Organic bioelectronics

Resume : Stretchable strain sensors play a pivotal role in wearable devices, soft robotics, and Internet-of-Things, creating a rapidly growing market globally. Yet these viable applications, which require subtle strain detection under various strain, are often limited by low sensitivity. This inadequate sensitivity stems from the Poisson effect in conventional strain sensors, where stretched elastomer substrates expand in the longitudinal direction but compress transversely. In stretchable strain sensors, expansion separates the active materials and contributes to the sensitivity, while Poisson compression squeezes active materials together, and thus intrinsically limits the sensitivity. Alternatively, auxetic mechanical metamaterials undergo 2D expansion in both directions, due to their negative structural Poisson’s ratio. Herein, it is demonstrated that such auxetic metamaterials can be incorporated into stretchable strain sensors to significantly enhance the sensitivity. Compared to conventional sensors, the sensitivity is greatly elevated with a 24-fold improvement. This sensitivity enhancement is due to the synergistic effect of reduced structural Poisson’s ratio and strain concentration. Furthermore, microcracks are elongated as an underlying mechanism, verified by both experiments and numerical simulations. This strategy of employing auxetic metamaterials can be further applied to other stretchable strain sensors with different constituent materials. For real-world application of stretchable strain sensors, we participated in Singapore Tech Factor Challenge themed of “Aging-in-Place”, which is an entrepreneur programme to solve practical problems. The stretchable strain sensor project was discussed and presented to specialists outside academia, including programme managers from entrepreneur company and therapists from hospital. Seed fund of this entrepreneur programme was granted, and high sensitive stretchable strain sensors are paving the way towards practical health monitoring. (Adv. Mater. 2018, 30, 1706589)

Resume : Nature inspired a broad spectrum of bio-mimetic systems – from soft actuators to perceptive electronic skins – capable of sensing and adapting to their complex erratic environments. Yet, they are missing a feature of nature’s designs: biodegradability. Soft electronic and robotic devices that degrade at the end of their life cycle reduce electronic waste and are paramount for a sustainable future. At the same time, medical and bioelectronics technologies have to address hygiene requirements. We introduce materials and methods including tough yet biodegradable biogels for soft systems that facilitate a broad range of applications, from transient wearable electronics to metabolizable soft robots. These embodiments are reversibly stretchable, are able to heal and are resistant to dehydration. Our forms of soft electronics and robots – built from resilient biogels with tunable mechanical properties – are designed for prolonged operation in ambient conditions without fatigue, but fully degrade after use through biological triggers. Electronic skins merged with imperceptible foil technologies provide sensory feedback such as pressure, strain, temperature and humidity sensing in combination with untethered data processing and communication through a recyclable on-board computation unit. Such advances in the synthesis of biodegradable, mechanically tough and stable iono-and hydrogels may bring bionic soft systems a step closer to nature.

Resume : Soft and stretchable electronic devices are important in wearable and implantable applications because of the high skin conformability. Due to the natural biocompatibility and biodegradability, silk protein is one of the ideal platforms for wearable electronic devices. However, the realization of skin-conformable electronic devices based on silk has been limited by the mechanical mismatch with skin, and the difficulty to integrate stretchable electronics. Here we demonstrate silk protein as the substrates for soft and stretchable on-skin electronics. The original high Young’s modulus (10 GPa) and low stretchability (<10%) are tuned into 0.1~2 MPa, and >400%, respectively. This plasticization is realized by the addition of CaCl2 and ambient hydration, whose mechanism is further investigated by molecular dynamics simulations. Moreover, highly stretchable (>100%) electrodes are obtained by the thin-film metallization and the formation of wrinkled structures after ambient hydration. Finally, our plasticized silk electrodes, with the high electrical performance and skin conformability, achieved on-skin electrophysiological recording comparable to that by commercial gel electrodes. Here proposed skin-conformable electronics based on biomaterials will pave the way towards the harmonized integration of electronics into human.

Resume : Globular and structural proteins have pattern repetitions in their primary amino acid sequences and nanostructures. However, the contribution of these repeats to the properties of protein-based materials remains elusive. The presence of molecular defects in the protein structure constitutes a great challenge for the control of physical and chemical properties of the material. To overcome this challenge, we developed synthetic tandem repeat polypeptides with a segmented sequence design inspired by squid proteins, that self-assemble into a semicrystalline network. With a careful design of the sequence tandem repetition, we can control the molecular defects in the protein network and optimize the nanostructure and properties of the material beyond those found in nature. Hence, we developed biomimetic protein-based materials with programmable mechanical properties (strong and stretchable up to 300% strain), proton conduction (higher proton conductivity than state-of-the-art biological proton conductors reported to date), and thermal conduction (dynamic thermal conductivity with on/off switching ratios larger than state-of-the-art thermal switches). Programming physical properties through tandem repetition introduces a new approach for understanding transport phenomena in protein-based materials and introduces new design rules for the development of biological stretchable proton and thermal conductors.

Resume : With the expanding research on flexible and stretchable electrodes for health monitoring and disease treatment, the biological tissue-electronics interface needs to be better understood for avoidance of side effects and efficient electrode functioning. One question remaining unanswered is how cells and soft electrodes mechanically interact during electrical stimulation, in vEF (vertical electric field). In this work, a hydrogel-based soft and stretchable electrode is fabricated for directly interfacing with cultured cells, which allows for in-situ vEF stimulation under continuous microscopic observation of cellular behaviors. Additionally, the unique microcracked surface morphology enables CTF (cell traction force) mapping, to quantify cell-substrate mechanical interactions. Preliminary results indicate cell spreading area changes with application of vEF, which may depend on vEF direction and sequence of application. Further statistical study is needed to reach a conclusion.

Resume : Wearable and textile electronics are fast developing fields attracting a considerable industrial and commercial interests thanks to their ease of integration onto clothing and their natural conformability with the wearer. To allow the fabrication of wearable electronic devices various approaches have been developed to integrate active and passive electronic components on fibers or directly onto the fabrics. Recently, organic electronic materials demonstrated great processability together combined with textile substrates. We have developed a simple technique for the patterning of conducting water-based polymers using an elastomeric stencil to confine the spreading of the functional ink on the textile. This method allowed the fabrication of wearable PEDOT:PSS electrodes which were able to record high-quality ECGs with an outstanding stability in movement. The remaining PDMS stencil that surrounds the active electrode area can be further manipulated to yield a complete and versatile health monitoring system. To this end, we developed a process that allows the fabrication of 3D PDMS sponge structures. Its compatibility to integrate the fabrication of active devices on textiles is evaluated. Interestingly, this approach has the potential for on-textiles fluid handling. Indeed, integrated spongy structures allows to have an open capacity to manipulate, extract, sense and quantify solutes in wearable electronics applications.

Resume : Biocompatible, flexible and stable materials able to transduce biological information into electrical signals are of central interest to fabricate wearable electrochemical sensors. Wool- and human hair- extracted keratin biopolymers have shown to form self-assembled arrangements for regulating cellular behavior, for wound healing (Aluigi et al., ACS Appl. Mater. Interfaces 2015, 7, 17416−17424) and tissue engineering (Baker et al., Tissue Eng. Part A 2017, 23, 572-584). Here, we present the fabrication and characterization of an all-keratin made microelectrode array used as humidity sensor. Reversible binding and extraction of ions from the sensor volume was observed using cyclic voltammetry in controlled-humidity conditions. Pure keratin acts as an active proton conductor and can be chemically doped according to the functionalities that the biopolymer has to fulfill. The addition of glutaraldehyde to the pristine chemical recipe leads to the insolubility of the keratin active layer which can be then exposed to highly humid environment. Furthermore, we added glycerol to increase the mechanical stability in order to implement the doped biopolymer as a bendable, biocompatible and transparent substrate. Finally, we explored the possibility to develop a composite with higher proton conductivity by adding melanin. Palladium electrodes passivated with hydrogen were integrated into the sensor to efficiently extract/inject protons and collect a reliable amperometric output signal. The optimized insoluble all-keratin made ionic sensor showed practical bending properties that can pave the way for the use of naturally derived biopolymer in wearable electronics.

Resume : Flexible, high-surface area devices based on conducting polymers (for example, PEDOT) have shown great advantages in interfacing electroactive tissues such as the neural cells. These devices are mainly fabricated through conventional micro-fabrication and printing techniques. We have developed a wax-printing method for facile prototyping organic electronic devices on paper and for transferring them onto other flexible substrates. We print hydrophobic barriers wax on cellulose paper to define hydrophilic patterns for casting aqueous dispersion of PEDOT. This method fully maintains the microfluidic properties of the paper while making it electrically conducting. We use these printed conductors to integrate an organic electrochemical transistor, OECT, monolithically integrated with paper microfluidic structures. We show that both planar and vertical OECT can be facilely fabricated using this method. We also show multiplexing of devices by stacking or folding different layers of papers. In another approach, we pattern the microfluidic OECT devices by filtering the materials through filtration membranes with wax-defined patterns. We transfer the devices onto other flexible substrates through tape-and-peeling. Heterogeneous, multiple devices can be created by stacking different functional layers together. Our methods provide an easy platform for microfabrication of advanced multilayer devices, especially towards bio-interfacing applications.

Resume : The Microfluidic Paper-based Analytical Device (μPAD) is an emerging technological platform for point- of-care molecular diagnostics. Diagnostics of infectious diseases caused by pathogenic bacteria is typically done through Nucleic Acid Tests (NATs). Many research groups have developed μPADs that incorporate various NAT methods. However, most of these devices do not integrate the sample preparation step, which for bacteria-containing samples includes lysis of the bacteria to extract the DNA. We have developed a simple, and easy to fabricate, sample preparation device for vertical flow μPADs. This device consists of metal meshes that sandwich a paper. The paper absorbs a sample that is applied through the metal mesh. The mesh can then act as electrodes to apply voltage spikes through the paper and lyse the bacteria through irreversible electroporation. The advantage of this lysis method is that it eliminates the need for sample dilution and the need to add chemicals or enzymes which could affect downstream processes. Additionally, a hydrophobically coated metal mesh at the output end acts as an electrically controlled valve for downstream release of the lysed sample.

Resume : Nucleic acid test (NAT) is a well-known diagnostic test which has a great potential for Point of Care (POC) diagnostics. High sensitivity and specificity are the main advantages of NATs compared to conventional antibody-antigen based detection techniques. NAT tests, however, require expensive thermal cyclers and well-trained operators to be conducted which make them costly (7-8 USD per sample) and time consuming (about 2 hr). Therefore, to make the most of NAT for POC purposes we need to develop low cost integrated sample to answer NAT microfluidic device [1]. We fabricated NAT devices using textiles and paper. Using these low cost, yet highly functional materials as a platform we have integrated the three necessary steps of NAT: 1) cell lysis, 2) nucleic acid amplification and 3) detection. Considering the significance of detection step in NATs, we integrated sequence-specific electrochemical DNA (E-DNA) detection technique in woven fabric substrates to detect DNA. While most of the developed NATs POC devices are based on qualitative detection methods (fluorescence, color change) [2], E-DNA sensing is a promising qualitative method with high sensitivity, specificity and fast answer time with low power demands which makes this technique fitting for developing portable POC diagnostic devices. 1. Sua, W. Gao, X. Jiang, L. Qin, J. Microfluidic Platform towards Point-Of-Care Diagnostics in Infectious Disease. J. Chromatogr. A. 1377, 13–26 (2015). 2. Rodriguez, N. M. Wong, W. S. Liu, L. Dewarb, R. Klapperich, C. M. A fully Integrated Paper Fluidic Molecular Diagnostic Chip for the Extraction, Amplification, and Detection of Nucleic Acids from Clinical Samples. Lab Chip. 16, 753-763 (2016).

Resume : Receptor layers of organic field-effect transistor (OFET) biosensors are responsible for the analyte binding and the initial generation of an electronic signal. It is important to maximize the number density of receptor groups while allowing for process stability and preservation of the electronic signal. Polymer receptor layers rich in carboxylic acid (COOH) groups are effective choices for receptor attachment because of the availability of coupling chemistry for those groups. At the same time, a certain level of hydrophobicity is helpful in stabilizing receptor polymers to exposures to aqueous solutions. In this study, we compared the retention of immobilized biomolecules on various acrylic copolymers after multiple washing steps. Four different copolymers that combine hydrophobicity and high COOH concentrations (polystyrene-co-methacrylic acid (PS-MA), polystyrene-co-acrylic acid (PS-PAA) poly(methyl methacrylate-co-methacrylic acid) (PMMAMA) and poly(d,l-lactide-block-acrylic acid) (PDLLA-PAA)) were chosen for bioreceptor layers. We utilized the neurologically important myelin basic protein (MBP), with isoelectric point of 12, and its corresponding antibody as a representative antibody– antigen pair. Fluorescein isothiocyanate-labeled antibody was used to assess the retention of the antibody during aqueous rinsing. We compared the sensing responses the four receptor layer materials by measuring drain current changes upon exposure to 100 ng mL−1 of MBP. For PSMA, the best-performing polymer, sensitivity in the 1-10 ng/mL range was achieved. Selectivity experiments were also performed by using PS-MA as the receptor layer. Glial fibrillar acidic protein, GFAP, a known brain injury biomarker with isoelectric point of 5.4, was chosen as an interference protein. MBP is positively charged in pH 7.4 phosphate-buffered saline (PBS) while GFAP is negatively charged in pH = 7.4 PBS. Besides the anti-MBP device being selective for MBP over GFAP, it gave the opposite polarity responses to what we had previously reported for GFAP, as expected for its opposite net charge in PBS. In an extension of this work, we also prepared polymers on which the COOH groups were partially masked by trityl protecting groups. The deprotection of the groups induced by analyte binding is proposed as an additional mechanism for inducing electronic detection signals.

Resume : Most biological fluids contain high levels of water, so low voltage operation is critical to the development of reliable, stable and fully reversible biosensors. Employing field-effect transistors (FETs) as a sensor platform high gate capacitance materials are required. Solid‐state double‐layer‐dielectrics allow unraveling the working mechanisms of such sensors under physiological relevant conditions. Due to the formation of double‐layer capacitor while maintaining high insulating properties, such dielectrics enable stable low‐voltage devices, giving access to high current output even below 0.5 V.[1] To address their capability for sensors, proof‐of‐concept experiment are performed: i.e. field‐effect dependent photo-response and pH response with the semiconductor directly exposed to pH solutions.[2] Dual‐gate FETs with semiconducting polymer and SiOx as the topmost active sensing layer permit monitoring of pH in a fast and reversible fashion. pH response of bare SiOx is evaluated independently by means of voltmeter. Assembled in dual‐gate architecture, pH response scales in agreement with the theoretical model, assuming capacitive coupling, exhibiting an amplification of up to 10.[3] This opens up the possibility for reversible and reliable sensing based on organic semiconductors well beyond pH sensors. [1] C. Wang, et al. Sci. Rep., 5, 17849, 2015 [2] R. Pfattner, et al. Adv. Electron. Mater. 4, 1700326, 2018 [3] R. Pfattner, et al. Adv. Electron. Mater. 5, 1800381, 2019

Resume : Despite the great potential of polymer microfibers in human-friendly wearable electronics, most previous polymeric electronics have been limited to thin-film-based devices due to practical difficulties in fabricating microfibrillar devices, as well as defining the active channel dimensions in a reproducible manner. Herein, we report on conducting polymer microfiber-based organic electrochemical transistors (OECTs) and their application in single-strand fiber-type wearable ion concentration sensors. We developed a simple wet-spinning process to form very conductive poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) microfibers using aqueous sulfuric acid solutions and carefully examined their electrical/electrochemical properties. In conjunction with fabricating substrate-free PEDOT:PSS microfiber-based OECT devices, we developed single-strand fiber-type skin-mountable OECTs by introducing a source-gate hybrid electrode and demonstrated that the resultant microfiber sensors can perform real-time repetitive measurements of the ion concentration in human sweat.

Resume : The interface between biological cells and non-biological materials has profound influences on cellular activities, chronic tissue responses, and ultimately the success of medical implants and bioelectronic devices. For instance, electroactive materials in contact with cells can have very different composition, surface topography and dimensionality. Dimensionality defines the possibility to have planar (2D), pseudo-3D (planar with nano-micropatterned surface)1 and 3D conductive materials (i.e. scaffolds) in bioelectronics devices. Their success for both in vivo and in vitro applications lies in the effective coupling/adhesion of cells/tissues with the devices’ surfaces. It is known how a large cleft between the cellular membrane and the electrode surface massively affects the quality of the recorded signals or ultimately the stimulation efficiency of a device. However, this field is hindered by lack of effective means to directly visualize in 3D cell-material interface at the relevant length scale of nanometers. In this work, we explored the use of ultra-thin plasticization technique2 to cells for the first time on materials which differ in dimensionality3, particularly focusing on the optimization of this procedure for 3D cell-materials interfaces which have been unexplored so far. We have characterized how cells differently elongate and deform their membranes in response to the dimensionality of the electroactive materials and the relevant processes at the biointerface. In this way, we are able to define a set of optimal conditions for cell-chip coupling which enable an appropriate approach for designing bioelectronics platforms for both in vivo and in vitro applications in 3 dimensions. 1. Santoro, F., Zhao, W., Joubert, L.-M., Duan, L., Schnitker, J., van de Burgt, Y., Lou, H.-Y., Liu, B., Salleo, A., Cui, L., Cui Y., Cui B., Revealing the Cell–Material Interface with Nanometer Resolution by Focused Ion Beam/Scanning Electron Microscopy. ACS Nano, 2017 2 Li X., Matino L., Zhang W., Klausen L., McGuire A., Lubrano C., Zhao W., Santoro F., Cui B., A nanostructure platform for live cell manipulation of membrane curvature, Nature Protocols, just accepted. 3 Iandolo D., Pennacchio F. A., Mollo V., Rossi D., Dannhauser D., Cui B., Owens R. M., Santoro F., Electron Microscopy for 3D Scaffolds–Cell Biointerface Characterization, Advanced Biosystems, 2018.

Resume : Organ-chips are microfluidic cell culture models that can recapitulate complex functions of live human organs in vitro. We have recently demonstrated how coupled Organ-Chips of the neurovascular unit can reveal unknown metabolic interactions (1). In an Organ-Chip model of the heart, we further monitored drug actions on beating frequency and blood-vessel integrity using integrated electrode arrays (2). Our reported models have however limitations in detection sensitivity of bioelectric signals and long-term electrode-cell interaction. Here we report our approach for generating a new generation of organic electrochemical transistors (OECTs) for neural Organ-Chips. We are using conducting polymer blends and chemical conjugation of cell-specific cues to combine high electronic/ionic conductivity with a functional OECT/cell interface and long-time operation stability in physiological conditions. To gain high translational relevance, we populate the neural Organ-Chips with human primary and stem cell-derived neurons, astrocytes, and endothelial cells. Human cells have high translation value but demand long-term maturation, and for initial OECT evaluations, rat cells are used. Our studies include direct stimulation and recording of cell electrical activity, as well as blood-brain barrier function. We additionally use state-of-the-art proteomic and transcriptomic tools to evaluate the function and maturation of the neural Organ-Chip. 1) Maoz B, Herland A et al Nat. Biotech 2018, 36(9):865-874 2) Maoz B, Herland et al Lab Chip, 2017,17, 2294-2302

Resume : Organic semiconductor materials, including photo-sensitive conjugated polymers, are promising platform for visual prostheses offering novel retinal biocompatible devices. Despite ongoing research efforts in artificial retina field, full-colour sight restoration remains very challenging. We demonstrate tri-colour optoelectronic devices based on three different band-gap conjugated polymers with absorption in red, green and blue (RGB) spectral regions, mimicking absorption of human retinal cones responsible for full colour vision. Photo-response of these devices, interfaced with biological electrolyte solution, is demonstrated with long-pulsed excitation from monochromator-filtered light source, and spectral response is shown to deviate from optical absorption of dry polymeric films. Ink-jet printed devices are fabricated in the form of an array of semiconducting 60 to 90 micron diameter polymeric round pixels-photoreceptors with specific RGB colour sensitivity. The devices do not require wiring or external bias to operate, and are stable in aqueous physiological conditions. We compare polymeric pixels response with retinal photoreceptors colour sensitivity and comment on polymer-electrolyte interface capacitive charging during light-transduction process. Due to biological compatibility of organic semiconductors, high absorption coefficients and wide spectral tuneability, this device technology is expected to find medical applications as retinal bio-engineered prostheses towards the restoration of human vision lost due to common eye diseases, including Age Related Macular Degeneration and Retinitis Pigmentosa.

Resume : Organic electrochemical transistors (OECTs) are electronic devices having conjugated polymers in conducting or semiconducting form as core components. The mixed electronic/ionic conductivity of conjugated polymers allows for low operating voltages, high amplification, and adaptability to various form factors. These, together with operation in physiological conditions make OECTs promising devices for bioelectronics.[1] We have previously demonstrated that counterion exchange can be used to modify the hydrophilic character of conjugated polyelectrolytes (CPEs) and develop OECTs having high performance and operational stability in aqueous electrolytes.[2] Here we focus our attention to the side groups of CPEs to develop active materials combining efficient operation and specific conjugation with biological systems (i.e. cells and tissues). PEDOT having carboxyl side groups[3,4] is used to couple functional groups that can undergone click-chemistry. These introduce the bio-recognition properties needed to establish effective OECT/cell interfaces. Blending with a self-doped CPE provides the conductivity needed for efficient device performance. Electrochemistry and spectroscopy techniques are used to explore the effects of side groups, counter-ions and blending on films properties, such as stability in aqueous electrolytes and conductivity. [1] E. Zeglio, O. Inganäs, Adv. Mater. 2018, 30, 1. [2] E. Zeglio, J. Eriksson, R. Gabrielsson, N. Solin, O. Inganäs, Adv. Mater. 2017, 29, 6. [3] D. Mawad, A. Artzy-Schnirman, J. Tonkin, J. Ramos, S. Inal, M. M. Mahat, N. Darwish, L. Zwi-Dantsis, G. G. Malliaras, J. J. Gooding, A. Lauto, M. M. Stevens, Chem. Mater. 2016, 28, 6080. [4] L. Jiang, C. Gentile, A. Lauto, C. Cui, Y. Song, T. Romeo, S. M. Silva, O. Tang, P. Sharma, G. Figtree, J. J. Gooding, D. Mawad, ACS Appl. Mater. Interfaces 2017, 9, 44124.

Resume : Organic mixed conductors and electrochemical phenomena at solid–liquid interface have garnered significant attention for applications in bioelectronics, electrochromics, energy storage/generation, neuromorphic computing, and thermoelectrics. These devices operate in electrolytes that render ions mobile in the film, making the coupling between electronic and ionic charges crucial. A prime example for such devices is the organic electrochemical transistors (OECTs). The most common mixed conductor studied for these applications is poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate), PEDOT:PSS, with the newly synthesized hydrophilic organic semiconductors showing high potential to replace PEDOT derivatives. In this work, using in operando techniques, we find that the ions enter the semiconducting polymer channel hydrated and the excess swelling of the material has a significant effect on device characteristics, which can be traced back to changes in the overall structural order. 1 We show that infiltration of the hydrated dopant ions into the polymer film irreversibly changes the polymer structure and negatively impacts the OECT mobility, as well as the efficiency, reversibility and speed of charge generation. We conclude that minimizing swelling of the polymer films during doping is a key parameter to design fast and highly efficient ion-to-electron transduction devices. These results are in contrast to the general understanding built upon the standard material PEDOT:PSS – that we should control excessive swelling. As such they present a new direction for the design of mixed conductors. Our work also highlights the importance of characterizing the properties of these films in-situ (in their electrolyte swollen state) for drawing conclusions related to materials properties/device performance, which has tremendous impact on the performance of biosensors. 1 Savva, A et al Influence of Water on the Performance of Organic Electrochemical Transistors Chem. Mater. 2019, DOI: 10.1021/acs.chemmater.8b04335

Resume : The US National Institute of Health defines biomarkers as molecules that can be objectively measured and evaluated as indicators of normal or disease processes and pharmacologic responses to therapeutic intervention. Among the plethora of biomarkers, the sensitive detection of proteins is of paramount importance in a number of clinical fields.1 The clinical use of protein biomarkers as indicators of the onset of pathological states requires the measurement of low concentrations of proteins in complex samples. Attempts to develop ultra-sensitive assays for the detection of protein biomarkers have been done by several groups in the last few years. Although in the last decade many approaches to achieve ultra-sensitive detection have been developed, most of them require complicated assay set-ups, hindering their adoption in point-of-care applications. In this perspective, Electrolyte-Gated Field-Effect-Transistors (EG-FETs) 2-4 with a bio-functionalized gate electrode, appear as very promising biosensing platforms. The EG-FET device herein presented, able to operate in physiologically relevant fluids such as blood serum and saliva, will set the ground to a major revolution in biosensing applications for early clinical detection. 1) Barletta J.M. et al. 2004, Am. J. Clin. Pathol., 122, 20-27. 2) Macchia E. et al. 2018 Nature Communications, 9, 3223. 3) Macchia E. et al. 2019 Chemistry of Materials in press. 4) Macchia E. et al. 2019 Analytical and Bioanalytical Chemistry in press.

Resume : Proteins are macromolecules with a very broad array of biological functions: signals for cells, carriers of molecules, machines to perform reactions and structural elements in tissues. In the last few decades proteins have been studied from biomedical applications for the delivery of drugs or for the fabrication of scaffold for tissue engineering and regenerative medicine. In recent years proteins are been studied with a material science approach, with structural proteins, in particular, being regarded as biological and biodegradable alternatives to polymers. In this contribution I will present some recent advancements in the creation of a protein-based electronics. Conductive protein materials were developed by combining different proteins with carbon nanomaterials and used to produce devices such as fuel cells, antennas, electronic components and analogue electronic devices. Thanks to the protein matrix these devices proved to be flexible and conformable, while the carbon nanomaterials provided electrical properties that could match the ones reported for nanocomposites of conventional polymers.

Resume : Over the last few years, the development of polymer semiconductors that support both ionic and electronic transport led to the realization of n-type, accumulation mode organic electrochemical transistors (OECTs). These devices exhibit strong technological potential for a number bioelectronic applications, especially for low-cost, point-of-care metabolite biosensors. Here we show that a simple solvent engineering enable more than 3 times increase in transconducatnce of n-type, accumulation mode OECT as a result of the simultaneous increase of the volumetric capacitance (C*) and electronic mobility (μOECT). The improved electrochemical activity of the n-type polymer films is leveraged to build glucose biosensors with double glucose sensitivity, detection limit at 10 nM and a dynamic range of more 8 orders of magnitude. The approach described here utilizes fundamental principles and presents qualitative insights that could be used to identify different solvent systems applicable to a range of polymer semiconductors for OECTs and OECT-based metabolite biosensors.

Resume : In recent years the boundary between electronic and biology is thinning highlighting an interesting scientific scenario where the technological potential of this mutual collaboration is evident. Organic electronics is offering exciting opportunities in terms of materials and technologies and among them, electrolyte-gated organic field effect transistors (EGOFETs) represent an approach which can redefine the concept of device transduction. However, the organic semiconductor (OSC)/electrolyte interface which is pivotal during device operation is still misunderstood and consequently, several phenomena behind the gating mechanism of the OSC channel are unclear. Our aim is the better understanding of this interface by using EGOFETs where a liquid or a solid electrolyte is employed. The use of a solution of Hg2+ ions has allowed for the modulation of the device’s electrical behavior due to redox reactions occurring exclusively in the first few nanometers of the OSC. By exchanging the liquid electrolyte with a hydrogel layer, the device has turned into a pressure sensitive platform. Thanks to the hydrogel which acts as a water reservoir, pressure affects directly the water molecules at the OSC/hydrogel interface and the control of the electrical characteristic of the EGOFET is possible. Such a sensitive and reliable device has been further tested for the continuous monitoring of the electrical activity of cardiomyocytes revealing the potential of the platform.

Resume : Biosensors are becoming invaluable tools in healthcare industry, safety control, environmental monitoring. . Optical-based assays such as ELISA still are the golden standard of biosensing, thanks to their sensitivities, despite significant drawbacks. Organic bioelectronic devices, and in particular Electrolyte Gated Organic Transistors (EGOTs), hold the promise of outperforming state-of-the-art solutions in biosensing. EGOTs exploit the intrinsic amplification of the field effect transistor, increasing signal to noise ratio and lowering detection limits. In the last years, we demonstrated EGOTs (both EGOFETs and OECTs) to monitor a wide range of biorecognition events, differing in terms of size of the surface bound biomolecule and of the chemical nature and lateral dimensions of the biological partner in solution. Examples of label-free, ultra sensitive biosensors for analytes ranging in size from small chemicals (dopamine, urea) to proteins (cytokines) and viruses will be presented. I will also describe novel insights that we gained into the working mechanism of these family of devices, whose operational mechanism is yet far from being fully elucidated, despite the countless applications described so far in the literature. We gratefully acknowledge Euronanomed III Project “AMI” for support.

Resume : Chronic wounds are serious health issues that are currently becoming a major human and economic burden due to the steady increase of the population of diabetics and bed-ridden elderly. Chronic wounds indeed lead to nearly 500,000 amputations each year worldwide and are globally generating direct and indirect costs (stays in hospital) totaling 35 billion ¤ globally. Therefore, there is an urgent need for novel therapies to trigger and speed-up healing at early stages.It happens that monolayer graphene film with its bio stimulating effect (1) is providing a very promising technology to unlock these challenges. For that purpose, we are currently assessing in the lab its ability for a better induce cells regrowth and promote tissue engineering. On the application side, we are developing a technology platform that exploits the features of graphene to improve the management of woundcare. We are taking advantage of the combined biostimulating, transparent and electrically conducting properties of graphene to generate an interface iuseful for tissue engineering. I will present also the perspective both academic and industrial developments of a novel technology involving monolayer of graphene on polymers. Our bandage platform (2) is based on the integration of a monolayer graphene polycrystalline layer back-bonded onto a biocompatible polymer layer. The resulting film can directly be applied onto the bed-wound and is inserted in a commercial bandage. Graphene surface combines healing (speed-up of wound closure) and antibacterial action, optical transparency and electrical conductivity. The specific properties of graphene make it a substrate useful for providing wound dressing enabling a novel wound healing technology involving electrostimulation and detection . [1] F. Veliev et al. Biomat. 86, 33-41, (2016) [2] www.grapheal.com

Resume : The race in biomedical diagnostics between optical detection principles (UV/Vis absorption, fluorescence, surface plasmon spectroscopy, etc.) and electrical/ electro-chemical/ electronic concepts has not been decided yet. Both approaches continue to offer solutions for fast, multiplexed, simple and cheap detection of oligonucleotides, PCR amplicons, genomic DNA (fragments), etc. Using graphene as both the channel material in transistor configurations as well as for SPR chips gives access to an unique analytical tool to investigate bioaffinity reactions at the same time from an electrical and optical point of view. It is well established that a significant change in the spatial organization of an aptamer upon ligand binding is leading to a massive change in the charge distribution at the surface. Hence, the graphene-FET (gFET) approach is a particular promising approach for bioanalyte detection as it translates this reorganization into a change in the surface double layer potential and thus into an easily detectable modulation of the source-drain current. In the case of graphene-based SPR signal enhancement can be achieved making it an attractive sensing platform (2-5). However, one crucial step in the formation of a graphene-based sensor is the suppression of non-specific absorption. The results of an in depth investigation on graphene interfaces modified with pyrene ligands carrying COOH and PEG units on the absorption of lysozyme will be presented here. References: 1. Alsager, O.A.; Kumar, S.; Willmott, G.R.; McNatty, K.P., Small Molecule Detection in Solution via the Size ContractionResponse of Aptamer Functionalized Nanoparticles, Biosens. Bioelectron. 57, 262-268 (2014) 2. Szunerits, S., Maalouli, N., Wijaya, E., Vilcot, J.-P., Boukherroub, R., Recent advances in the development of graphene- based surface plasmon resonance (SPR) interfaces, Anal. Bioanal. Chem. 405, 1435-1443 (2013) 3. Zagorodko, O., Spadavecchia, J., Yanguas Serrano, A., Larroulet, I., Pesquera, A., Zurutuza, A., Boukherroub, R., Szunerits, S., Highly sensitive detection of DNA hybridization on commercialized graphene coated surface plasmon resonance interfaces. Anal. Chem. 86, 11211-11216 (2014) 4. Singh, M., Holzinger, M., Tabrizian, M., Winters, S., Berner, N. C., Cosnier, S., Duesberg, G. S., Noncovalently functionalized monolayer graphene for sensitivity enhancement of surface plasmon resonance immunosensors, J. Am. Chem. Soc. 4;137(8), 2800-2803 (2015)

Resume : Electrophoretic deposition (EPD) is a versatile technology for surface coating and thin film deposition. Compared to other processing methods, EPD is readily adaptable to materials with different dimensions and forms and has become an important methodology for the deposition of nanoscale materials of controlled thickness, in particular graphene-based materials. While the EPD technique has been used to develop different reduced graphene oxide (rGO) coated interfaces for a variety of applications, the basic deposition kinetics and the influence on the current applied during the process has been largely omitted so far. We will show here the advantages of low potential EPD of graphene oxide based solutions onto gold thin film interfaces as well as integrated electrode systems over high potential EPD. Highly homogenous, chemically and mechanically stable coatings are formed using 2.5 V and can be further modified using diazonium based chemistry without any alteration of the coating layer, making it an attractive interface for the construction of electrochemical, electrical and plasmonic sensors. Some of our preliminary results will be discussed here.

Resume : stablishing a reliable bidirectional communication interface between the nervous system and electronic devices is crucial for exploiting the full potential of neural prostheses. Despite recent advancements, current technologies evidence important shortcomings, e.g. low signal-to-noise ratio for signal mapping, low charge injection capacity for nerve stimulation, poor long-term stability, challenging high density integration, etc. Thus, efforts to explore novel materials are essential for the development of next-generation neural prostheses. Graphene and graphene-based materials possess a rather exclusive set of physicochemical properties holding great potential for biomedical applications, in particular neural prostheses. This presentation will provide an overview on fundamentals and applications of several graphene-based technologies and devices aiming at developing an efficient bidirectional communication with the nervous system. In this respect, the presentation will review recent technology developments exploring the capability of graphene-based devices for recording and stimulating electrical activity in the central and peripheral nervous systems. The main goal of this talk is to discuss the potential of graphene technologies in the field of neural interfaces and prostheses, and at the same time to identify the main challenges ahead.

Resume : Organic electronics devices (electrolyte gated organic field effect transistors –EGOFET- and organic electrochemical transistors -OECT) are ultra-sensitive and specific biosensors. EGOFET operate in accumulation due to electrostatic doping of ions at the electrical double layer at the interface between the organic semiconductor and the electrolyte; OECT operate in depletion by electrochemical doping upon gate-modulated cation exchange. A unified view of ion-gating mechanism in the two architectures can be drawn, based on the strong non covalent ion-pi interaction. Such interaction allowed us to demonstrate a new organic sensor for dopamine (DA), which is ultra-sensitive and specific at the same time, even without a recognition group. The sensor is made of two poly(3,4-ethylenedioxythiophene):polystyrene sulfonate -PEDOT:PSS– electrodes and is operated upon frequency modulation: one electrode mimics the pre-synaptic neuron and is pulsed with voltage square waves, the other is used to record the displacement current, thus mimicking the post-synaptic neuron. The response in current is either facilitated or depleted depending on the frequency and the duty cycle, thus mimicking that of a biological synapse. In the presence of different DA catabolites, else carboxylic acids, the sensor gives rise to a selective and quantifiable response typical of DA.

Resume : MicroRNA (miRNA), are non coding RNA molecule consisting 19-22 nucleotides, acts as a regulator of gene expression. Still now, 2000 miRNA has been discovered in human, many of these have played a profound role in human development, cell proliferation and diseases. Among these miRNA, miRNA-1 recognised as most abundant microRNA. miRNA-1 perform important role in cardiac development, function and disease such as such as hypertrophy, myocardial infarction, and arrhythmias. Also, recent study disclosed that miRNA-1 is downregulated in myocardial infected tissue. As a result, Selective, sensitive and rapid detection of miRNA is of great significance. In this work, high sensitive and selective detection miRNA-1 using branched DNA (b-DNA) based field effect transistor (FET) has been developed. Here, we fabricated 30 micron long conducting channel using individual 17 nm long b-DNA which is confirmed by atomic force microscopy (AFM) study. As far our knowledge, this is first time, long range charge transport has occurred in b-DNA based field effect transistor, fabricated without attaching any functional material with very low operating voltage (-1.5 V). Bio-sensing results confirmed that b-DNA based FET shows excellent selective response towards miRNA-1.

Resume : Non-invasive extracellular recording is of great interest for developing implantable devices, neuroprothesis, brain-computer interfaces and in vitro drug screening or cytotoxicity tests. These recording can be achieved either by conventional Microelectrode Arrays (MEAs) made of metallic or organic conductors or a semiconductor in a transistor channel which is capacitively coupled to the cell medium, acting as liquid gate. Compared to conventional MEAs, transistor-based devices offer intrinsic local signal amplification and the possibility for downscaling and high density integration. Electrolyte Gated Organic transistors (EGOFETs) have recently been exploited as biosensors and transducers as the active organic semiconductor in contact with the cells offer biocompatibility, mechanical flexibility, and high sensitivity to electrostatic potential changes at device interfaces. In this work, we present a solution processed flexible and semi-transparent EGOFET composed of a blend of DiF-TES ADT and polystyrene (PS) working as an electronic transducer to monitor extracellular activity of human pluripotent stem cell derived cardiomyocyte cells. Transistor current was monitored over time during the beating of the cardiac cells placed on the channel of the transistor. Due to the cardiac action potential, the effective gate voltage of the transistor changes resulting to a change in source-drain current. The spikes of the current occur at a frequency of about 0.7Hz equivalent to the frequency of the beating cardiac cells. To demonstrate that the spikes in the electrical recording is due to the beating cardiomyocyte cells, norepinephrine which is a cardio stimulant drug was added to the cell culture and spikes of higher frequency (~1.3Hz) were recorded due to the faster beating of the cells in the presence of the drug. However, when the drug was washed away, the spikes were recorded at a lower frequency of 0.8 Hz similar to the basal medium before the addition of the drug. Furthermore, by blocking the voltage gate calcium ion channels which causes the beating of the cardiomyocytes by adding 100µM concentration of Verapamil drug on the culture, no spikes were observed. We will highlight the remarkable stability of these EGOFETs which allowed us to have electrical recording for weeks.

Resume : Antimicrobial resistance is the result of microorganisms including bacteria, viruses, and parasites changing when they are exposed to antimicrobial drugs. The Centers for Disease Control and Prevention (CDC) has estimated the excess direct healthcare costs associated with AMR to be as high as £16 billion. Infections with carbapenemase-producing strains are associated with high mortality rates (up to 50%) and thus, represent a major public health concern worldwide. Multidimensional standard curves extract information from amplification curves which allows for simultaneous classification and multiplexing. This research aims to develop a scalable, rapid, quantitative, label-free, sample-to-answer POC diagnostic device for carbapenemase-producing genes. The final stage would be the pH detection using complementary metal-oxide semiconductor (CMOS) based ion- sensitive field-effect transistors (ISFETs) as biosensors. CMOS technology is compatible with real-time isothermal amplification. The ultimate goal for this research is to transfer the multidimensional approach to a point-of-care platform for the rapid screening of CPE.

Resume : A label-free single-molecule detection platform based on electrolyte-gated organic transistors has been recently proposed [1]. In contrast to state-of-art approaches based on nano-transducers [2], the aforementioned single-molecule transistor (SiMoT) technology is based on a millimeter-sized transistor where the gate is bio-functionalized with ~1012 bio-probes. Analogously to systems in nature, SiMoT provides a high interaction cross-section by means of a large number of highly packed receptors. Basing on the SiMoT technology, label-free detection of 1 IgG has been demonstrated in diluted saliva and 15 IgGs have been assayed in whole serum. The rational design of SiMoT bio-sensors urgently requires the development of models able to reproduce and predict the behavior of this new class of devices. Here we show a physical-based model of single-molecule organic electrolyte-gated transistors. The characteristics of SiMoT are accurately and consistently reproduced in the whole range of ligand concentrations with a unique set of parameters. The model reveals that nano-scale single-protein interaction results in a macro-scale variation of the gate electrode work function and the number of binding sites involved upon the protein binding is quantified. The model provides insights on the SiMoT operation and is an essential tool for further developments of the SiMoT technology. 1 E. Macchia et al. Nat. Commun. 9, 3223, 2018 2 J. J. Gooding et al. Angew. Chem. Int. Ed. 55, 11354, 2016

Resume : Organic Bioelectronics applications are largely dictated by the chemical nature of the materials that transduce signals across the biotic/abiotic interfaces1. The human pigment eumelanin is currently gaining increasing interest as valuable material for functional biocompatible interfaces. This black insoluble pigment of human skin, hair, eyes and nigral neurons (neuromelanin)2, featuring unique assortment of chemical physical properties3, arises biogenetically from the aminoacid tyrosine via the oxidative polymerization of 5,6-dihydroxyindole (DHI) and/or 5,6-dihydroxyindole-2-carboxylic acid (DHICA)2,3. and lacks of any defined structural order. This is associated to the actual eumelanin insolubility in any solvents, preventing easy processability of the pigment as well as the devices fabrication, and to its low conductivity, limiting both the range of possible working potential and functional applications. To improve the electrical performances of the eumelanin thin films, a clear-cut approach lies in the hybridization/integration with a suitable conductive counterpart. In this view, π-conjugated molecules featuring conductive pathways appear a key choice in the production of new organic materials for electronic (nano)devices. Here, we present the first (at the best of our knowledge) preparation of an eumelanin-PEDOT blend, featuring valuable functional and processing properties, like easy films preparation, high adhesion, good electrical conductivity and biocompatibility. The effect of eumelanin on conductivity was thus related to structural features in Wide Angle X-ray Scattering (WAXS) and diffraction (XRD) patterns of films with different eumelanin content and fixed PEDOT:PSS ratio. The biocompatibility and toxicity was investigated in view of its potential exploitation as bio-interface material. As a proof of concepts an OLED featuring an eumelanin-PEDOT anode was fabricated and characterized. References [1] Berggren M., and Richter-Dahlfors A. (2007). Adv Mater, Vol.19, p.3201-3213. [2] d’Ischia M., Wakamatsu K., Napolitano A., Briganti S., Garcia-Borron J. C.et al. (2013). Pigment cell & melanoma research, Vol.26, p.616-633. [3] d’Ischia M., Napolitano A., Pezzella A., Meredith P. and Sarna T. (2009).AngewChemIntEdit,Vol.48, p.3914-3921.

Resume : Organic thin-film transistor–based pressure sensors have received huge attention for wearable electronic applications such as health monitoring and smart robotics. However, there still remains a challenge to achieve high sensitivity and low power consumption at the same time for truly wearable active sensor systems. Here, we introduce a flexible pressure-sensitive contact transistor (PCT), a new type of organic thin-film pressure-sensing device. Similar to the point-contact transistor, the first solid-state transistor, the PCT consists of deformable S/D electrodes contacted on an organic transistor body. The laser-patterned interdigitated S/D electrodes were fabricated by embedding conducting single-walled carbon nanotubes on surface of a microstructured PDMS. Under pressure loads, the deformation of the electrodes on an organic semiconductor layer leads to the direct dependence of drain current on variation in both channel geometry and contact resistance in the device. By operating the device in subthreshold regime (VGS = 1.2V), we have achieved ultralow power consumption (down to 10 nW) while maintaining high-sensitivity (up to 18.96 kPa-1). Finally, we demonstrate a 5 × 5 an active PCT matrix for sensory arrays on a 3-micron-thick parylene substrate. The ultralow power consumption, high-sensitivity, flexible bio-compatible substrate, and high repeatability make the PCT promising candidate for next-generation skin electronic devices.

Resume : By 2030, cancer incidences and mortalities worldwide are expected to rise to 18.1 million and 13.2 million individuals respectively. As health systems are under increasing strain at having to provide costly care to the growing number of patients, practitioners require the ability to diagnose cancer at early stages and to monitor their patients' response to treatment. Within this context, point-of-care (PoC) devices utilising genomic and epi-genomic biomarkers can serve as invaluable sources of information for treating disease. This project aims to develop novel assays for the quantification of DNA methylation biomarkers on ovarian-cancer related genes (MLH1 and MGMT), using isothermal amplification chemistries, that can be further utilised within low-cost PoC devices towards the realisation of a more targeted cancer monitoring system. Epigenetic methylation profiles may be converted into changes in the gene sequences using the bisulfite treatment method. Gene sequences are then selectively amplified for the target disease biomarker, by loop mediated isothermal amplification (LAMP). Detection of the amplified strands is carried out by optical methods and pH monitoring. The analysis of clinical samples of ovarian tissue will be carried out in order to facilitate the application of the technique to a working PoC device.

Resume : Poly(vinylidene fluoride) (PVDF) has so far been widely used for flexible pressure sensors. In order to obtain a sufficient voltage output from PVDF-based pressure sensors, a poling treatment of PVDF thin films is necessary. The conventional poling method usually requires quite a high electric field or high annealing temperature, which leads to increase in cost of sensor fabrication. Here, we propose a simple method to control the polarization of PVDF thin film by controlling the direction of the surface dipole on the underlying Au electrode. The polarization can be controlled by orienting the PVDF molecules along the direction of the surface dipoles on the Au electrode that is controlled by surface modification with thiol reagents. This novel method for the PVDF poling significantly simplifies the fabrication process of PVDF-based pressure sensors. We confirmed that this treatment increased the output sensitivity of the PVDF-based pressure sensors by approximately 5 times compared to that of the sensors without this treatment. The proposed method can be applied to various flexible sensing devices.

Resume : Organic electronics is one of the most rapidly developing fields of science and technology. A considerable attention has been paid recently to the exploration of memory devices based on bistable organic field-effect transistors. Here we report for the first time the application of the self-assembled monolayers of donor-acceptor dyads with porphyrin moieties as light-sensitive components integrated at the semiconductor/dielectric interface in OFET-based optical memory elements. The designed devices operated at low voltages (<15 V), showed wide memory windows and reliable switching between multiple quasi-stable electrical states characterized by Ids current ratios of 1E2-1E4 when measured at the same Vgs voltage. The operation mechanism of the designed light-switchable transistors has been revealed and will be discussed in the presentation. Exploring a series of porphyrin-based dyads with appended acceptor units based on [60]fullerene or ruthenium pyridyl complexes allowed us to restablish some important molecular structure – electrical performance relationships, which should facilitate future design of advanced organic memory devices possessing all the advantages of organic electronics while being cheap, flexible, biodegradable and hence more environmentally friendly.

Resume : Non-invasive and early diagnostics of various diseases is one of the most relevant problems of modern medicine. Analysis of the chemical composition of exhaled air represents a powerful approach to perform express diagnostics. Sensor arrays fabricated using conventional silicon-based resistors, diodes or field-effect transistors were used recently to identify and distinguish 17 different diseases with impressive 86% accuracy (ACS Nano 2017, 11, 112). Sensors based on organic electronics might offer largely improved selectivity and sensitivity to certain analytes particularly because of chemical diversity and unlimited potential for fine-tuning properties of organic semiconductor materials. Here we report the application of several organic semiconductor materials in gas sensors for detection of ammonia and various amines using organic field effect transistor (OFET) as a platform. Top-contact bottom-gate OFETs based on the selected materials have delivered decent charge carrier mobilities in combination with a long-term operation stability under ambient conditions. Scanning electron microscopy revealed that some of the materials form highly porous films readily accessible to the gaseous analytes, which enables their efficient operation in sensors. Different spectra of the analytical responses of the fabricated sensors with respect to a panel of analytes paves a way to design of "electronic nose" potentially suitable for medical diagnostics.

Resume : A new experimental setup combining a well-established optical characterization method, namely Surface Plasmon Resonance (SPR), with an experimental, electronic setup based on a reduced Graphene-Oxide Field Effect Transistor (rGO-FET) was developed. By using a gold gate electrode which modulates the electric behavior of the rGO-FET as the sensing area for the SPR and designing a corresponding flow cell, both systems can be combined while getting a simultaneous read-out for SPR and rGO-FET. A layer-by-layer approach utilizing charged polyelectrolytes (poly(diallyldimethylammonium chloride) and poly(sodium 4-styrenesulfonate) ) (PDADMAC/PSS) is used for system characterization. With few limitations, electrical measurement of the rGO-FET as well as angle-dependent measurements for the SPR can be done. All in all, this new platform gives an interesting insight and comparative capabilities for new, electronic-based biosensors which can be easily used for real-time comparisons to a well-established optical technique.

Resume : Monitoring of bioelectric signals in peripheral sympathetic nerves is crucial to gain understanding of how the autonomic nerve system controls specific body functions related to disease states such as inflammatory response. Advances in low-invasive electrodes for such recordings in chronic conditions rely on electrode materials that show low-impedance ionic/electronic interfaces and elastic mechanical properties compliant with the soft and fragile nerve strands. Here we report a highly stretchable low-impedance electrode realized by microcracked gold films as metallic conductors covered with stretchable conducting polymer composite to facilitate ion-to-electron exchange. The composite based on Pedot:Pss obtains its adhesive, low impedance properties by controlling thickness, plasticizer content and deposition conditions. Atomic Force Microscopy measurements under strain show that the optimized conducting polymer coating is compliant with the micro-crack mechanics of the underlying Au-layer, necessary to absorb the tensile deformation when the electrodes are stretched. We demonstrate functionality of the stretchable electrodes by performing high quality recordings of renal sympathetic nerve activity under chronic conditions in rats.

Resume : For most cancer patients, surgery is considered to be their primary option for curative treatment, alongside chemotherapy and radiotherapy. Through successful tumor resection removing both the gross and microscopic tumor, the surgical oncologist may effectively render a patient cancer-free. A more complete resection can be achieved with fluorescence-guided intraoperative imaging, using second near-infrared (NIR-II) probes. Imaging with the NIR-II (1000-1700 nm) is at the forefront of current biomedical research, due to a higher signal-to-noise ratio and deeper tissue penetration. However, the low quantum yields of NIR-II fluorophores limit their sensitivity of detection. Gold nanostars (AuNSs) may act as plasmonic agents for metal enhanced fluorescence (MEF) of these NIR-II fluorophores. The AuNSs are ideal MEF agents for biomedical applications, due to their stability, biocompatibility and tunable optical properties resulting from their multispiked morphology. In this work, two classes of AuNSs are synthesized and characterized. The AuNSs are conjugated to Ag2S quantum dots – the chosen NIR-II fluorophore in this study – and show enhanced fluorescence in the biological NIR-II region with steady-state fluorescence measurements.

Resume : Mechanical metamaterials are artificial structures with unique mechanical properties originated from their structure rather than their compositions. There are several types of mechanical metamaterials such as acoustic metamaterials, auxetic metamaterials, and metamaterials with negative mechanical properties, etc. Kirigami-based mechanical metamaterials are fabricated by cutting process of flexible thin sheets or films. By designing of the cutting patterns on the sheet, it is possible to fabricate auxetic metamaterial which has a negative Poisson’s ratio. In this study, we designed and fabricated kirigami-based mechanical metamaterials for a substrate of stretchable electronics. To design of meta-patterns, finite element analysis is performed to estimate their stretchability. In addition, we demonstrated stretchable energy and optical devices by transferring thin devices based on semiconducting materials onto the mechanical meta-structure of the flexible substrate. This study could help the design and fabrication of flexible electronic devices that can endure various mechanical deformations. In addition, it could enlarge the application of mechanical metamaterials to a wide area.

Resume : Implantable stretchable devices that perform electrical recording on specific site during optical modulation are effective tools in revealing the origins behind the optogenetic therapies. From the material perspective, previously reported devices have shown a clear evolution towards higher compliance and higher biocompatibility, yet very few reports has ever addressed on highly transparent, stretchable, biodegradable, all-organic biopolymer-based device to meet the implantation need. This is limited by lack of mechanical robustness in natural polymers and also the incompatibility of them toward electronics fabrication. Besides elastomers and hydrogels, silk fibroin has been an excellent option for its natural biocompatibility and biodegradability. In this work, we develop a highly transparent, stretchable, conductive microelectrode platform based on PEDOT:PSS and silk fibroin composite. The original water-soluble (dissolved in seconds in water), high strength (E ~ 5-12 GPa) and low stretchability (<20%) silk fibroin are modified into soft and stretchable in water with a young’s modulus down to 1 MPa and stretchability >400%. This transition is enabled by the effect of poly(ethylene glycol) diglycidyl ether(PEGDE) and the aqueous environment, the proof comes from Molecular Dynamic analysis between silk fibroin and PEGDE. Moreover, both traditional Silicon wafer-based process and sacrificial transfer process were utilized to enable the micro-electrode patterning on silk fibroin. The as-fabricated PEDOT:PSS microelectrode shows a high transmission(> 85%), high conductivity (> 1500 S/cm) and high stretchability up to 250%. Its impedance in bio-environment is much lower than thin gold film. In addition, this micro-electrode platform shows stable performance after 1000 stretching-release cycles (under 20% strain) and even after several months of incubating in PBS solution. This microelectrode platform is being applied to the study of pathological mechanisms in the optical modulation in cerebral thrombosis. Our work provides an advanced strategy for assisting the study of optogenetic therapy by highly transparent, conductive, stretchable biopolymer-based microelectrode, which is essential for implantable need.

Resume : Self-assembled micro- and nanotubes of diphenylalanine (C18H20N2O3, FF) represent advanced functional biomaterial for developing new medical equipment [1], such as laboratory-on-chip, due to its outstanding piezoelectric [2] and mechanical [3] properties. After the self-assembly in aqueous solution water molecules remain inside the nanochannels and stabilize its structure [4]. In this work we performed experimental and theoretical study of water adsorption on the inner walls of nanochannels in FF microtubes. Adsorption measurements were performed at various temperatures thus allowing us to observe variations of water adsorption at temperature. Time dependence of adsorbed mass was analyzed in frameworks of Fick’s law and allowed to estimate water diffusion coefficient. Experimental part of this work was performed under financial support by national funds (OE), through FCT – Fundação para a Ciência e a Tecnologia , I.P., in the scope of the framework contract foreseen in the numbers 4, 5 and 6 of the article 23, of the Decree-Law 57/2016, of August 29, changed by Law 57/2017, of July 19. Theoretical part of the work was supported by Russian Science Foundation (Grant No. 18-72-00052). [1] Kholkin A., Amdursky N. et al., ACS Nano, 4, 610 (2010). [2] Vasilev S., Zelenovskiy P. et al., J. Phys. Chem. Solids, 93, 68 (2016). [3] Azuri I., Adler-Abramovich L. et al., J. Am. Chem. Soc., 136, 963 (2014). [4] Andrade-Filho T., Martins T. et al., Theor. Chem. Acc., 135, 185 (2016).

Resume : Proteins and relevant protein-protein interactions play an essential role in cellular functions and biological processes. Protein analysis can therefore obtain significant information for better understanding of physiological and pathological mechanisms. Nanopore sensors, particularly solid-state nanopores, has been emerging as a powerful tool for single-molecule analysis in biophysics due to its simplicity and versatility. However, there are still key challenges in direct protein analysis with solid-state nanopores, due to their heterogeneous charge distribution, fast translocation speeds, poor signal-to-noise ratios, and lack of selectivity. To address these problems, one effective strategy is binding proteins to aptamer-modified dsDNA carriers. The selectivity can be enhanced by using DNA aptamers with high specificity and affinity, and the dsDNA backbone may dominate the complex translocation, slowing down translocation speeds and improving signal-to-noise ratios. The biophysical information can be subsequently achieved via the sub-peak analysis during individual DNA translocation events. This label-free approach allows us to identify and quantify specific biomarkers in the early diagnosis and further to recognize protein-protein interactions, such as ligand-receptor interactions and protein dimerization or oligomerization, in complex biological samples.

Resume : Recently, poly(3,4-ethylenedioxythiophene): polystyrenesulfonate (PEDOT:PSS) electrodes have been employed as a component for water-related electrochemical catalysis but their poor stability in aqueous environments and limited catalytic activities have limited their wide range impact in this research area. Herein, we report PEDOT:PSS-Pt nanocomposite electrodes by in situ electroplating Pt nanoparticles within PEDOT:PSS nanofibrillar matrix and their application to electrochemical-catalysis. The resultant nanocomposite exhibited the successful impregnation of Pt nanoparticles into partially crystallized PEDOT: PSS films with high aqueous stability, large electrochemically active surface area, and high reactant permeability. Furthermore, we also investigated the catalytic activities, electrical, optical and structural characteristics of PEDOT:PSS nanocomposites depending on Pt electroplating parameters and PEDOT:PSS ratio/crystallinity.

Resume : Enzyme-based biochemical sensors based on organic thin film transistors (TFTs) have gained much attention for their potential applications as low-cost and bio-compatible wearable sensors. In such applications, the enzymatic redox reaction integrated into individual TFT induces an amplified concentration-dependent drain current. For the realization of wearable devices, however, low power consumption is essentially required and not to mention high sensitivity. In this work, we exploit subthreshold operation of an extended-gate type dual-gate TFT for lactate detection with low power and high sensitivity. In the dual-gate TFT configuration, the top gate is separated and extended from the device to serve as an extended sensing gate (ESG) on which lactate oxidase enzyme is functionalized. The enzyme-functionalized ESG composes biofuel cell with Ag/AgCl reference electrode in aqueous media. We have observed that the enzymatic redox chain reaction of lactate occurring in the biofuel cell causes potential difference between the ESG and the reference electrode, which results in threshold voltage shift in the dual-gate TFT. Moving forwards, through strategic subthreshold operation of dual-gate TFT where its subthreshold slope (SS) is higher than single-gate transistor, it enabled not only lower power consumption but also higher sensitivity in comparison to operation in single-gate transistor. The device is fabricated on a flexible substrate for a skin-like wearable sensor, illustrating its potential as a wearable biochemical sensor.

Resume : The trend of organic nanostructured thin films research toward conductivity - photovoltaic chip has allowed using the/films from self-assembled nanocarbon/DNA molecular layers obtained by biotechnology. On the base of the review deals to analysis of electronic properties, photosensitivity, photoelectron moving force (PhEMF) and their stability under UV-vis irradiation for nanocarbon films with DNA molecules, we selected the thin films from silf-assembled layers of fullerene C60/C60 oxygen derivatives/ds-DNA on silicon for the detail investigations. The developing model of conductivity, and photovoltaic effect, in these layerss takes in account that C60 molecule is an acceptor of electrons. And the effect enhances with formation of C60 oxygen derivatives: 6-5 open fullerene C60 as we showed in first time [1].The evidence of self-assembling of these layers with (ds-DNA) in the nanostructured films on Si surface were obtained on the base of STM and SEM images of the films with the assembles (8-10 and 30-40 nm in diameter).The conductivity of the films was modulated by diode characteristics of fullerene C60/6-5 open fullerene C60 and C60/ ds-DNA contacts for n-type semiconductors fullerenes witch were determined by STP - tunneling spectroscopy. The discovered dynamic behavior of photosensitivity to 200-400 nm irradiation and PhMF appearance (0,25-0,37 eV) at 400-1000 nm irradiation (during 10 min - 1 h) of these films with several structures allow to consider these nanostructured layers/films as conducting/ photovoltaic chips. The examples for an application of these chips based on conductivity/photovoltaic models which have been developed for organic nanostructured thin films from C60 fullerene/ds-DNA molecular assemblies are discussed. Ref.,{1] E. Buzaneva, A. Gorchinskiy, P. Scharff, K. Risch, A. Nassiopoulou, C. Tsamis, Yu. Prilutsyy, O. Ivanuta, A. Zhugayevych, D. Kolomiyets, A. Veligura, DNA, DNA/Metal Nanoparticles, DNA/Nanocarbon and Macrocyclic Metal Complex/Fullerene Molecular Building Blocks for Nanosystems: Electronics and Sensing, In Book Frontiers of multifunctional integrated nanosystems, Eds: Eugenia Buzaneva and Peter Scharff, NATO Science Series, II-Mathematics, Physics and Chemistry–Vol 64, Kluwer Akademic Publishers, Dordrecht, 251-276, 2004.

Resume : The characterization of functionalized gate electrodes is an important step to develop Electrolyte Gated – Thin Film Transistor (EG-TFT) Biosensors [1, 2]. To this aim, the bioreceptor immobilization protocol may involve the preparation of a self-assembled monolayer (SAM). SAMs prepared on gold have often been investigated by peculiar infrared spectroscopic techniques, such as polarization modulation–infrared reflection adsorption spectroscopy (PM-IRRAS) [3]. However, such an approach is not so widespread, and the use of more popular IR techniques could be appealing in this field. In this work, attenuated total reflectance infrared spectroscopy (ATR-IR) was successfully employed to probe functionalized gold surfaces at different steps of the modification protocol in order to gather information about characteristic peaks ascribed to functionalities involved in the binding event and their eventual modification. [1] K. Manoli, M. Magliulo, M.Y. Mulla, M. Singh, L. Sabbatini, G. Palazzo, L. Torsi, Angewandte Chemie - International Edition 54 (2015) 12562-12576. [2] B. Holzer, K. Manoli, N. Ditaranto, E. Macchia, A. Tiwari, C. Di Franco, G. Scamarcio, G. Palazzo, L. Torsi, Advanced Biosystems 1 (2017) 1700055 (10pp). [3] B.L. Frey and R.M. Corn, Analytical Chemistry 68 (1996) 3187-3193.

Resume : Anthropogenic activities generate a large number of contaminants (heavy metals, polychlorinated biphenyls (PCBs), pesticides, drugs ...) that endanger both the sustainability of ecosystems and human health. The measurement of surface water contaminants is traditionally carried out in an analytical laboratory using conventional techniques allowing the detection of a large panel of molecules. The representatively and reliability of the final results depend on the handling from water source to the laboratory. Because of water quality monitoring technologies are numerous but are not totally integrated, human and time consuming as well as expensive, the improvement of this surveillance involves the development and the optimization of tools accounting for all (eco-)toxic risks. In this way, monitoring the effects of chemical contamination using biological tools associated with networks of suitable integrated fluidic systems represents a very promising approach. The project focuses on the societal problem of water pollution and federates all the expertises needed to develop a micro-fluidic platform to offer a sample-to-answer demonstrator in a multi-measure/multi-response Lab-On-a-Disc (LOD) format. Since water quality is defined according to its chemical, biological and physical characteristics, the LOD system will integrate a network of complementary sensors and algal cell biosensors of which the transduction system will be adapted to the parameters to be assessed.

Resume : Several analytical methods for Human Immunodeficiency Virus type-1 (HIV-1) diagnosis are employed in laboratory infrastructures, where high cost procedures are needed for a complete clinical profile of the disease1. These assays can be used for the diagnosis of HIV infection in the acute phase (first months from the infection), when viremia is at its highest level2. However, the goal of fourth generation analytical tests is to detect the virus as soon as possible, reducing the diagnostic window, by also using a disposable low-cost device. This is advantageous especially in the most affected countries, which cannot afford expensive diagnostic tools, and where a mass screening of population can prevent HIV spreading. However, among the different already available “rapid tests”, none had meet yet the aim of being fast, low-cost and effective in the acute phase of the illness. Here we report on an electrolyte-gated transistor EG-FET3 used to detect HIV-1 p24 antigen with single molecule precision. Moreover, the EG-FET was powered by a bio-fuel cell4 completely made by inexpensive techniques and degradable components, opening the prospective implementation of a point-of-care device capable of the earliest possible diagnosis. An optimization of the biosensor’s geometry was performed, to make it more compact and easily interfaced with the bio-FC. 1O.I.Iweala, Contraception 2004, 70, 141-147. 2J.M.Barletta et al., Am J Clin Pathol 2004, 122:20-27. 3E.Macchia et al., Nat. Commun. 2018, 9:3223. 4J.P.Esquivel et al., Adv. Energy Mater 2017, 1700275.

Resume : Flexible fabric biosensors can find promising applications in wearable electronics. The issues of detection limit and low sensitivity have hindered the development of conventional electrochemical biosensors in wearable applications. The noninvasive detection of glucose by wearable biosensor requires higher sensitivity and wearability than that of amperometric biosensor. Furthermore, high-performance fabric biosensors have been rarely reported due to many special requirements in device fabrication. Here, the preparation of organic electrochemical transistors (OECTs) on Nylon fibers is reported. The OECT is one type of novel biosensor which can provide in situ amplification of detection signal with high sensitivity to the target analyte. The three terminal structure of OECT is quite similar to the amperometric biosensor and the operation voltage is less than 1V which is safe for continuous monitoring of analyte on the surface of skin by using this device. By introducing metal/conductive polymer multilayer electrodes on the fibers, the OECTs show very stable performance during bending tests which is important to apply this device into the wearable electronics. By different gate modification strategies (functional materials, and cellulose), the devices with functionalized gates are successfully used as glucose biosensors with high sensitivity and selectivity. The detection limit of the functionalized sensor to the glucose can be down to 30 nM. The selectivity of the biosensor to glucose is about two orders magnitude higher than that to the interferences. The fiber-based OECTs are woven together with cotton yarns successfully by using a conventional weaving machine, resulting in flexible and stretchable fabric biosensors with high performance. The fabric sensors show much more stable signals in the analysis of moving aqueous solutions than planar devices due to a capillary effect in fabrics. The fabric devices are integrated in a diaper and remotely operated by using a mobile phone with custom-made app through Bluetooth. The fabric device integrated into the diaper is connected to the external miniature readout circuit by the wires which are suitable for wearable biosensing because of its light-weight and compactness. By using the advantages of wearability and sensitivity of fabric biosensor and integrated wireless readout circuit, it can offer a unique platform for convenient wearable healthcare monitoring. Reference A.N. Yang, Y.Z. Li, C.X. Yang, Y. Fu, N.X. Wang, L. Li, F. Yan, Fabric Organic electrochemical Transistors for Biosensors, Adv. Mater. 30 (2018) 201800051.

Resume : The integration of ultrasensitive tactile sensors onto ultra-thin, and possibly conformable, substrates still represent a crucial aspect in the development of innovative solutions for artificial skin applications, and organic electronics, thanks to its well-known features, has been lately explored as one of the most interesting candidates. We present here two different approaches based on high-performance Organic Field-Effect Transistors (OFETs) devices for the development of multimodal artificial skin patches. The first approach relies on the development of a particular OFET-based strain sensors: its innovative layout, which has been specifically designed in order to enhance the sensitivity of the structure to isotropic deformations, will be presented and discussed. As a second approach, an organic device named vertical Organic Charge-Modulated Field-Effect Transistor (vOCMFET) will be presented as a convenient solution to transduce pressure and temperature stimuli, thanks to its integration with piezo/pyro-electric materials such as inkjet-printed polyvinylidene difluoride (PVDF). These two novel approaches represent an interesting step forward toward the development of a new generation of conformable, high density and multimodal tactile devices, which can substantially contribute to the advancement of scientific fields such as robotics and rehabilitation.

Resume : In the 21st century, consumers are rapidly gaining access to a novel suite of wearable electronic devices such as smart watches and garments. This technology promises both comfort and ease of use, and it also provides a wealth of health-monitoring information. Advances in the field of electronic textiles and recent achievements in organic electronics have enabled the development of new flexible and conformable technologies that can perform the same sensing as current solid state devices, for a fraction of the cost. Such progress relies on the subtle engineering of organic functional materials to model their properties. I will present the potential of using organic ionic and electronic conducting materials in wearable monitoring systems for muscles and the heart. We have shown that electrodes made of such organic materials can lower contact impedance in cutaneous applications with the skin resulting in higher quality recordings compared to metal–based electrodes. Moreover, by combining these materials with textiles we have reduced the mechanical mismatch at the interface with the skin, which enables the recording of electrophysiological activities for long time intervals with an enhanced signal to noise ratio. These achievements were possible thanks to a direct patterning technique developed to selectively deposit organic materials onto fabrics. These results pave the way for the seamless integration of organic electronics and the textile platform to provide low-cost and tailored solutions in interfacing smart devices with the human body.

Resume : This contribution reports on a disposable skin adhered patch that detects minute changes on the chemical composition of sweat, namely on lactic acid concentration. The sensing device is based on an inkjet printed conducting polymer, the poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). The electrodes are printed on soft biocompatible bacterial cellulose substrates. The polymer sensing electrodes are arranged to establish an electrical double-layer with the skin surface due to the presence of electrolytes in the sweat. The device was tested in vitro using artificial solutions of sweat. The nano-fibrous nature of the cellulose substrate acts as a sponge soaking the sweat solution. Significant changes on the low frequency impedance (f <10 Hz) are observed when the lactic acid concentration changes in the range of a few hundreds of nano-molar in concentration. The sensing impedance is integrated into a voltage divider circuit excited with a small ac signal. The divider circuit comprised of the reference and sensing impedance produces an output voltage proportional to the differences between the two impedances. This approach simplifies the electronic readout because the output is a voltage signal and not an impedance parameter. This strategy simplifies the implementation as a disposable patch sensor. The performance of this impedance sensor for sweat is compared with other strategies reported in literature and its application as a health-monitoring device is discussed.

Resume : Electrical impedance measurements through microfluidic channels have been extensively studied over the last years, because electrical impedance is a simple and essentially a non-invasive technique that allows characterization of nano- and microparticles or other inorganic nano- and microstructures in a dielectric medium. Electrical impedance sensing has successfully been used in flow cell cytometry, allowing the classification of different cell types. Here are presented results for polystyrene microspheres in a custom electrical impedance system composed of a modified commercial microfluidic channel along with optical micro-imaging characterization in an inverted microscope, quantifying the relationship between microspheres density, wavelength illumination range and magnitude of the electrical impedance signal for carboxyl and amino functionalized-microspheres in different fluid media. These observations are sustained by numerical modeling and discussed within a general theoretical framework. The obtained results might have potential application to classify novel nano- and micro-objects and further develop artificial intelligence-enabled drug delivery platforms.

Resume : The process of cell osteogenic differentiation is associated with a number of events such as the secretion of Collagen type I, osteopontin, osteonectin, osteocalcin and Bone Morphogenic Protein 2. These molecules could, indeed, be used as markers to monitor cells’ differentiation. Currently available techniques, such as the evaluation of expression levels of specific genes through end-point biochemical assays, do not allow real-time monitoring of cellular processes, therefore overlooking potentially interesting information. Here, we present a functionalization strategy based on the biotin-streptavidin interaction to develop a smart biosensor for BMP-2 detection. Our strategy is based on the use of PEDOT:PSS, a semiconducting material having a variety of advantages such biocompatibility, chemical and thermal stability as well as its mixed ionic and electronic transport. Indeed, it is its ability to conduct both ions and electrons that makes it suitable for bioelectronic applications, allowing to couple an electronic readout to a biological event. Our strategy entailed a number of functionalization steps leading to the creation of an anchoring point for the desired antibodies. The process was characterized using multiple techniques (e.g. Static Contact Angle, Conductive-AFM, QCMD and FTIR) in order to optimize every deposition step. Electrical conductivity, as well as device stability, was assessed running Electrochemical Impedance Spectroscopy measurements after each deposition. Finally, a proof-of-concept electrical measurement was performed to test our devices. This study explores a promising functionalization strategy towards in-line electrical monitoring of stem cell differentiation process.

Resume : Electrophysiological recordings, with varying degrees of invasiveness, are the traditional method for measuring neural activity, possessing the capability to measure both individual neurons and populations of neurons. Imaging methods, such as computed tomography scans and functional magnetic resonance imaging, have been developed to accomplish less invasive characterization of neuronal activity; traditionally offering good spatial or relatively high temporal resolution, yet resolution of individual neurons cannot be achieved. Two-photon (2P) imaging enables network-wide analysis with cellular resolution on a faster timescale with high spatial fidelity. This technique has a continuous spatial resolution containing the entire area of 3D tissue measured and a temporal resolution also acceptable to capture the desired activity. Unfortunately, there has not been an electrode technology particularly compatible with 2P investigation to truly benchmark this modern method against the classical standard of electrophysiological measurement with electrodes. Here we demonstrate the simultaneous use of state-of-the-art organic electrodes based on transparent materials, in combination with modern 2P optical imaging in vivo. This provides a valuable vehicle for complementing classical high temporal resolution electrophysiological analysis with optical imaging. We monitor the activity of a 3D in vivo neural network and demonstrate good correlation of pathological activity using this dual characterization method, providing the best of the two methods: high spatial resolution from 2P imaging combined with high temporal resolution of the multi-electrode array.

Resume : Optical imaging of biological activities is used to monitor the functional aspects of neural circuits by reporting these activities via fluorescent and luminescent molecular probes. Current approaches encompass microscopy and different optical detection units, such as cameras equipped with high affinity inorganic sensors and image processing elements in order to measure the optical signals. Organic photodetectors (OPD) have numerous advantages versus their inorganic counterparts such as, a low dark current and a linear behavior in sub-µW/cm2 light intensity. However, their performance has never been shown in the detection of fluorescent biological signals, reported by molecular probes or genetically encoded-indicators, to date. In this work, we fabricated a simple structure OPD in open air, with an active layer consisting of eXtra Large bandgap Polymer (XPL) blended with fullerene. For the first time, we demonstrate the capability of organic photodetectors for the detection of calcium signals from living brain cells, reported by chemical and genetically encoded fluorescent calcium indicators. This work paves the way for the integration of OPDs in implantable biomedical devices with broad range of biomedical applications.

Resume : The ever-growing demands in the healthcare industry require the development of low-cost and easy-to-use tools and strategies for the early diagnosis and prevention of diseases such as diabetes. Monitoring human metabolite levels (for instance glucose, lactate, cholesterol etc) can provide useful information regarding key metabolic activities in the human body and detect associated irregularities. In this work, we present the development of a disposable analytical device which can measure physiologically relevant glucose concentrations in the human saliva based on an enzymatic electrochemical detection. We use inkjet-printing technology for the rapid and low-cost deposition of all the components of this glucose sensor, from the electrodes to the biorecognition elements, on commercially available paper substrates. We propose a simple method to realize noninvasive disposable devices that can be a promising alternative to routine blood screening exams faced by diabetic patients.

Resume : The development of portable and wearable sensors is of high importance in several fields, such as point-of-care medical applications and environmental monitoring. To this end, Organic Electrochemical Transistors (OECTs) offer consistent advantages such as easy and cheap readout electronics, low supply voltage (usually < 1 V), low power operation (< 100 μW), bio-compatibility, ease of integration. Moreover, the transistor configuration provides intrinsic amplification of the output signal and gives design freedom in terms of device geometries and substrates (flat/flexible). In this contribution, we show the design of a new composite material based on Ag/AgCl nanoparticles (NPs) and PEDOT:PSS (poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)) to build up a chloride (Cl-) sensor inspired by the OECT architecture.[1] We integrated a Ag/AgCl gate electrode into the semiconducting polymer channel in the form of NPs, thus basically providing a PEDOT:PSS stripe with sensing ability towards Cl- and signal amplification. Electrostatic Force Microscopy and Electrochemical Impedance Spectroscopy analyses demonstrate the electronic coupling between the electrochemically active NPs and the semiconducting polymer, which allows to explain the sensor amplified transduction. The analytical signal is the current that flows in the composite polymer and its variation is directly proportional to the logarithm of Cl- concentration in the range 10−4 to 1 M. The sensor was used for in-situ detection of salinity in sea, river and tap water and the results were validated with a standard analytical method. Moreover, the main advantage of the sensor is its simple, two terminal electrical connection, with relevant implications on the needed read-out electronics, adaptability to unconventional geometries and faster response time than a conventional OECT endowed with an Ag/AgCl gate electrode. Thanks to these favourable features, a textile device was obtained by depositing the composite material directly onto a cotton yarn for real-time sweat monitoring. [1] I. Gualandi, M. Tessarolo, F. Mariani, T. Cramer, D. Tonelli, E. Scavetta and B. Fraboni, Sensors & Actuators: B. Chemical 2018, 273, 834

Resume : Real-time, non-invasive pH monitoring of biofluids such as human sweat is currently attracting a great deal of interest for accessing information from our body. However, such emerging bioelectronic application poses several constraints to existing sensing technologies, as configurational versatility and ultra-sensitivity stand out as essential requirements. In this scenario, organic electrochemical transistors (OECTs) are promising electronic platforms that can interface the biological domain providing intrinsic signal amplification and they can be exploited as sensing devices without the need of a freestanding reference electrode. In this contribution, we show the optimisation of pH responsive materials, able to successfully convert a pH chemical signal into an electrical one, which are exploited to modify the gate electrode of the OECT. The semiconducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) was electrochemically doped with pH dyes (Bromothymol Blue or Methyl Orange). After that, the PEDOT:dye composites were thoroughly investigated by electrochemical and spectroscopic analyses, exhibiting Nernstian response to pH. It was demonstrated that the transduction mechanism of the proposed materials originates from the pH-dependent change of the dyes’ electronic charge. Due to its electrostatic interaction with the polymer backbone, this phenomenon affects the doping level of the semiconducting polymer. Once assessed the transduction mechanism, the PEDOT:dye composites were employed as sensing element in an OECT configuration to obtain a device that can reliably detect pH variations in the range 1-9 with super-Nernstian sensitivity. Finally, thanks to the OECT major advantages with respect to conventional electrochemical sensors, we assessed the sensor adaptability to a plastic substrate, thus making our device compatible with wearable applications. With our flexible sensor, we were able to estimate the pH of an artificial sweat sample with a standard deviation equal to 0.06 pH units within a medically relevant range.[1] [1] F. Mariani, I. Gualandi, M. Tessarolo, B. Fraboni and E. Scavetta, ACS Appl. Mater. Interfaces, 2018, 10 (26), 22474

Resume : Breast cancer (BC) is the second most common cancer type in the world causing more than 11,000 deaths annually in the UK alone. 80% of the patients can be cured if cancer is detected early. However, misdetection, drug resistance, and relapses occur frequently due to the heterogeneity and mutation of BC genes which can lead to aggressive metastatic complications. Traditional BC detection method applies invasive and inefficient tissue biopsy. A non-invasive liquid biopsy involving the analysis of plasma circulating free DNA (cfDNA) has been established in providing a more patient-directed clinical profile through the study of genetic variations and gene expression patterns indicative of BC progressions. The status of BC can be validated, and its metastatic progression and treatment outcome can also be correlated. This project aims to develop an affordable, rapid and sensitive Lab-on Chip platform for detecting BC relevant single nucleotide polymorphisms (SNPs) from plasma cfDNA. This will be achieved by combining: i) loop-mediated isothermal amplification; ii) unmodified self-stabilizing competitive primers and iii) complementary metal-oxide semiconductor based ion-sensitive field-effect transistors pH biosensors. The successful completion of this project will be highly valuable for BC patients, predicting the types, grade and prognosis of BC at the point-of-care.