Graphene oxide electrodes enable electrical stimulation of distinct calcium signalling in brain astrocytes.

Astrocytes are responsible for maintaining homoeostasis and cognitive functions through calcium signalling, a process that is altered in brain diseases. Current bioelectronic tools are designed to study neurons and are not suitable for controlling calcium signals in astrocytes. Here, we show that electrical stimulation of astrocytes using electrodes coated with graphene oxide and reduced graphene oxide induces respectively a slow response to calcium, mediated by external calcium influx, and a sharp one, exclusively due to calcium release from intracellular stores. Our results suggest that the different conductivities of the substrate influence the electric field at the cell-electrolyte or cell-material interfaces, favouring different signalling events in vitro and ex vivo. Patch-clamp, voltage-sensitive dye and calcium imaging data support the proposed model. In summary, we provide evidence of a simple tool to selectively control distinct calcium signals in brain astrocytes for straightforward investigations in neuroscience and bioelectronic medicine.

Innovative solutions for disease management.

The increasing prevalence of chronic diseases is a driver for emerging big data technologies for healthcare including digital platforms for data collection, systems for active patient engagement and education, therapy specific predictive models, optimized patient pathway models. Powerful bioelectronic medicine tools for data collection, analysis and visualization allow for joint processing of large volumes of heterogeneous data, which in turn can produce new insights about patient outcomes and alternative interpretations of clinical patterns that can lead to implementation of optimized clinical decisions and clinical patient pathway by healthcare professionals.With this perspective, we identify innovative solutions for disease management and evaluate their impact on patients, payers and society, by analyzing their impact in terms of clinical outcomes (effectiveness, safety, and quality of life) and economic outcomes (cost-effectiveness, savings, and productivity).As a result, we propose a new approach based on the main pillars of innovation in the disease management area, i.e. progressive patient care models, patient-centric approaches, bioelectronics for precise medicine, and lean management that, combined with an increase in appropriate private-public-citizen-partnership, leads towards Patient-Centric Healthcare.

Improved Performance of Organic Light-Emitting Transistors Enabled by Polyurethane Gate Dielectric.

Organic light-emitting transistors (OLETs) are multifunctional optoelectronic devices that combine in a single structure the advantages of organic light-emitting diodes (OLEDs) and organic field-effect transistors (OFETs). However, low charge mobility and high threshold voltage are critical hurdles to practical OLET implementation. This work reports on the improvements obtained by using polyurethane films as a dielectric layer material in place of the standard poly(methyl methacrylate) (PMMA) in OLET devices. It was found that polyurethane drastically reduces the number of traps in the device, thereby improving electrical and optoelectronic device parameters. In addition, a model was developed to rationalize an anomalous behavior at the pinch-off voltage. Our findings represent a step forward to overcome the limiting factors of OLETs that prevent their use in commercial electronics by providing a simple route for low-bias device operation.

Development of Quantum Dot (QD) Based Color Converters for Multicolor Display.

Many displays involve the use of color conversion layers. QDs are attractive candidates as color converters because of their easy processability, tuneable optical properties, high photoluminescence quantum yield, and good stability. Here, we show that emissive QDs with narrow emission range can be made in-situ in a polymer matrix, with properties useful for color conversion. This was achieved by blending the blue-emitting pyridine based polymer with a cadmium selenide precursor and baking their films at different temperatures. To achieve efficient color conversion, blend ratio and baking temperature/time were varied. We found that thermal decomposition of the precursor leads to highly emissive QDs whose final size and emission can be controlled using baking temperature/time. The formation of the QDs inside the polymer matrix was confirmed through morphological studies using atomic force microscopy (AFM) and transmission electron microscopy (TEM). Hence, our approach provides a cost-effective route to making highly emissive color converters for multi-color displays.

Glial Interfaces: Advanced Materials and Devices to Uncover the Role of Astroglial Cells in Brain Function and Dysfunction.

Research over the past four decades has highlighted the importance of certain brain cells, called glial cells, and has moved the neurocentric vision of structure, function, and pathology of the nervous system toward a more holistic perspective. In this view, the demand for technologies that are able to target and both selectively monitor and control glial cells is emerging as a challenge across neuroscience, engineering, chemistry, and material science. Frequently neglected or marginally considered as a barrier to be overcome between neural implants and neuronal targets, glial cells, and in particular astrocytes, are increasingly considered as active players in determining the outcomes of device implantation. This review provides a concise overview not only of the previously established but also of the emerging physiological and pathological roles of astrocytes. It also critically discusses the most recent advances in biomaterial interfaces and devices that interact with glial cells and thus have enabled scientists to reach unprecedented insights into the role of astroglial cells in brain function and dysfunction. This work proposes glial interfaces and glial engineering as multidisciplinary fields that have the potential to enable significant advancement of knowledge surrounding cognitive function and acute and chronic neuropathologies.

On the Nature of Charge-Injecting Contacts in Organic Field-Effect Transistors.

Organic field-effect transistors (OFETs) are key enabling devices for plastic electronics technology, which has a potentially disruptive impact on a variety of application fields, such as health, safety, and communication. Despite the tremendous advancements in understanding the OFET working mechanisms and device performance, further insights into the complex correlation between the nature of the charge-injecting contacts and the electrical characteristics of devices are still necessary. Here, an in-depth study of the metal-organic interfaces that provides a direct correlation to the performance of OFET devices is reported. The combination of synchrotron X-ray spectroscopy, atomic force microscopy, electron microscopy, and theoretical simulations on two selected electron transport organic semiconductors with tailored chemical structures allows us to gain insights into the nature of the injecting contacts. This multiple analysis repeated at the different stages of contact formation provides a clear picture on the synergy between organic/metal interactions, interfacial morphology, and structural organization of the electrode. The simultaneous synchrotron X-ray experiments and electrical measurements of OFETs in operando uncovers how the nature of the charge-injecting contacts has a direct impact on the injection potential of OFETs.

A Glial-Silicon Nanowire Electrode Junction Enabling Differentiation and Noninvasive Recording of Slow Oscillations from Primary Astrocytes.

The correct human brain function is dependent on the activity of non-neuronal cells called astrocytes. The bioelectrical properties of astrocytes in vitro do not closely resemble those displayed in vivo and the former are incapable of generating action potential; thus, reliable approaches in vitro for noninvasive electrophysiological recording of astrocytes remain challenging for biomedical engineering. Here it is found that primary astrocytes grown on a device formed by a forest of randomly oriented gold coated-silicon nanowires, resembling the complex structural and functional phenotype expressed by astrocytes in vivo. The device enables noninvasive extracellular recording of the slow-frequency oscillations generated by differentiated astrocytes, while flat electrodes failed on recording signals from undifferentiated cells. Pathophysiological concentrations of extracellular potassium, occurring during epilepsy and spreading depression, modulate the power of slow oscillations generated by astrocytes. A reliable approach to study the role of astrocytes function in brain physiology and pathologies is presented.

Stimulation of water and calcium dynamics in astrocytes with pulsed infrared light.

Astrocytes are non-neuronal cells that govern the homeostatic regulation of the brain through ions and water transport, and Ca2+ -mediated signaling. As they are tightly integrated into neural networks, label-free tools that can modulate cell function are needed to evaluate the role of astrocytes in brain physiology and dysfunction. Using live-cell fluorescence imaging, pharmacology, electrophysiology, and genetic manipulation, we show that pulsed infrared light can modulate astrocyte function through changes in intracellular Ca2+ and water dynamics, providing unique mechanistic insight into the effect of pulsed infrared laser light on astroglial cells. Water transport is activated and, IP3 R, TRPA1, TRPV4, and Aquaporin-4 are all involved in shaping the dynamics of infrared pulse-evoked intracellular calcium signal. These results demonstrate that astrocyte function can be modulated with infrared light. We expect that targeted control over calcium dynamics and water transport will help to study the crucial role of astrocytes in edema, ischemia, glioma progression, stroke, and epilepsy.

Epitaxial multilayers of alkanes on two-dimensional black phosphorus as passivating and electrically insulating nanostructures.

Mechanically exfoliated two-dimensional (2D) black phosphorus (bP) is epitaxially terminated by monolayers and multilayers of tetracosane, a linear alkane, to form a weakly interacting van der Waals heterostructure. Atomic force microscopy (AFM) and computational modelling show that epitaxial domains of alkane chains are ordered in parallel lamellae along the principal crystalline axis of bP, and this order is extended over a few layers above the interface. Epitaxial alkane multilayers delay the oxidation of 2D bP in air by 18 hours, in comparison to 1 hour for bare 2D bP, and act as an electrical insulator, as demonstrated using electrostatic force microscopy. The presented heterostructure is a technologically relevant insulator-semiconductor model system that can open the way to the use of 2D bP in micro- and nanoelectronic, optoelectronic and photonic applications.

Noncovalent Functionalization of 2D Black Phosphorus with Fluorescent Boronic Derivatives of Pyrene for Probing and Modulating the Interaction with Molecular Oxygen.

We studied the chemical-physical nature of interactions involved in the formation of adducts of two-dimensional black phosphorus (2D BP) with organoboron derivatives of a conjugated fluorescent molecule (pyrene). Time-resolved fluorescence spectroscopy showed a stabilization effect of 2D BP on all derivatives, in particular for the adducts endowed with the boronic functionalities. Also, a stronger modulation of the fluorescence decay with oxygen was registered for one of the adducts compared to the corresponding organoboron derivative alone. Nuclear magnetic resonance experiments in suspension and density functional theory simulations confirmed that only noncovalent interactions were involved in the formation of the adducts. The energetic gain in their formation arises from the interaction of P atoms with both C atoms of the pyrene core and the B atom of the boronic functionalities, with a stronger contribution from the ester with respect to the acid one. The interaction results in the lowering of the band gap of 2D BP by around 0.10 eV. Furthermore, we demonstrated through Raman spectroscopy an increased stability toward oxidation in air of 2D BP in the adducts in the solid state (more than 6 months). The modification of the electronic structure at the interface between 2D BP and a conjugated organic molecule through noncovalent stabilizing interactions mediated by the B atom is particularly appealing in view of creating heterojunctions for optoelectronic, photonic, and chemical sensing applications.

LRRC8A is essential for swelling-activated chloride current and for regulatory volume decrease in astrocytes.

Consolidated evidence indicates that astroglial cells are critical in the homeostatic regulation of cellular volume by means of ion channels and aquaporin-4. Volume-regulated anion channel (VRAC) is the chloride channel that is activated upon cell swelling and critically contributes to cell volume regulation in astrocytes. The molecular identity of VRAC has been recently defined, revealing that it belongs to the leucine-rich repeat-containing 8 (LRRC8) protein family. However, there is a lack of evidence demonstrating that LRRC8A underpins VRAC currents in astrocyte. Nonetheless, direct evidence of the role of LRRC8A in astrocytic regulatory volume decrease remains to be proved. Here, we aim to bridge this gap in knowledge by combining RNA interference specific for LRRC8A with patch-clamp analyses and a water-permeability assay. We demonstrated that LRRC8A molecular expression is essential for swelling-activated chloride current via VRAC in primary-cultured cortical astrocytes. The knockdown of LRRC8A with a specific short interference RNA abolished the recovery of the cell volume after swelling induced by hypotonic challenge. In addition, immunoblotting, immunofluorescence, confocal imaging, and immunogold electron microscopy demonstrated that LRRC8A is expressed in the plasma membrane of primary cortical astrocytes and in situ in astrocytes at the perivascular interface with endothelial cells. Collectively, our results suggest that LRRC8A is an essential subunit of VRAC and a key factor for astroglial volume homeostasis.-Formaggio, F., Saracino, E., Mola, M. G., Rao, S. B., Amiry-Moghaddam, M., Muccini, M., Zamboni, R., Nicchia, G. P., Caprini, M., Benfenati, V. LRRC8A is essential for swelling-activated chloride current and for regulatory volume decrease in astrocytes.

Electrical Stimulation by an Organic Transistor Architecture Induces Calcium Signaling in Nonexcitable Brain Cells.

Organic bioelectronics have a huge potential to generate interfaces and devices for the study of brain functions and for the therapy of brain pathologies. In this context, increasing efforts are needed to develop technologies for monitoring and stimulation of nonexcitable brain cells, called astrocytes. Astroglial calcium signaling plays, indeed, a pivotal role in the physiology and pathophysiology of the brain. Here, the use of transparent organic cell stimulating and sensing transistor (O-CST) architecture, fabricated with N,N'-ditridecylperylene-3,4,9,10-tetracarboxylic diimide (P13), to elicit and monitor intracellular calcium concentration ([Ca2+ ]i ) in primary rat neocortical astrocytes is demonstrated. The transparency of O-CST allows performing calcium imaging experiments, showing that extracellular electrical stimulation of astrocytes induces a drastic increase in [Ca2+ ]i . Pharmacological studies indicate that transient receptor potential (TRP) superfamily are critical mediators of the [Ca2+ ]i increase. Experimental and computational analyses show that [Ca2+ ]i response is enabled by the O-CST device architecture. Noteworthy, the extracellular field application induces a slight but significant increase in the cell volume. Collectively, it is shown that the O-CST is capable of selectively evoking astrocytes [Ca2+ ]i , paving the way to the development of organic bioelectronic devices as glial interfaces to excite and control physiology of non-neuronal brain cells.

Contact Resistance in Ambipolar Organic Field-Effect Transistors Measured by Confocal Photoluminescence Electro-Modulation Microscopy.

Although it is theoretically expected that all organic semiconductors support ambipolar charge transport, most organic transistors either transport holes or electrons effectively. Single-layer ambipolar organic field-effect transistors enable the investigation of different mechanisms in hole and electron transport in a single device since the device architecture provides a controllable planar pn-junction within the transistor channel. However, a direct comparison of the injection barriers and of the channel conductivities between electrons and holes within the same device cannot be measured by standard electrical characterization. This article introduces a novel approach for determining threshold gate voltages for the onset of the ambipolar regime from the position of the pn-junction observed by photoluminescence electro-modulation (PLEM) microscopy. Indeed, the threshold gate voltage in the ambipolar bias regime considers a vanishing channel length, thus correlating the contact resistance. PLEM microscopy is a valuable tool to directly compare the contact and channel resistances for both carrier types in the same device. The reported results demonstrate that designing the metal/organic-semiconductor interfaces by aligning the bulk metal Fermi levels to the highest occupied molecular orbital or lowest unoccupied molecular orbital levels of the organic semiconductors is a too simplistic approach for optimizing the charge-injection process in organic field-effect devices.

Organic Light-Emitting Transistors with Simultaneous Enhancement of Optical Power and External Quantum Efficiency via Conjugated Polar Polymer Interlayers.

Organic light-emitting transistors (OLETs) show the fascinating combination of electrical switching characteristics and light generation capability. However, to ensure an effective device operation, an efficient injection of charges into the emissive layer is required. The introduction of solution-processed conjugated polyelectrolyte (CPE) films at the emissive layer/electrode interface represents a promising strategy to improve the electron injection process by dipole formation. However, their use in optoelectronic devices also involves some limitations because of the ionic nature of CPEs. In this context, neutral conjugated polar polymers (CPPs) represent a valid alternative to CPEs because the conjugated backbones of CPPs are functionalized with polar nonionic side groups, thus avoiding ion-dependent drawbacks. By introducing a layer of polyfluorene-containing phosphonate groups underneath the metal electrodes, we here demonstrate a substantial improvement of the electron injection properties into the OLET-emissive layer and, accordingly, a more than 2-fold increased light power and a 5 times higher external quantum efficiency of p-type OLETs in comparison with reference devices without any interlayer. The great benefit of using a transparent glass substrate allowed to selectively investigate the morphological and photoluminescent characteristics of both CPE- and CPP-buried interlayers within complete OLETs by means of an optical scanning probe technique. This, together with a thorough optoelectronic characterization of the figures of merit of working light-emitting devices, allowed to disclose the origin of the improved optical performance of CPP-based devices as well as the operation mechanisms of the investigated interlayer in the corresponding OLETs.

Portable Bio/Chemosensoristic Devices: Innovative Systems for Environmental Health and Food Safety Diagnostics.

This mini-review covers the newly developed biosensoristic and chemosensoristic devices described in recent literature for detection of contaminants in both environmental and food real matrices. Current needs in environmental and food surveillance of contaminants require new simplified, sensitive systems, which are portable and allow for rapid and on-site monitoring and diagnostics. Here, we focus on optical and electrochemical bio/chemosensoristic devices as promising tools with interesting analytical features that can be potentially exploited for innovative on-site and real-time applications for diagnostics and monitoring of environmental and food matrices (e.g., agricultural waters and milk). In near future, suitably developed and implemented bio/chemosensoristic devices will be a new and modern technological solution for the identification of new quality and safety marker indexes as well as for a more proper and complete characterization of abovementioned environmental and food matrices. Integrated bio/chemosensoristic devices can also allow an "holistic approach" that may prove to be more suitable for diagnostics of environmental and food real matrices, where the copresence of more bioactive substances is frequent. Therefore, this approach can be focused on the determination of net effect (mixture effect) of bioactive substances present in real matrices.

A Nanoscale Interface Promoting Molecular and Functional Differentiation of Neural Cells.

Potassium channels and aquaporins expressed by astrocytes are key players in the maintenance of cerebral homeostasis and in brain pathophysiologies. One major challenge in the study of astrocyte membrane channels in vitro, is that their expression pattern does not resemble the one observed in vivo. Nanostructured interfaces represent a significant resource to control the cellular behaviour and functionalities at micro and nanoscale as well as to generate novel and more reliable models to study astrocytes in vitro. However, the potential of nanotechnologies in the manipulation of astrocytes ion channels and aquaporins has never been previously reported. Hydrotalcite-like compounds (HTlc) are layered materials with increasing potential as biocompatible nanoscale interface. Here, we evaluate the effect of the interaction of HTlc nanoparticles films with primary rat neocortical astrocytes. We show that HTlc films are biocompatible and do not promote gliotic reaction, while favouring astrocytes differentiation by induction of F-actin fibre alignment and vinculin polarization. Western Blot, Immunofluorescence and patch-clamp revealed that differentiation was accompanied by molecular and functional up-regulation of both inward rectifying potassium channel Kir 4.1 and aquaporin 4, AQP4. The reported results pave the way to engineering novel in vitro models to study astrocytes in a in vivo like condition.

Synthesis and characterization of benzodithiophene and benzotriazole-based polymers for photovoltaic applications.

Two high bandgap benzodithiophene-benzotriazole-based polymers were synthesized via palladium-catalysed Stille coupling reaction. In order to compare the effect of the side chains on the opto-electronic and photovoltaic properties of the resulting polymers, the benzodithiophene monomers were substituted with either octylthienyl (PTzBDT-1) or dihexylthienyl (PTzBDT-2) as side groups, while the benzotriazole unit was maintained unaltered. The optical characterization, both in solution and thin-film, indicated that PTzBDT-1 has a red-shifted optical absorption compared to PTzBDT-2, likely due to a more planar conformation of the polymer backbone promoted by the lower content of alkyl side chains. The different aggregation in the solid state also affects the energetic properties of the polymers, resulting in a lower highest occupied molecular orbital (HOMO) for PTzBDT-1 with respect to PTzBDT-2. However, an unexpected behaviour is observed when the two polymers are used as a donor material, in combination with PC61BM as acceptor, in bulk heterojunction solar cells. Even though PTzBDT-1 showed favourable optical and electrochemical properties, the devices based on this polymer present a power conversion efficiency of 3.3%, considerably lower than the efficiency of 4.7% obtained for the analogous solar cells based on PTzBDT-2. The lower performance is presumably attributed to the limited solubility of the PTzBDT-1 in organic solvents resulting in enhanced aggregation and poor intermixing with the acceptor material in the active layer.

Enhanced Ultraviolet Stability of Air-Processed Polymer Solar Cells by Al Doping of the ZnO Interlayer.

Photostability of organic photovoltaic devices represents a key requirement for the commercialization of this technology. In this field, ZnO is one of the most attractive materials employed as an electron transport layer, and the investigation of its photostability is of particular interest. Indeed, oxygen is known to chemisorb on ZnO and can be released upon UV illumination. Therefore, a deep analysis of the UV/oxygen effects on working devices is relevant for the industrial production where the coating processes take place in air and oxygen/ZnO contact cannot be avoided. Here we investigate the light-soaking stability of inverted organic solar cells in which four different solution-processed ZnO-based nanoparticles were used as electron transport layers: (i) pristine ZnO, (ii) 0.03 at %, (iii) 0.37 at %, and (iv) 0.8 at % aluminum-doped AZO nanoparticles. The degradation of solar cells under prolonged illumination (40 h under 1 sun), in which the ZnO/AZO layers were processed in air or inert atmosphere, is studied. We demonstrate that the presence of oxygen during the ZnO/AZO processing is crucial for the photostability of the resulting solar cell. While devices based on undoped ZnO were particularly affected by degradation, we found that using AZO nanoparticles the losses in performance, due to the presence of oxygen, were partially or totally prevented depending on the Al doping level.

Silk fibroin film from golden-yellow Bombyx mori is a biocomposite that contains lutein and promotes axonal growth of primary neurons.

The use of doped silk fibroin (SF) films and substrates from Bombyx mori cocoons for green nanotechnology and biomedical applications has been recently highlighted. Cocoons from coloured strains of B. mori, such as Golden-Yellow, contain high levels of pigments that could have a huge potential for the fabrication of SF based biomaterials targeted to photonics, optoelectronics and neuroregenerative medicine. However, the features of extracted and regenerated SF from cocoons of B. mori Golden-Yellow strain have never been reported. Here we provide a chemophysical characterization of regenerated silk fibroin (RSF) fibers, solution, and films obtained from cocoons of a Golden-Yellow strain of B. mori, by SEM, (1) H-NMR, HPLC, FT-IR, Raman and UV-Vis spectroscopy. We found that the extracted solution and films from B. mori Golden-Yellow fibroin displayed typical Raman spectroscopic and optical features of carotenoids. HPLC-analyses revealed that lutein was the carotenoid contained in the fiber and RSF biopolymer from yellow cocoons. Notably, primary neurons cultured on yellow SF displayed a threefold higher neurite length than those grown of white SF films. The results we report pave the way to expand the potential use of yellow SF in the field of neuroregenerative medicine and provide green chemistry approaches in biomedicine.