt% graphite and polymer for 24h. After fabricating this paste, we sandwiched this paste between two electrodes and pressed 1 hour. The thickness of temperature sensor film is only 25 mu;m and total thickness of temperature sensor is less than 200 mu;m. The temperature sensor shows large resistivity change around 30 degree Celsius. This temperature sensor also shows good repeatability more than 2000 times. In addition, we can control the sensitivity range by changing the mixing ratio of two kinds of monomer from 20 to 36 degree Celsius.
We also connect an organic transistor and a temperature sensor. When temperature of device is over 31 degree Celsius, the ON current is decreased from 2 mA to 10 nA. This result means that our temperature sensor is worked as thermal protection circuits by itself.
[1] M. Imran, et al., IEEE Sens. J., 6, 6 (2006).
[2] D. H. Kim, et al., Science. 333, 6044 (2011).

Effective medical devices are those that provide intended medical functions, are biocompatible, and are biostable. Most implants have some effects on the host biology that can be biological, chemical, or physical. The host responds to the implants by either eliminating them or remodeling themselves to minimize the impacts. These device-biological interactions feature the major differences between medical devices and commercial electronic devices. Effective management of the interactions is a key to success of medical technologies.
This talk will present a review of biological reactions to the implants including cardiac rhythms management, drug delivery, and sensing devices. The “lesson learned” in the past decades may provide a guidance for us to explore new implantable technologies such as implantable flexible electronics.

Electrophysiological recordings of neuronal activity are necessary for diagnostic purposes and brain-machine interfaces. Organic electronic devices constitute a promising candidate because of their mechanical flexibility and biocompatibility. In the last years, active devices like transistors have shown their advantage of providing increased SNR due to local amplification compared to simple electrodes. These devices combine ease of fabrication, compatibility with mechanically flexible substrates, facile miniaturization, stable operation in aqueous environments, and high transconductance, thereby constituting a low-cost and efficient means to transduce low amplitude signals of biological origin. The use of organic electrochemical transistors (OECT) has also shown the capability of recording in vivo specific low amplitude signals (Khodagholy 2013).
Clinical electrophysiology is fundamental for the monitoring of vital information like the cardiac activity. An other measurement, the one of the eyeball movement is used in drawsiness monitoring or even in marketing studies. In this work we show that OECTs are able to measure a wide range of typical clinical physiological signals on a healthy volunteer. We confirm that OECTs can monitor the cardiac cycle (electrocardiography, ECG), then use OECTs to track eye movement (electrooculography, EOG), and we measure a neurological rhythms (electroencephalography, EEG).
Then, we show how the geometry of the OECT changes the performance of the transistor itself, inducing large changes in the quality of the recorded biological activity.
Finally, we show the facile incorporation of the OECT on a flexible substrate, and the convenience of the measurement of clinical activity directly on the skin.

One of the main issues when dealing with the reproduction of the sense of touch is the capability of fabricating, possibly with similar fabrication processes, different kinds of sensing devices on the same system. In this work we introduce a novel approach for the fabrication, using a single device, of a bimodal sensing element that it is able to detect at the same time both mechanical stimuli and temperature variations. The approach is very simple, and can be employed for fabricating devices on highly flexible, and possibly compliant, substrates that can be easily transferred on unconventional, no necessarily planar substrates, for artificial skin applications.
The core of the sensing system is a low voltage charge modulated Field Effect Transistor in which a floating gate is fabricated on a flexible substrate and partially coated with a combination of two ultrathin insulating materials, namely Al₂O₃ and Parylene C, with a nominal thickness of 6 nm and 30 nm respectively. Thanks to the very high capacitance coupling such devices can be operated at very low voltages. On the top of the coated area source and drain electrodes are fabricated and the organic semiconductor is deposited in order to have the final OFETs structure. Moreover, a third electrode called control gate is also fabricated and used for setting the working point of the device. In all the reported cases TIPS-Pentacene was used as organic active layer allowing to achieve mobilities up to 0.4 cm²/Vs with remarkably small leakage currents (50/100 pA) and Ion/Ioff around 10⁴.
Finally, on the uncoated area of the floating gate (sensing area), a thin film of a piezo(pyro)-electric polymer, namely PVDF-TrFE, is deposited from liquid phase by spin coating and also by inkjet printing, and subsequently poled. In this way, the charges induced on the PVDF-TrFE film by and external mechanical and/or thermal stimulus will induce a charge separation in the floating gate of the sensing structure, thus leading to a variation of the output current of the OFETs.
We will demonstrate that such devices can be employed for detecting forces up to 2 N with a resolution of 0.05 N, and are able to detect dynamic stimuli at a frequency up to 100 Hz. Moreover, at the same time, they are also capable to detect temperature variations ranging from 10° up to 45 °C. We will also demonstrate that the sensitivity of this structure can be tuned by properly changing the layout of the sensing area of device.
Interestingly, since the responses of the device to the two different physical stimuli are characterized by marked differences in sensitivity and response time, it is possible to employ these devices for the fabrication of multimodal tactile sensing systems.

As neural interfaces improve, active prosthetics are becoming increasingly viable. One challenge for active prosthetics is to create biomimetic sensors that can collect data about the environment and transduce the data for interpretation by the nervous system. In order to achieve this type of bio-integrated sensing in an efficient manner, tactile sensors must be developed that produce signals that can be interpreted by the nervous system. Biological mechanoreceptors transduce a tactile signal by creating a series of voltage pulses, the frequency of which depends on the magnitude of the tactile stimulus. This frequency-based approach is advantageous for several reasons: (1) digital signal transmission facilitates low error rates, and (2) digital signals provide the possibility of lower power consumption than analog sensing and signal transduction methods. We describe a method for fabricating compact sensor systems that produce an oscillating signal that varies with tactile stimulation. Biological systems often display a linear relationship between the magnitude of the stimulus and the frequency output of the mechanoreceptor. Similar biomimetic sensor outputs can be achieved by tuning the sensor design. The sensor output can be interfaced with living neurons to stimulate the production of action potentials. This work is an important step toward simple artificial mechanoreceptors that can be directly interfaced with the nervous system.

We will report recent progress of ultraflexible and stretchable organic thin-film devices that are manufactured on ultrathin plastic film with the thickness of 1 mu;m and their applications to implantable and wearable electronics. Especially, I will report on sheet-type electrocardiogram measurement sheets as an example of implantable devices and sheet-type 64-channel surface electromyogram measurement sheets as an example of wearable devices. Remaining issues such as bio-compatibility and long-term stability will be also argued.