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[Abastract]: In the last decade, solution-gated graphene field effect transistors (GFETs) showed their versatility in the development of a miniaturized multiplexed platform for electrophysiological recordings and sensing. Due to their working mechanism, the surface functionalisation and immobilisation of receptors are pivotal to ensure the proper functioning of devices. Herein, we present a controlled covalent functionalisation strategy based on molecular design and electrochemical triggering, which provide a monolayer-like functionalisation of micro-GFET arrays retaining the electronic properties of graphenes. The functionalisation layer as a receptor was then employed as the linker for serotonin aptamer conjugation. The micro-GFET arrays display sensitivity toward the target analyte in the micromolar range in a physiological buffer (PBS 10 mM). The sensor allows the in-flow real-time monitoring of serotonin transient concentrations with fast and reversible responses.

Tomato (Solanum lycopersicum) is consumed worldwide as it isrich in vitamins and mineral salts. QfosfiK®is a biostimulant that increases yieldand improves fruit quality in different crops. The objective of the research was toevaluate the effect of foliar application of potassium phosphite on the growth andyield of tomato cultivars Paipai and Cid. The experiment was conducted undergreenhouse conditions at the Faculty of Agricultural Sciences, during 2019 on avertisol soil, in a randomized block design with 10 treatments and 4 replications. Thetreatments applied arose from the factorial arrangement of the two tomato cultivarsand five concentrations of potassium phosphite (0, 1.2, 1.5, 1.5, 1.8 and 2.1 L ha−1)prorated at transplanting, vegetative stage and beginning of the reproductive stage.Leaf number, leaf area index, net assimilation rate, berry yield and morphologicalcomponents: number of clusters and fruit were evaluated. The cultivar Cid had thebest yield due to the highest number of leaves, leaf area index, net assimilation rateand number of bunches plant−1. Regarding the doses, when 1.2 L ha−1was added,yield was optimized. The cultivar×dose interaction revealed that the highest fruityield was achieved by Cid (3.18 kg plant−1) when 1.2 L ha−1of product was added,while Paipai with 1.5 L ha−1produced 2.74 kg plant−1., El tomate (Solanum lycopersicum) se consume en él mundo, porquees rico en vitaminas y sales minerales. El QfosfiK®es un bioestimulante queincrementa el rendimiento y mejora la calidad de fruto en diferentes cultivos. Elobjetivo de la investigación fue evaluar el efecto de la aplicación foliar de fosfitode potasio sobre el crecimiento y rendimiento de los cultivares de tomate Paipaiy Cid. El experimento se realizó en condiciones de invernadero en la Facultad deCiencias Agrícolas, durante 2019 sobre un suelo vertisol, en un diseño de bloquesal azar con 10 tratamientos y 4 repeticiones. Los tratamientos aplicados surgierondel arreglo factorial de los dos cultivares de tomate y cinco concentraciones defosfito de potasio (0, 1,2, 1,5, 1,8 y 2,1 L ha−1) prorrateados en el trasplante, estadovegetativo e inicio de la etapa reproductiva. Se evaluó el número de hojas, el índicede área foliar, la tasa de asimilación neta, el rendimiento de baya y los componentesmorfológicos: número de racimos y frutos. El cultivar Cid tuvo el mejor rendimientodebido al mayor número de hojas, índice de área foliar, tasa de asimilación netay número de racimos planta−1. Respecto a las dosis, cuando se adicionó 1.2 Lha−1se optimizó la producción. La interacción cultivar×dosis reveló que la mayorcantidad de fruto la logró Cid (3.18 kg planta−1) cuando se añadieron 1.2 L ha−1deproducto, mientras qué, Paipai con 1.5 L ha−1produjo 2.74 kg planta−1.

Graphene solution-gated field-effect transistors (gSGFETs) offer high potential for chemical and biochemical sensing applications. Among the current trends to improve this technology, the functionalization processes are gaining relevance for its crucial impact on biosensing performance. Previous efforts are focused on simplifying the attachment procedure from standard multi-step to single-step strategies, but they still suffer from overreaction, and impurity issues and are limited to a particular ligand. Herein, a novel strategy for single-step immobilization of chemically modified aptamers with fluorenylmethyl and acridine moieties, based on a straightforward synthetic route to overcome the aforementioned limitations is presented. This approach is benchmarked versus a standard multi-step strategy using thrombin as detection model. In order to assess the reliability of the functionalization strategies 48-gSGFETs arrays are employed to acquire large datasets with multiple replicas. Graphene surface characterization demonstrates robust and higher efficiency in the chemical coupling of the aptamers with the single-step strategy, while the electrical response evaluation validates the sensing capability, allowing to implement different alternatives for data analysis and reduce the sensing variability. In this work, a new tool capable of overcome the functionalization challenges of graphene surfaces is provided, paving the way toward the standardization of gSGFETs for biosensing purposes.

In the last decade, solution-gated graphene field effect transistors (GFETs) showed their versatility in the development of a miniaturized multiplexed platform for electrophysiological recordings and sensing. Due to their working mechanism, the surface functionalisation and immobilisation of receptors are pivotal to ensure the proper functioning of devices. Herein, we present a controlled covalent functionalisation strategy based on molecular design and electrochemical triggering, which provide a monolayer-like functionalisation of micro-GFET arrays retaining the electronic properties of graphenes. The functionalisation layer as a receptor was then employed as the linker for serotonin aptamer conjugation. The micro-GFET arrays display sensitivity toward the target analyte in the micromolar range in a physiological buffer (PBS 10 mM). The sensor allows the in-flow real-time monitoring of serotonin transient concentrations with fast and reversible responses.

Organs-on-a-chip (OoC) are cell culture platforms that replicate key functional units of tissues in vitro. Barrier integrity and permeability evaluation are of utmost importance when studying barrier-forming tissues. Impedance spectroscopy is a powerful tool and is widely used to monitor barrier permeability and integrity in real-time. However, data comparison across devices is misleading due to the generation of a non-homogenous field across the tissue barrier, making impedance data normalization very challenging. In this work, we address this issue by integrating PEDOT:PSS electrodes for barrier function monitoring with impedance spectroscopy. The semitransparent PEDOT:PSS electrodes cover the entire cell culture membrane providing a homogenous electric field across the entire membrane making the cell culture area equally accountable to the measured impedance. To the best of our knowledge, PEDOT:PSS has never been used solely to monitor the impedance of cellular barriers while enabling optical inspection in the OoC. The performance of the device is demonstrated by lining the device with intestinal cells where we monitored barrier formation under flow conditions, as well as barrier disruption and recovery under exposure to a permeability enhancer. The barrier tightness and integrity, and the intercellular cleft have been evaluated by analyzing the full impedance spectrum. Furthermore, the device is autoclavable paving the way toward more sustainable OoC options.

Portal hypertension (PH) is a frequent and severe clinical syndrome associated with chronic liver disease. Considering the mechanobiological effects of hydrostatic pressure and shear stress on endothelial cells, we hypothesised that PH might influence the phenotype of liver sinusoidal endothelial cells (LSECs) during disease progression. The aim of this study was to investigate the effects of increased hydrodynamic pressure on LSECs and to identify endothelial-derived biomarkers of PH.

Mapping the entire frequency bandwidth of brain electrophysiological signals is of paramount importance for understanding physiological and pathological states. The ability to record simultaneously DC-shifts, infraslow oscillations (<0.1 Hz), typical local field potentials (0.1–80 Hz) and higher frequencies (80–600 Hz) using the same recording site would particularly benefit preclinical epilepsy research and could provide clinical biomarkers for improved seizure onset zone delineation. However, commonly used metal microelectrode technology suffers from instabilities that hamper the high fidelity of DC-coupled recordings, which are needed to access signals of very low frequency. In this study we used flexible graphene depth neural probes (gDNPs), consisting of a linear array of graphene microtransistors, to concurrently record DC-shifts and high-frequency neuronal activity in awake rodents. We show here that gDNPs can reliably record and map with high spatial resolution seizures, pre-ictal DC-shifts and seizure-associated spreading depolarizations together with higher frequencies through the cortical laminae to the hippocampus in a mouse model of chemically induced seizures. Moreover, we demonstrate the functionality of chronically implanted devices over 10 weeks by recording with high fidelity spontaneous spike-wave discharges and associated infraslow oscillations in a rat model of absence epilepsy. Altogether, our work highlights the suitability of this technology for in vivo electrophysiology research, and in particular epilepsy research, by allowing stable and chronic DC-coupled recordings.

The invention relates to a material with opto-mechanical behaviour characterized in that it comprises a cured elastomeric material layer with a corrugated surface, forming wrinkles in the form of ridges and valleys, and a plurality of metallic, dielectric or dielectric-metal coated nanostructures, embedded in the elastomeric material, that generate a Fabry-Perot elastic cavity enhanced by plasmons and or dielectric resonances, and modulated by the wrinkled surface; and a process to obtain it and its uses. Therefore, the present invention can be placed in the area of materials comprising plasmonic metamaterials and their applications.

[EN] The device limits the leakage current in an electronic system for recording electrophysiological signals, where the transducer element is an active device, the device comprising an active transducer (1), intended to contact a human tissue, connected to a transimpedance amplifier (2), and a first resistor (6) connected parallel to the transimpedance amplifier (2), an alternate voltage source (7) and a direct voltage source (8), both connected to the active transducer (1), a first capacitor (3) connected between the alternate voltage source (7) and the active transducer (1), a second resistor (4) connected between the direct voltage source (8) and the active transducer (1), parallel with the first capacitor (3) and the alternate voltage source (7), and a second capacitor (5), connected between the active transducer (1) and the transimpedance amplifier (2)., [FR] L'invention concerne un dispositif qui limite le courant de fuite dans un système électronique pour enregistrer des signaux électrophysiologiques, l'élément transducteur étant un dispositif actif, le dispositif comprenant un transducteur actif (1), destiné à entrer en contact avec un tissu humain, connecté à un amplificateur de transimpedance (2), et une première résistance (6) connectée en parallèle à l'amplificateur de transimpedance (2), une source de tension alternative (7) et une source de tension continue (8), toutes deux connectées au transducteur actif (1), un premier condensateur (3) connecté entre la source de tension alternative (7) et le transducteur actif (1), une deuxième résistance (4) connectée entre la source de tension continue (8) et le transducteur actif (1), parallèle au premier condensateur (3) et à la source de tension alternative (7), et un second condensateur (5), connecté entre le transducteur actif (1) et l'amplificateur de transimpédance (2).

[EN] The invention relates to a material with opto-mechanical behaviour characterized in that it comprises a cured elastomeric material layer with a corrugated surface, forming wrinkles in the form of ridges and valleys, and a plurality of metallic, dielectric or dielectric-metal coated nanostructures, embedded in the elastomeric material, that generate a Fabry-Perot elastic cavity enhanced by plasmons and or dielectric resonances, and modulated by the wrinkled surface; and a process to obtain it and its uses. Therefore, the present invention can be placed in the area of materials comprising plasmonic metamaterials and their applications., [FR] L'invention concerne un matériau à comportement opto-mécanique caractérisé en ce qu'il comprend une couche de matériau élastomère durci présentant une surface ondulée, formant des plis sous la forme de crêtes et de vallées, et une pluralité de particules métalliques, des nanostructures à revêtement diélectrique ou diélectrique, incorporées dans le matériau élastomère, qui génèrent une cavité élastique de Fabry-Perot améliorée par des plasmons et des résonances diélectriques, et modulées par la surface plissée ; et son procédé d'obtention et ses utilisations. Par conséquent, la présente invention peut être placée dans la zone de matériaux comprenant des métamatériaux plasmoniques et leurs applications.

The device limits the leakage current in an electronic system for recording electrophysiological signals, where the transducer element is an active device, the device comprising an active transducer (1), intended to contact a human tissue, connected to a transimpedance amplifier (2), and a first resistor (6) connected parallel to the transimpedance amplifier (2), an alternate voltage source (7) and a direct voltage source (8), both connected to the active transducer (1), a first capacitor (3) connected between the alternate voltage source (7) and the active transducer (1), a second resistor (4) connected between the direct voltage source (8) and the active transducer (1), parallel with the first capacitor (3) and the alternate voltage source (7), and a second capacitor (5), connected between the active transducer (1) and the transimpedance amplifier (2).

The emerging stretchable photonics field faces challenges, like the robust integration of optical elements into elastic matrices or the generation of large optomechanical effects. Here, the first stretchable plasmonic-enhanced and wrinkled Fabry–Pérot (FP) cavities are demonstrated, which are composed of self-embedded arrays of Au nanostructures at controlled depths into elastomer films. The novel self-embedding process is triggered by the Au nanostructures’ catalytic activity, which locally increases the polymer curing rate, thereby inducing a mechanical stress that simultaneously pulls the Au nanostructures into the polymer and forms a wrinkled skin layer. This geometry yields unprecedented optomechanical effects produced by the coupling of the broad plasmonic modes of the Au nanostructures and the FP modes, which are modulated by the wrinkled optical cavity. As a result, film stretching induces drastic changes in both the spectral position and intensity of the plasmonic-enhanced FP resonances due to the simultaneous cavity thickness reduction and cavity wrinkle flattening, thus increasing the cavity finesse. These optomechanical effects are exploited to demonstrate new strain-sensing approaches, achieving a strain detection limit of 0.006%, i.e., 16-fold lower than current optical strain-detection schemes.

The emerging stretchable photonics field faces challenges, like the robust integration of optical elements into elastic matrices or the generation of large optomechanical effects. Here, the first stretchable plasmonic-enhanced and wrinkled Fabry-Perot (FP) cavities are demonstrated, which are composed of self-embedded arrays of Au nanostructures at controlled depths into elastomer films. The novel self-embedding process is triggered by the Au nanostructures catalytic activity, which locally increases the polymer curing rate, thereby inducing a mechanical stress that simultaneously pulls the Au nanostructures into the polymer and forms a wrinkled skin layer. This geometry yields unprecedented optomechanical effects produced by the coupling of the broad plasmonic modes of the Au nanostructures and the FP modes, which are modulated by the wrinkled optical cavity. As a result, film stretching induces drastic changes in both the spectral position and intensity of the plasmonic-enhanced FP resonances due to the simultaneous cavity thickness reduction and cavity wrinkle flattening, thus increasing the cavity finesse. These optomechanical effects are exploited to demonstrate new strain-sensing approaches, achieving a strain detection limit of 0.006%, i.e., 16-fold lower than current optical strain-detection schemes., Funding Agencies: Ramon y Cajal Fellowship Spanish Government [RyC2013-14479, MCIN/AEI/10.13039/501100011033]; Generalitat de Catalunya General Electric [2017-SGR-292]; CERCA programme/Generalitat de Catalunya; Swedish Foundation for Strategic Research (SFF) grant [FFL15-0026, RMX18-0039]; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linköping University (Faculty Grant SFO-Mat-LiU) [2009-00971]; [MAT201677391-R]; [PID2019-106229RB-I00]; [PCIN2016-093]; [DPI201568197-R]; [DPI2015-72948-EXP]; [SEV-20170706]

"YouTube com a eina de comunicació política: El cas de les eleccions del 14F a Catalunya" analitza la campanya electoral de 2021 a el Parlament de Catalunya. Es centra en l'ús de les xarxes socials que fan els partits polítics amb representació al Parlament i com aquest s'enfoca als perfils dels votants definits pel CEO de cada un dels partits en qüestió. S'analitza YouTube al ser una de les eines més versàtils, amb més ús per part dels internautes i més audiovisuals. Aquest treball també compara les diferents estratègies proposades entre si a partir d'un anàlisi tant quantitatiu com qualitatiu., "YouTube como herramienta de comunicación política: El caso de las elecciones del 14F en Cataluña" analiza la campaña electoral de 2021 al Parlamento de Catalunya. Se centra en el uso de las redes sociales que hacen los partidos políticos con representación en el Parlamento y cómo se enfoca al perfil de los votantes definidos por el CEO de cada uno de dichos partidos. Se analiza YouTube al ser una de las herramientas más versátiles, con más uso por parte de los internautas y más audiovisuales. Este trabajo también compara las diferentes estrategias propuestas entre si a partir de un análisis tanto cuantitativo como cualitativo., "YouTube as a political communication tool: The case of the 14F election in Catalonia." Is an analysis of the 2021 election campaign for Parliament of Catalonia. It analyses the use of social media made by the political parties that have representation in that particular chamber and how the campaigns are designed towards each of the parties voter's profile. YouTube is the chosen social media platform as it is a versatile tool, broadly used and the most audiovisual. This paper also compares the different strategies with each other based on a quantitative and qualitative analysis.

Aquest Treball de Fi de Grau ha tingut com a principal objectiu analitzar la representació dels personatges femenins al cinema de l'Època Daurada de Hollywood a partir de la filmografia d'una de les seves actrius més representatives: Bette Davis. Tenint en compte el context històric i social de la seva vida, el projecte també investiga el paper que va jugar l'artista en una indústria hipotèticament misògina i dominada per homes., Este Trabajo de Final de Grado ha tenido como principal objetivo analizar la representación de los personajes femeninos del cine de la Era Dorada de Hollywood a partir de la filmografía de una de sus actrices más representativas: Bette Davis. Teniendo en cuenta el contexto histórico y social de su vida, el proyecto también investiga el papel que jugó la artista en una industria hipotéticamente misógina y dominada por hombres., This Final Project has been aimed at analysing the representation of female characters in the Hollywood Golden Age cinema through the examination of the filmography of one of their most representative actresses: Bette Davis. Considering the historical and social context of her life, the project also investigates the role played by the artist in a hypothetically misogynistic and male-dominated industry.

Altres ajuts: ICN2 is funded by the CERCA programme/Generalitat de Catalunya., New multi-stimuli responsive materials are required in smart systems applications to overcome current limitations in remote actuation and to achieve versatile operation in inaccessible environments. The incorporation of detection mechanisms to quantify in real time the response to external stimuli is crucial for the development of automated systems. Here, we present the first wireless opto-magnetic actuator with mechanochromic response. The device, based on a nanostructured-iron (Fe) layer transferred onto suspended elastomer structures with a periodically corrugated backside, can be actuated both optically (in a broadband spectral range) and magnetically. The combined opto-magnetic stimulus can accurately modulate the mechanical response (strength and direction) of the device. The structural coloration generated at the corrugated back surface enables to easily map and quantify, in 2D, the mechanical deflections by analyzing in real time the hue changes of images taken using a conventional RGB smartphone camera, with a precision of 0.05°. We demonstrate the independent and synergetic optical and magnetic actuation and detection with a detection limit of 1.8 mW·cm -2 and 0.34 mT, respectively. The simple operation, versatility, and cost-effectiveness of the wireless multiactuated device with highly sensitive mechanochromic mapping paves the way to a new generation of wirelessly controlled smart systems.

Objective. The development of experimental methodology utilizing graphene micro-transistor arrays to facilitate and advance translational research into cortical spreading depression (CSD) in the awake brain. Approach. CSDs were reliably induced in awake nontransgenic mice using optogenetic methods. High-fidelity DC-coupled electrophysiological mapping of propagating CSDs was obtained using flexible arrays of graphene soultion-gated field-effect transistors (gSGFETs). Main results. Viral vectors targetted channelrhopsin expression in neurons of the motor cortex resulting in a transduction volume 1 mm3. 5-10 s of continous blue light stimulation induced CSD that propagated across the cortex at a velocity of 3.0 0.1 mm min-1. Graphene micro-transistor arrays enabled high-density mapping of infraslow activity correlated with neuronal activity suppression across multiple frequency bands during both CSD initiation and propagation. Localized differences in the CSD waveform could be detected and categorized into distinct clusters demonstrating the spatial resolution advantages of DC-coupled recordings. We exploited the reliable and repeatable induction of CSDs using this preparation to perform proof-of-principle pharmacological interrogation studies using NMDA antagonists. MK801 (3 mg kg-1) suppressed CSD induction and propagation, an effect mirrored, albeit transiently, by ketamine (15 mg kg-1), thus demonstrating this models' applicability as a preclinical drug screening platform. Finally, we report that CSDs could be detected through the skull using graphene micro-transistors, highlighting additional advantages and future applications of this technology. Significance. CSD is thought to contribute to the pathophysiology of several neurological diseases. CSD research will benefit from technological advances that permit high density electrophysiological mapping of the CSD waveform and propagation across the cortex. We report an in vivo assay that permits minimally invasive

La presente invención se refiere a un material que absorbe radiación electromagnética de longitudes de onda de entre 300 nm a 18 µm que comprende un sustrato polimérico y una pluralidad de nanocápsulas. Además, la presente invención se refiere a un fotodetector no refrigerado, un actuador fotomecánico alimentado con luz solar y una pupila dinámica artificial autorregulada con luz/radiación incidente y una prótesis ocular que comprende dicho material. Por último, la presente invención se refiere al uso del material como soporte en voladizo para la fabricación de una pupila artificial dinámica para el tratamiento de trastornos de la pupila. Por tanto, la presente invención se puede encuadrar en el área de los materiales que comprenden metamateriales y sus aplicaciones.

pH sensing for healthcare applications requires sensors with mechanically stable materials of high sensitivity and high reproducibility combined with low-cost fabrication technologies. This work proposes a fully printed pH sensor based on a specially formulated conducting polymer deposited on a microelectrode in a flexible substrate. A formulation, which combined polyaniline (PANI) and polypyrrole (PPy) with integrated polyelectrolyte poly(sodium 4-styrenesulfonate) (PSS), was specially prepared to be printed by inkjet printing (IJP). The sensor has good sensitivity in the physiological region (pH 7-7.5) key for the healthcare biosensor. This mixture printed over a commercial gold ink, which has a singular chemical functionalization with phthalocyanine (Pc), increased the sensor sensitivity, showing an excellent reproducibility with a linear super-Nernstian response (81.2 ± 0.5 mV/pH unit) in a wide pH range (pH 3-10). This new ink together with the IJP low-cost technique opens new opportunities for pH sensing in the healthcare field with a single device, which is disposable, highly sensitive, and stable in the whole pH range.

Data and python code for reproducing the main results of the paper "Full bandwidth electrophysiology of seizures and epileptiform activity enabled by flexible graphene micro-transistor depth neural probes."

The present invention refers to a method for exfoliating and transferring graphene from a doped silicon carbide substrate to another substrate, the method being based on exfoliation induced by hydrogen bubbles produced in the electrolysis of water

New multi-stimuli responsive materials are required in smart systems applications to overcome current limitations in remote actuation and to achieve versatile operation in inaccessible environments. The incorporation of detection mechanisms to quantify in real time the response to external stimuli is crucial for the development of automated systems. Here, we present the first wireless opto-magnetic actuator with mechanochromic response. The device, based on a nanostructured-iron (Fe) layer transferred onto suspended elastomer structures with a periodically corrugated backside, can be actuated both optically (in a broadband spectral range) and magnetically. The combined opto-magnetic stimulus can accurately modulate the mechanical response (strength and direction) of the device. The structural coloration generated at the corrugated back surface enables to easily map and quantify, in 2D, the mechanical deflections by analyzing in real time the hue changes of images taken using a conventional RGB smartphone camera, with a precision of 0.05°. We demonstrate the independent and synergetic optical and magnetic actuation and detection with a detection limit of 1.8 mW·cm-2 and 0.34 mT, respectively. The simple operation, versatility, and cost-effectiveness of the wireless multiactuated device with highly sensitive mechanochromic mapping paves the way to a new generation of wirelessly controlled smart systems.

Objective. The development of experimental methodology utilizing graphene micro-transistor arrays to facilitate and advance translational research into cortical spreading depression (CSD) in the awake brain. Approach. CSDs were reliably induced in awake nontransgenic mice using optogenetic methods. High-fidelity DC-coupled electrophysiological mapping of propagating CSDs was obtained using flexible arrays of graphene soultion-gated field-effect transistors (gSGFETs). Main results. Viral vectors targetted channelrhopsin expression in neurons of the motor cortex resulting in a transduction volume 1 mm3. 5-10 s of continous blue light stimulation induced CSD that propagated across the cortex at a velocity of 3.0 0.1 mm min-1. Graphene micro-transistor arrays enabled high-density mapping of infraslow activity correlated with neuronal activity suppression across multiple frequency bands during both CSD initiation and propagation. Localized differences in the CSD waveform could be detected and categorized into distinct clusters demonstrating the spatial resolution advantages of DC-coupled recordings. We exploited the reliable and repeatable induction of CSDs using this preparation to perform proof-of-principle pharmacological interrogation studies using NMDA antagonists. MK801 (3 mg kg-1) suppressed CSD induction and propagation, an effect mirrored, albeit transiently, by ketamine (15 mg kg-1), thus demonstrating this models' applicability as a preclinical drug screening platform. Finally, we report that CSDs could be detected through the skull using graphene micro-transistors, highlighting additional advantages and future applications of this technology. Significance. CSD is thought to contribute to the pathophysiology of several neurological diseases. CSD research will benefit from technological advances that permit high density electrophysiological mapping of the CSD waveform and propagation across the cortex. We report an in vivo assay that permits minimally invasive

Understanding the brain from genes and circuits to behavior is a major scientific challenge. The large repertoire of cell activities supporting behavior stems from an equally diverse range of specialized cell types, from neuron to glia. To untangle mechanisms underlying brain function, elementary processes should be dissected, from the complex machinery of signaling pathways at the level of single cells and synapses, to the intricate phenomena leading to orchestrated ensemble activity and the establishment of engrams driving memory-guided behaviors. In this chapter we identify the main key tasks required to address some of the open questions in the field, and discuss on the main issues and strategies.

Advanced Therapy is considered one of the fastest growing areas of biomedical research and with the greatest potential to influence society by offering solutions for unmet medical needs, including the possibility of curing diseases with negligible or scarce herapeutic alternatives and developing personalized medicine. We describe here the current positioning, weaknessess and potential of the CSIC in Gene therapy, Cell therapies and Bioengineering and analyze the major goals to be achieved in these research fields in order to translate basic science to clinical applications.

Stroke and traumatic injury in brain or spinal cord are often life-threating conditions and major causes of death or permanent disability with high impact in the health care system. There are several stages of intervention to improve the neurological outcome. Acutely, fast interventions aiming to reestablish cerebral blood flow in ischemic stroke, to stop bleeding after brain hemorrhage, and to reduce edema after contusions are amongst mandatory actions. Current studies aim to develop accompanying strategies for brain cell protection based on enhancing endogenous protective mechanism, blocking cell death pathways, or through immunomodulation. After the acute phase, interventions are intended to promote recovery of function using rehabilitation with state-of-the-art technologies enabled by robotics. Other advanced strategies include cell, gene, and immune therapies, and brain function modulation with the aid of smart nanotechnologies. There is great expectation in the fast evolving novel approaches for improvement of neurological deficits in these unpredictable and devastating condition

Developing new standardized tools to characterize brain recording devices is critical to evaluate neural probes and for translation to clinical use. The signal-to-noise ratio (SNR) measurement is the gold standard for quantifying the performance of brain recording devices. Given the drawbacks with the SNR measure, our first objective was to devise a new method to calculate the SNR of neural signals to distinguish signal from noise. Our second objective was to apply this new SNR method to evaluate electrodes of three different materials (platinum black, Pt; carbon nanotubes, CNTs; and gold, Au) co-localized in tritrodes to record from the same cortical area using specifically designed multielectrode arrays. Hence, we devised an approach to calculate SNR at different frequencies based on the features of cortical slow oscillations (SO). Since SO consist in the alternation of silent periods (Down states) and active periods (Up states) of neuronal activity, we used these as noise and signal, respectively. The spectral SNR was computed as the power spectral density (PSD) of Up states (signal) divided by the PSD of Down states (noise). We found that Pt and CNTs electrodes have better recording performance than Au electrodes for the explored frequency range (5-1500 Hz). Together with two proposed SNR estimators for the lower and upper frequency limits, these results substantiate our SNR calculation at different frequency bands. Our results provide a new validated SNR measure that provides rich information of the performance of recording devices at different brain activity frequency bands (<1500 Hz).

Basado en matrices flexibles de transistores grafeno de efecto de campo epicorticales y intracorticales, que pueden registrar señales infralentas y señales en un ancho de banda típico de potenciales de campo local. El objeto de la invención se basa en el sistema del transistor del grafeno para medir señales electrofisiológicas, comprendiendo una unidad de proceso, y al menos un transistor del grafeno con el grafeno como material del canal contactado por dos terminales, a los cuales se une una fuente de tensión variable en los terminales de drenador y de fuente del transistor referido a la tensión de la puerta, y al menos un filtro de adquisición y división de la señal del transistor en al menos dos bandas de frecuencia, baja y alta, en el que las señales primera y segunda se amplifican respectivamente con un valor de ganancia. [ES], The invention is based on flexible matrices of graphene transistors with epicortical and intracortical field effects, which can register infraslow signals and signals in a bandwidth that is typical of local field potentials. The object of the invention is based on the graphene transistor system for measuring electrophysiological signals, comprising a processing unit and at least one graphene transistor with the graphene as the channel material contacted via two terminals, to which a variable voltage source is joined at the drain and source terminals of the transistor, with a reference as a gate terminal, and at least one filter for acquiring and dividing the signal of the transistor into at least two frequency bands, low and high, in which the first and second signals are amplified respectively with a gain value. [EN]

Sistema de transistores de grafeno para medir señales electrofisiológicas. El objeto de la invención se basa en las matrices flexibles de transistores grafeno de efecto de campo (gSGFETs) epicorticales y intracorticales, que pueden registrar señales infralentas junto con señales en un ancho de banda típico de potenciales de campo local. El objeto de la invención se basa en el sistema del transistor del grafeno para medir las señales electrofisiológicas, comprendiendo una unidad de proceso, y por lo menos un transistor del grafeno (gSGFET) que comprende el grafeno como material del canal contactado por dos terminales, a los cuales se une una fuente de tensión variable en los terminales de drenador y de fuente del transistor (gSGFET) referido a la tensión de la puerta, y al menos un filtro configurado para adquirir y dividir la señal del transistor en al menos dos bandas de frecuencia, banda de baja frecuencia y banda de alta frecuencia, en el que las señales primera y segunda se amplifican respectivamente con un valor de ganancia.

Sensor arrays used to detect electrophysiological signals from the brain are paramount in neuroscience. However, the number of sensors that can be interfaced with macroscopic data acquisition systems currently limits their bandwidth. This bottleneck originates in the fact that, typically, sensors are addressed individually, requiring a connection for each of them. Herein, we present the concept of frequency-division multiplexing (FDM) of neural signals by graphene sensors. We demonstrate the high performance of graphene transistors as mixers to perform amplitude modulation (AM) of neural signals in situ, which is used to transmit multiple signals through a shared metal line. This technology eliminates the need for switches, remarkably simplifying the technical complexity of state-of-the-art multiplexed neural probes. Besides, the scalability of FDM graphene neural probes has been thoroughly evaluated and their sensitivity demonstrated in vivo. Using this technology, we envision a new generation of high-count conformal neural probes for high bandwidth brain machine interfaces.

[EN] The Bologna process has meant a methodological change in University Teaching, whose objective is to improve the teaching-learning process in a context enriched by the use of technologies, responding to students' requirements. The objective of this Work is to present a learning experience based on the game implemented in the area of Architectural Constructions, in the first year of University teaching, to inform about the process, result and the opinions obtained from the students., [ES] El Plan Bolonia ha supuesto un cambio metodológico en la Enseñanza Universitaria, cuyo objetivo es mejorar el proceso de enseñanza-aprendizaje en un contexto enriquecido por el uso de las tecnologías, respondiendo a los requerimientos de los estudiantes.El objetivo de este Trabajo es presentar una experiencia de aprendizaje basada en el juego, implementada en el área de Construcciones Arquitectónicas, en el primer curso de enseñanza Universitaria, para informar sobre el proceso, resultado y las opiniones obtenidas del alumnado.

[EN] The Bologna process has meant a methodological change in University Teaching, whose objective is to improve the teaching-learning process in a context enriched by the use of technologies, responding to students' requirements. The objective of this Work is to present a learning experience based on the game implemented in the area of Architectural Constructions, in the first year of University teaching, to inform about the process, result and the opinions obtained from the students., [ES] El Plan Bolonia ha supuesto un cambio metodológico en la Enseñanza Universitaria, cuyo objetivo es mejorar el proceso de enseñanza-aprendizaje en un contexto enriquecido por el uso de las tecnologías, respondiendo a los requerimientos de los estudiantes.El objetivo de este Trabajo es presentar una experiencia de aprendizaje basada en el juego, implementada en el área de Construcciones Arquitectónicas, en el primer curso de enseñanza Universitaria, para informar sobre el proceso, resultado y las opiniones obtenidas del alumnado.

[EN] The Bologna process has meant a methodological change in University Teaching, whose objective is to improve the teaching-learning process in a context enriched by the use of technologies, responding to students' requirements. The objective of this Work is to present a learning experience based on the game implemented in the area of Architectural Constructions, in the first year of University teaching, to inform about the process, result and the opinions obtained from the students., [ES] El Plan Bolonia ha supuesto un cambio metodológico en la Enseñanza Universitaria, cuyo objetivo es mejorar el proceso de enseñanza-aprendizaje en un contexto enriquecido por el uso de las tecnologías, respondiendo a los requerimientos de los estudiantes.El objetivo de este Trabajo es presentar una experiencia de aprendizaje basada en el juego, implementada en el área de Construcciones Arquitectónicas, en el primer curso de enseñanza Universitaria, para informar sobre el proceso, resultado y las opiniones obtenidas del alumnado.

[EN] The Bologna process has meant a methodological change in University Teaching, whose objective is to improve the teaching-learning process in a context enriched by the use of technologies, responding to students' requirements. The objective of this Work is to present a learning experience based on the game implemented in the area of Architectural Constructions, in the first year of University teaching, to inform about the process, result and the opinions obtained from the students., [ES] El Plan Bolonia ha supuesto un cambio metodológico en la Enseñanza Universitaria, cuyo objetivo es mejorar el proceso de enseñanza-aprendizaje en un contexto enriquecido por el uso de las tecnologías, respondiendo a los requerimientos de los estudiantes.El objetivo de este Trabajo es presentar una experiencia de aprendizaje basada en el juego, implementada en el área de Construcciones Arquitectónicas, en el primer curso de enseñanza Universitaria, para informar sobre el proceso, resultado y las opiniones obtenidas del alumnado.

[EN] The Bologna process has meant a methodological change in University Teaching, whose objective is to improve the teaching-learning process in a context enriched by the use of technologies, responding to students' requirements. The objective of this Work is to present a learning experience based on the game implemented in the area of Architectural Constructions, in the first year of University teaching, to inform about the process, result and the opinions obtained from the students., [ES] El Plan Bolonia ha supuesto un cambio metodológico en la Enseñanza Universitaria, cuyo objetivo es mejorar el proceso de enseñanza-aprendizaje en un contexto enriquecido por el uso de las tecnologías, respondiendo a los requerimientos de los estudiantes.El objetivo de este Trabajo es presentar una experiencia de aprendizaje basada en el juego, implementada en el área de Construcciones Arquitectónicas, en el primer curso de enseñanza Universitaria, para informar sobre el proceso, resultado y las opiniones obtenidas del alumnado.

The present invention refers to a method for exfoliating and transferring graphene from a doped silicon carbide substrate to another substrate, the method being based on exfoliation induced by hydrogen bubbles produced in the electrolysis of water

Con motivo del Día de la Mujer y la Niña en la Ciencia, el 11 de febrero, reunimos a investigadoras de reconocido prestigio del CSIC y a algunos de sus discípulos. ¿Cómo han influido en su carrera científica? ¿Qué han aprendido de ellas?

Although pristine graphene is one of the most relevant materials this decade, several important shortcomings must be overcome before it can step from fundamental physics to applied technology. In particular, its extreme chemical inertness and the absence of an electronic band-gap present important limitations to its use as an active element in electronic devices and hybrid structures. Thus, technologically useful and robust graphene-based interfaces for nano-bio-hybrid devices require highly selective, stable and covalently bonded functionalities on the graphene surface, but in order to be effective and competitive they must essentially retain the electronic properties of the pristine graphene surface. There have been many attempts to modify graphene via non-destructive methodologies that aim to preserve its extraordinary properties and incorporate added value. The most common covalent functionalization methods are via chemical routes, mainly by reacting free radicals or dienophiles with the C=C bonds of pristine graphene, and although well-developed wet chemistry may succeed in linking diverse groups to the surface, the resulting graphene platforms are usually poor performers either due to low functionalization yield or to the nature of the reaction conditions that disrupt the graphene layer with an unacceptable amount of defects. In this work, we describe a relatively straightforward route to the covalent chemical functionalization of graphene sheets with a robust thiol-terminated moiety. We employ a recently reported and patented strategy for the selective functionalization of graphene through the controlled formation of atomic vacancies, obtaining a graphene surface uniformly covered with a covalently bound spacer molecule that is formed from the spontaneous bonding of p-aminothiophenol (pATP) molecules at the vacancies. The result is a controlled decoration of the graphene surface with active thiol moieties, which can subsequently be directly used to bind diver

Technologically useful and robust graphene-based interfaces for devices require the introduction of highly selective, stable, and covalently bonded functionalities on the graphene surface, whilst essentially retaining the electronic properties of the pristine layer. This work demonstrates that highly controlled, ultrahigh vacuum covalent chemical functionalization of graphene sheets with a thiol-terminated molecule provides a robust and tunable platform for the development of hybrid nanostructures in different environments. We employ this facile strategy to covalently couple two representative systems of broad interest: metal nanoparticles, via S–metal bonds, and thiol-modified DNA aptamers, via disulfide bridges. Both systems, which have been characterized by a multitechnique approach, remain firmly anchored to the graphene surface even after several washing cycles. Atomic force microscopy images demonstrate that the conjugated aptamer retains the functionality required to recognize a target protein. This methodology opens a new route to the integration of high-quality graphene layers into diverse technological platforms, including plasmonics, optoelectronics, or biosensing. With respect to the latter, the viability of a thiol-functionalized chemical vapor deposition graphene-based solution-gated field-effect transistor array was assessed.

Prussian Blue (PB)-modified graphite screen-printed electrodes are increasingly being used in electrochemical biosensors. However, they do not allow the observation of the electrochromism of PB. This work presents the construction of PB-based, electrochromic screen-printed biosensors. Although electrically more resistive than their graphite counterparts, these new PB-based electrodes enable both the amperometric and colorimetric detection of hydrogen peroxide. This is the first time that this has been achieved using screen-printed electrodes, and we demonstrate it spectroelectrochemically on a glucose biosensor. The biosensor electrochemical performance equals that of previously reported PB/graphite electrodes, being able to detect down to 4 µM H2O2 and 54 µM glucose. At the same time, and in contrast to PB/graphite electrodes, the new PB-based electrodes afford the optical detection of these two analytes down to 1.2 µM and 15 µM, respectively. The dynamic ranges of the glucose biosensors obtained at the PB-based electrodes are 0.1-1 mM (amperometric) and 0.025-2.5 mM (Colorimetric), matching the physiological glucose concentration range in body fluids other than blood or serum.

A novel sensing device for simultaneous dissolved oxygen (DO) and pH monitoring specially designed for biofilm profiling is presented in this work. This device enabled the recording of instantaneous DO and pH dynamic profiles within biofilms, improving the tools available for the study and the characterization of biological systems. The microsensor consisted of two parallel arrays of microelectrodes. Microelectrodes used for DO sensing were bare gold electrodes, while microelectrodes used for pH sensing were platinum-based electrodes modified using electrodeposited iridium oxide. The device was fabricated with a polyimide (Kapton®) film of 127 µm as a substrate for minimizing the damage caused on the biofilm structure during its insertion. The electrodes were covered with a Nafion® layer to increase sensor stability and repeatability and to avoid electrode surface fouling. DO microelectrodes showed a linear response in the range 0-8 mg L-1, a detection limit of 0.05 mg L-1, and a sensitivity of 2.06 nA L mg-1. pH electrodes showed a linear super-Nernstian response (74.2 ± 0.7 mV/pH unit) in a wide pH range (pH 4-9). The multi-analyte sensor array was validated in a flat plate bioreactor where simultaneous and instantaneous pH and DO profiles within a sulfide oxidizing biofilm were recorded. The electrodes spatial resolution, the monitoring sensitivity, and the minimally invasive features exhibited by the proposed microsensor improved biofilm monitoring performance, enabling the quantification of mass transfer resistances and the assessment of biological activity., Peer Reviewed, Postprint (published version)

Al abordar el proyecto de un edificio hay que tener muy en cuenta la envolvente y los factores que influyen en su diseño para alcanzar el bienestar térmico en el interior del mismo (en base a la limitación de la demanda energética . establecida por la normativa); estos factores son: localidad, estación climática, uso del edificio, características constructivas del muro, inercia térmica, permeabilidad al aire y radiación solar. Para determinar las pérdidas de calor de un edificio a través de los elementos que componen la envolvente surge el concepto de Transmitancia térmica U, que es una característica específica de cada elemento constructivo. Los parámetros característicos que definen la envolvente térmica, serán inferiores a unos valores establecidos de transmitancia térmica U para los cerramientos de la envolvente y un factor solar modificado F para huecos y lucernarios. En el presente artículo nos vamos a centrar en el cálculo de la transmitancia de la parte opaca de una fachada de un edificio

Al abordar el proyecto de un edificio hay que tener muy en cuenta la envolvente y los factores que influyen en su diseño para alcanzar el bienestar térmico en el interior del mismo (en base a la limitación de la demanda energética . establecida por la normativa); estos factores son: localidad, estación climática, uso del edificio, características constructivas del muro, inercia térmica, permeabilidad al aire y radiación solar. Para determinar las pérdidas de calor de un edificio a través de los elementos que componen la envolvente surge el concepto de Transmitancia térmica U, que es una característica específica de cada elemento constructivo. Los parámetros característicos que definen la envolvente térmica, serán inferiores a unos valores establecidos de transmitancia térmica U para los cerramientos de la envolvente y un factor solar modificado F para huecos y lucernarios. En el presente artículo nos vamos a centrar en el cálculo de la transmitancia de la parte opaca de una fachada de un edificio

Cell microencapsulation is an attractive strategy for cell-based therapies that allows the implantation of genetically engineered cells and the continuous delivery of de novo produced therapeutic products. However, the establishment of a way to retrieve the implanted encapsulated cells in case the treatment needs to be halted or when cells need to be renewed is still a big challenge. The combination of micro and macroencapsulation approaches could provide the requirements to achieve a proper immunoisolation, while maintaining the cells localized into the body. We present the development and characterization of a porous implantable macrocapsule device for the loading of microencapsulated cells. The device was fabricated in polyamide by selective laser sintering (SLS), with controlled porosity defined by the design and the sintering conditions. Two types of microencapsulated cells were tested in order to evaluate the suitability of this device; erythropoietin (EPO) producing C2C12 myoblasts and Vascular Endothelial Growth Factor (VEGF) producing BHK fibroblasts. Results showed that, even if the metabolic activity of these cells decreased over time, the levels of therapeutic protein that were produced and, importantly, released to the media were stable.

Al abordar el proyecto de un edificio hay que tener muy en cuenta la envolvente y los factores que influyen en su diseño para alcanzar el bienestar térmico en el interior del mismo (en base a la limitación de la demanda energética . establecida por la normativa); estos factores son: localidad, estación climática, uso del edificio, características constructivas del muro, inercia térmica, permeabilidad al aire y radiación solar. Para determinar las pérdidas de calor de un edificio a través de los elementos que componen la envolvente surge el concepto de Transmitancia térmica U, que es una característica específica de cada elemento constructivo. Los parámetros característicos que definen la envolvente térmica, serán inferiores a unos valores establecidos de transmitancia térmica U para los cerramientos de la envolvente y un factor solar modificado F para huecos y lucernarios. En el presente artículo nos vamos a centrar en el cálculo de la transmitancia de la parte opaca de una fachada de un edificio

Al abordar el proyecto de un edificio hay que tener muy en cuenta la envolvente y los factores que influyen en su diseño para alcanzar el bienestar térmico en el interior del mismo (en base a la limitación de la demanda energética . establecida por la normativa); estos factores son: localidad, estación climática, uso del edificio, características constructivas del muro, inercia térmica, permeabilidad al aire y radiación solar. Para determinar las pérdidas de calor de un edificio a través de los elementos que componen la envolvente surge el concepto de Transmitancia térmica U, que es una característica específica de cada elemento constructivo. Los parámetros característicos que definen la envolvente térmica, serán inferiores a unos valores establecidos de transmitancia térmica U para los cerramientos de la envolvente y un factor solar modificado F para huecos y lucernarios. En el presente artículo nos vamos a centrar en el cálculo de la transmitancia de la parte opaca de una fachada de un edificio

Premi Extraordinari de Doctorat concedit pels programes de doctorat de la UAB per curs acadèmic 2017-2018, Los sistemas microfisiológicos (MPS) son modelos in vitro microfabricados que emulan las condiciones in vivo fisiológicamente relevantes, como la organización celular y las señales microambientales. Las microtecnologías han permitido el desarrollo de sofisticados MPS capaces de recapitular fielmente la fisiología a nivel de tejido y órgano. Los MPS son particularmente útiles para modelar barreras biológicas, es decir, epitelios y endotelios que separan la circulación sanguínea de los compartimentos tisulares. Su función de barrera es crucial para mantener la homeostasis en los órganos y su desregulación juega un papel importante en la fisiopatología de muchas enfermedades humanas prevalentes. La función principal de un tejido barrera es controlar el transporte transepitelial de solutos. Por lo tanto, la capacidad de cuantificar el transporte en un modelo de barrera es crítico. La espectroscopía de impedancia eléctrica (EIS) permite su cuantificación con las ventajas de ser no destructiva, sin utilizar marcadores y de fácil aplicación en tiempo real. EIS puede determinar 1) la resistencia eléctrica transepitelial (TEER), que evalúa la integridad de la barrera (estrechamente relacionada con la rigidez del espacio intercelular); 2) la capacitancia de la capa celular (Ccl), que puede proporcionar información sobre el área superficial de la membrana; y 3) la contribución de la solución del medio a la impedancia. Mientras que el EIS es fácil de realizar mediante electrodos extracelulares, es difícil lograr la distribución de corriente uniforme requerida para mediciones precisas dentro de los canales de cultivo celular miniaturizados. Entonces, se puede suponer erróneamente que todo el área de cultivo de células contribuye igual a la medición, lo que puede conducir a errores de cálculo del TEER. Esto puede explicar parcialmente la gran disparidad de los valores de TEER reportados para tipos de células idénticas. Aquí, se presenta un estudio numérico para dilucidar este pro, Microphysiological systems (MPS) are biologically inspired microengineered in vitro models that emulate physiologically relevant in vivo conditions, such as cell organization and microenvironmental cues. Microtechnologies have enabled the development of significant MPS that are able to faithfully recapitulate tissue- and organ-level physiology. MPS are particularly useful for modelling biological barriers, that is, epithelia and endothelia that separate the blood circulation from tissue compartments. Their barrier function is crucial to maintain organ homeostasis and their deregulation play an important role in the pathophysiology of many prevalent human diseases. The primary function of a barrier tissue is to control the transepithelial transport of solutes. Therefore, the ability to quantify transport in a barrier model is critical. Electrical impedance spectroscopy (EIS) permits its quantification with the advantages of being non-destructive, label-free, and easily applicable in real time. EIS can determine 1) the transepithelial electrical resistance (TEER), which evaluates the barrier integrity (closely related with the tightness of the intercellular space); 2) the cell layer capacitance (Ccl), which can yield information about the membrane surface area; and 3) the contribution of the medium solution to the impedance. While EIS is easy to carry out by means of extracellular electrodes, it is challenging to achieve the uniform current distribution required for accurate measurements within miniaturized cell culture channels. Then, it may be erroneously assumed that the entire cell culture area contributes equally to the measurement leading to TEER calculation errors. This can partially explain the large disparity of TEER values reported for identical cell types. Here, a numerical study is presented to elucidate this issue in some cell cultures previously reported and to propose a geometric correction factor (GCF) to correct this error and be applied retrospective

Cell microencapsulation is an attractive strategy for cell-based therapies that allows the implantation of genetically engineered cells and the continuous delivery of de novo produced therapeutic products. However, the establishment of a way to retrieve the implanted encapsulated cells in case the treatment needs to be halted or when cells need to be renewed is still a big challenge. The combination of micro and macroencapsulation approaches could provide the requirements to achieve a proper immunoisolation, while maintaining the cells localized into the body. We present the development and characterization of a porous implantable macrocapsule device for the loading of microencapsulated cells. The device was fabricated in polyamide by selective laser sintering (SLS), with controlled porosity defined by the design and the sintering conditions. Two types of microencapsulated cells were tested in order to evaluate the suitability of this device; erythropoietin (EPO) producing C2C12 myoblasts and Vascular Endothelial Growth Factor (VEGF) producing BHK fibroblasts. Results showed that, even if the metabolic activity of these cells decreased over time, the levels of therapeutic protein that were produced and, importantly, released to the media were stable.