Organic electrochemical transistors (OECTs) have shown promising applications in biosensors due to the high sensitivity, low working voltage and the simple design of the devices. OECTs have no gate dielectric and the gate voltages are applied directly on the solid/electrolyte interfaces and electric double layers near the channel and the gate, which lead to very low working voltages (about 1 V) of the transistors. On the other hand, the devices can be easily prepared by solution process or other convenient methods because of the much simpler device structure compared with that of a conventional field effect transistor with several layers. Many biosensors can be developed based on the detection of potential changes across solid/electrolyte interfaces induced by electrochemical reactions or interactions. The devices normally can show high sensitivity due to the inherent amplification function of the transistors. Here, I will report several types of OECT-based biosensors studied by our group recently, including protein, micro-RNA, glucose, dopamine, uric acid, cell, and epinephrine sensors. The biosensors show high sensitivity and selectivity when the devices are modified with functional nano-materials (e.g. graphene, Pt nanoparticles) and biomaterials (e.g. enzyme, antibody, DNA) on the gate electrodes or the channel. Furthermore, the devices are miniaturized successfully for the applications as sensing arrays. It is expected that the solution-gated transistors will find more important applications in the future.

Organic Electrochemical Transistor (OECT) is a popular electronic device used as biosensing platforms for metabolic analyte including glucose, lactate and uric acid. The reaction between these metabolic analyte and their corresponding enzyme, followed by the electrochemical oxidation of the hydrogen peroxide, would result in the transfer of electrons to the gate electrode. The change of the electrical double layer in the gate and electrolyte interface will increase the effective gate voltage apply on the active channel made by poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) and hence decrease the drain source current that is proportional to the analyte concentration. Generally, conventional OECT-based biosensors require a beaker or a relatively large PDMS reservoir to hold the electrolyte as the ion exchange medium, and it has several disadvantages such as the large volume consumption of the analyte, uneven distribution of the analyte and the limited potentials for portable applications. As a result, there is a strong need to develop OECT-based biosensors with not only high sensitivity, but also low dose detection ability and in compact chip size scale for practical usage. Here we integrate microfluidic channels with OECT sensor to achieve the glucose and lactate detection in the human saliva and sweat. Instead of using a suspended gate electrode, here we use planar OECT with platinum gate modified by carbon nanomaterials, biocompatible polymer and the corresponding enzyme. The transconductance of the device can be up to 2mS. Micro-channel is used in the device to contain the electrolyte with total volume as small as 3µL which can achieve fast and low dose detection. The response time of the device after introducing analyte with different concentration is less than 1minute that is much lower compared with conventional OECT based device with beaker or large PDMS reservoir. We optimize the gate area over channel area ratio to ensure the best device performance before the gate electrode modification. Glucose solution with different concentration is injected to the micro-channel and the detection limit can be up to10^-6M, which is sufficient to cover the glucose concentration range in the human saliva or sweat. Besides, we will also report the lactate detection in sweat when the object is under different levels of anaerobic exercise. The combined glucose and lactate sensing device has extremely high potentials for real time metabolic analyte sensing and health monitoring.

Conducting both ionic and electronic charge carriers, conjugated polymers are impacting on a large variety of biology-related applications as the electronic material interfacing with living systems. A device type that has predominantly utilized these polymers as its active component is the organic electrochemical transistor (OECT) - a bioelectronic device for enhanced ionic-to-electronic signal transduction. Poly(3,4- ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) has been a model material for OECTs, mostly due to its chemical stability. There is, however, room for improving these mixed conductors for better performing or specialized OECTs for targeted applications. Despite the demonstrated influence of balanced charge transport on the device performance, no design rules exist linking the polymer architecture and device characteristics [1].
In this work, we perform a comprehensive study on the thin film properties of a series of conjugated polymers and evaluate the concomitant performance of OECTs comprising these polymers in the active channel. For depletion mode OECTs, i.e. transistors that turn OFF upon application of a gate bias, we use PEDOT-based water dispersible polymers stabilized by a new class of polyanionic dopants replacing the traditionally used PSS. We investigate how systematic chemical modifications such as counter ion and chain length impact the device performance. We find that the polyanion phase governs the water uptake and the ion motion within the film, and can therefore be used to tune the device performance. Furthermore, with a hydrophilic thiophene-based conjugated polyelectrolyte in the active channel, we, for the first time, achieve a high transconductance accumulation mode OECT working fully in the electrochemical regime [2]. In particular, we show the effect of a co-solvent additive on the ionic and electronic mobility of the film, and discuss the tradeoff between the two conduction mechanisms for high transconductance OECTs. Highlighting the materials properties that enable enhanced ion-to-electron transduction, this work offers an understanding of materials-device performance relations for the development of optimized active channel materials.
1. J. Rivnay et al. Sci. Adv. 1, e1400251 (2015).
2. S. Inal et al. Adv. Mater. 26, 7450 (2014).

Through photosynthesis, plant cells generate photosynthetic electrons by splitting water into molecular oxygen, protons, and electrons with the aid of solar energy. Generation and transport of photosynthetic electrons within the plant cells is highly efficient and has recently drawn much attention for a new type of biosolar cells. Previously, we reported the feasibility of direct extraction of photosynthetic electrons from living single algal cells using custom-fabricated AFM nanoelectrodes. However, insertion of the AFM nanoelectrode was extremely difficult and had very low success rates. In addition, planar triangular-shaped electrode often damaged the cell membrane and resulted in leakage of cellular components. Therefore, for long-term stable monitoring and extraction of photosynthetic electrons, we have developed a horizontally-tilted cantilever NE system (H-CNE) in combination with an optical microscope. This system enables full optical monitoring of NE insertion into single cells as well as in situ measurement of insertion forces. Furthermore, embedding Au layer between the silica and silicon nitride passivation layers of H-CNEs allows highly-localized measurement of electrochemical activity within the cytosol space of the algal cells. Commercial AFM tips were milled to have the diameter of 100 ~ 700 nm by focused ion beam (FIB). After sputter deposition of Au layer on the FIB-milled NEs, they were insulated using SiNx layer. Only the tip portion of the H-CNE was cut-exposed to detect subcellular electrochemical activities. By recording the degree of cantilever deflection, insertion force of each H-CNE into an algal cell (Chlamydomonas reinhardtii) was measured and the effect of H-CNE diameter on the insertion force and stability was analyzed. After nanoelectrode insertion, the inserted cell was monitored to observe its survival duration. H-CNEs with the diameters smaller than 500 nm had no adverse effect on cell survival for 24 hrs and even cell division was observed. Cyclic voltammetry analysis using potassium ferricyanide (K₃[Fe(CN)₆], 0.01M) as a redox system and potassium nitrate (KNO₃, 0.1M) as an supporting electrolyte, also confirmed the electrochemical performance of the H-CNEs as an ultra-microelectrode. The light-triggered currents were monitored using the H-CNEs for the case of DI water, TAP media, TAP media/cells, and algal cells inserted by H-CNE. Light intensity was 99 mu;mol/m²/s¹ and the potential of 0.4V (versus Ag/AgCl) was applied to the H-CNEs. There was no significant photo-responsive currents for DI water, TAP media, and TAP media/cells. Noise-level fluctuation of less than about 200 fA was observed. Only when the H-CNE was inserted into an algal cell, photo-responsive currents of about 500 fA were successfully monitored. This H-CNE system allows for stable insertion of NE into the cell interior space as well as measurement of highly-localized photo-electrochemical reactions in photosynthetic living algal cells.

Despite recent interest in organic electrochemical transistors (OECTs), sparked by their straightforward fabrication and high performance, the fundamental mechanism behind their operation remains largely unexplored. OECTs use an electrolyte in direct contact with a polymer channel as part of their device structure. Hence, they offer facile integration with biological milieux and are currently used as amplifying transducers for bioelectronics. Ion exchange between electrolyte and channel is believed to take place in OECTs, although the extent of this process and its impact on device characteristics are still unknown. We recently showed that the uptake of ions from an electrolyte into a film of poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) leads to a purely volumetric capacitance of 39 F/cm³. I will show that this results in a dependence of the transconductance on channel thickness, a new degree of freedom that can be exploited to demonstrate high-quality recordings of human brain rhythms. Our results bring to the forefront a transistor class in which performance can be tuned independently of device footprint and provide guidelines for the design of materials that will lead to state-of-the-art transistor performance.

Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 sec electrodeposition of PEDOT/GO produces the most optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to improved adsorption of DA&’s oxidation product (DA-o-quinone) onto the PEDOT/GO film. Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo.

Complementary metal-oxide-semiconductor (CMOS) electronics have revolutionized computing and communication technology, offering unprecedented levels of performance and integration densities. CMOS technology, leveraging a huge manufacturing base, is now aggressive moving into new application spaces in the life sciences, which require CMOS to be augmented with new materials and devices and to conform to new form factors. CMOS interfaces allow for direct transduction to electrons in interfacing to biological systems, offering many advantages over optical approaches, but require proximity.
In the area of molecular diagnostics, CMOS technology is being used to advance electronic techniques for single-molecule DNA sequencing, including those based on nanopores. CMOS integration brings advantages in supporting highly multiplexed array platforms and in improving achievable bandwidths and noise performance of these technologies. Other molecular diagnostics exploit exposed-gate nanotube devices integrated with CMOS for specific recognition of genomic and proteomic samples. Exploitation of CMOS for these applications requires “post processing” to add electrochemically compatible metals and packaging technology to make the chips compatible with electrolytic solutions and to allow for microfluidics.
CMOS technology can also be used to produce arrays of potentiostats able to electrochemical analyze biological systems in direct contact with the chip. This has been used to study signaling in bacterial colonies, exploiting the redox activity of the signaling molecules, enabling new tools for microbiology.
CMOS technology also creates new opportunities to dramatically scale electrophysiological interfaces to neural tissue. Active CMOS multielectrode arrays allow electrode densities to exceed 1000 electrodes/mm², bringing new opportunities to study planar system such as the retina. CMOS technology can also be thinned to the point of pliability making it possible to produce flexible electronics that fully exploits the capabilities of CMOS, improving mechanical compatibility for implanted systems. Examples here include 65,000-channel arrays for surface recording and fully wireless shanks for electrophysiological recording and stimulation in the brain.

Biomarkers are used in life science to signal the onset of specific biological events. For example, changes in temperature can microscopically signal the degradation of certain proteins, or macroscopically signal the onset of a fever. Changes in blood-pressure may microscopically signal fluctuations in cholesterol levels, or macroscopically signal the onset of a stroke. In neuroscience, particularly in epilepsy, the classical biomarker to signal the onset of a seizure is an electrophysiological biomarker. Although an electrophysiological biomarker will very clearly represent the onset of the seizure, it is a very poor predictive indicator. This is because the pathological electrophysiological activity is the seizure itself. Far more useful would be a biomarker which predicts the seizure, well-before the onset of the pathological electrophysiological activity. Here we demonstrate the use of metabolic sensors, primarily for glucose and lactate, which are capable of detecting the onset of a seizure before the pathological electrophysiological activity begins. Sensor fabrication is carried out via processing techniques which produce enzymatic sensors based on flexible, non-invasive neural probes. Using the conducting polymer (CP) PEDOT:PSS {poly(3,4-ethylenedioxythiophene) doped with poly(styrenesulfonate)}, we include organic electrochemical transistors (OECTs) on these neural probes. This allows us to take advantage of the high transconductance of these devices, creating a highly amplified signal which is sensitive and selective to specific analytes due to incorporation of a bio-recognition element functionalized on the OECT. Such devices provide higher currents in comparison to standard electrodes functionalized with similar bio-recognition elements. Furthermore, we incorporate a secondary enzymatic layer to reduce cross talk between neighbouring sensors as well as toxicity to neuronal cells.

There is an increasing need for the development of multifunctional lightweight materials with high strength and toughness. Natural systems have evolved efficient strategies, exemplified in the biological tissues of numerous animal and plant species, to synthesize and construct composites from a limited selection of available starting materials that often exhibit exceptional mechanical properties that are similar, and frequently superior to, mechanical properties exhibited by many engineering materials. These biological systems have accomplished this feat by establishing controlled synthesis and hierarchical assembly of nano- to micro-scaled building blocks. This controlled synthesis and assembly require organic that is used to transport mineral precursors to organic scaffolds, which not only precisely guide the formation and phase development of minerals, but also significantly improve the mechanical performance of otherwise brittle materials. However, Nature goes one step further, often producing materials with that display multi-functionality in order to provide organisms with a unique ecological advantage to ensure survival.
In this work, we investigate a variety of organisms that have taken advantage of hundreds of millions of years of evolutionary changes to derive structures, which are not only strong and tough, but also demonstrate multifunctional features dependent on the underlying organic-inorganic components. Specifically, we discuss (i) an ultrahard and light diffusing shell of a bioluminescent gastropod that uses its thick shell not only for protection but also to ward off predation through illumination, (ii) the hyper-mineralized combative dactyl club of the stomatopods, a group of highly aggressive marine crustaceans, (iii) the heavily crystallized radular teeth the chitons, a group of elongated mollusks that graze on hard substrates for algae. From the investigation of structure-property relationships in these unique organisms, we are now developing and fabricating cost-effective and environmentally friendly multifunctional engineering composites with impact resistance and biologically inspired nanomaterials for energy conversion and storage.

Unperceivable personal monitoring systems to be used in healthcare and sport can be enabled by the development of conformable electronics. Ultra-thin polymeric films are envisioned as candidate substrate materials in particular for skin-contact applications[1] because of their intrinsic ultra-conformability on any surface, without compromising structural integrity and function of electrodes (physiological signals recording) and other on-board electronic components. [2] On the other hand, portability and comfort of devices is improved: they are almost unnoticeable to the user.[3] Such unusual ultra-thin substrates impose severe restrictions to the suitable fabrication methods and challenges for the reliable integration of key electronic components. As a matter of fact, alternative strategies are needed also as regards release, manipulation and transfer on the skin of conformable devices. With the aim of providing robust, low cost and safe solution to these problems, we recently reported about conductive tattoo nanosheets. These disposable ultraconformable electrodes were fabricated by ink-jet printing of PEDOT:PSS on top of decal transfer paper and were transferred on skin as temporary transfer tattoos. They successfully performed as dry electrodes for surface electromyography (sEMG) for recording muscle activity, and permitted the myographic control of a robotic hand.[4]
Aiming at expanding the recording capabilities of these tattoo electrodes and at providing a full on board integration of the necessary external connections, we report here a fabrication and multi-layer assembly process. PEDOT:PSS multichannel electrode pads are ink-jet printed on top of decal transfer paper, commercially available in temporary tattoo kits (layer 1), while gold connectors are patterned on top of a poly(ethylenenaphtalate) (PEN) ultra thin sheet (1.3 µm) (layer 2). An acrylic glue layer, (available in the same tattoo kit) is also used (layer 3) for the assembly. Reliable connections to the external recording systems are provided by means of gold coated polymer film strips with graded thickness. The shape and pattern of each individual layer is defined with a laser cutter. Dry lamination of different layers permits the final assembly of the fully-integrated multichannel electrodes tattoo. The assembled tattoo can then be released on the user skin as in standard temporary transfer tattoos. Thanks to the adopted strategy as many as 6 different recording channels were fabricated on top of each tattoo which permits high density sEMG recording with stable adhesion and operation. These achievements can permit to envision other on-skin application of multichannel tattoos as electrodes for electroencephalography (EEG) or electrocardiography (ECG).
References
1. M. Kaltenbrunner et al., Nature499, 458 (2013).
2. D. H. Kim et al., Science333, 838 (2011).
3. J.-W. Jeong et al., Adv. Mater.25, 6839 (2013).
4. A. Zucca et al., Adv. Healthc. Mater.4, 983 (2015).

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 bio sensors 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 was able to sense low concentrations of mercury ions in sea water.[2,3]
Here we would like to present the second generation of this highly sensitive bio-sensor platform based on organic field-effect transistors developed in our group able to operate at even lower voltages which is 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 detect its corresponding analytes. This methodology allows preparing a scalable, easy producible and high performing sensor platform suitable for portable biosensing in aqueous media.
[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

Pi conjugated peptides have attracted wide attention due to their potential applications in bioelectronics and tissue engineering. The molecular architecture for this family of materials can be very precisely controlled by rationally varying the amino acids involved, affecting the hydrogen bonding and packing of the core which in turn leads to unique photophysical characteristics and tunability of properties. Electronic functionality imparted to biological systems via these pi conjugated peptides provides a platform for influencing cell growth and behavior in a systematic way for varied applications in cell engineering.
Our study utilizes one-dimensional pi-conjugated peptide nanostructures assembled under aqueous conditions to establish the influence of amino acids on the electronic functionality of pi-conjugated units embedded in the nanostructures. The peptide nanostructures, with nanowire morphologies, are investigated as semiconductors and conductive materials in an OFET structure by utilizing them as semiconductor and as gate material. Although these self-assembled nanowire films primarily consist of non-conducting peptide units, the mobility values achieved are comparable to standard organic semiconductors. The mobility values achieved could be tuned by up to three orders of magnitude (~0.02 to 5x10^-5 cm² V^-1 s^-1) by varying the amino acids in the peptide parts.
Control peptides without the quaterthiophene core are used to demonstrate that the pi-core semiconducting behavior is mainly responsible for the transport properties of the device,not just ionic rearrangements. The effect of dielectric layer thickness was studied in devices with pentacene as the semiconductor and the nanowire mats as the gate. Optimum OFET performance was achieved with 35 nm dielectric thicknesses establishing that an electrical signal can be easily conveyed using these materials over biological relevant distances.

Nanoscale electronic devices have the potential to achieve superior sensitivity as sensors for the detection of molecular interactions, thereby decreasing diagnostics costs and enabling previously impossible sensing in disparate field environments. Using integrated silicon nanowire field-effect transistors (NW-FETs) that are compatible with CMOS technology [1] we study a wide range of biochemical and macromolecular sensing applications. Direct, label-free detection of biomolecules such as proteins and DNA enables the study of binding kinetics by real-time measurements [2, 3]. Multiplexed NW-FETs allow for differential [4] and multianalyte sensing. Indirect methods such as the detection of enzyme-substrate interactions in physiological buffers [5] present ways to overcome critical limitations of nanowire sensors such as the Debye screening limitation [6], the competing surface reactions [7], and the lack of internal calibration for analyte quantification, which have prevented their use in clinical applications and physiologically relevant solutions. We will present approaches that solve these longstanding problems, which demonstrates the detection at clinically important concentrations of biomarkers from whole blood samples [8], integrated assays of cancer biomarkers [9], and the use of these as a quantitative tool for drug design and discovery.
[1] E. Stern, J. F. Klemic, D. A. Routenberg, P. N. Wyrembak, D. B. Turner-Evans, A. D. Hamilton, et al., Nature, vol. 445, pp. 519-22, 2007.
[2] X. Duan, Y. Li, N. K. Rajan, D. A. Routenberg, Y. Modis, and M. A. Reed, Nat Nanotechnol, vol. 7, pp. 401-7, 2012.
[3] M. Wipf, R. L. Stoop, G. Navarra, S. Rabbani, B. Ernst, K. Bedner, et al., Submitted to ACS Nano, 2015.
[4] M. Wipf, R. L. Stoop, A. Tarasov, K. Bedner, W. Fu, I. A. Wright, et al., ACS Nano, vol. 7, pp. 5978-5983, 2013.
[5] L. Y. Mu, I. A. Droujinine, N. K. Rajan, S. D. Sawtelle, and M. A. Reed, Nano Letters, vol. 14, pp. 5315-5322, 2014.
[6] E. Stern, R. Wagner, F. J. Sigworth, R. Breaker, T. M. Fahmy, and M. A. Reed, Nano Letters, vol. 7, pp. 3405-3409, 2007.
[7] R. L. Stoop, M. Wipf, S. Müller, K. Bedner, I. A. Wright, C. J. Martin, et al., Sensors and Actuators B: Chemical.
[8] E. Stern, A. Vacic, N. K. Rajan, J. M. Criscione, J. Park, B. R. Ilic, et al., Nat Nanotechnol, vol. 5, pp. 138-42, 2010.
[9] A. Vacic, J. M. Criscione, E. Stern, N. K. Rajan, T. Fahmy, and M. A. Reed, Biosensors and Bioelectronics, vol. 28, pp. 239-242, 2011.

Printed electronics have been garnering significant attention because it enables thin, lightweight and low-cost electronic devices and systems. The uniformity of electrical performance is a key issue for printed electronic devices and systems to be used as biosensors. Here, we report on a flexible biosensor device using printed organic circuits with a high degree of electrical performance and uniformity [1]. Both the drop volume and layer area of small molecule semiconducting solution can be controlled by the printing system, and this results in large single-domain crystalline grains that grew reproducibly along the channel. The organic TFT devices exhibit excellent exceptionally uniform electrical characteristics, as well as almost 100% device yields. The average threshold voltage is -0.12 ± 0.09 V, which corresponds to a 0.4% spread in the operation voltage. This remarkable uniformity for our printed devices is comparable to the evaporated TFT devices. We have used these printed devices to make a differential amplifier of a biosensor for detecting immunoglobulin G [2]. A positive shift in the input-output characteristics of the differential amplifier with increasing concentration in target IgG was clearly observed and a linear relationship was observed at low concentrations (<15µg mL^-1). An easily readable sensing signal is obtained in the form of a shift in the output voltage in the biosensor, indicating the potential ability of our printed organic circuits in practical sensor applications.
The Authors are grateful to Tosoh Corporation for providing semiconducting materials.
[1] K. Fukuda et al., Adv. Electron. Mater. DOI: 10.1002/aelm.201400052.
[2] T. Minamiki et al., Materials, 7, 6843-6852 (2014).

One of the major goals of organic bioelectronics relies on the development of low-cost sensitive label-free biosensors, as also recently reviewed [1]. On the other hand, unreproducible detection and poor stability may represent typical drawbacks of such devices. For example, organic semiconductors used for preparing functional bio-interlayer organic field effect transistors (FBI-OFETs) can be very sensitive to aqueous environment as well as biological receptors (e.g. proteins, enzymes, DNA) can degrade with time. To this aim, the implementation of inorganic nanostructures in OFET-based biosensors could improve device performance. Our research group developed an electrochemical approach to prepare ZnO nanoparticles (ZnO-NPs) based on the dissolution of a zinc anode under galvanostatic control in a slightly alkaline sodium bicarbonate aqueous solution adding an anionic stabilizer (poly(sodium 4-styrenesulfonate), PSS) [2]. The electrosynthesis with low-cost non-toxic chemicals of nano-gels is followed by their calcination at temperatures ge; 300°C for complete conversion to ZnO-NPs. A multi-technique characterization (TEM, UV-Vis, XPS, FTIR spectroscopies, Zeta-potential measurements) allowed assessing their morphology and chemical composition, useful for their subsequent processing. In this communication, we present results regarding the implementation of the ZnO nanophases in the active layer of ultrasensitive FBI-OFET devices [3]. Two model bioreceptors (Streptavidin and Avidin) were employed for biotin sensing. Bioreceptor/ZnO-NP aqueous suspensions were prepared and directly spin coated on dielectric surface followed by the deposition of poly(3-hexylthiophene-2,5-diyl) (P3HT) semiconductor film over the active layer. It was shown that detection limits in the low ppt range could be repeatably and reproducibly recorded. Moreover, the addition of ZnO-NPs allowed extending FBI-OFET durability for months under laboratory conditions without significant reduction of biosensor performance.
[1] M. Magliulo, K. Manoli, E. Macchia, G. Palazzo, L. Torsi, Adv. Mater. (2014), DOI: 10.1002/adma.201403477.
[2] R.A. Picca, M.C. Sportelli, D. Hötger, K. Manoli, C. Kranz, B. Mizaikoff, L. Torsi, N. Cioffi, submitted.
[3] M. Magliulo, A. Mallardi, R. Gristina, F. Ridi, L. Sabbatini, N. Cioffi, G. Palazzo, L. Torsi, Anal. Chem. 85 (2013) 3849-3857.

A floating-gate transistor can transduce the capture of biomolecules on the floating-gate surface from the neighboring electrolyte. In order to define the origin of previously reported electronic signals we performed a systematic study of floating-gate organic transistors fabricated with electrolyte gating media. The device was first tested without a floating gate and approximated as a simple circuit of two capacitors by measuring the potential of the electrolyte bulk via a quasi-reference Pt electrode. Introduction of a floating gate required modification of the circuit to account for charge storage in the floating gate that enhances the device sensitivity to changes in floating-gate capacitance. Finally, the floating gate was selectively functionalized with self-assembled monolayers (SAM) to observe how changing its work function altered the effective gate voltage. We found that the direction of the voltage change was dependent on the orientation of the SAM but independent of the end group chemistry due to charge screening by electrolyte ions. The presented results outline the operation modes our previous organic electronic biosensor and will help guide the design of other electronic devices utilizing electrolyte dielectrics.

Cancer treatments that exploit inherent differences in redox active enzymes to induce selective DNA damage represent a promising strategy for circumventing common therapeutic resistances. Challenges in attaining full understanding of the activity and lethality of these DNA damaging drugs involve controlling the pathways and cofactors present within the system and precisely understanding damage repair activity at the level of DNA. The Slinker Lab at UT Dallas has designed a chip platform of arrayed DNA modified electrodes that can be used to mimic the cellular environment and follow DNA repair activity. This approach enables selective management of biological cofactors and preservation of critical features of the cellular environment for real-time, selective study of repair activity, offering benefits over conventional alternatives such as gel shift, Western Blot, and comet assays. These devices were shown to sense damage-specific sensitivity thresholds on the order of femtomoles/nanograms of proteins with response times of seconds. These chips were subsequently implemented in the study of the anticancer agent beta-lapachone, which catalytically generates DNA damaging peroxide in the presence of overexpressed NAD(P)H:quinone oxidoreductase 1, a hallmark of many cancer cells. These electrochemical devices have shown real-time, selective response to drug-induced damage repair, demonstrating their utility in tracking environmental damage. Ongoing study will clarify the mechanism of selective cancer cell death induced by the DNA base-excision repair pathway.

Within 1.3 L volume of human brain billions of neurons connected by quadrillions of synapses are exchanging electrical, chemical and mechanical signals. Our ability to study this complexity is currently limited by the lack of technologies available for interrogating the nervous system across all of its signaling modalities without inducing foreign-body reaction.
We have recently demonstrated that fiber-drawing process can be applied to produce probes that enable simultaneous electrical, optical and chemical communication with neural tissues. We have evaluated these flexible multi-material structures with micron features in vivo. Our findings indicate that fiber-based probes can simultaneously record, stimulate and chemically modulate brain activity of freely moving mice. Furthermore, their highly compliant structures allow for implantation into the spinal cord where they can be used to control locomotor activity. Finally, fiber-drawing process can be applied to produce optoelectronic scaffolds allowing for topographic control of the developing neuronal processes and intimate electronic and optical interfaces with neural tissues integrated directly within these devices.

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.

New generation of organic bioelectronics requires devices that are constructed within the biological environment of interest aiming direct interface and better matching. Usually, devices that induce or record biological phenomena are placed in close proximity or implanted into a biological unit having minimal invasiveness in the first and better resolution in the latter case. There is a necessity for both new materials and novel manufacturing approaches for developing devices integrated within the biological structure having as ultimate goal maximum compatibility, functionality and sensitivity.
PEDOT-S, a self-doped p-type conducting polymer where the sulfonate side groups play the role of the dopant, is a promising material for new generation bioelectronic devices as it can self assemble in aqueous environments. It has already been shown that it self assembles onto DNA and amyloid polymer structures due to electrostatic interactions forming conducting networks for nano-electronic devices.
We were able to form cm scale PEDOT-S conducting wires in confined spaces of aspect ratio larger than 1000. The wires were a result of the interplay between unidirectional flow of the diluted polymer and cross-linking due to the presence of ions. Electrical characterization revealed ohmic behavior and conductivity on the order of 0.1S/cm. The conductivity of PEDOT-S can be modulated upon application of voltage and exchange of ions between an electrolyte and the wire. Hence we constructed an OECT based on a single PEDOT-S wire that serves not only as the transistor channel but also as the source and drain. Gating is realized through the electrolytic medium surrounding the confined space. Taking this a step further, we build a NOR logic gate by combining two transistor in series with an external resistor. By applying different combinations of input signals we measured the Boolean logic function of the NOR gate at the output terminal. This work, although still in its infancy paves the way towards new generation of organic biolectronic devices.

Electronic transducers of neuronal cellular activity are important devices in neuroscience and neurology. Organic field-effect transistors (OFETs) offer tailored surface chemistry, mechanical flexibility, and high sensitivity to electrostatic potential changes at device interfaces. These properties make them attractive for interfacing electronics to neural cells and performing extracellular recordings and stimulation of neuronal network activity.
I will present an emerging area of interest where OFETs fabricated on biodegradable films are used to supply a variety of electrical, chemical and electrochemical stimuli to neuronal cells and to record their response. The context is to develop a new treatment for Spinal Cord Injury (SCI) where the multifunctional organic device is used as a tool for stimulating residual plasticity and control inflammation. In this talk, I will overview some of the results of the EU-FP7 project “Implantable Organic Nanoelectronics” (iONE-FP7). I will discuss the principles of transduction, the bidirectional operations in vitro and in vivo, the technology for prototyping biodegradable devices that integrate several transistors and a microfluidics, and present the outcomes of in-vivo stimulation of SCI-contused mouse as a model of the pathology. I will finally discuss direction of further development of the technology towards loco-regional therapy and POC applications.
This work has been carried out with my coworkers at UNIMORE: Stefano Casalini, Giulia Foschi, Michele Di Lauro, Marcello Berto, Carlo A. Bortolotti, Nadja Saendig, and CNR-ISMN Bologna: Tobias Cramer, Mauro Murgia, Alessandra Campana, Adrica Kyndiah, Silvia Tortorella. It involves the collaboration of several European partners, that I would like to acknowledge through the principal investigators: Stefano Pluchino (Univ. of Cambridge), Magnus Berggren and Daniel Simon (Univ. Linkoeping), Francesco Zerbetto and Stefania Rapino (Univ. di Bologna), Pierpaolo Greco (Scriba Nanotecnologie Srl Bologna), Dominique Vuillaume (CNRS, Lille), Ricardo Garcia (CSIC Madrid), Henrique Gomes (Univ. do Algarve).
This work was supported by EU NMP Project I-ONE-FP7 Grant Agreement n. 280772 and Bilateral Project Italy-Sweden “Poincaré”.
References
[1] S. Casalini, F. Leonardi, T. Cramer, F. Biscarini, Org. Electr., 14, 156-163 (2013).
[2] T. Cramer, B. Chelli , M. Murgia et al., Phys. Chem. Chem. Phys., 15, 3897-3905 (2013) .
[3] T. Cramer, A. Campana, F. Leonardi, et al., J. Mater. Chem. B, 1 3728-3741 (2013).
[4] A. Campana, T. Cramer, D. Simon, et al., Adv. Mater., 26, 3874-3878 (2014).
[5] S. Casalini, A. C. Dumitru, F. Leonardi et al., ACS Nano, 9, 5051-5062 (2015).

To effectively interface materials with single living cells and tissues, we need to understand the molecular interactions of the extracellular matrix and cell surface components such as the glycocalyx, lipids and protein receptors. A way forward will be to use functionalized nanoscale probes to directly measure the specificity, binding forces and kinetics of interacting molecules responsible for transmitting information at the cell-material interface. With organic electromaterials such as conducting polymers and graphene emerging as materials for in vitro and in vivo applications (e.g. implantable electrodes, conductive cell scaffolds), there is also the ability to apply electrical stimulation to control cell function, including adhesion and proliferation/differentiation, leading to potential “bioelectric” medicines. In this presentation, we discuss our work on the development of Bio-Atomic Force Microscopy (Bio-AFM) for materials research and enabling detection of cell-material interactions at the molecular level. We will specifically discuss the combination of Bio-AFM with electrochemical techniques to study conducting polymers, their interactions with single proteins and cells, and effect of electrical fields on biomolecular interactions.

Electrically active implants and catheters for neuromodulation, neural prostheses, and cardiac rhythm management depend on the safe, stable, and efficient transmission of electrical signals across the tissue-electrodes interface in order to provide maximal therapeutic benefit. Traditionally devices have relied on machined precious metal electrodes sometimes with metallo-ceramic coatings for this due to their high conductivity and inert nature. However as the size of electrodes for mapping and stimulation decreases in order to provide higher spatial resolution and to minimize device size and invasiveness, the impedance of such electrodes increases dramatically leading to lower safe charge injection limits and increased noise levels. Thus in order to enable these electrodes to operate effectively, electrode materials are needed that can increase the safe and reversible charge delivery and reduce recording noise and artifacts. Electrode coatings made from inherently conductive polymers can address these issues by facilitating electronic transfer at the interface through their high effective surface area, dual electro-ionic conductivity, and mechanical compliance. Due to their chemical structure and morphology, they are able to exchange between electronic and ionic charge carriers more efficiently than metal or metallo-ceramic materials or similar size. Biotectix has developed coatings for medical implants and catheters based on a highly durable form of the inherently conductive polymer poly(3,4-ethyelenedioxythiophene), or PEDOT. In this talk we will present recent results on the durability and therapeutic benefits of such materials for cardiac and neural applications.

Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. We developed an organic, ultra-conformable, biocompatible and scalable neural interface array (the ‘NeuroGrid&’) that can record both LFP and extracellular action potentials from cortical neurons without penetrating the brain surface. Spiking activity demonstrates consistent phase modulation by ongoing oscillations and is stable in recordings exceeding one week. We also record LFP-modulated spiking activity intra-operatively in patients undergoing epilepsy surgery. We demonstrate large-scale hippocampal and cortical interactions from the entire dorsal cortical surface and hippocampus in rats. We investigate the spatiotemporal interactions of the hippocampus with diverse functional cortical regions, as well as the interactions of these cortical regions with each other.
The ability to acquire and analyze LFP simultaneously from multiple functionally distinct brain regions will enhance comprehension of neural network processes and has implications for brain disorders characterized by disordered network function such as epilepsy.

Organic light-emitting diode (OLED) microdisplays are a new type of optoelectronic device that finds applications in electronic viewfinders, video cameras, or personal video players. Typically, they comprise of a silicon chip containing electronics that addresses over hundred thousand individual top-emitting OLED pixels deposited directly on the chip. Here, we demonstrate a completely novel application of OLED microdisplays, namely to use them as platform for advanced cell biology and optical cell manipulation. In our study, each pixel of the displays has a size of about 6 µm x 9 µm, dimensions that allow resolving, addressing and interfacing not only single living cells but even parts of individual cells. The displays also provide a high temporal resolution with a response time <10 µs that enables investigation of fast cellular processes, e. g. activity of ion channels. Advanced thin film encapsulation prevents OLED degradation despite immediate (< 2 µm) contact with cell culture medium.
As a proof-of-concept, we investigated the blue light-controlled locomotion (phototaxis) of the green alga Chlamydomonas reinhardtii. As a direct result of the small size of the individual pixels of our OLED displays, this approach allows one to study the behaviour of individual cells. We found that the phototactic response of the C. reinhardtii depends on the optical power provided by the OLEDs and we were able to clearly distinguish different strains by their different phototactic behaviour.
C. reinhardtii is a famous biological model organism and, in addition, it is the natural source of the photoreceptors that are at the centre of the fast-growing field of optogenetics, a method that combines genetic manipulation and light exposure to gain control over cells or tissue, specifically to investigate processes in selected neurons without altering the behaviour of other nearby neuronal cells. We will show preliminary data on the use of OLED microdisplays to control membrane voltage in genetically modified cells expressing optogenetic constructs.

Organic Electrochemical Transistors (OECTs) have been proposed as low cost chemical sensors for the detection of several analytes thanks to their remarkable features such as signal amplification, the use of an easy and cheap readout electronics, low supply voltage (usually < 1 V), low power operation (< 100 mu;W), bio-compatibly, and, moreover, they can be easily miniaturized and adapted to non-flat or/and flexible devices. An OECT is composed by a stripe of conductive polymer that works as a channel, and by another electrode, usually a metal, that works as a gate. When the device is dipped in an electrolyte solution, the current flowing in the channel can be modulated through the gate voltage because it promotes electrochemical reactions that change the charge carrier concentration in the polymer and, consequently, its conductivity. Redox compounds can act on such processes by varying the doping degree of the conductive polymer, thereby changing the current density inside the channel.
This contribution describes the development of sensors based on an OECT made only by poly(ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) as conductive material. The sensor was optimized by studying the response to ascorbic acid (AA)¹, a biological compound that is important in different fields of science and technology, such as medicine and food and pharmaceutical industry. AA reacts with PEDOT:PSS by extracting charge carriers from transistor channel, and consequently an increase of its concentration leads to a decrease of the absolute value of drain current that results linear dependent on the logarithm of AA concentration. The best sensing conditions show a very low limit of detection that is equal to 10^-8 M, highlighting performances that are better than the ones obtained with common amperometric transduction. Such results demonstrates the potentiality of all-PEDOT OECTs as platform for developing chemical sensors for the detection of redox-active molecules. Nevertheless the OECT sensors displays similar responses to other redox active compounds. In order to increase the selectivity and the sensitivity of the device, the “click chemistry” approach was exploited to chemically modify PEDOT:PSS with ferrocene. The procedure is very easy and require only two steps consisting of the electrodeposition of PEDOT-N₃ followed by copper-catalyzed azide-alkyne cycloaddition of ethynylferrocene. The coated electrodes have been characterized by XPS, showing successful ferrocene immobilization, by AFM, and by cyclic voltammetry which is dominated by the stable and highly reversible response of ferrocene. Firstly, such material was used for producing an amperometric sensor for dopamine detection, and we are now applying the same technique for functionalizing the gate electrode or the channel of our OECT using ferrocene.
¹Gualandi et al., J. Chem. Mater. B, In press
²Scavetta et al., J. Mater. Chem. B, 2014, 2, 2861-2867.

The use of conducting polymers as materials for bioelectronics is a rapidly-growing research field. Their mechanical and electrical properties, together with their excellent biocompatibility, make them more suitable for being used as an interface between electronics and cell tissues than “traditional” inorganic semiconductors. Moreover, since the physical and chemical properties of conducting polymers can be modified in response to electrical stimuli, these materials can be used as active substrates for cell growth.
Recently, conducting polymers were proved to influence cell behavior, in terms of cell adhesion and growth, by a change in their oxidation state. The cell-substrate interaction involves many different parameters, both physical (surface roughness, surface energy), chemical (pH, oxidation state) and biological (extra-cellular matrix formation, protein conformation), but the way these parameters are related to each other and to cell behavior is still not clear. Gaining a better understanding of the processes that control cell adhesion is crucial in order to use conducting polymers as a new tool in basic research, medical diagnostics, and tissue engineering.
We employed two different techniques, spin-coating and electro-polymerization, to deposit thin films of a bio-compatible conducting polymer widely used in organic electronics, poly(3,4-ethylene dioxythiophene) doped with poly(styrenesulfonate) (PEDOT:PSS). These techniques impart quite different physical and chemical properties to the films, namely surface roughness, electrical conductivity, and electrochemical properties. The oxidation state of the polymer films was subsequently modified by applying a continuous bias in electrolyte solution for one hour. We characterized the effects of these deposition methods by atomic force microscopy, optical absorption, wettability, electrical and electrochemical analyses as a function of the oxidation state of PEDOT:PSS. The time-stability of the induced redox state was also assessed in different aqueous media, as distilled water, phosphate buffer and cell culture medium.
Finally, we studied the effects of cell adhesion and proliferation on the PEDOT:PSS films by growing tumoral glioblastoma multiforme (T98G) cell cultures. Cell adhesion and proliferation were on line monitored for a time interval up to 72h (three days) by automatized optical microscopy. An increase in T98G growth rate was observed on all the reduced substrates, and a correlation was found between this effect and the K⁺ channel activity of this cell line.

The recording of neural signals is a very important task as they play a crucial role in central nervous system&’s physiology and pathophysiology. Nevertheless, recording these signals is far from being trivial mostly due to difficulties in coupling electronic materials and biology. Lately, conducting polymers have proven themselves the most promising candidates for the next generation of recording devices both in vitro and in vivo. Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT: PSS) ,in particular, has the unique ability to conduct both electronic and ionic carriers, offering a new level of communication between biological systems and electronics. In addition, it demonstrates ease of processability and property tunability in contrast with its inorganic counterparts. In this work we demonstrate a PEDOT:PSS based platform for in vitro measurements. With the use of PEDOT:PSS coated electrodes, we were able to record neural activity , such as local field potentials (LFPs) and Actions Potentials (APs),both from hippocampus brain slices and primary hippocampal cells. We have also used this platform for measuring activity from spinal cord/muscle co -cultures, while investigating at the same time, the possibility of achieving similar recordings with Organic Electrochemical Transistors (OECTs).OECTs, due to local amplification compared with electrodes, promise superior signal to noise ratio during the measurements. Our results demonstrate that PEDOT: PSS dramatically improves the resolution of recordings and paves the way for the use of OECTs in electrophysiology. Above all, the PEDOT:PSS platform presented here provides a vehicle for fundamental research in the life sciences, facilitates the study of neural activity and opens new horizons in the understanding of the physiology and the neuropathology of the biological systems.

Organic bioelectronics is the underpinning of new technologies that bring unique capabilities at the interface between electronics and biology, such as sensors based on organic electrochemical transistors, electrodes for in vitro and in vivo stimulation and recording, drug delivery devices, devices to promote or hinder cell adhesion, ion pumps to deliver charged biomolecules in vitro and in vivo.
Organic electrochemical transistors (OECTs) are excellent candidates for application in bioelectronics devices, e.g. for sensing, drug delivery and brain activity measurements.
3,4-polyethylenedioxythiphene doped with polystyrene sulfonate (PEDOT:PSS) is the conducting polymer that has been mostly used as active material for fabrication of OECTs. The application of positive gate voltages will de-dope the polymer channel and hence modulate the channel current. Since OECTs involve a bulk electrochemical doping mechanism, the thickness of semiconducting material (channel) plays a significant role in OECT characterization.
We investigated the device characteristics of organic electrochemical transistors based on thin films of poly(3,4-ethylenedioxythiophene) doped with poly(styrene-sulfonate). We employed various channel thicknesses and two different electrolytes: the micelle forming surfactant cetyltrimethyl ammonium bromide (CTAB) and NaCl. The highest ON/OFF ratios were achieved at low film thickness using CTAB as the electrolyte. Cyclic voltammetry suggests that a redox reaction between oxygen dissolved in the electrolytes and PEDOT:PSS leads to low ON/OFF ratios when NaCl is used as the electrolyte. Electrochemical impedance spectroscopy reveals that doping/dedoping of the channel becomes slower at high film thickness and in presence of bulky ions.
Our results, besides opening new opportunities to study the operating mechanism of OECTs, pave the way to new exciting bioelectronics applications since micelles play a primary role in biological processes and drug-delivery systems.

Owing to the high performance, low-cost, flexibility and simple fabrication processes, organic thin film transistors (OTFTs)-based devices have emerged as a viable platform for biological and chemical sensing applications. Organic electrochemical transistors (OECTs), an important type of OTFTs, have shown huge potentials for state-of-the-art sensor platforms in various sensing applications, including pH, ions, glucose, dopamine, bacterial and DNA, etc,. Normally, OECTs is a three-terminal (source, drain and gate electrodes) device with a thin layer of organic material deposited on the channel area located between source and drain electrodes. Poly(3,4-ethylenedioxythiophene) : poly(styrene sulfonate) (PEDOT: PSS), as the common p-type semiconducting material, is widely used in the fabrication of OECTs devices.
Flexible OECTs device was achieved by fabricating sensor device on the thin film polyethylene terephthalate (PET) substrates. The flexible OECTs could be easily attached on various deformable surfaces to accommodate the movements and show stable electric performance during bending tests up to 1000 times. The OECTs device modified with PANI/Nafion-graphene bilayer could detect H₂O₂ level down to 3×10^-9 M with a remarkable enhanced selectivity, considering that the interferences are extensively blocked by the positively/negatively charged bilayer film induced by electrostatic interactions. The flexible OECTs device was then functionalized with specific enzyme layer for the detection of uric acid (UA), glucose and cholesterol. The flexible device with UOx-glutaraldehyde/PANI/Nafion-graphene/Pt gate electrode shows linear responses to UA in a wide concentration region from 10 nM to 10 µM, and interfering effects caused by glucose, dopamine and L-ascorbic acid are almost negligible for practical applications. The flexible glucose sensor were realized by immobilizing the enzyme glucose oxidase (GOx) on the PANI/Nafion-graphene/Pt gate electrode by using GO. The devices show a detection limit of about 3×10 ^minus;8 M
, which is two orders of magnitude better than that of the device to AA and DA. The glucose sensors also show an excellent selectivity for practical applications. Similarly, highly sensitive and selective cholesterol sensor was fabricated by the functionalization of gate electrode with cholesterol oxidase-GO/ PANI/Nafion-graphene. The cholesterol sensor shows a low detection limit of 1×10 ^minus;7 M , which is sensitive enough to detect cholesterol levels in human body (3.36 - 6.72×10^minus;3 M). Employing the same principle, the application of flexible organic electrochemical transistors could be further explored by taking different gate electrode modification techniques.

Most of the state-of-art brain studies for monitoring the dynamics of individual neurons in vivo are performed using two main technologies: electrophysiological recording and optical imaging, which have advanced our insights and knowledge of the organization and the function of the brain. Electrophysiological recording performed by micro electrode can probe into different brain regions and record single-unit activities with precise temporal resolution. However, the spatial resolution of the recording is restricted by the number and size of electrodes, which makes it still challenging to study the brain activity on a circuit level. While optical imaging yields large-scale visualization of the dense cellular activities, it relies on the fluorescent reporters of neuronal dynamics, for instance, calcium and voltage indicators. Multiple factors, including their sensitivity, kinetics, labelling efficiency, etc., limit its capability to monitor brain activities, especially in the deep brain. Here a label-free microscopy device based on field-effect sensor, i.e., the light-addressable potentiometric sensor(LAPS) with insulator-semiconductor structure, and flexible polymer fibers integrated with electrode and optical waveguide bundles, is proposed for deep brain imaging. The LAPS, as a surface potential sensor, is able to convert the brain activity to carrier redistribution due to the field effect with high sensitivity. In addition, thanks to the photoelectronic effect within the semiconductor, localized surface potential change at the brain-insulator interface of the LAPS can be read out in the form of a photocurrent induced by a modulated light beam. In this way, the imaging of brain activity can also be performed by mapping the photocurrent at each measurement spot illuminated by light modulated at different frequencies. The LAPS with surface dimensions of < 800 mu;m, as sensing element, will be integrated on the tip of a polymer fiber with good flexibility, which will be capable of delivering 16 modulated light to the LAPS and leading the electrical signal out for imaging process. This microscopy device can be implanted into deep brain regions, and it will be able to achieve spatial resolution down to 100 mu;m and frame rate up to 1000 fps, which will be capable of obtaining cellular level brain imaging with precise temporal resolution to study brain functions on the circuitry level.

Conventional electronic circuits can perform multi-level logic operations; however, this capability is rarely achieved by logic gates based on biological molecules such as DNA, RNA, enzymes, etc.[1] In addition, the question of how to close the gap between biomolecular computation and silicon-based electrical circuitry is still a key issue in the bioelectronic field. The integration of target recognition, biomolecular computation, and transduction of these informations into an electrical signal is an important challange until now.
Here we explore a novel split aptamer-based multi-level logic gate built from INHIBIT and AND gates that performs a net XOR logic analysis.[2] It combines the aptamer-based biochemical logic gate responses of the sensor receptor with the logic gates of the electrochemical transduction scheme. In addition, the concept of electrochemical rectification is introduced into the whole system with a relayed charge transfer occuring upon target binding between split aptamer linked redox probes and solution phase probes. This strategy amplifies the sensor signal, facilitates the robust detection of different but related targets and supports a straightforward and reliable diagnosis. Furthermore, the biochemical binding process is transduced into an electrical signal, and several (bio-) chemical input signals are converted into one output signal which reports on the overall status of the system.
Our work reveals a new route to design bioelectronic logic circuits that can realize multi-level logic operations, which has the potential to simplify an otherwise complex diagnosis to a “yes” or “no” decision.
References (see example below)
E. Katz, Bimolecular Computing-From Logic Systems to Smart Sensors and Actuators, Willey-VCH, Weinheim (2012)
L. Feng, Z. Lyu, A. Offenhäusser and D. Mayer, Angew. Chem. Int. Ed., DOI: 10.1002/anie.201502315. (2015)

Solution processed ZnO based thin film transistors have attracted great deal of attention during the past few years due to their high charge-carrier mobility, high optical transparency and excellent chemical/mechanical stability[1]. ZnO has a wide band gap (3.37 eV) and it is non-toxic, environmentally stable, biocompatible and biodegradable. Recently solution processed ZnO thin-films and nano-rods have been successfully implemented as active layers in electrolyte gated TFT configurations [2-4]. However, one major factor that limits the application of these devices for biosensing purpose is the solubility of ZnO in water and in buffer such as phosphate buffered saline (PBS) [3]. One way to fix this issue is the modification of the ZnO thin film surface with an hydrophobic layer. In this study, we are presenting a solution-processed electrolyte gated ZnO based TFT fabricated by e-beam lithography in which the ZnO surface is hydrophobized with a layer of Hexamethyldisilazane (HMDS). The HMDS has been deposited with three different techniques i.e. spin coating, vapour deposition and dip-coating. The HMDS treated ZnO thin films were characterized with X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, scanning electron microscopy (SEM) and atomic force microscopy (AFM). The electrical performance of water gated ZnO TFT after the treatment with HMDS were evaluated. The stability of the devices in aqueous environment and their implementation in biosensing applications will be discussed.
References:
[1] G. Adamopoulos et al. Adv. Mater. 23 (2011) 1894 .
[2] A. Al Naim et al., Appl. Phys. Lett. 101 (2012) 141603.
[3] M. Singh et al., Faraday Discuss.,174 (2014) 383.
[4] S. Thiemann et al., ACS Appl. Mater. Interfaces, 5 (2013), 1656.

Thin-film transistors (TFTs) comprise a solid dielectric or electrolytes as gating medium. In the latter case, upon application of the gate voltage, mobile ions form an electric double layer (EDL) at the interfaces with the gate electrode and the semiconductor layer. The EDL holds a very high capacitance (few tens of mF/cm²) and allows operation at low voltages (below 1V). Solid electrolytes, ionic liquids, water and buffer solutions such as phosphate buffered saline have been used as gating materials both in p-type (hole) and n-type (electron) semiconductors^[1-3]. Recently, TFTs gated through organic solvents, mainly polar and water miscible solvents, have been reported^[6]. The ability of certain solvents to act as gate medium has been attributed to the presence of trace amounts of dissolved salts. However, the mechanism of gating is not clearly understood.
In this study we investigate different organic solvents as the gate medium in TFTs and analyze in detail the underlying mechanism behind their gating ability. The selected solvents covered a wide range of dipole moments and dielectric constants. Both p- and n-type semiconductors are used, namely poly (3-hexylthiophene-2, 5-diyl) P3HT and zinc oxide (ZnO) respectively. Interestingly, the drain current was found to be proportional to the ratio of dipole moment with the dielectric constant for all tested organic solvents and water. To examine the hypothesis that the formation of EDLs for organic solvents was due to the inevitable presence of salts traces dissolved in the organic liquids, we evaluated the electrical performance of TFTs gated using organic solvents solutions of different ionic strength.
The current study might open the way to the development of TFTs based sensors for the detection of metabolites produced from cells such as yeast or bacteria during the fermentation process or for environmental applications. Quality control of pure solvents is another possible application.
References:
[1] Kergoat, L., L. Herlogsson, D. Braga, B. Piro, M.-C. Pham, X. Crispin, M. Berggren, and G. Horowitz, Advanced Materials. (2010), 22, p. 2565-2569.
[2] De Tullio, D., M. Magliulo, G. Colafemmina, K. Manoli, L. Torsi, and G. Palazzo, Science of Advanced Materials. (2013), 5, p. 1922-1929.
[3] Singh, M., G. Palazzo, G. Romanazzi, G.P. Suranna, N. Ditaranto, C. Di Franco, M.V. Santacroce, M.Y. Mulla, M. Magliulo, K. Manoli, and L. Torsi, Faraday Discussions. (2014), 174, p. 383-398.
[4] Al Naim, A.F. and M. Grell, Journal of Applied Physics. (2012), 112, p. 114502.

The use of conducting polymers as electrode material on neural probes has gained substantial interest in the past years as consequence to the outstanding electrochemical properties of such materials in comparison to conventional metals. The most relevant aspect is thereby the possibility to fabricate micro-sized electrodes with low impedance and high charge injection capacity for bi-directional communication with neuronal tissue. Further promising qualities such as spatially confined release of drugs and good biocompatibility are known. Considering the relatively simple and cheap fabrication routes of such films conducting polymers, e.g. poly(3,4-ethylene dioxythiophene) (PEDOT), offer great potential as electrode coatings. Nevertheless, these coatings suffer from poor adhesion to the substrate which stands in the way of using the systems for chronic applications. Consequently, strategies for improving the adhesion of PEDOT on neural probes are highly demanded.
We have previously reported on the finding that PEDOT shows excellent adhesion to IrOx and we here investigate the difference between a purely mechanical adhesion promoter, based on a nanostructured platinum layer, and a chemical/mechanical support in terms of iridium oxide (IrOx). These materials are either known as electrode material themselves and thus commonly available in the electrode fabrication process (IrOx) or can easily be applied electrochemically on already fabricated probes (Pt-nanostructures). The polymer deposition is not affected by the adhesion promoter and can be realized independently using standard techniques. Cyclic voltammetry sweeps (-0.6V/0.9 V vs Ag:AgCl) were employed to inflict stress and thus investigate the adhesion quality of the polymers during long-term experiments.
Both methods proved efficient for stabilizing the films. While PEDOT on sputtered Pt showed a breakdown within less than 100 CV sweeps, the film on the Pt-nanostructures remained stable over 600 CV sweeps before degradation could be observed. The polymer on IrOx showed no degradation over 1500 CVs. The adhesion to the IrOx was outstanding, implying that not only a mechanical anchoring, as given by the Pt-nanostructures, is responsible for the adhesion but also a chemical contribution exists. This assumption is investigated in XPS measurements targeting the actual interface of the two materials. SEM imaging shows homogenous integration of the polymer with either of the films. The structure and topography of the polymer are not influenced by the supporting layers so that the polymer functionality is retained as confirmed by electrochemical measurements.
In summary, we successfully address the weakest link of conducting polymer based microelectrodes for biomedical applications with two strategies that can easily be integrated with standard microfabrication processes. IrOx shows by far the best adhesion promotion as consequence to a chemical and mechanical interaction with the polymer.

The bioconjugation of photosynthetic proteins with efficient organic light harvesting antennas is a very intriguing approach to build novel hybrid organic-biological machineries that, mimicking nature, employ solar energy to generate photocurrents or to drive thermodynamically unfavoured reactions, reaching efficiencies higher than those obtainable by their natural counterparts.[1] Such hybrid systems are potentially useful as active materials in new generation devices for photovoltaics and biosensing.
In the frame of our studies on organic-biological hybrids for solar energy conversion,[2] here we present the design, synthesis and preliminary characterization of a series of heptamethine cyanine dyes particularly suitable as light harvesting antennas for the photosynthetic Reaction Center (RC) of the purple bacterium Rhodobacter sphaeroides strain R26. These molecules have been properly tailored to have efficient light absorption in the visible spectral range, where the RC absorbance is very low, and efficient emission in the near infrared region, in correspondence of the highest RC absorption peaks. Moreover, the charged sites within their molecular structure make these molecules highly soluble in detergent aqueous environment where the RC is stable, this allowing them to approach the bioconjugation sites of the protein. Our preliminary results show that the bioconjugation of these organic antennas to the RC is expected to be a very profitable strategy to afford highly efficient organic-biological hybrids for solar energy conversion.
[1] A. Operamolla, R. Ragni, F. Milano, R. R. Tangorra, A. Antonucci, A. Agostiano, M. Trotta, G. M. Farinola, J. Mater. Chem. C, 2015,3, 6471-6478
[2] F. Milano, R. R. Tangorra, O. Hassan Omar, R. Ragni, A. Operamolla, A. Agostiano, G. M. Farinola, M. Trotta, Angew. Chem. Int. Ed., 2012, 51, 11019-11023

Optogenetics is a method for delivering millisecond precision control, for activation and inhibition, of targeted cells using light. The components of this method, as practiced today, involve (1) lasers and fiber optics for light delivery into the nervous system and (2) genes called microbial opsins [1]. Opsins are light-activated proteins that conduct or inhibit electrical signals in neurons. Membrane depolarization of neurons induces transient electrical signals, namely action potentials, which convey information between neurons within the same circuit. Direct electrical recording technologies of neural activity have been essential to our understanding of the dynamics and structure of neural circuits and behaviors. However, electrical recording has relatively low spatial resolution and low signal to noise ratio. The focus of this work is the development of an in-vitro organic photodetector (OPD) platform to detect the neural activity of cerebral tissue based on light emitted from neurons. This platform contains heterojunction photodiodes based on poly(3-hexylthiophene) (P3HT) as donor and [6,6]-phenyl-C61 butyric acid methyl ester (PCBM) as an acceptor. Neurons in-vitro are genetically modified to express Channelrhodopsin-2 (ChR2), a light-sensitive transmembrane protein responsive to blue light. Chr2-modified neurons emit photons in the spectral range of 550 to 700 nm; in fact, with the wide variety of organic materials available, the spectral response of the OPD can be tailored for almost any Channel rhodopsin-2. We show that neural activity is recorded based on our light-sensing platform by stimulating neurons with a blue LED with a peak wavelength of 470 nm.
[1] K. Deisseroth, A. Etkin, R. C. Malenka. JAMA, 2015, 313, 2019-2020.

The development of effective implantable micro-scale bioelectronics has been challenging due to high impedance and low charge storage capacity that result in both low signal-to-noise ratio (S/N) and low charge injection electrode-tissue interfaces. Further, these devices without anti-inflammatory compounds are less likely to maintain their functionality because of unfavorable reactive tissue responses. Thus, there is substantial incentive to produce devices capable of delivering therapeutic compounds while maintaining their electrical performance. Poly(pyrrole) (PPy) has gained significant interest for biomedical applications owing to its excellent biocompatibility, electrical properties, and mechanical actuation. Poly(lactic-co-glycolic) acid (PLGA) is biodegradable and highly biocompatible, making it an ideal matrix for drug encapsulation. We previously demonstrated that electrospun PLGA nanofibers and the electropolymerized PPy could be effectively combined to produce conductive nanotubes that dramatically decreased the impedance of microelectrodes while exhibited in tunable drug release kinetics. To further improve electrical properties, in this study we have produced PLGA microspheres coated with PPy poly(styrenesulfonate) (PSS) on Au electrodes, which were fabricated on Si wafers (two circles with diameters 1.5mm and 5.0mm connected with a rectangle 1mm X 10mm). These conducting polymer microstructures have large surface areas, granting low impedance values and high charge storage capacities, as well as controllable release avenues for drug delivery. Briefly, 4/2wt% PLGA/ benzyltriethylammonium chloride (BTEAC) was dissolved in chloroform and was electrosprayed on the electrodes using an applied electrical field of 100kVm^-1 and 500mu;l/hr flow rate. PLGA particles were then coated with PPy/PSS using electrochemical deposition in galvanostatic mode with current density 0.5mA/cm² for 8 minutes. Hollow spheres were also fabricated by dissolving PLGA in chloroform. Impedance Spectroscopy (IS) reveals that the PPy-coated microspheres decreased the bare gold impedance about 40% (from 585#8486; to 346#8486; at 1kHz). Cyclic voltammetry (CV) showed that PPy coated microspheres significantly enhanced the charge storage capacity (from 0.712mC/cm² to 53.84mC/cm²). In conclusion, we successfully demonstrated: (1) electrochemical deposition of PPy around the electrosprayed PLGA microspheres and (2) improvement of electrical properties of Au electrodes by decreasing impedance and increasing charge storage capacity. This study demonstrates the potential of our conductive microstructures for neural interfacing and neural regeneration while retaining functionality for drug delivery. Future studies will focus on the incorporation of bioactive compounds such as nerve growth factor and antitumor agents for controlled drug delivery using electrical actuation of PPy microstructures.

Abstract not available.

Organic electroactive materials and devices have been applied to several biological and medical settings to translate electronic signals into biological ones, and vice verse. Ion- and electron-conducting organic polymers, being flexible, bio-compatible and also bio-stable, represent a unique class of materials that can bridge the signalling gap between biology and electronics. Several new pathways in therapy and diagnostics have been identified and are explored based on organic bioelectronics. Here, we demonstrate using organic bioelectronic circuits as the signal bridge to translate between signals in plants and electronic addressing. The growth and physiology of plants are regulated by a set of plant hormones, a vast array of internal and external signals and nutrients, and also by sugar produced in the leaves. We report using organic bioelectronics, devices and circuits, as a novel platform to sense and regulate several key-functions in plants. Our findings open up for a radically new pathway for organic electronics, i.e. to control and to harvest from the physiology of plants.

Pathophysiological responses in a tissue, no matter the cause, are characterized by dramatic changes of biomolecular activities in the local tissue microenvironment. Our understanding of disease development and ability to administer critical treatment depends heavily on the amount of accurate information we can collect from the molecular tissue microenvironments at any time. To date, however, no sensing platform has been able to achieve this on molecular level. In this study, an in vitro condition that mimics the progression of inflammation/infection on a sensing platform was created in order to investigate how bio-molecular dynamics changes in the local microenvironments. The novel concept underlies the use of a cell-membrane-mimetic surface, where a custom polymer mimics phosphorylcholine (PC) as an alternative receptor for the human acute phase protein C-reactive protein (CRP) on the eukaryotic cell membrane. The role of CRP is to bind to damaged host cells or invading microbes at the site of inflammation, thus activating the complement pathway leading to clearance by innate-immune cells. To further replicate the local ionic microenvironments of a pathogenic site, a conducting polymer-based organic bioelectronic ion pump (OEIP) delivering [Ca²⁺] and [H⁺] with a well-defined spatiotemporal control was integrated with the sensing platform. Since Ca²⁺-dependent binding of CRP to the artificial PC surface models the interactions occurring between systemic CRP and cell membrane-bound CRP receptors; the biomimetic interface allows for the first time the binding constants (k_on, k_off, and K_d) of CRP to PC to be determined. These values are important to understand the binding affinity of CRP to the receptor on cell membrane and why the serum CRP level needs to be elevated for 100- to 1000-fold in acute-phase. By presenting a more coherent picture of the host response in which the active local form of CRP is obviously different from measuring systemic CRP level, the biomimetic interface emerge as a powerful tool in revealing the whole picture of well-organized acute phase responses at molecular resolution. This study further extends the applicability of the OEIP into studies of pathophysiological host responses to infection and inflammation, where its advantage of non-convective control of ion delivery added valuable knowledge of the binding dynamics of CRP in real-time.

Semiconducting polymer/water interfaces are gaining increasing attention due to a variety of promising applications in the fields of biology and neuroscience. Recently, they have been widely exploited for the realization of organic field effect transistors, electrochemically-gated transistors and photodetectors. Practical applications range from biosensing, to devices for cell activity stimulation and recording, optical excitation of in vitro and in vivo systems. Despite the huge interest, a detailed understanding of the phenomena occurring at the conjugated polymer surface in presence of an aqueous environment is still missing. In particular, the combined effect of contact with electrolytes and visible illumination should be taken into account, since many applications rely on exposure to light, or are meant to work in ambient room light conditions.
Here, we provide a comprehensive characterization of the chemical/physical processes occurring in polythiophene thin films exposed to water saline solutions and visible light. We employed a combination of several experimental techniques, including optical spectroscopy, electrical characterization, morphology studies and electrophysiology. A computational approach, based on molecular dynamics simulations as well as on first principles theoretical investigations, usefully complements this study.
Overall, our contribution will provide a complete description of the main phenomena occurring at the polymer/water interface upon the effect of visible light, including electrochemical reactions, capacitive charging, thermal effects, oxygen doping, and their implications in the interaction with living cells. Hopefully, this study will foster further rationalization and optimization of organic/electrolyte interfaces in all their possible applications.

The electronics surrounding us in our daily lives rely almost exclusively on electrons as the dominant charge carrier. In stark contrast, biological systems rarely use electrons, but rather ions and molecules of varying size. Due to the unique combination of both electronic and ionic/molecular conductivity in conducting polymers, these materials have emerged in the last decade as an excellent tool for translating signals between these two realms, and therefore providing a means to effectively interface biology with conventional electronics - thus the field of organic bioelectronics. As this utility of organic bioelectronics relies on the electron-mediated flow of ions (or the ion-mediated flow of electrons), a great deal of effort has been devoted to the development of so-called “iontronic” components and circuits. That is, devices where ions are the dominant charge carrier. This effort has resulted a range of technologies including electroactive surfaces for controlled cell adhesion, scaffolding for cell and tissue growth, as well as ionic resistors, diodes, transistors, and basic logic circuits for the precisely controlled (and neuro-mimetic) delivery of biologically-active chemicals. In this presentation, I will present a brief overview of some of these organic bioelectronic technologies, and proceed to focus on a range of applications in vitro and in vivo, in the animal kingdom, and now even in the plant kingdom.

Recording minuscule electrical activity of cell populations is currently a major technical challenge to electrophysiology. For this purpose we built an extremely low-noise measuring system. The sensing system comprises a bidirectional transducer based on a metal/Si/SiO₂/interdigitated gold electrode. The highly doped Si substrate can be used as a common gate to stimulate the cells. In order to reduce external interferences the transducer was located inside an incubator and all the instrumentation shielded by a faraday&’s cage. The background noise level with only cell culture medium was less than 100 fA.
Bioelectric activity is recorded by measuring the capacitive current using zero bias at the electrodes. To validate the extreme sensitivity of the measuring system, we investigated the electrical activity of large populations of two cell lines known to be electrically quiescent. The cell lines studied were the human cervix carcinoma cell line, HeLa, and C6 glioma cells. HeLa cells are supposed to be electrically quit as they don&’t originate from the brain or any other electrically excitable tissue. However, due to the high sensitivity of our measurement system, even the HeLa cells demonstrate fluctuations of their basal current level, which is much higher in amplitude than the background acquisition noise. The low frequency analysis of the HeLa cells reveals clear current fluctuations of about 3 pA.
Non-neuronal cell types such as glia and their transformed counterparts, glioma cells, exhibit distinctive single-cell oscillations in membrane potential, which are highly functional and coordinated. However, measurement of their subtle electrical activity is typically hampered by the high background noise. Here we demonstrate that we can detect the electrical behavior of entire large cell populations of C6 glioma cells without any physical disruption or interference into their physiology.
Malfunctioning glioma cells can develop to brain tumors. Glioma patients often suffer from epileptic seizures due to the tumors impact on brain electrophysiology. Here we show that seizure-like events in glioma cells spontaneously appear and evolve from a few pA to more than 100 pA on a time scale of hours. A direct correlation between electrical bursting and extracellular pH reduction was accomplished. Furthermore, at constant pH levels, a current noise analysis could determine that the glioma cell activity is primarily caused by the opening of voltage-gated Na⁺ and K⁺ ion channels and can be efficiently abolished using specific pharmacological inhibitors. We argue that our measuring system is unique to study electrophysiological properties of large cancer cell populations as an in vitro reference for tumor bulks in vivo.

The use of organic conductors in medical bionic devices greatly expands the materials inventory available and in turn opens up the possibility of new areas of application.
Fascinating as the properties of organic conductors are they are only really useful when they can be seamlessly and effectively integrated with the other materials needed to create a bionic device. Such materials may include biopolymers for structural support and bioactives such as growth factors or even living cells. Printing provides an attractive approach in the quest to realise such structures.
Here we will report on our advances in the development of hardware and ink formulations to enable the printing of organic conductors including polypyrroles, PeDOT and graphene . We will also report on progress towards enabling the printing of such materials as sub micron features.

Due to excellent electrical properties, environmental stability, and decent biocompatibility, poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) has witnessed growing potentials not only in flexible electronics/photonics but also in biomedical devices such as biochemical sensors and neuronal probes. Particularly, chemically synthesized PEDOT:PSS coatings exhibit much higher conductivity and easier processability than electrochemically polymerized ones, however, their dissolution in aqueous solutions limits their versatile application toward underwater bio-electronic interfaces. In this work, we report the fabrication of crystalline PEDOT:PSS films (cPEDOT:PSS) and their dry-transfer printing onto plastic substrates. The resultant water-insoluble conjugated polymer films exhibit excellent electrical conductivity, very large electrochemically-active surface area, and long-term mechanical stability in aqueous conditions. Furthermore, it was also verified that our cPEDOT:PSS films support decent viability of mammalian cell and rat embryonic neuron cultures up to several weeks. Finally, we also demonstrate that electrophysiologically active cells deposited on top of cPEDOT:PSS electrodes (e.g., cardiac and neuronal cells) can be efficiently stimulated in an electrochemical fashion. We expect that our water-stable highly-conductive cPEDOT:PSS films will serve as a promising material platform for cell-based bio-electrical interfaces.

Conducting polymers comprise a unique class of materials capable of displaying semiconducting and, sometimes, metallic behavior. At the center of attention is poly(3,4-ethylenedioxythiophene) (PEDOT), an organic conducting polymer (OCP) with widespread interest for a variety of applications including bionic and optoelectronic devices, biosensors, organic photovoltaics, and light emitting diodes. The utilization of PEDOT as an OCP in electronic biomedical devices, however, has not reached its full potential due to a lack of comprehensive molecular-level understanding of biomolecular interactions at the PEDOT interface. To this end, computational methods can provide a valuable complementary tool to experimental data, to elucidate structural aspects of the adsorption of biomolecules at the PEDOT interface. However, there are currently no force fields (FFs) available that are specifically designed to capture bio-PEDOT interactions at the aqueous interface. One way to achieve this is by generating adsorption energies calculated using first-principles approaches for a range of various biologically-relevant small molecules.^1-3 Here, we report such first-principles data obtained from plane-wave density functional theory using the vdW-DF functional. These data are used to develop a new FF designed to capture biomolecular interactions at the aqueous PEDOT interface. Our findings will significantly boost our ability to more accurately describe the adsorption of peptides and proteins at PEDOT interfaces in solution using computational methods.
Wright, L.B., Rodger, P.M., Corni, S. and Walsh, T.R. J. Chem. Theory Comput., 2013, 9, 1616-1630.
Hughes, Z.E., Wright, L.B. and Walsh, T.R. Langmuir, 2013, 29, 13217-13229.
Hughes, Z.E., Tomasio, S.M. and Walsh, T.R. Nanoscale, 2014, 6, 5438-5448.

Cephalopods are well known for their remarkable camouflage abilities; they can modify their coloration, texture, pattern, and reflectivity to blend into the surrounding environment. Such dazzling camouflage abilities are partially enabled by specialized intracellular nanostructures that are composed of a unique structural protein known as reflectin. We have developed high throughput protein expression and purification strategies for the isolation of reflectin isoforms from the cephalopod species L. pealei and E. scolopes.¹ We have performed extensive biophysical characterization of these proteins, discovering that they possess common yet unique optical and electrical properties, including protonic conductivities that are on par with state-of-the-art artificial materials.² Our findings may hold implications for not only better understanding the mechanisms that cephalopods employ to dynamically control their coloration but also for the development of bioinspired proton conducting materials.
1. Phan, L.; Walkup IV, W. G.; Ordinario, D. O.; Karshalev, E.; Jocson, J.-M.; Burke, A. M.; Gorodetsky, A. A. Adv. Mater.2013, 25, 5621-5625.
2. Ordinario, D. O.; Phan, L.; Walkup IV, W. G.; Jocson, J.-M.; Karshalev, E.; Hüsken, N.; Gorodetsky, A. A. Nat. Chem.2014, 6, 596-602.

This talk will give an overview of our research into the development of new materials and materials-based characterisation approaches for regenerative medicine [1-3]. The ability to control the cell-material interface offers exciting possibilities for stimulating growth of new tissue for example through the development of conductive polymer scaffolds. By applying state of the art materials-based approaches we can also better elucidate the cell-material interface for applications in cardiac tissue engineering. Recent examples from our group will be presented.
References
[1] E. T. Pashuck, M. M. Stevens "Designing Regenerative Biomaterial Therapies for the Clinic."
Science Translational Medicine.2013. 4 (160) 160sr4.
[2] Chiappini C, De Rosa E, Martinez JO, Liu X, Steele J, Stevens MM, Tasciotti E.
“Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization.” Nature Materials. 2015. 14(5):532-9.
[3] M. D. Mager, V. LaPointe, M. M. Stevens “Exploring and exploiting chemistry at the cell surface.”
Nature Chemistry. 2011. 3(8): 582-589.

Proton conducting materials play a central role in a diverse array of renewable energy and bioelectronics technologies. Thus, a great deal of research effort has been expended to develop improved artificial proton conducting materials, including ceramic oxides, solid acids, porous solids, polymers, and metal-organic frameworks. Within this context, proton conductors from naturally occurring proteins have received relatively little scientific attention, despite advantages that include intrinsic biocompatibility, structural modularity, tunable physical properties, ease and specificity of functionalization, and generalized expression/purification protocols. We have recently discovered unexpected protonic conductivity in the cephalopod structural protein reflectin, and characterization of this material with a diverse array of electrical and electrochemical techniques has resulted in the finding that its electrical figures of merit compare favorably to those of artificial proton conductors. Moreover, reflectin&’s favorable electrical properties have enabled the fabrication of diverse protein-based protonic devices. Our findings may hold implications for the development of the next generation of biologically-inspired polymeric proton conductors.

The Reaction Centers (RCs) of photosynthetic micro-organisms are efficient billions-of-years optimized photoenzymes for conversion of light absorbed from sun into charge separated states with almost 100% efficiency. Combination of such effective and robust photoenzymes with tailored p-conjugated molecules discloses intriguing possibilities for a new generation of versatile hybrid bio-electronic materials with application ranging from photoconversion to photocatalysis and sensing.¹
The lecture will present highly selective covalent functionalization of the RC from the photosynthetic bacterium Rhodobacter sphaeroides R26 with tailored molecular fluorophores which act as antennas to enhance the light harvesting capability of the RC in a wavelength range where the unmodified biological enzyme does not absorb.²
Selective functionalization with proper linkers for anchoring the RC photoenzyme on hydrogen-bonded semiconductor layers will be also discussed. In particular, photoconductor devices with the hydrogen-bonded semiconductor epindolidione sensitized by the Reaction Centre have been demonstrated in aqueous conditions.³
Our study discloses new concepts for the generation of bio-hybrid supramolecular materials for sunlight photoconversion and for photoswitching based on functional photoenzymes, emphasizing the intriguing possibilities disclosed by biotechnological production of materials for optoelectronics.
References
[1] A. Operamolla, R. Ragni, F.Milano, R.R.Tangorra, A. Antonucci, A. Agostiano, M. Trotta, G.M. Farinola J. Mat. Chem. C 2015, 3. 6471-6478.
[2] F. Milano, R. R. Tangorra, O. Hassan Omar, R. Ragni, A. Operamolla, A. Agostiano, G. M. Farinola and M. Trotta, Angew. Chem. Int. Ed.2012, 124, 11181-11185.
[3] E. D. G#322;owacki, R. R. Tangorra, H. Coskun, D. Farka, A. Operamolla, Y. Kanbur, F. Milano, L. Giotta, G. M. Farinola and N. S. Sariciftci J. Mater. Chem. C 2015, 3, 6554 - 6564.

This contribution will describe recent work to incorporate pi-conjugated molecules of interest for organic electronics into self-assembling oligopeptides of interest for biomaterial applications. The assembly process leads to the formation of supramolecular polymers fashioned into 1-D nanomaterials ca. 10 nm in diameter. Using this general platform, a series of energy transport examples will be discussed, spanning transistor-based gating for carrier mobility, photonic activation for exciton transport, and the photonic creation of static electric fields. Prospects for using these hybrid electronic biomaterials to elicit biological adhesion or other specific responses in an externally tunable manner will be addressed.
Key references:
H. A. M. Ardoña and J. D. Tovar, “Energy transfer within responsive pi-conjugated peptide-based coassembled nanostructures in aqueous environments,” in Chemical Science, 2015 (6) 1474-1484 (DOI: 10.1039/C4SC03122A)
J. D. Tovar, “Supramolecular construction of optoelectronic biomaterials,” invited by Accounts of Chemical Research, 2013 (46) 1527-1537. (DOI: 10.1021/ar3002969)

This talk will describe our group&’s efforts to use intrinsically 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. In particular, we have found that highly plasticized films of PEDOT:PSS behave as stretchable strain gauges for human motion detection, while films of graphene decorated with metallic nanoparticles behave as ultrasensitive strain sensors in the low-strain regime. Applications include the first skin-mounted organic solar cell 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. This glove sensor can transmit data wirelessly to a computer for decoding of complex gestures.

The field of active prosthetics has the potential to greatly improve the quality of life for many people with amputations and disabilities, and sensory feedback plays an important role in maximizing the utility of active prosthetics. The nature of the sensor signal at the neuroelectronic interface is an important factor in minimizing negative effect[1]. We have developed an artificial mechanoreceptor that directly generates voltage pulses that mimic action potentials. The frequency of the voltage pulses can be modulated by a stimulus such as pressure. The resulting pressure-dependent frequency signal closely mimics the properties of human mechanoreceptors. The sensing system consists of a printed organic ring oscillator coupled to a resistive pressure sensor. Applying a pressure to the sensor increases the voltage supply to the oscillator, therefore increasing the frequency. Printed oscillators were used to demonstrate compatibility with large area processing methods. The resistive pressure sensors were optimized to be sensitive in the range of human pressure sensitivity for object manipulation (few kPa to few hundred kPa). The use of complementary oscillators provides mechanoreceptors with low power consumption (2 microW for a frequency of 70 Hz). The design is also compatible with other resistive sensors, such as sensors for temperature and pain. This receptor architecture provides a new strategy for biomimetic bioelectrionic interfacing.
[1] Daniel W. Tan et al, Sci. Transl. Med., Vol. 6, Art. 257ra138, 2014.

Classically, the removal of the meninges is required to monitor electrophysiological activity from the cortex by electrocorticography. The meninges is the fluid-filled sac surrounding the brain, which provides both a protective cushion and a means of waste removal. The two outermost layers of the meninges, the dura mater and the arachnoid which follow the inside of the skull, are separated from the third layer, the pia mater which follows the contours of the cortex, by continuously flowing cerebrospinal fluid. Rupturing these layers, for example in the standard process used to place ECoGs on the cortical surface, is extraordinarily invasive as it leads to inflammation and possible infection.
Here we present a generic solution to this challenge and demonstrate the use of non-invasive ECoG arrays which replace standard electrodes with organic electro-chemical transistors. Due to its high electrical connectivity and ion permeability, by utilizing Poly(3,4ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT: PSS) as the channel in the transistors, an high performance in harvesting biological signals is achieved. The high transconductance of the OECTs allows these ECoG arrays to monitor electrophysiological activity supradurally. We measured the transition from SWS (slow-wave-sleep) to REM (rapid-eye-movement) and pathological seizure activity with organic ECoG arrays placed on the surface of the dura mater.

Cochlear implants are neural prosthetic devices that help recover the sense of hearing to severe to profoundly deaf individuals. Current cochlear implants detect sound externally, which is then converted into electrical signal and sent into the cochlea to directly stimulating the auditory nerves. Current challenges of cochlear implants are spatial differentiation of sound, reduction of unwanted noise, and their usability under various conditions (e.g. in water). Here we present a PVDF-based microphone capable of detecting sound in the cochlea. Measuring sound in the cochlea can potentially address the aforementioned issues as it utilizes the external and middle ears, which were evolved to spatially perceive the source of sound, reduce unwanted noise, amplify, and efficiently transmit sound into the cochlea. Secondly, it is a step towards totally implantable cochlear implants, enabling users to have a sense of hearing under various conditions. Our device works by generating charge on the PVDF surface via sound pressure, which subsequently generates charge and modulates current across the organic film. To shield the device from electromagnetic field, we surrounded our device with a thin film of parylene, followed by a thin film of metal. Finally, to insulate the device electrically and from the fluid inside the cochlea, the entire device was surrounded with PDMS using injection molding. Using our microphones, we were able to detection sound with relatively high sensitivity (tens of mu;V/Pa) over a wide range of frequencies (20-20k Hz). In summary, we demonstrated a flexible PVDF-based microphone that can effectively detect sound in the cochlea, a promising step towards improved functionality of cochlear implants.

Scientific and engineering advances are rapidly adding to the toolbox of available hardware and measurement approaches for research in neuroscience. Soft neural interface technologies create new opportunities in measurement/stimulation that derive from unique options in noninvasive, conformal integration with the soft, curved surfaces and the compliant, heterogeneous depths of biological tissues. This talk summarizes recent progress in the development of flexible, multiplexed electronics for high resolution electrocorticography, with an emphasis on the semiconducting and encapsulating components of the systems, and on demonstrations in animal model measurements.

Thin-film pressure sensor arrays have applications ranging from consumer electronics applications, such as force-touchscreens and foot pressure mapping, to biomedical applications, such as blood flow and blood pressure monitoring as well as monitoring internal body pressures. However, these applications, especially within the biomedical device industry, require arrays of highly-dense, small pressure sensors that are sensitive enough to resolve small applications of pressure, such as that from an artery. This type of pressure sensor has not been demonstrated previously due to limitations in transducer technologies and processing capabilities. We have developed pressure sensors that are compatible with photolithography and typical semiconductor processing. Thus, we are able to design arrays of pressure sensors with pixels that can be as small as a few microns. Our sensors have a large sensitivity range, from hundreds of pascals to megapascals. These sensors can be used to accurately monitor pulse and blood pressure beat-by-beat, due to their flexible substrates, and can be used in commercial applications such as force-touchscreens, due to their transparency and ability to function under glass.
Our pressure sensors are based on proprietary ultrasoft elastomers. These elastomers have a Young&’s moduli on the order of 1 kPa and yet, are highly elastic, unlike low-crosslinked polydimethylsiloxane (PDMS). Most compressible materials used for pressure sensors incorporate air by microstructuring an elastomer or by using a microporous film, like a foam. These air-incorporated materials are difficult to process and integrate into typical semiconductor manufacturing. With our elastomers, a monomer solution can simply be coated onto a sample, polymerized using ultraviolet light, and patterned using photolithography. This compatibility allows us to make dense, pressure-sensitive arrays.
The pressure-sensitive arrays employ a novel device stacks on thin, polymeric substrates. The polymeric substrate that&’s compatible with photolithography enables the flexibility required to conform to the body to measure physiological data. Our device stack enables pressure sensors with high sensitivity under various cover materials, such as glass. This allows for a more robust device, which is required for most commercial applications. Our arrays can operate at voltages between 1 V and 5 V, enabling a low power consumption. This is required for continuous monitoring of physiological metrics. Our pressure sensor arrays have been engineered and optimized for biomedical and other commercial applications. These arrays will be used to gather continuous, relevant physiological metrics for tracking vital signs and developing correlations between the onset of health conditions and patterns of vital signs.

Wearable physiological sensors fabricated on flexible substrates using low-cost, additive printing of functional inks is ideal for sensing human vital signs. The conformal interface to human body improves the signal to noise ratio, and the flexible nature of the materials allows sensor designs in wearable form-factor. Furthermore, the printing-based manufacturing process enables high volume production. Here, we report on a wearable human monitor based on flexible hybrid electronics (FHE) for recording and transmitting biometric parameters, specifically, electrocardiogram (ECG) and body temperature. We employ a hybrid manufacturing process where printed sensors and conventional rigid electronics are interfaced on a flexible 50 µm thick polyimide substrate. The ECG electrodes and connecting traces are printed using gold nanoparticle ink, and the thermistor is printed using nickel oxide (NiO) nanoparticles. ECG electrodes demonstrate minimum feature size of 70 µm with sheet resistance of 0.35 Omega;/sq. Printed thermistors provide linear response from 25 °C to 50 °C with a controllable beta of 1000. Filtered ECG signals are amplified and recorded with a 12-bit resolution analog to digital converted (ADC). Preliminary human trials show the ability to record ECG signals comparable to those recorded using clinical Ag/AgCl electrodes and commercial ECG equipment. Overall, we report on the fabrication and implementation of a wearable sensor patch with inkjet-printed sensors, which accurately provide ECG signal and body temperature.

A new class of electronic devices based on stretchable materials can interact with the soft human body in an unprecedented manner. Conductive nanowires embedded in PDMS can be processed using screen-printing or regular photolithography to create stretchable conductive leads down to 10 micrometer resolution. The process parameters, e.g. type of PDMS, nanowire concentration and arrangement allow for precise tailoring of the electrical and mechanical properties of this composite material.
Stretchable and biocompatible microelectrode arrays can be created and used to stimulate intact spinal cord circuits below an injury to control the movement of the limbs aiding rehabilitation and increasing recovery of spinal-cord injured patients. [1,2]
The technology also allows for creating devices with arbitrary resistance-strain profiles enabling devices with up to 500% stretchability or with Gauge factors of over 100. [3]
References
[1] Electronic dura mater for long-term multimodal neural interfaces
I.R. Minev, et al.; Science, 347(6218):159-163, 2015;
[2] Stretchable electronics based on Ag-PDMS composites
Larmagnac et al. Scientific Reports 4: 7254, 2014, DOI:10.1038/srep07254.
[3] Stretchable silver nanowire-elastomer composite microelectrodes with tailored electrical properties
V. Martinez, et al., ACS Applied Materials & Interfaces, 2015, in press.

Technologies based on the use of organic optoelectronic materials for the realization of active interfaces with living tissues are emerging as promising tools to control bioelectrical signal in vitro and for targeted biomedical applications in vivo. Combining such interfaces with the high spatial and temporal resolution offered by optical excitation is one of the most interesting applications of these technologies, for example in the field of vision restoration in blind people.
In this contribution we show how thin-films of conjugated polymers can be used to transduce an optical excitation into a modulation of the membrane potential of cells grown on their surfaces. In particular, the attention is focused on the thermal effects caused by light absorption by the active material. This local temperature variation has different effects on the cell membrane, affecting both the lipid bilayer capacitance and ion channel conductivities. Using Human Embryonic Kidney cells (HEK-293) as a model system, we show how these processes can lead, on short time scales of few milliseconds, to a depolarization of the cell, while prolonged illumination of the interface triggers a sustained hyperpolarization of the membrane. Exploiting this hyperpolarizing effect we show that our bio-interfaces can be used to significantly reduce both spontaneous and evoked action potential firing in cultured neurons. We demonstrate that the polymeric interface can be activated by either visible or infrared light and is capable of modulating neuronal activity also in brain slices and explanted retinas. Finally, we conclude by showing that these interfaces can be used to modulate specific ionic conductances in cells expressing heat-sensitive channels like the transient receptor potential channels TRPV1.
These results can be usefully exploited in the development of bio-interfaces based on conjugated polymers towards the creation of a multi-functional platform for light-controlled cell manipulation, with possible applications in different fields of neuroscience and medicine.

In recent years, soft organic materials have raised conspicuous interest in the bioelectronics community as several novel biosensing and bioactuation devices have been proposed to address specific biomedical applications, e.g. neural recording and stimulation, artificial retina implants, controlled drug delivery and tissue regeneration. In this context, organic electronic devices and systems based on edible materials are emerging as a potentially pervasive platform technology. Indeed, research in this direction opens to a set of new medical devices designed to operate within the gastrointestinal tract, acting as biosensors and bioactuators, as well as tools to monitor patients compliance to medications. By all means, the integration of this technology with standard pharmaceuticals would naturally benefit of low-cost, easily up-scalable material deposition techniques, such as solution-based processes.
In this work, we exploit ink-jet printing to realize edible p-type and n-type transistors on a commercially available pharmaceutical capsule. The materials employed are either biocompatible, nature derived or commonly used in the food industry. PEDOT:PSS, a very well known biocompatible conducting polymer, constitutes the transistors&’ bottom-contacts and top-gate electrode. Alternative conductive materials can be adopted, e.g. graphene obtained by Liquid-Phase Exfoliation or edible gold. Shellac, a biodegradable bug secreted resin, acts both as smoothing layer and dielectric. Hydrogen-bonded organic pigments such as quinacridone, indigoids and perylene derivatives are natural candidates for the semiconducting layer thanks to both interesting electronic transport properties and high biocompatibility. Indeed, these pigments can be chemically synthesized with cleavable solubilizing tert-butoxycarbonyl (t-BOC) groups, which are removed after deposition by means of exposure to trifluoroacetic acid vapors. The t-BOC groups removal activates the latent H-bonds of the pigments which become completely insoluble and therefore exhibit an extremely low toxic potential, even lower than common food colorings. Moreover, these compounds can be functionalized with proteins without altering their electrical transport properties and the biological functionality of the proteins.
The present work thus demonstrates the all-printed realization of both p-type and n-type edible transistors, enabling robust complementary logic circuits, on a commercially available pharmaceutical capsule. The devices thus produced constitute an interesting approach for the integration of ingestible electronic systems with traditional pharmaceuticals and may act as platforms for future works on the emerging class of edible biomedical devices.
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Piezoelectric materials can convert mechanical energy into electrical energy, and piezoelectric devices made of various inorganic materials and organic polymers have been demonstrated. However, synthesizing such materials often requires toxic materials, harsh conditions and/or complex procedures. Recently, it was shown that hierarchically organized natural materials, such as bones, collagen fibrils and peptide nanotubes, can display piezoelectric properties. In my presentation, I will show our innovative approach to produce virus-based piezoelectric energy generation. Recently, we establish that the piezoelectric and liquid crystalline properties of M13 bacteriophage (phage) can be used to generate electrical energy. Using piezoresponse force microscopy, we characterize the structure-dependent piezoelectric properties of phage at the molecular level. We then show that self-assembled thin films of phage can exhibit piezoelectric strengths of up to 7.8 pm/V. We also demonstrate that it is possible to modulate the dipole strength of phage, and hence tune their piezoelectric response by genetically engineering the phage&’s major coat proteins. Finally, we develop a phage-based piezoelectric generator that produces up to 6 nA of current and 400 mV of potential, and use it to operate a liquid crystal display. Because biotechnology techniques enable large-scale production of genetically modified phages, phage-based piezoelectric materials potentially offer a simple and environment-friendly approach to piezoelectricity generation.

Microelectrode arrays (MEAs) find application both in vitro and in vivo to record and stimulate electrical activity in electrogenic cells such as neurons. MEA technology is optimized to measure action potentials from single cells with a high spatial resolution. However, there are number of other interesting and challenging biological phenomena. These are characterized by ultra-weak electrical fluctuations occuring in a time scale of seconds. An example are intercellular calcium waves (ICWs). These are Ca²⁺ elevations that propagate through a carpet of cells. ICWs are a widespread phenomenon by which a diversity of cell types communicate with each other to coordinate and synchronize their activity. These spatiotemporal events are important in both normal physiology as well as pathophysiological processes in a variety of organs and tissues including brain, liver, retina, cochlea, and vascular tissue. Our understanding of ICWs has arisen from investigations with real-time florescence imaging microscopy.
These slow and weak signals have not been electrically studied before, because conventional metal electrodes arrays do not have enough sensitivity to measure them. However, recently it has been shown that conducting polymer electrodes offer a low impedance interface that facilitates signal transduction from the cell to the recording electrode and yield better recordings when compared with bare metal electrodes.
Here we report the use poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonic acid) (PEDOT:PSS) electrodes to record extra-cellular calcium waves from a population of glioma cells in vitro. We take advantage of the impedance of polymer electrodes printed on nanofibrous bacterial cellulose substrates. These substrates are flexible, biocompatible and suited for implantable or skin adherent devices. Since we measure cell cooperative phenomena, we use relatively large area electrodes. This minimizes the intrinsic electrical noise. Furthermore, because the calcium waves propagate at slow speeds, a bandwidth of only 1.2 Hz is used. This allows us to use very high amplifier gains. By taking advantage of all these features we succeed to bring down the detection limit close to the fundamental level allowed by fundamental noise. The role of each impedance parameter on the signal enhancement is modelled and discussed.
The device ability to record extracellular signals was first validated by recording signals from cardiomyocytes. The full performance of the polymer electrodes was demonstrated by recording calcium waves on glioma C6 cells. Ultra-weak signals below one microvolt were measured. A variety of behaviors is observed ranging from quasi-periodic signals in a time scale of minutes, to bursting patterns with inter-spike intervals in a frequency range of 0.2 - 0.7 Hz.
This work received financial support from European Community Seventh Framework Programme (FP7/2007-2013) trough the project iONE-FP7 grant agreement n° 280772.

Conductive hydrogels have emerged as a promising new class of materials to functionalize electrode surfaces for enhanced neural interfaces and drug delivery. They consist of a conducting polymer, e.g. poly(3,4-ethylene dioxythiophene) (PEDOT), grown within a hydrogel matrix to form a composite system. The conducting polymer offers favourable electrical properties and the capability of drug delivery, while the hydrogel forms a water based matrix for the integration of biomolecules and provides mechanical properties that are more similar to brain tissue. Common weaknesses of such systems are delamination from the connection surface, and the lack of suitable patterning methods for confining the gel to the electrode site. We here present a novel conductive hydrogel which efficiently addresses these challenges. The proposed system consists of the hydrogel p(DMAA-co-PSS-co-BP) (which is a copolymer consisting of hydrophilic and cell-compatible dimethylacrylamide (DMAA) repeat units, polyanionic styrene sulfonate (PSS) repeat units, and UV-crosslinkable benzophenone (BP) repeat units), and the conducting polymer PEDOT. This composite material shows excellent electrical properties, can be patterned by a photolitographic process, and can be covalently bound to the substrate electrode.
The hydrogel was deposited onto microfabricated probes with patterned iridium oxide (IrOx) electrodes via a dip coating procedure. Prior to this, the IrOx was functionalized using UV-reactive silane to enable covalent bonding and thus facilitate adhesion between the hydrogel and the surface. The hydrogel film was cross-linked and patterned by UV-light exposure through a photomask. PEDOT was then grown galvanostatically within the hydrogel mesh. Since the counteranion PSS was provided by the hydrogel network, no additional supporting electrolyte was used. This enabled a homogenous growth of the polymer throughout the charged scaffold.
The hybrid material was electrochemically characterized by means of cyclic voltammetry (CV) and impedance spectroscopy (EIS), and compared to both the bare IrOx sites and the plain hydrogel. The conductive hydrogel overall compared well to the IrOx in terms of signal transmission properties. The material was further characterized with in vitro cell culture models, and with AFM to probe the mechanical properties. The conductive hydrogel presented here does address many of the challenges found with other conducting polymer/hydrogel based systems and thus shows great promise for a wide field of future applications.

There are several characteristics that are deemed essential for implantable devices: the substrate should be flexible, and conformal to the tissues; the devices should be biocompatible and biodegradable (in situ and environmentally). Collagen, one of the key components of mammalian tissues, emerges as an important candidate. Collagen type I is a triple helical molecule formed from three peptide chains and is found in all tissues particularly the connective tissue such as dermis/skin, cornea, tendon, and bone. It is also insoluble in water and has been found to be piezoelectric. Together, these properties show collagen as substrate for flexible electronics has key advantages over previous work with PLGA, cellulose, silk and other polymers. It offers a platform made of biological tissues on which flexible electronics can symbiotically integrated in a biological environment. The collagen films studied in this work were fabricated by a specialized process from native collagen samples. The result is a medical grade collagen film that is transparent, thin (~8µm) and flexible. SEM and AFM imaging together with FTIR analysis confirmed the presence of collagen. Mechanical characterization of the films using a micro tensile tester, showed an elastic modulus of E=2.04±0.26 GPa, a tensile strength of 90.71 ± 12.91 MPa, and sustain a failure strain of up to 16.8±2 % (n=5). Mechanical testing of E-beam deposited metal conductive patterns showed no significant change in mechanical properties. The resistors developed on collagen were tested at different radius of curvature showing a less than 2% change in resistance showcasing their flexibility. Resistive patterns encapsulated in collagen were placed in PBS buffer for two hours, showing no sign of being compromised. Using E-beam evaporation, we developed many devices for proof of concept applications. Strain gauges are the main component behind many sensor designs such as pressure and load sensors so a reliable strain sensor unlocks many possibilities when designing devices. Our traditionally designed strain gauge, calibrated on a cantilever, showed a linear relation between strain and change in resistance with a gage factor of 1.58. When placed on a balloon, increases in pressure showed increases in resistance, qualitatively showing possible medical applications in vascular related diseases such as aneurysms, which result in an increase in diameter of vascular vessels. An antenna was also deposited on collagen showing how devices (an LED for this experiment) could be wirelessly powered for up to 1m. Together, these demonstrations show the viability of collagen as a substrate that is biocompatible, flexible, and transparent, on which devices can be powered and built to sense strain and temperature. Reference: Moreno et. al “Biocompatible Collagen Films as Substrates for Flexible Implantable Electronics” Advanced Electronics Materials 10.1002/aelm.201500154

The lipid bilayer comprises the elemental structure of cell membrane, forming a stable barrier between the interior and exterior of the cell while hosting membrane proteins for selective transport of materials (e.g. ions) and cellular recognition. Planer lipid bilayers provide a highly promising biomimetic model system for investigating physical, chemical and biological processes at the cell surface such as pathogen attack. The generation of stable lipid bilayers on traditional supports such as silicon and glass is possible, however, integration with characterization methods which allow monitoring of lipid layer integrity, or ion flow through embedded proteins, remains challenging. An exciting new alternative is to use non-traditional, smart materials such as electroactive polymers. Recently, conducting polymers (CP) have been intensively explored as electroactive materials for applications in bioelectronics. Unique properties of CPs including mixed conductivity, easy processing, flexibility in design as well as chemical tunability have resulted in the large scale uptake of these materials for biomedical applications. Research in our group has used the CP poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate) (PEDOT:PSS) as the active material in the organic electrochemical transistor (OECT) to highly efficiently monitor cell layer formation and destruction. We have now turned our attention to integration of lipid bilayers with CP devices. To facilitate the integration of lipid bilayers with conducting polymers, for future use in electrical characterization, an understanding of the nature of the interaction between lipids and the CP is crucial. Herein, we focus on the optimization of stable lipid bilayer formation on the conducting polymer PEDOT:PSS. We demonstrate for the first time vesicle fusion on PEDOT:PSS, providing an exciting new avenue for characterization of these highly versatile biomimetic systems.