We are continuing to investigate the molecular design, electrochemical synthesis, and characterization of functionalized polythiophene copolymers based on poly(3,4-ethylene dioxythiophene) (PEDOT) and poly(3,4-propylene dioxythiophene) (PProDOT). Our most recent efforts have focused on the use of multifunctional monomers for introducing controlled amounts of crosslinking and branching and for promoting adhesion with solid inorganic substrates and specific interactions with soft living tissue. By introducing various amounts of these comonomers, we have created families of materials with tailored electronic and ionic charge transport and mechanical properties. We will specifically discuss the use of a tri-functional EDOT monomer 1,3,5-tri[2-(3,4-ethylenedioxythienyl)]-benzene (EPh), an amine-functionalized EDOT (EDOT-amine), and a multiply ProDOT-modified polyhedral oligomeric silsequioxane (POSS). The structure and properties of these functionalized copolymers were determined using UV/Vis, FTIR, and NMR spectroscopy; optical and electron microscopy; and cyclic voltammetry and electrochemical impedance spectroscopy (EIS).

Cardiac patches are a highly promising tissue engineering solution, to treat one of the most common cardiovascular diseases, myocardial infarction [1]. Conductive polymers are of particular interest as scaffolds for cardiac tissue engineering, primarily for their potential ability to transport the electrical pulses which are vital to the contractions of the heart. However, they need further manipulation in order to impart the properties necessary of a cardiac tissue scaffold [2], [3]. Herein the need for improved mechanical and topological properties, particularly the anisotropy of stiffness, is addressed by the auxetic micropatterning of a cardiac patch. Auxetic materials are those with a negative Poisson&’s ratio, they expand laterally when stretched longitudinally. The negative Poisson&’s ratio can also explain the other distinctive properties of auxetic materials, such as shear resistance, indentation resistance and anisotropy, which make it appealing as a possible feature of biomaterials [4]. A thin layer of a cell adhesive was successfully micropatterned with a re-entrant honeycomb design by excimer laser microablation. The high precision of this pattern is maintained upon coating and crosslinking with a conductive polymer layer. The micropatterned samples, both before and after coating have been characterised by optical microscopy, scanning electron microscopy and x-ray photoelectron spectroscopy. The ability to control the porosity, effective stiffness and anisotropy of the cardiac patch, by modifying pattern dimensions, has been confirmed by mechanical tests. In addition, measurements for the mode of fracture, stress, effective stiffness and anisotropy have been compared to finite element analysis models. In vitro cell studies have also been conducted to demonstrate the level of support, adhesion and alignment of cardiac cells on the patches. Hence it can be seen, that through the incorporation of an auxetic micropattern, a material&’s properties&’ can be directed to more closely match those of native cardiac tissue, which in turn could lead to improved scaffold design for cardiac tissue engineering.
References
[1] A. Silvestri, M. Boffito, S. Sartori, and G. Ciardelli, “Biomimetic materials and scaffolds for myocardial tissue regeneration.,” Macromol. Biosci., vol. 13, no. 8, pp. 984-1019, 2013.
[2] J. G. Hardy, J. Y. Lee, and C. E. Schmidt, “Biomimetic conducting polymer-based tissue scaffolds.,” Curr. Opin. Biotechnol., vol. 24, pp. 1-8, 2013.
[3] E. S. Place, N. D. Evans, and M. M. Stevens, “Complexity in biomaterials for tissue engineering.,” Nat. Mater., vol. 8, no. 6, pp. 457-70, 2009.
[4] K. E. Evans and A. Alderson, “Auxetic Materials: Functional Materials and Structures from Lateral Thinking!,” Adv. Mater., vol. 12, no. 9, pp. 617-628, 2000.

Conducting polymers are often employed as coatings on smooth metal electrodes to improve the electrode performance with respect to the signal-to-noise ratio (SNR) for neural recording, charge-injection capacity for neural stimulation, and inducement of neural growth for electrode-tissue integration. However, adhesion of conducting polymer coatings on metal electrodes is poor, making the coating less durable and the electrical property of the electrode less stable. Moreover, conventional conducting polymers have relative low conductance, preventing their direct use as the electrode and lead material; and they are brittle, making it difficult for flexible neural electrodes to incorporate conducting polymer coatings.
We have developed a new polypyrrole/polyol-borate composite film with concurrent excellent electrical and mechanical properties. We further developed a method to fabricate a stretchable multielectrode array, directly, using this new material as the sole conductor for both electrodes and leads, in contrast with the conventional approach of incorporating conducting polymers only through coating on non-stretchable metal electrodes. The resulting stretchable polymeric multielectrode array (SPMEA) was stretchable up to 22.84% uniaxial tensile strain with minimal losses in electrical conductivity. Electrochemical testing revealed the SPMEA&’s impressive advantage for recording local field neural potentials and for epimysial stimulation of denervated skeletal muscles.
As a neural interface engineer, I would also like to compare the compliant neural interfacing technology to other technologies, such as optogenetics, radiogenetics, and even a living neural interface that is currently under development in our lab.

Implantable electrodes are being used for diagnostic purposes, for brain-machine interfaces, and for delivering electrical stimulation to alleviate the symptoms of diseases such as Parkinson&’s. The field of organic electronics made available devices with a unique combination of attractive properties, including mixed ionic/electronic conduction, mechanical flexibility, enhanced biocompatibility, and capability for drug delivery. I will present examples of organic electrodes, transistors and other devices for recording and stimulation of brain activity and discuss how they can improve our understanding of brain physiology and pathology, and how they can be used to deliver new therapies.

Active and multifunctional prosthetics could provide amputees with improved quality of life by restoring the sense of touch that is so essential to many human experiences. In order to make active prosthetics a reality, fabricated sensors must be able to communicate information about stimuli to the nervous system of the wearer. Consequently, sensing systems must be developed that produce signals that can be interpreted by the nervous system. Mechanoreceptor cells in humans transduce a force signal into a frequency signal, and the frequency is reflective of the magnitude of the force. We have created an artificial mechanoreceptor system that mimics the frequency-based force sensing properties of human skin by integrating a resistive pressure sensor with a ring oscillator. The use of printed organic ring oscillators is important for future applications in large area, low cost sensor skins. The pressure sensor functions based on the contact-area dependent tunneling resistance between a counter electrode and a micropatterned composite of CNTs and insulating polymer. The pressure sensors were optimized to function in the appropriate impedance range to facilitate the frequency-dependent operation of the oscillators. The oscillators are operated at biologically-relevant frequencies in the range from 0 to ~200 Hz. By controlling the concentration of CNTs, the pressure sensing range can be widely tuned. This can be used to mimic the different sensitivities of mechanoreceptors located in different parts of the body. By using switch-like pressure sensors with a large pressure threshold, the devices can mimic pain receptors, which act as switch-like sensors that turn on at large pressure values. The frequency signal of the sensors was used to stimulate mouse neurons using an optoelectronic approach. There was a direct correspondence between the frequency of the sensor and the resulting frequency of action potentials in the neurons. These simple, neutrally-interfaced pressure sensors are a substantial step toward the development of cost effective active prosthetics.

Soft, flexible electrode arrays have been proposed for improving the chronic performance of bioelectronic devices. Conducting polymers (CP) are the technology of choice for producing soft electrode coatings [1, 2]. Despite CPs being softer than conventional metal electrodes, brittle and friable mechanical properties have limited their use. As such, researchers have studied copolymers of CPs with flexible materials such as hydrogels [3, 4]. Although approaches have been developed for fabricating such copolymer electrode coatings, the integration of CPs within hydrogels remains suboptimal [3]. Furthermore, most of these approaches require electropolymerisation of the CP from an underlying substrate, which limits them to being coatings rather than freestanding electrode arrays. This research explored the fabrication of freestanding conductive hydrogels (CHs) by seeding hydrogels with chains of pre-synthesised CP. The dispersed CP chains were hypothesised to provide nucleation sites, from which subsequent CP could be electropolymerised.
Chemically synthesised poly(3,4-ethylene dioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS) was dispersed within a 20 wt% poly(vinyl alcohol) (PVA) solution at 0.01, 0.05, 0.1 and 0.5 wt%. PEDOT:PSS is a dispersion of polymer chains, and cannot meet the fast charge transfer requirements of medical electrodes [5]. The hydrogels were crosslinked by photopolymerisation and then PEDOT was electropolymerised through the PVA-PEDOT:PSS at 0.5 mA/cm². The electrical properties and physical appearance of the gels were analysed at varied time points between 10 and 160 mins of electrodeposition.
Nucleation and growth of CP through the PEDOT:PSS loaded PVA was macroscopically observed (opaque blue particulate was seen) at the highest loading after only 10 min of electropolymerisation. No CP was observed in the lower loadings even at 160 min. The 0.5 wt% PEDOT:PSS loaded PVA, showed a significant increase in CSC from 3.8 mC/cm² at 0 min to 16 mC/cm² at 160 min. There was also a statistically significant decrease in the impedance at 1Hz with the average impedance magnitude decreasing from 1990 Omega; to 715 Omega;.
These studies demonstrate that nucleation and CP growth within an insulative material can be achieved through secondary nucleation, being the use of a CP chain from which subsequent CP can grow. Loading the PVA with 0.5 wt% PEDOT:PSS enabled the fabrication of a free-standing, electroactive material, but this was time consuming and the electroactivity achieved was still relatively low compared to other CP materials. Future work will explore loading the hydrogel with a higher percentage of PEDOT:PSS.
References
[1] R.A. Green, et al, Biomaterials, 29 (2008) 3393-3399.
[2] G.G. Wallace, G.M. Spinks, Soft Matter, 3 (2007) 665-671.
[3] S. Sekine, Y. et al, Journal of the American Chemical Society, 132 (2010) 13174-13175.
[4] R.A. Green, et al, Macromol Biosci, 12 (2012).
[5] L. Basiricograve;, et al, Organic Electronics, 13 (2012) 244-248.

The recent developement of high performance organic and carbon-based materials demonstrated charge carrier mobility and conductivity over 10 cm²V^-1s^-1 and 10³-10⁴ Scm^-1, respectively, which outperform industrial standard materials such as amorphous silicon and indium-tin-oxide. Although these outstanding electrical properties from the soft matters envision them as promising building blocks for next generation flexible electronics, reliable and scalable fine-patterning technology should be also accompanied toward realization of high-density and multi-functional soft electronics. Typically, a proper isolation/patterning of the functional materials is required to suppress parasitic and off current, leading to less cross-talk between neighboring devices and minimum power consumption in the high density integrated systems. For patterning the soft materials, fluorinated photoresist using an orthogonal solvent, pre-patterned self-assembled monolayers, and various direct printing techniques have been reported, however, several drawbacks such as the process complexity, limited choice of materials, low throughput, and resolution limit have been problematic for industrial realization. Here, we report a facile and general route to achieve scalable high-resolution (sub-micron) patterning of organic and carbon-based materials for device and material integrations via a photochemically induced molecular disordering. Upon deep ultraviolet (DUV) irradiation, the soft matters underwent dissociation of specific chemical bonds within molecules as well as loss of inter-molecular ordering, transforming them into non-functional state. Spatially-selective DUV irradiation enables large arrays of patterned functional devices on a substrate. Utilizing this patterning approach, various organic and carbon-based thin-film-transistors were fabricated demonstrating well-defined active material isolation (current on/off ratio: >10⁷) and minimized parasitic current (~pA), and low-power consumption integrated circuits on both rigid and flexible substrates without compromising their individual device performance.

Ionic transistors from organic and biological materials represent an emerging class of soft and flexible devices for bioelectronics applications. Within this context, protonic transistors are exciting targets for further research and development, despite the fact that they have received relatively little attention to date. Such devices represent a natural choice for interfacing rugged traditional electronics and biological systems due to the ubiquity of proton transport and transfer phenomena in biology. Recently, we have fabricated and characterized protonic transistors from the cephalopod structural protein reflectin.¹ We have investigated these devices with standard electrical and electrochemical techniques, discovering that they exhibit performance comparable to the best protonic transistors.¹ We have also developed simple strategies for improving the performance of our protein-based transistors by altering their active layer geometry and integrating them with flexible substrates. Overall, our findings may hold significance for a broad range of conformable biomedical and bioelectrochemical devices.
1. Ordinario, D. D.; Phan, L.; Walkup IV, W. G.; Jocson, J.-M.; Karshalev, E.; Hüsken, N.; Gorodetsky, A. A. Bulk protonic conduction in a cephalopod structural protein. Nat. Chem. 2014,6, 596-602.

Nanoparticles showed distinguishable physical properties from those of macroscopic substances since their properties are highly influenced by the surface moiety. Electrical conductivity and capacitance are the physical properties that are influenced by the surface moiety of the nanoparticles. However, only a little qualitative study has reported on this issue and quantitative analysis has not been fully explored particularly for the non-conductive nanoparticles. We present the measurement of capacitances of the non-conductive protein-immobilized nanoparticles using AC impedance spectroscopy combined with conductive scanning probe microscopy (Impedance-SPM). The impedance spectroscopy is a sensitive characterization method to monitor a subtile change of the non-conductive surface moiety and SPM offers a way to confine the region of interest in nanometer scale. A model core-shell nanoparticle with bovine serum albumin (BSA) protein shell layer on the silica nanoparticle core was prepared via layer-by-layer (LBL) method to monitor the electrical property changes. The obtained impedance spectra were analyzed using an electrical circuit model to obtain the capacitance of the surface BSA layer. The capacitance of the core-shell nanoparticle increased with increasing BSA shell thickness; approximately 5.42 pF increase was observed per single BSA layer increase. The electrical resistance was also increased with BSA thickness indicating the non-conductive property of biomolecule. This result suggests that the quantitative analysis on the electrical property of a non-conductive nanoscale material is possible using this impedance-SPM technique which is applicable for various non-conductive substance including biomolecules.

Improvement of electrode interfaces for the development of bioelectronic devices such as microelectrode arrays (MEAS) has gained attention, especially in terms of coupling with electrogenic cells [1]. Conducting polymers are highly attractive for MEAS because, they offer low impedance in physiological environment and they are biocompatible [2].
This work reports about the use of inkjet printed poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonic acid) (PEDOT:PSS) to record extra-cellular signals from a cell population in vitro. Signals using gold electrodes were also measured and compared with the ones recorded using PEDOT:PSS electrodes. The signals measured using PEDOT:PSS are 100 times higher than the ones measured using gold electrodes. This is the result of a better electrical interface between the cells and the polymer electrode. The very high signal/noise of approximately 40 allows the observation of clear bioelectrical signals with well-defined shapes.
To gain insight into this enhanced electrical coupling, the cell/electrode interface was characterized using small-signal impedance measurements and modeled using equivalent circuits. When compared with gold electrode the PEDOT:PSS interface has a double-layer resistance several orders of magnitude lower and a significant higher capacitance.
The time dependence of the impedance also reveals that the interface cell/electrode is highly dynamic, and both the interfacial capacitance and resistance change with time due to the deposition of substances from the cell-culture medium and to the release of bio-products from the cells which eventually adhere to the polymer surface and change the double-layer electrical properties.
For these experiments C6 glioma cells were used. These cells are capable of firing spikes spontaneously or after electrical perturbation.
This work received financial support from European Community Seventh Framework Programme (FP7/2007-2013) trough the project iONE-FP7 grant agreement n° 280772.
[1] M.E. Spira and A. Hai, Nature Nanotechnol. 8, 83-94 (2013).
[2] M. Sessolo, D. Khodagholy, J. Rivnay, F. Maddalena, M. Gleyzes, E. Steidl, B. Buisson, and G. G. Malliaras, Adv. Mater. 25, 2135-2139 (2013).

Recent developments in nanotechnology have brought us new advances in materials and device-fabrications by emerging technologies from physicists, chemists, engineers, biologist, and materials science. There are many challenges for chemists to play an important role in this area since nanotechnology is a part of the chemical domain, which builds up materials at the molecular level. We demonstrate a bio-sensing material, “Molecularly Imprinted Polymer,” which is widely investigated for sensor applications. MIP&’s system is prepared by “molecular imprinting technique,” which produces synthetic “receptor sites” or “binding sites” with specific molecular recognition. In this study, MIP&’s particles are prepared by microfluidic synthesis. The microfluidic synthesis has gotten a great attention; because, it offers us a number of advantages over existing technology. Chemical reactions run in microfluidic reactors have high thermal and mass transfer rates with an opportunity to use more aggressive reaction conditions allowing for increasing product yields. Additionally, high chemical homogeneity, especially for a nanoparticle synthesis can be also achieved by mixing multiple components at the micro-scales in the microfluidic reactors. MIP&’s system can be also fabricated on a variety of substrates to develop bio-sensors or detection devices. MIP&’s system has “high affinities binding sites” to detect specific target bio-molecules and thus suitable to develop advanced bio-sensors. Synthesis of “high affinity receptor sites” is a key contribute to achieve high performance biological sensors based on MIP&’s system.

Living cell membranes produce electrical noise, caused by ion channel movements generating electrical current on the order of femto-amperes. Measurement of this electrical noise can reveal valuable knowledge of underlying biochemical, physiological and pathological processes.
In this work we describe how basic electrode array can be used to probe cell cultures in vitro using electrical noise as a probing technique. The aim is to build a very simple platform for drug screening. To optimize the electrodes for low noise and low coupling impedance, we electrodeposited conducting polymers on top of gold electrodes. The parameters controlling the sensitivity of the electrodes are discussed. These parameters are related with the establishment of a double-layer at the electrode surface. We discuss how the impedance of this double-layer can be tuned to optimize the electrode sensitivity and measure extremely small fluctuations in current.
As test bed we used rat glioma-derived C6 cell line and Neuro 2A (Mouse neuroblastoma). Populations of cells were seed on top of electrodes were stimulated using a variety of neurotransmitters and the corresponding changes on the low-frequency (f<10 Hz) electrical noise recorded.
Artifacts caused by bad electrode design are also discussed.
This work received financial support from European Community Seventh Framework Programme (FP7/2007-2013) trough the project iONE-FP7 grant agreement n° 280772.

Due to its small fibril dimension, nano-cellulose materials possess unique optical and structural properties.^1-4 This has heightened the interest in nano-cellulose due to its potential in various optical, electrical and mechanical applications, to mention a few. The natural abundance of such environment friendly material makes it even more attractive.
Generally, nano-cellulose fibrils are prepared from natural cellulose fibers through chemical and mechanical treatments in aqueous solution. Their dry film is usually obtained by vacuum filtration followed by solvent evaporation. Because of the slow filtration and evaporation rate of water, the entire film preparation takes relatively a long time,which limits the use of such approach in an industrial setting.
This work will present a fast and economic blade coating approach that is potentially useful for industrial mass production of nano-cellulose film. In such approach, nano-cellulose films and their nano-composites of different optical properties were prepared in ca. one hour time, including the preparation period of the materials water suspension (gel). In particular, a film of only 800 nm thick was successfully made, which, to the best of our knowledge, is the thinnest nano-cellulose transparent paper ever reported to date.
References:
[1] Z. Fang, H. Zhu, Y. Y uan, D. Ha, S. Zhu, C. Preston, Q. Chen, Y. Li, X. Han, S. Lee, G. Chen, T. Li, J. Munday, J. Huang, L. Hu, Nano Letters 2013, 14, 765.
[2] H. Zhu, Z. Xiao, D. Liu, Y. Li, N. J. Weadock, Z. Fang, J. Huang, L. Hu, Energy & Environmental Science 2013, 6, 2105.
[3] J. Huang, H. Zhu, Y. Chen, C. Preston, K. Rohrbach, J. Cumings, L. Hu, ACS Nano 2013, 7 , 2106.
[4] D. Klemm, F. Kramer, S. Moritz, T. Lindström, M. Ankerfors, D. Gray, A. Dorris, Angew. Chem. Int. Ed. 2011, 50, 5438.

Surface wrinkling, a rapid self-assembly method for surface patterning, is very attractive in the design of biomimetic scaffolds for cell culturing and guidance, since wrinkled surfaces are suitable for mimicking the topographical cues of the extracellular matrix (ECM), with aligned features ranging from nano- to micrometers. Recently wrinkled polymer surfaces (heat-shrinkable polyethylene and polystyrene) proved to be effective in promoting the alignment of cardiomyocytes and human embryonic stem cells (hESCs).[1-3] On the other hand, organic semiconductors and, in particular, conducting polymers (CPs), are increasingly used as soft, biocompatible, functional interfaces with cells in the emergent area of organic bioelectronics for the development of smart biointerfaces and bioelectronic devices.[4-5] By combining surface wrinkling with the functional properties of CPs, we recently reported the alignment and electrical patterning of C2C12 mouse myoblasts and normal human dermal fibroblasts (nHDF).[6]
Here we report the results of culturing neuron-like cells (human SH-SY5Y neuroblastoma) on biomimetic PEDOT:PSS wrinkled surfaces fabricated by thermally-induced shrinking of commercial polystyrene sheets. Tuning of surface topography -with uniaxial wrinkles periodicity in the range 0.2 - 3 mu;m and multiscale wrinkles amplitude (from tens of nanometers up to 1.5 - 2 mu;m)- is demonstrated by varying the thickness of the surface thin film made of PEDOT:PSS or bilayer Au/PEDOT:PSS. A comprehensive characterization by means of SEM, AFM and profilometry is reported, combined with electrical resistivity measurements. Investigation of proliferation of SH-SY5Y onto fabricated substrates is carried out to assess the optimal topography for cell culturing. The effect of wrinkled substrates on the process of neuritogenesis is investigated up to 6 days of retinoic acid - induced differentiation, by measuring neurite length and orientation in comparison with flat PEDOT:PSS. The effectiveness of wrinkled surfaces in enhancing and orientating the outgrowth of neurites is demonstrated with 40% increase in length and 85% of neurites aligned along wrinkles direction (angle 0 < theta; < 15°) after 6 days. Thanks to the conductive properties of the substrates, the combined effect of electrical stimulation and topography is studied and discussed.
References
1. A. Chen et al., Advanced Materials23, 5785 (2011).
2. J. I. Luna et al., Tissue Engineering C17, 579 (2011).
3. A. Chen et al., Biomaterials35, 675 (2014).
4. G. G. Malliaras, Biochimica et Biophysica Acta (BBA) - General Subjects1830, 4286 (2013).
5. M. Berggren, A. Richter-Dahlfors, Advanced Materials19, 3201 (2007).
6. F. Greco et al., ACS Applied Materials & Interfaces5, 573 (2013).

The development of reliable in vitro models for toxicological testing and pharmacological investigation of chemical substances is urgently required to move away from animal testing and animal models. The need of innovative tools for testing of the real-time effect of drugs and toxins on living in vitro tissues models is driven both by societal distaste and also the large cost of using animals.
The predictive ability of in vitro based models is limited by poor reproducibility of the microenvironments and the physiological behavior of tissue in organs. Limitations in technology are a major factor in the failure of the cell-based models. In this regard ‘organ-on-a-chip&’ technology represents the transition from stand-alone 3D tissue models to more integrated micro-fluidic devices, in which a network of micro-channels is used to transport nutrients and other soluble substances to 3D cell culture, e.g. cell cues and drugs.
We take advantage of recent advances in materials research and tissue engineering to yield a highly performant 3D model of the kidney tubule integrated with microfluidics and in-line monitoring with on-board electronics. The system has been designed in a 12-well plate format, with simultaneous acquisition to allow medium-throughput screening. We demonstrate multi-parameter monitoring of relevant parameters to predict renal tubule toxicology, including TEER, and glucose levels, under fluidic conditions. Our system is compatible with high-resolution imaging and has been demonstrated for in situ immunofluorescence staining. In addition, analysis of secreted biomarkers is possible by periodic sampling of efflux from the microfluidic chambers. We have monitored both canine and human kidney proximal tubule epithelial cells, in the presence or absence of endothelial cells to more closely mimic in vivo conditions.

Ferroelectric materials can maintain an electric polarization state in the absence of an externally applied electric field. The polarization state and the resulting surface charge density originate from a bistable, switchable dipole moment, maintained across the ferroelectric domains of the material. The net surface charge density can be induced to be either positive or negative depending on the direction of the applied polarizing electric field. Here, we demonstrate that ions can provide surface charge compensation for ferroelectric dipoles, resulting in the formation of an electric double-layer (EDL) at the ferroelectric/electrolyte interface. This ferroelectric-induced EDL is successfully exploited to introduce hysteretic functionalities in new organic electronic devices. The ability to electrically switch the reactivity of a surface could form the basis for new classes of thin-film biochemical actuators.

Protonic activity is an essential driving force for processes in cellular biology, including the production of ATP. Palladium (Pd) can uniquely interact with protons (H⁺) in solution due to its ability to selectively react with H⁺ to form palladium hydride (PdH_x) according to Pd + xH⁺ + xe^- harr; PdH_x. As such PdH is a versatile bioprotonic transducer for bioelectronics applications. Here, we enhance the rate of the electrochemical reaction of Pd with H⁺ by adding a Nafion film. The Nafion film acts to increase the local concentration of H⁺ at the Pd surface, reducing the required potential to produce PdH_x. In addition, we demonstrate the exchange of cations, such as H⁺ and Na⁺, between Nafion and solution to change the concentration of H⁺, or pH of solution. This cationic exchange with solution, coupled with the selective injection or removal of H⁺ using PdH_x electrode, could be used to modulate the pH of solution using only the applied potential.

Palladium Hydride (PdH_x) is a versatile proton-electron transducer that translates protonic currents into electronic currents. Recent protonic devices with PdHx contacts include complementary field effect transistors, memories, and pH sensors. Here, I describe a PdH_x shift register (1D) and a Charge Coupled Device - CCD (2D) that enable new applications of bioprotonic devices. These devices function by storing and passing protons between adjacent bits, in a mechanism similar to electron transfer in a CCD. This architecture allows the measurement or control of many biological systems with minimal circuitry. Applications include highly parallel, two-dimensional imaging of biological protonic events occurring at the micro-scale. In the future, individually functionalizing each bit would allow for highly parallel testing of multiple protonic systems. This research can be generalized to the fabrication of a broad class of protonic bioelectronics devices.

Optochemical sensors are an alternative for conventional chemical sensors. Their importance has grown due to advantages as size, cost, response time, unnecessary reference electrodes and the absence of electrical and electromagnetic interference. The optochemical structure is composed by the target analyte, the transduction platform, and the electronics to process the information. All the three basic components have a recently grown interest. The electrochromic conducting polymer polyaniline (PANI) can optically measure variations in the pH value of a specific solution. Its electrochromic property states that each oxidation state of PANI exhibit a different color. The protonation and deprotonation reaction that occurs in the imine nitrogen atoms changes PANI from the blue non-conductive emeraldine base to the green conductive emeraldine salt. The degree of PANI protonation has a specific optical response. By techniques of bias-enhanced setup the response of the sensor changed according to the polyaniline protonation state. Electrodeposited PANI thin films had varied thickness according to deposition time. Thickness is important because the optical response is proportional to this parameter. Quick and easy spectra measurement process is obtained using a handset spectrophotometer in the visible region (from 400 to 700 nm), which provides the reflective response and the CIE Lab color scale parameters (L* lightness, a* position between red and green, and b* position between yellow and blue). A bias-enhanced response is obtained by applying an electrical potential, relative to an Ag/AgCl electrode, to the PANI thin films in acid medium. The resulting integrated reflectance of the green band (from 475 to 570 nm) presented a linear response (about 25/pH) for the PANI film deposited during 120 minutes in the pH range from 2 to 8. The linear range for the others films are proportional to their amount of deposited polymer. The protonation reaction saturates the film keeping the optical response equal. Films deposited for 15 and 30 minutes are linear from pH 6 to 8, film deposited for 60 minutes is linear from pH 5 and the film deposited for 90 minutes is linear from pH 4. The intensity of the reflectance of the sensor increases about 2.4 times with the applied 1000 mV bias voltage, compared to 0 V bias. The sensitivity of the sensor increases with the applied bias voltage, reaching 32/pH for 700 mV, while the linearity decreases, down to 77 % for 1000 mV. The combination of these factors lead us to the determination of an optimized working point. CIE Lab color scale results also indicate changes from the blue to the green oxidation state due to polymer protonation. The parameter a* changes for more negatives values (greenish films) while the parameter b* changes for more positives values (yellowish films). More results and future applications of the sensor will be discussed. This work was supported by CAPES, CNPq and FAPESP Brazilian agencies.

Producing and upgrading pH sensors is an important field at scientific area due to the dependency of many chemical and biological processes on this parameter. Alterations of pH sensors using the proper surface functionalization can lead to the development of specific ionic sensors. Field effect sensors can be used to that aim, and the extended gate field effect transistor configuration (EGFET) is very useful for the development of either reusable or disposable non-expensive sensors. Two different configurations can be used: S-EGFET (S-single, using a single MOSFET) and IA-EGFET (IA-instrumental amplified). The first needs an intrinsic applied step voltage to overcome the threshold of the transistor, and the last not. Conductive oxides were more intensively used as the main sensing thin film, but the research using conducting polymers and organic materials has evolved also very quickly. Polyaniline (PANI) is a strong candidate for that technological application. Here polyaniline (PANI) was used as a sensing film of an EGFET pH sensor, using both configurations described above. The interference of an applied electric step potential from the reference electrode in an acid buffer solution on the properties and structure of PANI films were analyzed. Polyaniline has several oxidation states according to the amount of protons existing in its structure. Emeraldine base polyaniline changes to emeraldine salt (protonated polyaniline, due to an increase in its number of protons) when submitted to a convenient voltage, on acid solution (electrochemical doping). PANI conducting films were fabricated using the cyclic potential sweep method in the electrodeposition system. Potential range of 1V (from -0.2 up to 0.8V), total time of 15 minutes, and frequency of 25mHz were used. The samples had a total area of 1 x 1 mm² and thickness below 100nm. Electrodeposited PANI films were used in EGFET sensors varying the buffer solution pH from 2 to 8. Starting sensitivities of the order of 80mV/pH were found for the condition of no-extra applied potential. The effect of distinct reference potentials over the sensitivity (the response in voltage due to the pH of the solution) of the film was studied. The reference electrode electric potential was also varied in a range from 3.5V to 6V. Electrodes separation was about 3 cm in a total solution volume of 50mL. Results show that the intensity of the reference potential does have influence in sensitivity (the sensitivity values decreased 36% up to 46%, respectively, for 3.5V and 6V reference potential values). The more intense the potential, the lower the sensitivity. The reversibility of the protonation process was studied by applying a reverse potential on an alkali buffer. Results show an almost complete reversibility: sensitivity can recover about 97% of its starting value. The implications of these facts for the possible technological applications will be discussed. This work was supported by CNPq and FAPESP agencies.

Stretchable electronics have many potential applications in advanced robotics, health monitoring technologies, and mechanically durable and adaptable consumer electronics. As the basic unit of electronic devices, it is important to develop stretchable transistors to enable these applications. Previous work in this area has largely focused on patterning conventional electronic materials into stretchable geometries. A second approach is to develop transistors based entirely on stretchable materials. However, this approach requires the implementation and development of a new set of materials and processes. Organic semiconductors are compatible with mechanical deformation based on their partly amorphous structure. We investigate the effect of semiconductor properties, such as branched vs unbranched side chains on the strain-dependent electrical properties of stretchable transistors. The mobility of devices with polydimethylsiloxane (PDMS) dielectrics is ~0.16 cm²/Vs, and the devices exhibit negligible hysteresis. The nature of the semiconductor deformation mechanism has important considerations for the behavior of the devices with repeated strain cycles.
In many of the applications mentioned above, mechanical robustness is an important parameter to consider. For example, in sensor skins for robotics, transistors must not only sustain strains, but also large normal and shear forces. Robustness can be optimized by selecting elastomers that have a large tear strength, such as thermoplastic polyurethanes. CNTs are known for their excellent mechanical properties, and the incorporation of CNTs as the semiconductor in stretchable transistors leads to devices that are highly robust to the application of forces and impacts.

We have fabricated fully printed organic thin-film transistors (TFT) devices and inverter circuits by employing solution-processable organic semiconductors and silver nanoparticle inks on ultra-thin polymer film substrates. The TFT devices exhibited excellent electrical performance, with a field-effect mobilities of 1.0 cm²/Vs at operating voltages of 10 V. Moreover, the organic TFT devices exhibited remarkable mechanical stability, whereby the mobility and on/off current levels were virtually unchanged even under a 50% compressive strain. A p-type diode-load inverter exhibited good transfer characteristics. The inverter operated successfully at low supply voltages and the measured rise/fall times were relatively short, which were also maintained under the same compressive strain. These results help demonstrate the potential opportunities for flexible organic devices in unobtrusive or disposable electronic applications printed over large areas.
A glass coated with an amorphous fluoropolymer was used as a support substrate, upon which a 1-µm-thick parylene-C layer was deposited and a polymer solution was subsequently spin-coated to form a planarization layer. Then, silver nanoparticle ink (JAGLT-01, DIC) lines were formed using inkjet printing equipment (Fujifilm Dimatix, DMP2830) and dried at 30 0C and 95% RH in order to flatten the profiles of the silver lines [1], after which the substrate was sintered at 120 0C to form low-resistance gate electrodes. Next, an insulating material (lisicon^® D207, Merck) was spin-coated to form a 360 nm-thick gate dielectric layer. Silver nanoparticle ink (NPS-JL, Harima Chem.) was then inkjet printed and sintered at 120 0C to form the source-drain electrodes, which were modified using a self-assembled monolayer (lisicon^® M001, Merck). 200-nm-thick fluoropolymer bank layers were printed using dispenser equipment (Image Master 350PC, Musashi Engineering) and Lastly a p-type organic semiconducting ink (Merck, lisicon^® S1200) was printed using the same dispenser equipment and annealed at 100 0C for 1 min. [2].
The estimated field-effect mobility in the saturation region was 1.0 cm²/Vs, the threshold voltage was -0.53 V, and the on/off current ratio was greater than 10⁶ at an operating voltage of -10 V.. We applied a 50% compressive strain to the substrate while observing the transistor characteristics. After applying the strain, the mobility decreased by only 1% and the on/off current ratio remained higher than 10⁶. We also fabricated diode-load inverters, which worked well at operating voltages as low as 2 V. The total delay time for the unstrained inverter circuit was 1.1 ms at an operating voltage of 10 V, and 1.2 ms under the same compressive strain. These operating speeds are considered quite fast among fully-printed organic devices.
[1] K. Fukuda et al., ACS Appl. Mater. Interfaces, 5, 3916 (2013).
[2] K. Fukuda et al., Nature Communications, 5, 4147 (2014).

Organic transistors fabricated on plastic substrates are flexible, printable, and lightweight. These unique features inspire their use for wearables in consumer electronics, healthcare and biomedical diagnostic tools. Applications of electronics on, or even in the human body require devices to be safe and consume low energy, which requires an aggressive scaling of the operating voltage ideally down to sub-1V levels. Here we demonstrate organic transistor with a high-k titanium oxide gate dielectric with a mobility of 1.45 cm²/Vs when operated at 1V. We show organic pseudo-CMOS inverter able to invert an input 0.3V driving-voltage and the inverter with 0.5V driving-voltage able to operate at a 10Hz square wave input. The total delay time of the inverter under such conditions is 24 ms. We employ an all room-temperature fabrication to meet the requirements of conventional, flexible polymer film substrates like PEN. Key enabling component of our ultralow voltage TFTs is a 20 nm thick amorphous high-k titanium dioxide dielectric formed by potentiostatic anodization. The amorphous oxide is passivated with an n-octadecylphosphonic acid SAM [3], resulting in a hybrid gate dielectric with a high capacitance of 612 nF/cm². We use 30 nm-thick dinaphtho[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT)[4] as air stable p-type organic semiconductor layer, source and drain electrodes with a channel length of 50 µm are realized by depositing 70 nm-thick gold. The here-developed methods allow low voltage operational organic transistor circuits to be fabricated in a highly reliable manner on virtually any substrate, applicable for flexible, wearable and implantable electronics in health care, medical diagnostics and patient monitoring as well as consumer appliances.
[1] Xie, W. & Frisbie, C. D. J. Phys. Chem. C115, 14360-14368 (2011).
[2] L. A. Majewski et al. Adv. Mater.17, 192 (2005).
[3] H. Klauk & et al. Nature445, 745 (2007).
[4] T. Yamamoto & K. Takimiya J. Am. Chem. Soc.129, 2224 (2007).

Organic field effect transistors (OFETs) have gained significant interest due to their proprieties, many of which are not available in silicon technologies, including mechanical flexibility, low-temperature processing, roll-to-roll processability, large area coverage, biocompatibility, light weight, and low cost. In spite of the significant progress in organic electronics, OFETs still face challenges. N-type semiconductors have inferior performance when compared with their p- counterparts, both in terms of mobility (> 10× lower in n- devices) and threshold voltages. The lack of a good n-type semiconductor among organic materials, complicates the integration of complementary metal-oxide semiconductor (CMOS) for logic applications. While in silicon technology p-type devices are moderately weaker (sim; 2×) and upsized to balance the rise and fall delay, in organic electronics the strong strength imbalance forces designers to upsize the n-type by 10× (or more) to keep the resistivity comparable in the pull-down and pull-up networks. Different ways to approach this problem exist. One solution involves the use of resistor-load gates or a zero-Vgs saturated load. These techniques use only p-type OFETs to implement digital gates, eliminating the problems related to the use of n-type semiconductors. But they suffer from limitations such as large static current, high power consumption and limited output swing. In order to mitigate this challenges, we propose a modified complementary pass-transistor logic (mCPL) family. We introduce mCPL inverters which use both n- and p-type OFETs in the pull-down network, which helps reducing the fall delay. The mCPL design also allows for an equal sizing of the p- and n- OFETs in the inverter design reducing the area overhead, and making the design more robust toward process variations. It also allows the use of smaller devices while significantly improving delay and efficiency. mCPL NAND and NOR gates are designed such that their critical paths are dominated mostly by p-OFETs, improving switching times. We report the integration and characterization of this new class of gates and compare them with the equivalent CMOS structures. The characterization of inverters shows improved tolerance to process variation, up to 2.5× better delay, and 1.7× smaller area for the mCPL devices. The performance of the mCPL NOR gate show a 1.5× better rise time and almost comparable fall time and rising delay (1.2×), and a 1.8× better fall delay. The NAND gate shows an improved speed for the mCPL logic with a 3× and 1.4× faster slew rate in the rising and falling case respectively as well as 2.1× better falling delay and 4.1× better rising delay. Due to the difference in input capacitance of the two logic design, the estimation on the power consumption per operation indicates a 3× more efficient gate in the mCPL. The improved performance of the mCPL design makes it an alternative architecture for logic application of organic electronics.

Central nervous system disorders affect brain, spinal cord and nerves that connect them. There are around one billion people who suffer from more than 600 mental diseases. Basic study of brain&’s chemical and its dynamic voltage provides the opportunity for early diagnose and control of these disorders. Also progress in the drug discovery requires comprehensive knowledge of neurotransmitters as drugs can affect neurotransmitter&’s synthesis rate. Neurochemicals play significant role in human metabolism and central nervous system and their measurement opens a way to correlate brain&’s chemicals to neuron behavior. In last few years organic electronics have emerged as a new direction for biosensors. Their high spatial and temporal resolution make them good candidate for biochemical sensors.
In this work, an organic electrochemical transistor (OECT) based on Poly (3,4-ethylenedioxythiophene) Polystyrene sulfonate (PEDOT:PSS) as transistor&’s active channel have been fabricated and utilized as Dopamine sensor. The PEDOT: PSS films were first characterized and then OECT were fabricated and characterized. The PEDOT: PSS films spin coated from solution of PEDOT: PSS, Ethylene glycol to enhance conductivity, dodecyl benzene sulfonic acid (DBSA) to adjust surface tension and (3-Glycidyloxypropyl) trimethoxysilane (GOPS) as cross-linker. Different spin rates (500- 3000 rpm) have been used and the film characteristics studied. Topography and roughness of film was studied by atomic force microscope. Ellipsometer was used to determine thickness and optical properties of film. Anisotropic optical model was used based on Lorentz and Drude oscillators for in plane and out of plane. Conductivity of film obtained using four point probes. As a preliminary result we obtained conductivity of 270 S/cm for a film with thickness of 260 nm.
Parylene C has been used as device&’s substrate. As electrode material, Ti/Au with thickness of 5/200nm has been deposited and patterned using standard lift-off technique. Another layer of Parylene is used for insulating the electrical connections and etched (ICP-RIE) to open a window for channel deposition. PEDOT:PSS spun and patterned using acid sensitive HFE photoresist (OSCoR). The patterned film of PEDOT:PSS have been Etched (ICP-RIE) to define channel and gate electrode of device. (I_D-V_D, I_D-V_G), transconductance (|gm|) and frequency dependence of transconductance will be measured. Device by Optimum geometry and characteristics will be tested as Dopamine sensor. Results from these devices with dopamine testing will be presented.

Graphene has been getting attraction in various research field including sensing strategy because of its outstanding properties. It is a well-known carbon 2D structure, with electrons of every atom exposed to analyte. This gives graphene an inherent high sensitivity and excellent performance. Its robustness towards chemicals and electrolytes makes it most effective candidate for biological sensors.
Recently, not only biological sensors using graphene, for cell, protein, glucose, DNA, etc. but also chemical sensors, for ions, pH, pesticides, etc. are being reported. Graphene as a sensing element has been used in different kind of sensors, like electrochemical, optical, FETs, etc. The natural tendency of DNA to form π-π bonds with graphene&’s carbon atom without any external linkers makes graphene an outstanding platform for DNA analysis.
In this study, a graphene based field effect transistor (GFET) was designed with a coplanar electrodes array structure for DNA sensing. The natural binding of DNA effects on the minimum current point of transistor, namely Dirac point. The detection and quantitative analysis of DNA was carried out on GFET. Microfluidic channel was integrated to achieve a self-sustained platform. Reproducible performance of GFET DNA sensor was obtained as microfluidic channel assured even distribution of analyte over the active layer.
A single stranded DNA sequence of 20 mer (AAA-ACT-CAA-ATC-AAC-AGG-CG) ranging from 10 to 100 µM concentration was analysed using the suggested microfluidic GFET.

Silk fibroin is one of solution-processible dielectric materials from natural source and its film has strong resistance to organic solvents. We have utilized silk fibroin as a gate dielectric for high-performance organic field-effect transistors (OFETs). Such OFETs showed increased field-effect mobility in comparison with OFETs with common inorganic dielectric layer and small hysteresis indicating very low charge trap sites at the surface of silk fibroin film. Acknowledgement: This research was supported by Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (MSIP) (2010-00525).

Sensors based on organic field-effect transistor (OFET) platform have attracted great interest due to their use as light-weight, low-cost, flexible electronics. Various OFET-based sensors have been demonstrated for sensing a various types of analytes including chemicals, biological species, light, and pressure. However, OFET-based sensors for detecting liquid-phase analytes have not been reported because of the poor resistance of the organic semiconductors in common organic solvents. From this critical drawback, OFET-based sensors have only frequently been demonstrated with vapor- or aqueous-phase analytes. Herein, we demonstrate highly sensitive, selective, solvent-resistant OFET-based sensors using crosslinkable organic semiconductor, P3HT-azide copolymer. The chemically cross-linked P3HT-azide copolymers have been introduced to enhance the chemical resistance of semiconducting layer to common organic solvents. Moreover, calixarene derivatives have been adopted to increase selectivity of the OFET-based sensors. Various liquid-phase organic solvents as well as pH solutions have been tested successfully and reliable sensing responses have been obtained. The computational studies at the atomistic level have also been conducted to analyze the interactions between the analytes and sensors, supporting the experimental results. Our findings demonstrate a novel methodology for the fabrication of high-performance organic sensors and substantially extend the practical applications of OFET-based sensors.

Implementation of inorganic nanophases in biosensing devices is an invaluable tool for the improvement of their analytical performances. Since the appearance of gold nanoparticles as promoters in biosensors [1], the field has faced the flourishing of novel approaches and nanostructures for the development of advanced devices [2]. The proper design of hybrid biomolecule-nanomaterial active components represents a key issue [3]. Zinc oxide nanoparticles (ZnO-NPs) respond to the needs of low-cost, high biocompatibility, and device versatility (e.g. excellent electron transfer and semiconducting properties), generally required in biosensing applications [4]. Despite the widespread use of ZnO-NPs in electrochemical biosensors [4] their application in field effect transistor (FET) based biosensors is less explored [5]. In this study, a green electrochemical-thermal process allowed the easy preparation of well-defined ZnO nanostructures in high yield and short time, in the presence of polystyrene sulphonate (PSS), as stabilizer [6].
Then, we followed a direct approach implementing ZnO-NPs into the active layer of a Functional Bio-Interlayer Organic FET (FBI-OFET) device [7], without making use of any covalent surface functionalization step. Briefly, a suitable amount of ZnO-NPs was added to the biomolecule aqueous solution in order to promote polar interactions between the negatively charged ZnO-NPs and the positively charged bio-receptor, based on the solution pH. Then, the conjugate was deposited as the first layer of the FBI-OFET architecture by conventional methods, which were critically compared and optimized. Poly(3-hexylthiophene-2,5-diyl) (P3HT) was finally used as outer device layer and as FET organic semiconductor. Streptavidin or Avidin were selected as biorecognition elements, while biotin was used as model analyte. Detection limits in the low ppt range could be repeatably and reproducibly recorded. Moreover, enhancement of the device stability towards storage (for months, under laboratory conditions) was observed when ZnO-NPs were used in the FBI-OFET architecture. All the main biosensor figures of merit, as well as the ultimate performance levels, were assessed and interpreted.
Nanomaterials and nanomaterial/bioreceptor conjugates were characterized by TEM, Z-potential measurements, UV-Vis, IR, and X-ray Photoelectron spectroscopies. The relevant results were used to draw conclusions about the device enhanced performances induced by ZnO-NPs.
[1] A.L. Crumbliss, et al., Biotechnology and Bioengineering 1992, 40, 483-490.
[2] C. Jianrong, et al., Biotechnology Advances 2004, 22, 505-518.
[3] B. Pelaz, et al., ACS Nano 2012, 6, 8468-8483.
[4] S. K. Arya, et al., Analytica chimica acta 2012, 737, 1-21.
[5] A. Choi, et al., Sensors and Actuators B 2010, 148, 577-582.
[6] M.C. Sportelli, et al., MRS Symp. Proc. 2014, 1675, 6 pp.
[7] M. Magliulo, et al., Analytical Chemistry 2013, 85, 3849-3857.

Organic Field-Effect Transistors (OFETs), comprising a functional biorecognition interlayer (FBI-OFET) sandwiched between the dielectric and the organic semiconductor layer, were recently proposed as label-free, ultrasensitive biosensors [1]. The morphology and the surface chemical composition of the stacked bilayer formed by the streptavidin (SA) protein biointerlayer and the overlying poly(3-hexylthiophene-2,5-diyl) (P3HT) organic semiconductor are here investigated for different protein deposition methods.
SA was deposited either by electrostatic layer-by-layer (LbL) deposition or by spin coating, on a thermally grown SiO₂ (300 nm thick) gate dielectric. In both cases, the P3HT layer was then spin coated, from a chloroform solution, directly over the protein capturing deposit. X-Ray Photoelectron Spectroscopy (XPS) was systematically used to characterize the multilayer device at each step of its assembly. Our aim was to probe the hypothesized mixing of the two phases of the biosensor reconstructing, by means of Parallel Angle Resolved XPS (PAR-XPS), non-destructive elemental depth profiles with sub-nanometer resolution [2]. XPS spectra were collected, at the same time, at different detection angles (theta;, angle measured with respect to the sample surface normal), ranging from 30.50° (most “bulk” sensitive angle) to 60.50° (most “surface” sensitive angle). From the analysis of PAR-XPS data, it was clear that the two deposition techniques used for the preparation of SA layers led to the formation of very different structures. With spin coating, a thick and irregular layer was obtained, and protein appeared rather aggregated on the sample surface. When the organic semiconductor layer was added, it perfectly resembled the underneath features; its percolation into the protein layer was quite probable, since protein-related signals showed a similar trend when P3HT was deposited above. With LbL deposition, the SA layer could be compared to a monolayer, few nm-thick, showing a different surface protein orientation as compared to the previous case. For layers obtained by LbL, P3HT deposition dramatically changed the surface composition. The semiconductor layer was, in fact, clearly distinguishable, covering the protein features completely. Hence, these differences could be held responsible for the different performances already reported in the literature for the two different FBI OFET devices [1, 3]. Scanning Helium Ion microscopy was also employed to gather relevant information on the structure and morphology of the protein and organic semiconductor layers and on the protein/organic semiconductor interface.
References:
[1] M. Magliulo et al., Anal. Chem., 85, 2013, 3849.
[2] R. Pilolli et al., Anal. Bioanal. Chem., 405, 2013, 713.
[3] M. D. Angione et al., PNAS, 109, 2012, 6429.

Organic electrochemical transistors (OECTs) have recently gained a great interest especially for bioelectronics. PEDOT.PSS is a conducting polymer commonly used for its mixed ionic and electronic transport properties that make it an ideal material for interfacing electronics with biology. PEDOT.PSS is usually spin-coated and then patterned using subtractive techniques such as lift-off or laser ablation. High conductivity channels with conductivity up to 700 S/cm can be obtained. Recently, PEDOT.PSS has been printed using an additive technology, by inkjet. These printed polymer films exhibit electrical conductivity in the range of 100 to 200 S/cm, which limits their use in the fabrication of highly sensitive OECTs.
In this work, we focused on printing highly conducting PEDOT.PSS inks for recording human electrophysiological signals. To fit with inkjet rheology requirements, a new PEDOT.PSS ink has been formulated and successfully printed with line width down 100 µm. Thin-films with thickness from 60 nm and up to 350 nm can be obtained after curing at 160°C for 30 min.
Inkjet-printed OECTs have been fabricated, having channels with an electrical conductivity up to 420 S/cm, and showing a transconductance in the mS range (1 to 2 mS, depending on device architecture). These printed OECTs exhibit a performance equivalent to state-of-the-art devices made by spin-coating technique.
Furthermore, we investigated a method to drastically increase the electrical conductivity of inkjet-printed PEDOT.PSS thin-films using acidic post-treatment. High electrical conductivity of 1330 S/cm is obtained after 5 min treatment in H₂SO₄ solution followed by 10 min curing in oven at 160°C. We showed also that this acidic treatment is not affecting ionic mobility by measuring the time response of OECTs.
These results demonstrate that inkjet-printing can be used as a facile and low-cost technique to fabricate high quality OECTs for customized bioelectronics devices.

Organic electrochemical transistors (OECTs) have been found to be an excellent transducer for various types of biosensors. Here, we report OECT-based epinephrine sensors for the first time. The device performance is optimized by immobilizing carbon-based nano-materials, including carbon nanotube, graphene and graphene oxide, and Nafion on the gate electrodes of the OECTs. The detection limit of the sensors is down to 0.1nM, which can cover the concentration level of epinephrine in medical use. Considering that the devices can be prepared by solution process with low cost, the highly sensitive epinephrine sensors are potential useful in disposal applications in the future

Electrophysiological recordings of neuronal activity are necessary for diagnostic purposes. Organic electronic devices constitute a perfect 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). In this work we show that OECT can also be used as active sensors to monitor vital electrophysiological information, directly on the skin. We confirm that OECT can record a wide range of signals with applications in multiple fields. The measurement of cardiac cycle (electrocardiography, ECG) can be used in sport, clinical and day-life applications. These OECTs also show great performances to track eyes movement (electrooculography, EOG) for drowsiness monitoring and ophthalmological diagnosis. Finally, we confirm that OECTs are serious competitors to replace passive sensors (electrodes) in measuring neurological rhythm on scalp (electroencephalography, EEG). Because tuning the geometry of the OECTs can fit those to a specific application or another and mostly because of the quality of their signal, they could be a great use for clinical purposes, like seizure detection, or for Brain Machine Interfaces.

Long-term measurements using organic electrochemical transistors often face the problem of a non-linear background due to temperature drift, evaporation and/or charged species other than the analyte in the electrolyte that interfere with the measurement. To circumvent this issue, we use a reference-based sensor circuit layout, termed “Wheatstone bridge”, including electrochemical transistors based on the conductive polymer poly(3,4-ethylenedioxythiophene) doped with polystyrenesulfonate. Using one transistor as a reference sensor and another one as a sample sensor, we are able to enhance the overall sensitivity and provide a signal-ON response contrary to a single transistor sensor, by differentially measuring the voltage drop across each transistor. Understanding this system on a micron scale is limited by the fabrication mismatch of the individual active components. Here, we report on refined microfabrication techniques for organic materials to reduce this fabrication mismatch. We are able to demonstrate full functionality of the device by measuring different ion concentrations in an aqueous salt electrolyte. Upon applying different biofunctionalisation methods to the sample transistor, such as e.g. covalent immobilisation of the biorecognition element, we can provide a selective in-vitro platform specific to one given analyte. With this device and an in depth understanding of its function, more accurate and stable measurements of glucose or lactate can be performed, allowing for a better fundamental study of biological systems for diagnostics application

Epileptogenesis has been associated with changes in electrophysiological activity, particularly the appearance of so-called preictal spikes, days before the occurrence of the first spontaneous seizure. The dynamic changes of these spikes during the early course of epileptogenesis may be predictive of initial seizure onset. There are procedures to analyze these time-dependent changes and to characterize the dynamics of interictal spikes during epileptogenesis, in both acute seizure states and resting behavioral states. However, these procedures are derived from models specifically focused on electrophysiological activity recorded with classical electrodes. These models ignore the underlying electrometabolic coupling which yields the measured electrophysiological activity.
Neurons and neuronal networks need energy, the primary sources of which are glucose, lactate, and oxygen. The relationship between extracellular glucose, lactate, and oxygen concentration, with large neuronal network activity, and the activity of single neuronal cells is not well-known. Additionally, the activity of single neuronal cells is fundamentally the fluctuations in Na⁺, K⁺, Cl^-, and Ca⁺⁺ across the neuronal membrane. The relationship of extracellular concentrations of these ion species with large neuronal network activity, and activity of single neuronal cells is also not well-known.
We have developed sensors made of poly(3,4 ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) capable of simultaneously measuring ionic concentration and electrophysiological activity, presented here in vitro, with experimental models of temporal lobe epilepsy (TLE). These sensors, in combination with our state-of-the-art PEDOT:PSS electrodes and transistors, are used in direct contact with neural tissue for sensing specific energy substrates and electrophysiologically relevant ions. This enables the characterization of the coupling between energy substrate delivery and cellular/network activity in vitro. We can determine whether energy delivery changes during behavioral states by selecting in vitro preparations during different periods of the sleep/wake cycle. We can also determine whether energy delivery is preferentially made where the most active synapses are located. Using an in vitro TLE model we determine when hypometabolism occurs and how it correlates to pathological cellular activity during the progression of epileptiform activity.
Fluctuations in energy substrate concentration and ionic gradients are a sign of many neurological disorders, not limited to epilepsy, but the functional outcomes are not well-known. We have previously demonstrated the use of organic electronics in vivo. The sensors presented here, when integrated into our already existing in vivo platforms, could open previously unavailable avenues for in vivo therapeutic devices.

Soft electronic materials that enhance compatibility with living tissues have attracted much attention in the field of electronics. Conventional electronics that are manufactured on rigid substrates with high controllability exhibit electric performances; however, when they are pressed against biological tissues, they cause biological reaction or discomfort. It is desirable that the contact surfaces of bio information sensing are to be made of soft materials. From this view point, building integrated circuits or sensors on plastic or rubber substrates, called flexible and stretchable electronics, have been intensively investigated. Especially, by reducing the total thickness of a bio information sensing system, bending strain is reduced, allowing the system to achieve incredibly small minimum bending radius. In fact, we have fabricated, on one micron thick plastic film, an organic thin film transistor (OTFT), an organic photovoltaics (OPV), and an organic light emitting diode (OLED), and have confirmed their excellent mechanical durability. Furthermore, besides the above mentioned organic devices, pressure and temperature sensors are also integrated on ultrathin plastic foils (total thickness of these devices are as thin as a few tens micrometers) achieving amazing conformability. In this talk, we will report recent progress of flexible organic thin-film devices and sensors. Those electronic devices are utilized for measuring biological signals such as body temperature, electromyogram (EMG) and/or electrocardiogram (ECG). We also address remarkable stability of these devices in physiological conditions. Finally, their outlook and future prospect in the field of biomedical applications will also be described.

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. This will open up application of these tough conducting materials as pressure and strain sensors for electronic skin devices for monitoring biological function.
In this presentation, I will describe our approach to the fabrication and characteristics of sensor devices based on electronically active soft materials (consisting of the edible biopolymers gellan gum and gelatin). Gellan gum and gelatin are versatile ingredients in well-known food products such as the commercially available product Aeroplane Jelly. These polymer are combined into ionic-covalent entanglement (ICE) gels consisting of ionically cross-linked gellan gum and covalently cross-linked gelatin networks. These ICE gels exhibit suitable mechanically and electrical characteristics for device applications. In addition, I will demonstrate that ICE gels can be prepared in a “one-pot” synthesis approach which facilitates their processing into devices through additive manufacturing (3D printing). Finally, I will present our understanding of the mechanical robust and electrical behaviour, and discuss the properties of the strain and pressure sensors in detail.

Electronics becomes highly conformable, with the prospect to fit to randomly shaped 3D-objects like skin, an area of research that is booming, evolving from laboratory curiosity to practical implementations. Here we describe a skin-spired electronic platform for highly stretchable interconnects with stretch independent electrical conductivity. With a total thickness below 2µm our electronic foil is practically imperceptible. In conjunction with a stretchable carrier, gold, and copper conductors with a resistivity close to that of the bulk metals are unimpaired by mechanical cycling up to 50% strain for up to 1000 cycles. These stretchable conductors can be readily combined with off-the-shelf electronic items to form stretchable LED stripes that remain functional when stretching up to 240% strain and twisting by 720°. In addition we demonstrate a hybrid 2D biaxial stretchable LED network that is readily stretched to 2.5 times its initial area repeatedly. Conducting polymer electrodes extend the concept of imperceptible electronics to transparent devices. The developed technology platform marks first steps towards imperceptible electronic devices that camouflage their presence with potential applications in mobile appliances, sports, health care, food and environmental quality monitoring.

We demonstrate a wearable tactile skin fitted to a human or robotic hand. Strain, proprioceptive-like, sensors cover the dorsal side of the fingers while pressure sensors are distributed along the inner side of the fingers. We manufacture the electronic skin combining conventional microfabrication techniques and rapid prototyping tools. Stretchable gold thin films on silicone are used to form parallel plate capacitive sensors with soft, compressible foam as dielectric layer. The same metal film technology is used to define stretchable resistive flexion sensors on a silicone substrate, which are then interconnected with highly conductive, strain insensitive liquid metal printed wires. An array of six pressure sensors is mounted on the palmar side of a textile glove, covering the entire length of the finger. Two flexion sensors are mounted on the dorsal side of the glove, one on top of the metacarpophalangeal joint and one on top of the proximal interphalangeal joint. Total thickness of the pressure-sensing layer (including sensor nodes, shielding, interconnects, and encapsulation) is less than 1.4 mm while the flexion-sensing layer is 0.5 mm thin. The sensors are read out in real time at 20 Hz using commercial microelectronic components.
Sensitivity of the foam-based pressure sensors is between 0.1 and 0.001 kPa^-1 over a 0 to 405 kPa range, which corresponds to standard forces exerted by a human hand, and can withstand uniaxial tensile strains to 30%. Flexion sensors exhibit a linear response to joint&’s rotation with a sensitivity of more than 0.75 rad^-1. The sensors were mounted on a textile glove and were used to monitor the manipulation of hard and soft objects. We also included our system in a closed sensory feedback loop to reach and maintain a defined pressure when grasping an object. These sensors work toward enabling generalized tactile sensing in robotic and prosthetic applications.

Flexibility, compliance and weight will turn out to be key metrics for future electronic appliances and power supplies. Imperceptible plastic electronic wraps integrate nanometer thin film active components on sub-2-mu;m polymer foils and create devices unmatched in mechanical flexibility, stretchability and weight.
Organometallic halide perovskites are capable of delivering very high power per weight when fabricated on ultrathin substrates, an important metric for wearable and ultraportable electronics, for remote sensing, powering electronic skins or for space applications.
Here we demonstrate methods to fabricate perovskite solar cells on 1.4mu;m thick PET substrates with 12% power conversion efficiency and a record high solar cell specific weight of 30W/g. The solar cells are less than 2mu;m in total thickness and can be bent into radii smaller than 50mu;m. Our devices are fabricated from solution in ambient air at temperatures below 120°C to ensure process compatibility with ultrathin polymer foil substrates. Their unique mechanical properties are achieved with an all ITO/FTO free device architecture that does not require titanium oxide interlayers and avoids high sintering temperatures typically employed for rigid devices on glass substrates. These potentially low cost power sources conform to arbitrary shapes and are expected to provide electrical energy wherever high specific power is critical, as in next generation ultra light portables, wearables, small-scale autonomous robots, electronic and robotic sensor skins or space technologies.
The authors acknowledge funding from the Wittgenstein award and the ERC advanced investigators grant “Soft Map”.

In this talk, I will present our recent progress in developing skin-inspired electronics in terms of materials and applications.

This talk will describe our group&’s efforts to use intrinsically—“molecularly”—stretchable electronic materials in wearable applications. Organic semiconductors have a wide range of mechanical behavior, which will significantly affect the ability of these materials to form conformal chemical interfaces with biological structures. There is also an apparent competition between good electronic properties and favorable mechanical properties. That is, state-of-the-art organic semiconductors tend to be stiff and brittle. We have developed several approaches based on molecular design, processing, and the use of plasticizers that can maximize semiconducting performance and mechanical softness. Mechanical measurements, combined with spectroscopic characterization of solid-state microstructure, inform our design of materials, while finite-element modeling is used to design device layouts and measure mechanical forces when deformed in operational environments. Applications include the first skin-mounted organic solar cell, all-elastomeric transistors, and a sensing “glove” that can be used to translate manual motions—e.g., sign language—into electronic signals for individuals with sensory impairment or for consumer electronic devices.

In this work we report on the fabrication of highly flexible, ultra-conformable free-standing organic thin film transistors (OTFTs) operating at low voltages. We have tested several sub-micrometer, free-standing plastic substrates, on which low voltage organic TFTs and inverters have been fabricated. At first, an aluminum gate electrode is patterned on the ultrathin substrate by standard photolithography, and afterwards the sample is baked overnight in order to obtain an ultrathin Al₂O₃ layer acting as first gate dielectric. In order to obtain a high performing nanometric gate dielectric, a 80 nm thick Parylene C film is deposited over the whole structure. Finally, on top of this structure gold source and drain are fabricated by a self-alignment process [1] in order to dramatically reduce the overlapping between source and drain electrodes with the underneath gate electrode, thus lowering the parasitic capacitances. Two different organic semiconductors have been employed, namely p-type TIPS-Pentacene and n-type N1400, both deposited from liquid phase.
Thanks to the high capacitance coupling induced by the ultrathin hybrid double-layer insulating film, such devices can be operated at ultra-low voltages, as low as 2V, showing hole mobility up to 0.4 cm²/Vs (electron mobility up to 1x10^-2 cm²/Vs), Ion/Ioff up to 10⁵ and remarkably low leakage currents (100 pA).
Full swing complementary inverters have been also fabricated, showing low noise margins and gains up to 20. Thanks to the properly engineered self-aligned structure, these devices are also characterized by a very good frequency response, with a cut-off frequency usually ranging around 100 kHz.
The fabricated structure is highly robust to mechanical stress: devices can be bent down to bending radii as small as 150 um without giving evidence of any significant variation of their electrical properties. In fact, since the electrical response of OTFTs to mechanical deformation is mainly related to the surface strain induced by the device substrate in the active layer, these effects are dramatically reduced (by orders of magnitude) by using ultra-thin free-standing substrates. Thanks to the extreme flexibility of the proposed structure and their ultra-conformability, such patterned films can be easily transferred on whatever kind of structure like paper, fabric, or 3D structures representing a step forward to the realization of highly flexible, compliant electronics particularly suited for smart wearable systems.
[1] S. Lai, P. Cosseddu, G.C. Gazzadi, M. Barbaro e A. Bonfiglio, Org. Electr. 14, 754-761 (2013)

Spontaneously coated epidermal electronics systems (EES) have demonstrated their unique advantages in healthcare and human-machine interface. These EES largely rely on external power supplies, which limit their convenience and mobility. Here, we introduce an epidermal radio frequency (RF) energy scavenger system based on ultrathin passive and active electronic components. This flexible and stretchable system offers tunable system parameters and stable performance under mechanical deformation. It can harvest environmental RF power directly and support the operation of microscale light-emitting diodes ( mu;-LEDs) and simple radio circuits, eliminating the need for external power sources that present in conventional medical sensors and most EES. A modularization process divides the system into several components based on their functions and fabrication requirements. Series of impedance matching LC circuits provides tunability to overall circuit efficiency. Each component is separately fabricated and tested before transfer-printing on a soft elastomer to enhance yield and the overall system performance. Here we report systematic characterization of individual components and overall system performance in various dielectric environments (air, skin, and wet sponge). In addition, we demonstrate long distance, wireless powering of mu;-LED in air and on skin. Infra-red thermal analysis is utilized to evaluate impedance matching efficiency and heat distribution on the device. The system is verified to be fully operational under IEEE regulation&’s maximum permissible exposure for RF energy. The cold-welded metal interface between interconnects is investigated by focus ion beaming milling and scanning electron microscopy. The results suggest a robust wireless epidermal system for RF power harvesting and represent important progress in developing self-supported mobile healthcare systems.

Electrocardiagraphy (ECG) is widely used to diagnose abnormal rhythms of the heart and other cardiovascular diseases non-invasively. Electrical impulses go through the heart with heartbeats and an ECG device detects small changes in electric field on the skin above the heart by the electrical impulses during heartbeats. ECG electrodes' tight attachment to the skin is a key function for reliable transmission of electrical signals from the skin to the electrodes with low impedance between skin and the electrodes. Thus, an electrically conductive gel is usually used on the ECG electrodes to remove gaps between skin and the electrodes. However, it is inconvenient for patients to apply and remove the conductive gel every time.
In this study, we develop stretchable and attachable ECG electrodes by utilizing printed metal nano-ink-based stretchable electrodes, which enables conformal contact to the skin without any conductive gel. The stretchable electrode is fabricated as a strain-relief pattern of thin silver electrodes shaped with crossing horseshoes is printed on a stretchable substrate via direct stamping of silver nano-ink. Conformal contact of the fabricated stretchable ECG electrodes to the chest allows for clear electrical signal from the heart. For a future study, wireless connection to the stretchable ECG device could be established, and then, even a simple self-diagnosis by an electrocardiogram obtained through the stretchable ECG system would be possible for smart phone applications.
[Ref] Jiseok Kim and Woo Soo Kim, " Stretching Silver: Printed Metallic Nano Inks in Stretchable Conductor Applications", IEEE Nanotechnology Magazine, 8[4] (2014).

There is a great interest to bridge the gap in between the signaling of electronics and the signaling of biological systems, aiming to establish a technology platform that enables new therapies, prostheses systems and also diagnostic tools. In traditional silicon-based electronics, electrons represent the signal carriers and device systems do not interface easily with biological systems, such as nerves and organs. In biological systems, ions and biochemical entities of various kinds represent the signals that are transported and processed in soft and water-rich junctions, such as in the nerves and in the synaptic junction. In electrochemical electrodes based on conjugated polymer and polyelectrolytes one can translate an electronic addressing signal into the release and transport of ions. Those released ions can then be processed in intronic devices based on mono- and bipolar polyelectrolytes. Here, we report electrochemical iontronic devices that convert electronic addressing signals into desired complex patterns of ionic signals aiming to regulate and control the physiology and signal patterns in different targeted biological systems and organs. The fundamental device characteristics of the iontronic resistor, diode and transistor will be described along with applications where these devices have been utilized in vitro as well as in vivo aiming at new bioelectronics therapy methods addressing several different diseases.

Motivated by the role of proteins in efficient charge transfer processes in nature, the idea of using them in electronics applications has been proposed. However, the materialization of the idea depends on understanding fundamental open questions regarding electron transport processes and the role of protein structure in controlling them, especially in the context of a solid state device. The ability to synthesize peptides (short proteins) with predefined sequence, opens the way to answer some of these important questions. In this study we use small cyclic peptides to demonstrate that protein side chains can play a significant role in controlling both proton and electron conduction.
Our design is based on eight residue alternating D, L α amino acid cyclic peptide, c(KX)₄.¹ In this design lysine (K) is used to control the assembly, and the amino acids in the X position are mutated in order to study their effect on charge transport. We show that the introduction of aromatic side chain improves intramolecular charge transport, with the indole side chain of tryptophan showing enhanced effects with respect tyrosine's phenol ring. In the case of intermolecular charge transport, a hybrid proton and electron transport is observed and correlated with the side chains of the peptides. Our results demonstrate the great potential of peptide based electronic materials.
References:
M. Mizrahi, A. Zakrassov, J. Lerner-Yardeni, and N. Ashkenasy, "Charge transport in vertically aligned, self-assembled peptide nanotube junctions" Nanoscale, 4, 518 (2012).
M. Amit, S. Appel, R. Cohen, G. Cheng, I. W. Hamley, and N. Ashkenasy, "Hybrid proton and electron transport in peptide fibrils", Adv. Func. Mat. 24, 5873 (2014) DOI:10.1002/adfm.201401111

In living systems, protonic and ionic currents are the basis for all information processing. As such, artificial devices based on protonic and ionic currents offer an exciting opportunity for bioelectronics. Proton transport in nature is important for ATP oxidative phosphorylation, the HCVN1 voltage gated proton channel, light activated proton pumping in bacteriorhodopsin, and the proton conducting single water file of the antibiotic gramicidin. In these systems, protons move along hydrogen bond networks formed by water and the hydrated biomolecules (proton wires). We have previously demonstrated complementary H⁺- and OH^-- FETs with acid and base doped biopolymer proton wires and PdH_x proton conducting contacts. Here, I will discuss proton-conducting devices based oh highly conductive proton wires that emulate brain synapses, display memristive behaviour, and are connected to form shift registries. Furthermore, I will present the integration of these devices with enzymatic logic gates for integrated biotic-abiotic protonic information processing.

Paul Meredith
Centre for Organic Photonics & Electronics, School of Mathematics and Physics, The University of Queensland, Brisbane, Queensland, Australia 4072
The melanins are a broad class of pigmentary macromolecules found through nature that perform a wide range of functions including photo-protection [1]. The most common melanin - the brown, black pigment eumelanin, has been much studied because of its role in melanoma and also for its functional material properties [2]. Synthetic eumelanin has been shown to be photoconductive in the solid state and also possess a water content dependent dark conductivity [3]. It is now well established that these electrical properties arise from hybrid ionic-electronic behaviour, leading to the proposition that melanins could be model biocompatible systems for ion-to-electron transduction in bioelectronics.
In my talk, I will discuss the basic physics behind these bioelectronics properties. In this context I will also describe recent paramagnetic spin studies which isolate the role of the various chemical moieties responsible for the hybrid ionic-electronic behaviour. I will also highlight preliminary results on prototype melanin-based bioelectronics devices and discuss possible architectures to realise elements such as switches and transducers.
[1] “The physical and chemical properties of eumelanin”, P. Meredith & T. Sarna, Pigment Cell Research, 19(6), pp572-594 (2006).
[2] “Electronic and optoelectronic materials and devices inspired by nature”, P Meredith, C.J. Bettinger, M. Irimia-Vladu, A.B. Mostert & P.E. Schwenn, Reports on Progress in Physics, 76, 034501 (2013).
[3] “Is melanin a semiconductor: humidity induced self doping and the electrical conductivity of a biopolymer”, A.B. Mostert, B.J. Powell, F.L. Pratt, G.R. Hanson, T. Sarna, I.R. Gentle & P. Meredith, Proceedings of the National Academy of Sciences of the USA, 109(23), 8943-8947 (2012).

Protons (H⁺) play an important role in controlling cell function and metabolic processes in biological systems. H⁺ concentration affects a broad range of biological activities including neuron signaling in the brain. Acidosis (low pH) is typically associated with decreased neuronal excitability, and high pH is associated with increased neuronal excitability. Being able to control H⁺ concentration with bioelectronic devices would provide new opportunities to understand the effect of H⁺ concentration on neuronal function and develop new therapies to control cell excitability. I will present recording and modulation of pH (- log (H⁺ concentration)) using proton conducting devices and monitor how changes in pH affect neuronal excitability in neuronal cell cultures.

Cephalopods are known as the chameleons of the sea - they can alter their skin&’s
coloration, patterning, and texture to blend into the surrounding environment. These
remarkable capabilities are enabled by unique proteins and self-assembled nanostructures
found within cephalopod skin. I will discuss our work on new types of photonic and
protonic devices fabricated from naturally occurring materials found in cephalopods. Our
findings hold implications for the next generation of stealth and bioelectronics
technologies.

Ionic species, especially protons, dominate signaling in natural systems, so the conversion of biochemical protonic signals into electronic signals is an essential part of biodevices to record and stimulate the biological functions at the biotic/abiotic interface. Here, we present a protonic transducer that translates biological signals from an enzyme reaction into readable electronic currents. This bioprotonic transduction is achieved through the electrochemical measurement of a protonic reaction at the interface between a Pd protode and a solution containing some enzymes such as glucose dehydrogenase (GDH) and alcohol dehydrogenase (ADH). These enzymatic cascades provide bistable pH modulation (an “Enzymatic Flip-Flop”), which triggers proton absorption inside the Pd electrode when injected a glucose for set of Flip-Flop system (lower pH, increase in protochemical potential) and subsequent applied the voltage for PdH formation. In addition to above electrochemical behavior at the interface between enzyme solution and palladium electrode, we demonstrate this biotransducer to protodes in our bioprotonic devices that can mimic synaptic-like biochemical signal transmission and bioprotonic network.

Eumelanin is a ubiquitous natural pigment responsible for the pigmentation of many plants and animals, whose electrical properties have been studied since the 1960&’s. Based on its charge carrier transport properties, biodegradability, and intrinsic biocompatibility, eumelanin is extremely attractive for a wide range of technological applications. The hydration dependent electrical conductivity, once studied in the frame of amorphous semiconductivity, is now interpreted in the perspective of a mixed ionic-electronic conductivity [1]. Eumelanin also exhibits strong affinity toward transition metal ions susceptible of redox activity in biological environments [2]. The electrochemical properties of eumelanin have been recently exploited for battery applications: it has been employed as anode material for sodium ion-storage devices and as cathode material in secondary batteries making use of multivalent cations [3,4]. Here, for the first time, we report about the potential of eumelanin as electrode material for supercapacitor applications. Indeed, during the electrochemical characterization of Sigma eumelanin, we observed that samples drop-cast from DMSO suspensions on carbon paper substrates exhibit a few orders of magnitude increase of the capacitive current with respect to bare substrates. These observations were collected during cyclic voltammetry and galvanostatic measurements in various aqueous electrolytes, such as ammonium acetate buffer solution (pH 5.5), ammonia buffer solution (pH 10), phosphate buffered saline (pH 7), Na₂SO₄ 0.5 M (pH 5.5). The choice of the electrolytes was based on the importance of the role of (i) the pH, in establishing the charge carrier transport properties of eumelanin [1], and (ii) the chelating and non-chelating nature of the cations in the electrolyte, in establishing the ion storage properties of eumelanin. We found that the maximum specific capacitance of eumelanin changes with the pH of the electrolyte and achieves a value exceeding 100F/g in ammonium acetate buffer. This value is of great interest for supercapacitor applications. We can attribute our results to two factors: (i) the low pH, considering the proton conduction properties of eumelanin and (ii) the favourable structure of the eumelanin deposits on the nanostructured carbon paper substrate, as deduced from atomic force microscopy. These new insights improve the current understanding of the charge transport and ion storage properties of eumelanin opening the possibility to advance the knowledge on the functions of eumelanin in biology and to assess its potential for energy storage applications.
[1] A.B. Mostert, J.B. Powell, F.L. Pratt, J.R. Hanson, I.R. Gentle and P. Meredith PNAS 109(23),2012
[2] P. Meredith and T. Sarna, Pigment Cell Res., 19(6),2006
[3] Y. J. Kim, W. Wu, S.E. Chun, J. F. Whitacre and C. J. Bettinger, Adv. Mat.,38(26),2014
[4] Y. J. Kim, W. Wu, S.E. Chun, J. F. Whitacre and C. J.Bettinger, PNAS, 110 (52), 20912-20917,2013

Living cells, like HEK 293, astrocytes or neuron can grow on top of an organic semiconductor films. Upon polymer photoexcitation, the cell can be excited by modification of the membrane properties. This establishes a photonic interface for communication with the living system that has important application in electrophysiology and neuroscience. Such interfaces have been recently proposed as artificial retina prosthesis and validated in vivo by studies on animal models. The phenomenon has however a broader scope and can be consider as a fundation for a new technological platform aiming at stimulation of cell activity with high temporal and spatial resolution. In the last years we have been investigating a number of systems for cell excitation. In this talk i will review the work done and report on recent results regarding the bio organic interface.

The communication mechanism through neurotransmitter release and rapid propagation of membrane depolarization by the flux of ions dictates the local function of the nervous system. [1] The development of multifunctional probes capable of releasing of drugs of interest as well as sensing the triggered neural activity is, thereof, a breakthrough in therapeutic strategies aiming to treat brain dysfunctions. Here, we report such a multifunctional probe that exploits the combined ionic and electronic transport properties of the biocompatible polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS). This probe involves electrically-controllable ion release channels which are located in the exact position of recording electrodes. While biomolecules such as GABA or NMDA are electrophoretically delivered through a PEDOT:PSS film at high spatial and temporal resolution, the low impedance of PEDOT:PSS electrodes allows for high signal-to-noise ratio recordings of broadband physiological activity at the delivery site. The function of these probes was evaluated in rat hippocampal slices through an in vitro design, as well as in the form of an implantable system. This targeted chemical stimulation and simultaneous monitoring of the electrophysiogical response of the neural tissue paves the way for long term implantable drug release devices with feedback regulation function.
[1] Jimison, L. H.; Rivnay, J.; Owens, R. M., Conducting Polymers to Control and Monitor Cells. In Organic Electronics, Wiley-VCH Verlag GmbH and Co. KGaA: 2013; pp 27-67.

Our ability to understand and map neural circuits associated with fundamental cognitive processes or treat neurological conditions such as the major depressive disorder or autism are currently limited by the lack of tools capable of adequately addressing signaling complexity of the brain. Recent advances in multimaterial fiber technology may enable an entirely new class of flexible multifunctional neural communication devices. These fiber-based probes permit simultaneous optical interrogation, drug delivery and electrophysiological recording at high spatial resolution in vivo. A scalable thermal drawing method is used to produce multimaterial fiber-probes presented here. During fabrication a macroscopic preform that incorporates all of the desired features of the probe is heated and stretched into hundreds of meters of fiber with a conserved cross sectional geometry identical to that of the preform and scaled down by a factor of 50-200. Our experiments demonstrate the utility of polymer-based fiber probes for neural recording during optical stimulation and infusion of neuromodulatory compounds in the mouse brain and spinal cord. We show that our devices maintain their electrical and optical performance over a 3 months chronic study and produce minimal foreign body response within the surrounding neural tissue. A combinatorial strategy for chemical and optical communication with neural tissue can now be combined with a concomitant readout of the neural response during free behavior via a single flexible optoelectronic fiber. We believe that our methodology allows for straightforward customization of devices based on their intended application in a specific brain region or for a particular neurobiological question.

Significant advances have been made in the last two decades in interfacing electronic devices with biology. To that end, significant research efforts are being pursued in order to achieve implantable multimodal devices integrating recording and stimulating features.
Such devices should be minimally invasive and be able to record and stimulate neurons. The electrochemical mechanisms which underlie neural stimulation and recording using electrodes with passive sites are well understood. Recent advances in organic electronics have demonstrated the benefits of using transistors to record electrical signals at very high quality in the brain. However, these recordings have been limited to low-frequency signals, and the use of the devices to stimulate was not demonstrated.
Here we show the use of organic transistors for stimulating and recording high-frequency electrical signals from individual neurons in the intact hippocampus. We found that by shorting the source and drain of devices, currents as low as 40 µA with pulse durations as short as 20 µs could be applied between the channel and the gate to stimulate targeted populations of neurons with no degradation in transistor performance. After returning devices to recording mode, we found that neurons located as close as 20 µm from the transistor channel showed no evoked electrophysiological activity to currents as high as 900 µA flowing between the source and drain of the device, as verified by two-photon excitation microscopy.
Recordings of high-frequency activity were made from organic transistors of the same type as used for stimulation. Additionally, the polymer depth probes hosting these organic transistors feature a mechanical delamination process after implantation to reduce the applied force on the implanted neural tissue, thus considerably reducing invasiveness. Our results demonstrate that organic transistors can in principal be used in place of passive electrodes in all aspects of electrophysiology.
Due to the probes unique biocompatibility and being equipped with high-fidelity organic transistors, we anticipate this work to be the starting point for new stimulation and recording paradigms in chronic implantation.

The area of printed electronics has been focused on the use of new classes of semiconducting and conducting materials in two main applications, displays and photovoltaics. Both applications require materials long-term stability, long shelf life as well the need for patterning and deposition over large areas. Over the past 10 years significant progress in the performance of printable materials has been reported including highly efficient solar cells, light emitting diodes and thin film transistors with mobilities as high as 10 cm²/Vs. The work is highly motivated by the potential for high throughput, high volume, low cost manufacturing. While large area electronics continues to be a good application for printed flexible devices, wearable medical devices, which benefit from new form factors, represent a good shift in direction of research in the field. We have developed methods to measure blood oxygenation, bio impedance and temperature using organic electronic devices as building blocks for flexible printed systems. In this talk, I will review the state of the art of devices produced by printing and introduce a blade coating method that yields highly homogeneous flexible thin films that are applied to LEDS, photodiodes and TFTs.

Conducting polymers offer many advantages when we interface them with biological objects. We have developed an original patterning technique which allows for the integration of conducting polymer directly on existing garments. Poly(3,4-ethylenedioxythiophene): polystyrene sulfonate (PEDOT:PSS) is coated onto fabric thanks to a negative masking pattern that allows the selective deposition of the PEDOT:PSS solution. We have evaluated the capacity of conducting polymers textiles in fully plastic wearable electrocardiography (ECG) and electromyography (EMG). In this work we compare recorded signals from the fabric electrodes with conventional medical electrodes, and underline the great potential of these textiles in wearable devices including for ECG, EMG and other health monitoring.

Development of flexible electronic healthcare devices with wireless communication could enable sophisticated and comfortable methods of monitoring human vital signs. Recently, many flexible healthcare and biomedical devices have been reported, however, most devices require a wired connection [1-3]. Here, we demonstrate fabrication techniques for a fully flexible wireless fever alarm system capable of sounding an alarm when a patient&’s body temperature rises above the normal level. This wireless fever alarm system is comprised of organic complementary circuits, a high sensitivity temperature sensor, piezoelectric speaker, and is powered by flexible solar cells.
Organic complementary ring oscillator circuits for driving the system were fabricated directly on a 50 mu;m-thick flexible polyimide substrate. The temperature sensor utilizes organic transistors and a printable polymer composite which changes resistivity by 10⁴ when physiological temperature is exceeded. For the flexible organic transistors and circuits, the p-type channel was formed using dinaphtho[2,3-b:2prime;,3prime;-f]thieno[3,2-b]thiophene (DNTT), the n-type channel was formed using N,N&’-bis (n-octyl)-dicyanoperylenediimide (PDI-8CN₂), and the gate dielectric was formed with 40-nm-thick parylene deposited by chemical vapor deposition (CVD). DNTT and PDI-8CN₂ transistors showed mobilities of 0.6 cm²/Vs and 0.05 cm²/Vs at 8 V, respectively. The 5-stage complementary organic ring oscillator was oscillated at 4.7 kHz at a driving voltage of 12 V.
[1] J. Viventi, et al., Nature Neurosciences, 14, 1599 (2011).
[2] K. Ishida, et al., IEEE ISSCC Dig. of Tech. Papers, pp. 308 Feb. (2012).
[3] G. Schwartz, et al., Nature Communications, 4, 1859, (2013).

Solution processable organic electroluminescent semiconductor materials enable low-cost, large area, and flexible light emitting diodes. Over the last two decades, organic light emitting diodes (OLEDs) have been developed primarily for lighting and display applications¹. However, OLEDs&’ flexibility and scalability make them ideal candidates for use in optoelectronic biomedical devices, which are limited by the rigidity and expensive scaling of standard inorganic optoelectronics. One such device is a pulse oximeter, used ubiquitously in the medical field to measure pulse rate and arterial oxygen saturation². Pulse oximetry is based on the fact that blood is the primary light absorber in human skin. The absorption of light by hemoglobin in the blood depends upon the wavelength of incident light and whether or not the hemoglobin is bonded to oxygen. By comparing the amount of light transmitted through the finger (and thus absorbed by the blood) at two different wavelengths, the arterial oxygen saturation can be derived. The pulse is determined by the measure time between peaks of transmitted light, which coincide with the pulsatile volume of arterial blood in the finger. We have successfully implemented solution processed red (626 nm) and green (532 nm) light emitting diodes made from polyfluorene blends in an all-organic optoelectronic pulse oximeter sensor³. The red and green OLEDs operate at 9 V, 1 kHz, and alternately transmit light through a human index finger. The transmitted light is sensed by an organic photodetector on the opposite side of the finger. The person&’s pulse and arterial oxygen saturation are then extracted from this signal, with only 1% and 2% error, respectively, compared to measurements taken by a hospital grade commercially available pulse oximeter. The most important figures of merit for the light emitting diodes in a pulse oximeter are irradiance (which should be maximized) and power consumption (which should be minimized). At 9 V, the green and red OLEDs used in our pulse oximeter sensor have irradiances of 20.1 mW/cm² and 5.83 mW/cm² while consuming 116 mW and 120 mW of electrical power, respectively.
1. R. Q. Ma, R. Hewitt, K. Rajan, J. Silvernail, K. Urbanik, M. Hack and J. J. Brown, J. Soc. Inf. Disp. 16 (1), 169-175 (2008).
2. M. Yelderman and W. New, Anesthesiology 59 (4), 349-352 (1983).
3. C.M . Lochner, Y. Khan, A. Pierre, and A.C. Arias, Nat. Comm., In Press (2014).

Organic electronic devices offer promising routes for in vivo electrophysiological recordings of neuronal circuits due to their mechanical flexibility and biocompatibility. Organic electrochemical transistors (OECTs) were shown to exhibit a superior signal-to-noise ratio due to local signal amplification and are able to record activities on the surface of rat brain[1]. Accessing the complex signal landscape over the whole brain surface area of larger mammals will require active signal multiplexing in order to achieve the necessary spatio-temporal resolutions.
Here we present a flexible bio-electronic signal sensor array and active multiplexing system that combines OECT sensor cells with an organic transistor (OFET) based multiplexer. Our organic transistors are ideally suited as signal switches due to their high on/off current ratio exceeding 6 orders of magnitude and are successfully interfaced with high transconductance (0.9 mS) OECT sensors. We fabricate an ultraflexible 12×12 matrix circuit (bio-electronic signal sensor and active multiplexing system) on a only 500 nm thick parylene (dix-SR) membrane deposited on Si wafer by chemical vapor deposition (CVD). The multiplexing system comprises p-type OFETs using dinaphtho[2,3-b:2prime;,3prime;-f]thieno[3,2-b]thiophene (DNTT) as semiconductor on top of a hybrid aluminum oxide - self assembled monolayer gate dielectric. Additional 500 nm parylene (dix-SR) and 60 nm gold were deposited on the active multiplexing system to serve as a passivation layer and to allow for photolithographical patterning of OECTs with Poly(3,4-ethylenedioxythiophene):Polystyrene sulfonate (PEDOT:PSS) as active sensor interface. The DNTT transistors exhibit mobilities exceeding 1 cm²/Vs at 5 V and high on/off ratio (6 order). The bio-electronic sensor showed trans-conductance values exceeding 1 mS at 0.8 V. Such highly flexible, actively multiplexed sensor arrays hold great promise for medical applications including real-time in vivo surface brain signal mapping.
This work is partially supported MERIT.
[1] D Khodagholy, et al. Nature Communications 4, 1575 (2013).

The characteristics of the gate electrode have significant effects on the behaviour of organic electrochemical transistors (OECTs), which are intensively investigated for applications in the booming field of organic bioelectronics. In this work, high specific surface area activated carbon (AC) was used as gate electrode material in OECTs based on the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) doped with poly(styrene sulfonate) (PSS).¹ We found that the high specific capacitance of the AC gate electrodes leads to high drain-source current modulation in OECTs.
Cyclic voltammetry studies, where PEDOT:PSS is used as the working electrode (WE) and AC is used as the reference electrode (RE) and counter electrode (CE), show that high double-layer capacitance and absence of Faradaic processes permit the development of stable OECTs where the channel potential is uniquely determined by the applied gate bias. The intrinsic quasi-reference characteristics of AC electrodes make unnecessary the presence of an additional reference electrode to monitor the OECT channel potential.
The ease of process of AC electrodes for in plane, flexible device architectures constitutes a step forward in the search of new electrode materials for OECTs to be used in iontronics, printed electronics, bio analytical sensing, and other organic bioelectronic devices.
¹ H. Tang, P. Kumar, S. Zhang, Z. Yi, G. De Crescenzo, C. Santato, F. Soavi, F. Cicoira, ACS Appl. Mater. Int. (under revision).

In this work, we present an extended model for the steady-state behavior of organic electrochemical transistors (OECTs). The proposed model assumes a Gaussian-distributed density of states for holes in the active material, and it assumes a hole mobility that is proportional to that density of states. This sets the proposed model apart from existing models by taking into account well-known physics in disordered semiconductors. Additionally, unlike existing models, the proposed model is valid for negative gate voltages and for positive gate voltages beyond the voltage at which the channel becomes pinched-off. We compare our model to the current-voltage characteristics of photolithographically-defined PEDOT:PSS-based OECTs with feature sizes ranging from 10 mu;m up to 1000 mu;m. The experimental results and theoretical predictions have important consequences for OECTs used as biosensors. For example, the proposed model can lead to rational modifications to device design and material properties in order to optimize the OECT transconductance. This will increase the signal to noise ratio of OECTs used as sensors in various biological applications, such as glucose detection and monitoring of epithelial cell integrity. The proposed model also describes material properties and operating voltages under which the mobility is maximized. This will allow better-informed device design and operation for the optimization of sensor bandwidth, an important parameter in sensing applications such as action potential measurements and electrocardiogram recording.

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. We study the response of the OECT to barrier tissue properties over a frequency sweep of the gate voltage. This impedance spectroscopy-based measurement associated to OECT allows a better characterization of the cell layer with an increased sensitivity. Moreover, the transparency of the PEDOT:PSS allows optical observation of the cells. This measurement platform allows to precisely correlate the electrical changes of the biosensor - which corresponds to the transepithelial 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.

Organic electrochemical transistors (OECTs) based on conducting polymers have undergone significant progress in recent years and are poised to become the device of choice for fabricating biosensors using semiconducting polymers. Due to their ability to support both efficient ionic and electronic transport, OECTs are able to transduce biological signals, which typically involve ion flux, into electrical signals with high gain. However, despite the increase interest in OECTs, a comprehensive analysis of their transient response characteristic and its correlations with membrane and device properties is still lacking. Here we present a simple circuit model for biological barrier layer-functionalized OECTs as it relates to their transient current-drain response. Our results show that both the biological barrier and channel can be successfully modeled by two parallel RC circuits, yielding crucial information about the impedances of both the device and the biological barrier. Device capacitance and membrane resistance, for instance, are of great interests in applications involving barrier tissue diagnostics and cell monitoring. In addition, we also model the transient current-drain response for OECTs equipped with several biological membranes and are able to extract their resistances under different conditions. Finally, our model allows us to be quantitative and is applicable in a wide range of configurations where OECTs are used as a transducer between ionic and electronic transport.

The present lecture aims to provide an overview on the development involving dielectric/organic semiconductor (OSC) interfaces for the realization of bio-functional organic field-effect transistors (OFETs). Specific focus will be given on bio-interfaces and recent technological approaches where biological materials serve as interlayers in back-gated OFETs for biosensing applications. To better understand the effects of the presence of biomolecules deposited at the dielectric/OSC interfacial region, the modification of the dielectric surface properties by means of self-assembled monolayers is discussed. Emphasis will be also given to the modification of solid-state dielectric surfaces, in particular inorganic dielectrics, with biological molecules such as peptides or proteins. Special attention is paid on how the presence of an interlayer of biomolecules and bio-recognition elements underneath the OSC impacts on the charge transport and sensing performance of the device. The role of metal contact/OSC interface in the overall performance of OFET based sensors is also discussed.

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 onto the device via functionalization can result in a one-step sensing platform. In this work, we incorporate catalytic nanomaterials (Pt) as well as functionalization sites to 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 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 electrochemicals transistors (OECTs) are used for a variety of biological applications, including sensors for the detection of biologically relevant species (ions, glucose, DNA, neurotransmitters) as well as to guide cell adhesion and growth. The majority of OECTs are based on spin-coated films of poly(3,4-ethylenedioxythiophene) doped by polystyrene sulfonate (PEDOT:PSS) or on electrochemically synthesized thin films, i.e. PEDOT or polypyrole (Ppy). Several approaches were explored to biofunctionalize such films. Bioactive species (such as growth factors) have been incorporated into the conducting polymer during the electropolymerization process. However, the entrapped biological molecules were shown to drastically reduce both the electroactivity and the mechanical properties of the resulting film. In order to counteract the aforementioned negative impacts, it was proposed to covalently graft the bioactive species at the surface of the conducting polymer. For this purpose, the entrapment of chemically-active polymers (such as hyaluronic acid) or the use of a Ppy monomers reaching a carboxylic group during the polymerization process were tested. However, also this method led do a drastic decrease of film conductivity. In this work, we propose to introduce chemical groups in a conducting polymer film by the addition of a biocompatible carboxymethylated dextran (CMD) to a PEDOT:PSS suspension prior to the spin-coating. The COOH groups, homogeneously distributed in the conductive film, are used to covalently graft bioactive compounds for guided cell culture or for antigen/antibody detection. As a first study, the impact of the dextran chains on the PEDOT:PSS film conductivity and stability was investigated. Compared to the conductivity of a pristine PEDOT:PSS film (0.03 S.cm-1), a slight increase in conductivity (two orders of magnitude) was obtained when 1% w/v of dextran chains (unmodified or carboxymethylated) were added to the PEDOT solution. No significant changes were observed when 5% v/v of glycerol was added to the mixture. The film stability was then evaluated after an immersion in water, which is a universal solvent for bioelectronic applications. 3-glycidoxypropyltrimethoxysilane (GOPS) was shown to drastically enhance the film stability. As a result, no significant changes in thickness were observed before and after 24h immersion in a phosphate buffered-based solution. In a preliminary study, the CMD carboxylic groups were used to chemically graft an antibody (Ab). An enzyme-linked immunosorbent assay (ELISA) revealed the presence and the absence of Ab when CMD and unmodified dextran were used, respectively. This result highlighted both the chemical reactivity of the CMD and the specificity of the biomolecule grafting. These results will have a major impact in the field of bioelectronics as the proposed device may guide future development of protein-enhanced biomaterials interfaces such as those of corneal and vascular implants.

There is a big need for electronic biosensors that can be operated in water for biomedical applications and environmental monitoring. Devices based on organic materials are currently attracting great attention for applications where low-cost, large area coverage and flexibility are required. Water is an aggressive medium and due to its chemical activity the operational voltage window for stable sensor operation is limited. Related to that, in the past, degradation under both ambient and aqueous environments have limited their application in biosensors for portable, label-free detection in the field of healthcare and environmental monitoring.
Quite recently, our group has demonstrated stable FET device operation based on organic active materials directly exposed to water and more interestingly, even sea water.[1,2,3] By pattering an array of gold nano-particles on top of the organic semiconductor but close to the transistor channel, the developed structure is able to sense selectively low concentrations of mercury ions in sea water.[2,3]
Here we would like to present the second generation of this highly sensitive biosensor platform based on organic field-effect transistors developed in our group able to operate at very low voltages which a necessary condition for stable device operation in water based environments. Functionalization is a powerful tool to attach receptor units close to the transistor channel which are able to selectively detect its corresponding analytes. This methodology allows to prepare a scalable, easy producible and high performing sensor platform suitable for portable biosensing in aqueos environments.
References:
[1] Mark E. Roberts et al., PNAS, 105, 12134 -12139, 2008.
[2] Mallory L. Hammock et al., ACSNano, 6, 3100-3108, 2012.
[3] Oren Knopfmacher et al., Nature Communications, 5, 2014. doi:10.1038/ncomms3954

Electrostatic interactions in an electrolyte solution are known to extend at most to the Debye&’s screening length lambda;. Indeed, if a charge resides at a distance further off than lambda;, it is shielded by the ions of the electrolyte solution. This suggest that OFET detections were possible only at salt concentration low enough so that lambda; is larger than the analyte size. We have performed a systematic study of a sensor response as a function of the Debye&’s length, the receptor charge and the distance at which the binding event takes place. The outcome of this study is that Electrolyte Gated OFET sensors, operated in highly concentrated solutions (lambda;= 0.7 nm), can sensitively probe a protein binding taking place at more than 20 nm far from the transistor channel. A successful proof-of-principle of their use as sensors directly in serum is also provided. The mechanism of sensing is mainly capacitive and has been ascribed to the formation of Donnan&’s equilibria within the protein layer originating an extra capacitance in series to the gating system. This capacitive tuning of the EGOFET response is virtually insensible to the Debye&’s length value. Systematic experiments carried out at different ionic strengths support this model.
G.Palazzo, D. De Tullio, M. Magliulo, A. Mallardi, F. Intranuovo, M.Y. Mulla, P. Favia, I. Vikholm-Lundin, and Luisa Torsi. Advanced Materials 2014 DOI: 10.1002/adma.201403541

The electrical conductivity of graphene-based transistors can be modified through interaction with chemical or biological species. Thanks to the high surface area of graphene, these devices exhibit high electrical sensitivity. Recently, several reports have demonstrated that graphene-nanoparticles hybrid structures can act synergistically to offer a number of unique physicochemical properties. Herein, we address the incorporation of gold (Au) nanoparticles on the graphene monolayer produced by chemical vapor deposition (CVD) process and their implementation into arrays of 64 FETs on SiO₂/Si substrates. These devices were then applied in the label-free detection of ErbB2, one of the most common proteins that act as biomarkers for breast cancer. The devices were produced using graphene monolayer obtained by CVD, which was then transferred onto a microchip with a 64 pairs of source and drain electrodes obtained by a conventional photolithography step followed by metal (Ti/Pd) deposition and formation by lift-off process on Si/SiO₂. After passivating the electrodes, only the graphene channels between source and drain electrodes were exposed to the environment. The Au nanoparticles were deposited on the graphene layer and the Erb2/Her2 Antibody was immobilized directly on Au nanoparticles, followed by a blocking step. The devices were then electrically characterized in each step of modification of the graphene layer. For the measurements in solution, an ionic liquid gate configuration was employed. The incorporation of Au nanoparticles on graphene enables us to detect ErbB2 protein at unprecedently low levels of few pg/mL. Our results show that the graphene-nanoparticle hybrid FET biosensor exhibits an additional synergistic property based on the capacitive coupling between graphene and the Au nanoparticles, thereby enhancing the achievable sensitivity for the electrical detection of breast cancer biomarker.

Insects have the exceptional ability to detect trace amounts of chemical vapors. The odor sensing occurs in receptors of the antenna where small proteins, called odorant-binding proteins, recognize analytes in the environment. In the case of sensing explosives, short peptide sequences derived from the odorant binding proteins of bumblebees are able to selectively recognize and discriminate the important nitroaromatics, TNT and DNT. ^1,2
This contribution describes the incorporation of selected short peptide sequences into organic semiconductor blends that are used to fabricate organic field effect transistors (OFETs) and electrolytically gated organic field effect transistors (EGOFETs). The charge mobility, source-drain current, and device threshold voltage were determined for devices exposed to vapors or solutions of TNT/DNT and controls. Evaluation of the multi-parametric response of the devices exposed to the analytes and controls showed that peptide recognition elements are able to effectively discriminate and quantify the nitro-aromatics TNT and DNT at sub-ppm concentrations as vapour and dissolved in water.
1. Z. Kuang et al. ACS Nano2010, 4, 452-458.
2. J. W. Jaworski et al. Langmuir2008, 24, 4938-4943.

Bioelectronics is a fast growing field and combines plastic electronics with biochemistry. One of the major aims is the detection of biologically important molecules. Here, organic electrochemical transistors (OECT) are very promising devices which use organic semiconductors to transduce chemical signals to electronic signals.^[1] Currently, the organic semiconductor of choice is PEDOT:PSS which does not allow selective detection for specific ions or molecules. There is a large demand for new biocompatible materials which can fulfil these requirements and detect specific molecules in biological processes.
We have developed polymers for the detection of alkali metal ions, especially sodium and potassium ions due to their relevance in biological processes. The detector component of the polymer is based on crown ether rings attached to thiophenes which coordinate with alkali metal ions when they are present. Here, the size of the crown ether ring will determine which alkali metal ion forms the most stable complex and this will create selectivity for certain ions.
In particular, we have synthesised alkali metal ion detecting conjugated polymers based on crown ether linked bisthiophene units and benzodithiophene (BDT). Our optimisation of crown ether bisthiophene^[2] synthesis has enabled us to incorporate the unit into a conjugated polymers for the first time. This unit was copolymerised with a BDT unit, which has already shown excellent performance in the field of plastic electronics. The ion detection mechanism works by virtue of a backbone twist which the bisthiophene unit undergoes when alkali metal ions, such as sodium ions, are incorporated into the crown ether. This twist alters the optoelectronic properties of the polymer, with the change in the polymers absorption profile already visually detectable. Moreover, we have shown that the ring size of the crown ether determines the polymer selectivity for the different sized alkali metal ions. The amount of ions incorporated along the backbone alters the magnitude of the polymer&’s response and this can be monitored by UV-Vis spectroscopy. Cyclic voltammetry measurements of thin films in water with alkali metal salts as the electrolyte showed electrochemical activity, which has prompted us to incorporate this new polymer into organic electrochemical transistors.
[1] J. Rivnay, R. M. Owens, and G. G. Malliaras, Chem. Mater., Chem. Mater. 2014, 26, 679minus;685.
[2] M. J. Marsella and T. M. Swager, J. Am. Chem. Soc., 1993, 115, 12214-12215.

In bio-electronics one attempts to explore the nature of conductivity in biological systems such as DNA, Peptide and proteins. Since some of these macromolecules are relatively large and can be easily attached to metal leads, one can investigate their electrical properties in the solid-phase and construct nano-sized devices in which the biological layers serve as the active part of the device.
In this talk I will describe our experimental efforts in this field. Specifically several examples of systems and devices will be shown: (i) Engineered Light-emitting bio-materials, which are made using the efficient nanometric separation in certain type of proteins, (ii) Control over the electrical properties of nano-sized junctions via “natural” and site-controlled doping of proteins monolayers (iii) construction and operation of reliable and reproducible bio-transistors and (iv) demonstration of bio-inspired solar cell.
1. Gordiichuk, P. I. et al. Solid-State Biophotovoltaic Cells Containing Photosystem I. Adv. Mater.26, 4863-+ (2014).
2. Hendler, N. et al. Efficient Separation of Conjugated Polymers Using a Water Soluble Glycoprotein Matrix: From Fluorescence Materials to Light Emitting Devices. Macromol. Biosci.14, 320-326 (2014).
3. Hendler, N., Mentovich, E. D., Belgorodsky, B., Rimmerman, D. & Richter, S. Controlled Electroluminescence from Films Composed of Mixed Bio-Composites and Nanotubes. Chemphyschem14, 4065-4068 (2013).
4. Mentovich, E. D., Belgorodsky, B., Kalifa, I., Cohen, H. & Richter, S. Large-scale fabrication of 4-nm-channel vertical protein-based ambipolar transistors. Nano Lett.9, 1296-1300 (2009).
5. Beilis, E., Belgorodsky, B., Fadeev, L., Cohen, H. & Richter, S. Surface-Induced Conformational Changes in Doped Bovine Serum Albumin Self-Assembled Monolayers. J. Am. Chem. Soc.136, 6151-6154 (2014).
6. Mentovich, E., Belgorodsky, B., Gozin, M., Richter, S. & Cohen, H. Doped biomolecules in miniaturized electric junctions. J. Am. Chem. Soc.134, 8468-8473 (2012).
7. Hendler, N., Belgorodsky, B., Mentovich, E. D., Gozin, M. & Richter, S. Efficient Separation of Dyes by Mucin: Toward Bioinspired White-Luminescent Devices. Adv. Mater.23, 4261-4264 (2011).

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 demonstrate that electronic transport can be maintained in such multicomponent systems upon blending with the insulating matrix, as well as displaying a tunable ability to conduct ions. Such straight-forward blending approach of conducting/insulating polymers also has the potential to bring multifunctionality to the final material systems, including biological activity, topological cues, etc., which in turn promises to enable more specific interactions with biological systems.
(1) R. M. Owens et al., MRS Bulletin, 35, pp. 449 (2010);
(2) S. Ghosh et al., Electrochemical and Solid-State Letters, 3 (5), pp. 213 (2000)

Conjugated polyelectrolytes (CPEs) are defined by a pi-delocalized backbone and pendant groups bearing ionic functionalities. Their oligomeric analogues, namely conjugated oligoelectrolytes (COEs), are simpler to characterize and to use as subjects for developing structure/property relationships due to a greater structural precision. The ionic component makes these materials unique, in that they combine the properties of organic semiconductors with the characteristics of polyelectrolytes. Solubility in polar solvents enables the fabrication of multilayer optoelectronic devices, with little disturbance of neutral underlying layers, in which the COE functions as an efficient electron injection/transport layer. Another well-established application of CPEs is in the area of optically amplified biosensors.
The pi-conjugated framework always retains a propensity for incorporating into hydrophobic environments. One consequence of this driving force is aggregation into various micellar structures wherein pi-stacking is observed, together with considerably different linear and nonlinear optical features. Similarly, cationic COEs based on oligophenylenvinylene repeat units have a tendency to accumulate within the lipid bilayer membranes of artificial vesicles or living microorganisms. A trivial application is that of membrane imaging. More interestingly, the incorporation of the COE allows for the fabrication of more efficient microbial fuel cells, which suggest that the “semiconducting” features of the molecule can facilitate transmembrane electron transfer. Electrodes can thereby be more intimately access redox reactions characteristic of metabolic processes. Additional studies show that, depending on the microorganism, it is possible to inject charges and stimulate metabolic processes. Additionally, it is possible to coordinate the function of more than one microorganism by way of improved electronic communication.
A comprehensive set of mechanistic studies will be discussed that shed light into the possible mode by which bioloelectrochemical function is modified.

An optically transparent poly(3,4-ethylenedioxythiophene) (PEDOT) based organic electronic devices have been developed to investigate the behavior of human mesenchymal stem cell (hMSC) and to sense and to capture circulating tumor cells. We first conducted a control experiment on electrical cell-substrate impedance sensing (ECIS) device by culturing the hMSC on the chip. According to our result, the impedance increased reflected the hMSC proliferation, attachment and motility during the first 16 hours of cell culture. In order to control the differentiation of human mesenchymal stem cell (hMSC) on chip, we also developed all-solution-processed multifunctional organic devices, comprising reduced graphene oxide (rGO) and dexamethasone 21-phosphate disodium salt (DEX) drug loaded poly(3,4-ethylenedioxythiophene) (PEDOT) microelectrode arrays on indium tin oxide glass, that can be used to manipulate differentiation. In our devices, the rGO micropatterns were used as the adhesive coating to attract the adhesion of hMSC cells whereas PLL-g-PEG coated PEDOT electrodes served as the anti-adhesive coating where no hMSC cells can attach. In addition, the PEDOT electrodes also work as drug releasing components where control DEX release from PEDOT matrix can be achieved via cyclic potential stimulation (CPS).
To capture the circulating tumor cells, we fabricated 3D PEDOT-based micro/nanorod array, which can be further surface-grafted with capture agents for directed specific recognition to study the cell-substrate interactions on bioelectronics interfaces (BEIs). This BEI platform features the advantageous characteristics: (1) diverse dimensional structures (tunable from the microscale to the nanoscale), (2) varied surface chemical properties (tunable from nonspecific to specific), (3) high electrical conductivity, and (4) reversible chemical redox switching. Furthermore, through systematic studies of PEDOT systems, we explore the effects of both chemistry and topography on the circulating tumor cell (CTC)-capture performance. The 400 nm PEDOT pillars exhibited the optimal cell-capture efficiency; it could be used to isolate CTCs with minimal contamination from surrounding nontargeted cells (e.g., EpCAM-negative cells, white blood cells) and negligible disruption of the CTCs&’ viability and functions. It is conceivable that PEDOT-based micro/nanorod array films function as a critical therapeutic intervention for monitoring tumor progression and metathesis, providing valuable insight into the use of electronics for tissue engineering and regenerative medicine.

Organic electrochemical transistor (OECT) is a preferable non-invasive sensing device for monitoring electrophysiological activities of electrogenic cells. It offers excellent sensing capabilities by converting tiny ionic current changes at cell-device interface into substantial channel current variations while its soft surface provides a strong coupling with cells. In the 2014 MRS Fall Meeting, our group reported the use of OECTs to monitor action potentials from HL-1 cell line at single OECT level. In this new study, we have expanded the project scope into multi-channel monitoring of action potentials from mammalian primary cardiomyocytes and mapping their intercellular action potential signal conduction.
Primary cardiomyocytes from neonatal Sprague Dawley rats were cultured directly on the surface of a 4×4 16-channel OECT array. After ~3-4 days, a cardiomyocytes layer was formed and cells started to beat spontaneously in a regular rhythm. The OECT array was then connected to a data acquisition (DAQ) system and signals were recorded simultaneously from all 16 OECTs. Excellent signal to noise ratios (SNRs) were achieved in our experiments with the highest ones reached up to 10σ_noise. By analyzing the spatial distribution and temporal differences of each spike, the direction and velocity of the cardiac action potentials&’ conduction were calculated. Furthermore an intercellular cardiac action potential conduction map was able to be drawn to study the electrical activity of the cells atop the entire transistor array.
Moreover, the role of each ion channel&’s activities in the recorded action potential profiles was investigated in this study. Ion channel inhibitors were applied onto cells for specifically inhibiting ion channels&’ activities. The resulting changes in signals recorded by OECTs revealed how exactly cardiomyocytes&’ action potential processes were coupled with OECTs.
In summary, cardiac action potentials from primary cardiomyocytes were successfully recorded by OECTs. The intercellular cardiac action potential conduction was also mapped by simultaneously recording signals from the entire OECT array. Ion channel inhibitors were used to illustrate the interactions between ion channels and OECTs. Our study provides device platform and understanding of OECTs for studying diseases related to excitable cells.

Organic bioelectronics refers to the coupling of conducting polymer based devices with biological systems, in an effort to bridge the biotic/abiotic interface(1). We focus on the unique properties of organic electronic materials that allow easy fabrication, and flexibility in design as well as chemical tunability, to develop state-of-the-art tools to (1) develop relevant in vitro models by creating more ‘in vivo&’ like environments and (2) monitor cells i.e. for diagnostic purposes following exposure to toxins or pathogens(2, 3). We work not only with commercially available materials, but are also optimizing custom materials for use in devices by changing morphology, adding biomolecules to increase biocompatibility(4), and incorporating biorecognition elements directly into the materials(5). Our goal is to develop physiologically relevant in vitro systems with integrated monitoring systems that obviate the need for animal experimentation in diagnostics, toxicology or drug development. To this end, we have successfully demonstrated the use of the organic electrochemical transistor (OECT) for monitoring in vitro models of the gastrointestinal tract, the kidney and the blood brain barrier. We show improved temporal resolution and sensitivity compared to existing techniques, and further, take advantage of the flexibility of design and fabrication of organic electronic devices to include microfluidics, optical monitoring and multiplex acquisition systems.

The kidney is not only responsible for filtering blood and removing waste products of metabolism, but also for regulating the homeostasis in the body. Some drugs which are designed for treating certain conditions also have nephrotoxic effects. Such toxicity is a significant problem during long term treatments. Nowadays, there are many efforts to test side effects in cellular models including immortalized cell lines and primary cell cultures. The Human Proximal Tubular Epithelial Cells (HPTEC) is an in vitro model use to analyze toxicological effects, because they keep almost all the kidney cell characteristics; however the TransEpithelial Electrical Resistance (TEER) value is prohibitively low. Our group previously developed a planar and a transparent Organic Electrochemical Transistor (OECT) to record the ion flux through the paracellular way, yielding quantitative metrics for barrier tissue integrity. The OECT is biocompatible and label free system that can monitor the health of the cell cultures; even if they show comparatively low TEER values. In this work, we analyzed the toxicological effect of a number of drugs on HPTEC cells using OECTs. Different concentrations of cisplatin, a chemotherapy drug, were tested. The measurements were performed continuously at 37°C, 5% CO₂ during 3 hours. The results showed unlike responses in a dose dependent manner and in a short time. Tobramycin and gentamicin, antibiotic drugs, were analyzed as well. KIM1, OAT1, and ZO-1 proteins were detected by immunofluorescence at the end of each experiment. We observed a protein delocalization which is related with cellular damage. Here we showed a new option for toxicology screening, especially to detect drug side effect.