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This thesis presents multiple characterization techniques applied to various organic materials with the ultimate goal of unraveling their structure-properties relationship once encapsulated as active materials in OFETs devices. Particular care is then dedicated to the structural characterization methods (2D-GIXRD, XRR and XRD) both from classical laboratory source and from synchrotron radiation. Various organic materials, comprising p- and n-type small molecules and polymers deposited from solution or by vacuum sublimation are investigated. In particular, the study on OFETs based two functionalized perylene isomers differing only in the shape of the alkyl side-chians demonstrates how the branched and asymmetric nature of the chains can lead to an improvement of the electrical performance with a simple post-deposition thermal treatment, while the fabrication of ambipolar polymeric devices by means of Langmir-Schaefer technique highligts the importance of the deposition method on the arrangement of the material on the substrate surface. A more unusual approach, named in-situ and real-time structural investigation, is also presented to evaluate structural modifications in organic thin films undergoing a particular process. Specifically, the structural responce of pentacene thin films to the application of VSG and VSD to the OFET and of TTF derivatives thin films to the variation of humidty were investigated.; Cette thèse présents plusieurs techniques de caractérisation appliqués à diverses matières organiques dans le but de démêler leur structure-propriétés relation once encapsulés comme matériaux actifs dans les dispositifs de OFET. Un soin particulier est alors dédié aux méthodes de caractérisation structurale (2D-GIXRD, XRR et XRD) à la fois de source de laboratoire classique et de rayonnement de synchrotron. Divers matériaux polymères organiques, compris de p- et n-type de petites molécules et polymères en solution ou déposés par sublimation sous vide sont étudiées. En particulier, l'étude de OFET basée sur deux fonctionnalisés isomères péryléne ne différant que par la forme des alkyle côté chaînes démontre comment la nature ramifié et asymétrique des chaînes peut conduire à une amélioration de la performance électrique avec un simple traitement thermique post-dépôt, tandis que la fabrication de dispositifs ambipolaire polymères au moyen de la technique Langmuir-Schaefer souligne l'importance de la méthode de dépôt sur l'agencement de la matière sur la surface du substrat. Une approche inhabituelle, nommé enquête structurelle in_situ et en temps réel, est aussi présenté pour évaluer les modifications structurelles dans les films minces organiques subissent un processus particulier. Plus précisément, la réponse de la structure des films minces de pentacene à l’application de VSG et VSD au OFET et des films minces dérivés de TTF à la variation d’humidité ont été étudiés.

Retinal prostheses have been developed to fight blindness in people affected by outer retinal layer dystrophies. To date, few hundred patients have received a retinal implant. Inspired by intraocular lenses, we have designed a foldable and photovoltaic wide-field epiretinal prosthesis (named POLYRETINA) capable of stimulating wireless retinal ganglion cells. Here we show that within a visual angle of 46.3 degrees, POLYRETINA embeds 2215 stimulating pixels, of which 967 are in the central area of 5 mm, it is foldable to allow implantation through a small scleral incision, and it has a hemispherical shape to match the curvature of the eye. We demonstrate that it is not cytotoxic and respects optical and thermal safety standards; accelerated ageing shows a lifetime of at least 2 years. POLYRETINA represents significant progress towards the improvement of both visual acuity and visual field with the same device, a current challenging issue in the field.

Transient electronics is a recent challenging research field aiming at the realization of functional electronic devices able to disappear in a controlled and predefined manner. Amongst different applications, biomedical devices based on transient technology have raised a lot of interest. Their ability to dissolve within the biological environment, thus avoiding infections due to a prolonged stay and risks related to surgical retrieval, is their main appealing characteristic. In many cases the device relies on silicon-based electronics, but the incorporation of polymers in the design, mostly as flexible substrate or for drug-release purposes, is becoming more and more exploited. Due to the intrinsic versatility of polymeric materials, which potentially allow for a great variety of customized application and fabrication techniques, fully polymer-based transient electronic devices represent the natural step forward in this research area. We therefore intend to contribute to the progress in the field of transient electronics by fabricating probes for neural signal recording based on biocompatible and biodegradable polymers, both as substrate and active material, thus introducing the edible neuroprosthetics concept. In the specific case, we relied on Polycaprolactone (PCL) or Poly Lactic-co-Glycolic Acid (PLGA) as substrate and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (Pedot:PSS) as conductive conjugated polymer. With these materials as building blocks, a series of passive neural probes were fabricated and implanted in mice brains (visual cortex area) to assess their in-vivo durability. Several time-points (1, 3, 6 and 9 months) have been established for the implants analysis in order to have a better comprehension of the degradation process within the biological environment and the response of the biological environment itself to the insertion of an external object. Preliminary results show that after one month of implantation the astrocytes are visibly activated as expected, whereas there is no evidence of activated microglia. In the near future, implantation of active neural probes will give insight also on the recording capacity of the devices.

Recording and stimulation of brain circuits have been widely used to treat neurological disorders, such as epilepsy1 and Parkinson’s disease2. Current available techniques in this field commonly require invasive surgery potentially entailing both transient and permanent complications3. A promising strategy designed to overcome4these risks involves the exploitation of the cerebrovascular system as access route of the neural tissue . Electrodes mounted on wires and catheters have been used as recording systems since early 1970s and the results have been proved to be comparable to those achieved via established methods6. On the other hand, deep brain stimulation (DBS) performed with an endovascular approach has only been studied at a computational level, by Teplitzky et al. showing the possible targets for an endovascular stimulation. In their study, it is also suggested the replacement of wire electrodes with ring ones, as these provide a better adaptation to the vessel walls, reducing the distance to the target and improving the neural activation7. Thus, the exploitation of stenting technology, exceptionally designed to adhere to blood vessel walls, represents an optimal scaffold for the recording/stimulating system. Oxley et al. mounted electrodes on commercially available, self-expandable Nitinol stents and pursued preliminary studies on sheep. Their results were comparable to those obtained with epidural electrodes arrays. However, device fractures owed to repetitive neck movements and chewing muscle artifacts were reported. Moreover, permanent metallic implants usually lead to delayed endothelialization, chronic local inflammation and thrombogencity8. A promising solution to minimize these drawbacks is the use of soft, biocompatible and biodegradable polymers, able to adapt to complex geometries and absorb impacts. Therefore, we designed a novel neurovascular interface where 6 electrodes and their interconnects made of (3‐glycidyloxypropyl)trimethoxysilane-doped poly(3,4-ethylenedioxythiophene) : poly(styrenesulfonate) (GOPS-doped PEDOT:PSS) are embedded in poly-ε-caprolaptone (PCL). The given shape (Fig. 1A) allows easy folding of the device inside tubes (Fig. 1C) for smooth in situ deployment. The 6 electrodes are placed at the struts junctions that can hold diameters up to 700μm (Fig. 1B). In summary, this innovative device entirely made of biodegradable and biocompatible materials will offer an alternative solution to the invasive techniques currently used for neural recording and brain stimulation. Its development potentially will have a huge impact in the treatment of neuropathological conditions.

Fighting blindness with retinal prostheses requires challenges not yet achieved: implanting a prosthesis (i) large enough to cover the retinal surface and (ii) embedding a high number of highly dense stimulatory elements. We developed an injectable, self-opening, and freestanding prosthesis restoring at least 40° of visual field, therefore covering at least a retinal surface of 12 mm in diameter. Moreover, the prosthesis has a hemispherical shape in order to minimize the distance from the targeted cells over its entire surface. It also operates according to a photovoltaic stimulation principle and it should be injected trough a minimal scleral incision. Our implant is based on PDMS as shell material, embedding 2345 organic photovoltaic stimulating pixels made of conjugated polymers (100 µm and 150 µm in diameter, density 54 px/mm2), with a biomimetic distribution in an active area of 13 mm (44° of visual field). Our results indicate that those pixels can deliver up to 54 mA/cm2 and generate an electrode potential of 182 mV when illuminated with a pulse light of 10 ms, 32 µW/mm2, at 530 nm. Accelerated aging tests and experiments with explanted retinas are currently under evaluation. These preliminary results show the potential of organic photovoltaics in the fabrication of a retinal prosthesis with large area and high stimulation efficiency. The biocompatibility and mechanical compliance of the materials represent a step forward in building advanced photovoltaic retinal prostheses.

Bioelectronic and neuroprosthetic interfaces rely on implanted microelectrode arrays (MEAs) to interact with the human body. Printing techniques, such as inkjet and screen printing, are attractive methods for the manufacturing of MEAs because they allow flexible, room-temperature, scalable, and cost-effective fabrication processes. Herein, the fabrication of all-printed electrocorticography arrays made by inkjet printing of platinum and screen printing of polyimide is shown. Next, mechanical and electrochemical characterizations are performed. As a proof of concept, in vivo visually evoked cortical potentials are recorded in rabbits upon flash stimulation. Lastly, it is shown that the all-printed electrocorticography arrays are not cytotoxic. Altogether, the results enable the use of printed MEAs for neurological applications.

Retinal prostheses have become in the past decade a promising and realistic technology to restore vision. Nonetheless, sight restoration with retinal prostheses in a clinically relevant perspective requires resolution and implantation challenges not yet achieved. Our goal is the development of a foldable and wide field-retinal prosthesis capable of achieving a wireless photovoltaic stimulation of retinal ganglion cells and restore at least 40° of visual field, though being injectable trough minimal incision. The 2345 organic photovoltaic stimulating pixels of our retina prosthesis are distributed into biomimetic pattern within an active area of 13 mm (44° of visual field) and the light-triggered current profile generated by those pixels shows a reproducible ability to elicit activity in explanted rodents’ retinas mimicking human retina dystrophies. Extracellular recordings of prosthetic-evoked spiking activity of retinal ganglion cells reveal both direct and network-mediated stimulation when the degenerating retina circuit is explanted on top of the stimulating device, while when retinas are layered on bare PDMS substrates, any light-evoked pattern of response can be detected among retina spontaneous activity. Screening of different conditions of illumination (pulse duration and intensity) with Rd10 retinas explanted on our prosthesis shows a direct activation from the minimal radiant exposure tested - that is 7 times smaller than the maximum permissible retinal irradiance allowed for ophthalmic applications in this case- while network-mediated activation requires higher light exposure and can be supressed using synaptic blockers. The clinical compliance of the so-designed prosthesis and those preliminary results on explanted retinas represent a step forward in building wide-field photovoltaic retinal prostheses.

A major obstacle to make retinal prostheses a realistic technology to restore a functional form of vision allowing normal mobility is the low resolution achieved by current devices. Aims. Using photovoltaic pixels based on organic materials, we aimed at building a wireless high-density epiretinal prosthesis able to restore a theoretical visual acuity of 20/600. Our high-resolution stimulation device also makes it possible to dissect the retinal circuitry activation under spatially confined stimulus to further investigate the mechanisms of neural response clustering. Methods. Extracellular recordings of photovoltaic prosthetic-evoked spiking activity were conducted on explanted Rd10 mice retinas upon increasing exposure conditions. A quantitative analysis of RGCs’ direct and indirect activation thresholds was performed using a custom-made MEA. Both square pulses and continuous photovoltage profiles, measured on top of photovoltaic pixels, were used as stimulation waveforms. Results. Direct and network-mediated light-evoked responses were both detected in retinas explanted on the photovoltaic pixels. Moreover, significant differences in the activation thresholds were observed between photovoltage pulses and square pulses injection. Conclusions. Both photovoltaic stimulation and electrical injection of light-triggered voltage profiles elicited a reproducible activity in explanted dystrophic retinas. Besides, the use of capacitive voltage profiles generated by the photovoltaic device enabled to lower the threshold for INL-mediated RGCs activation. Our results provide interesting insights for the use of non-diraquien pulses in neural tissues stimulation. They also suggest that the promotion of epiretinal indirect RGCs’ excitation could have a beneficial effect on the spatial confinement of the neural retina’s response to prosthetic stimulation.

Purpose:In the past decade, retinal prostheses emerged as promising technology to restore a primitive, although clinically useful, form of vision. However, fighting blindness with retinal prostheses require challenges not yet achieved. From a clinical perspective, sight restoration requires to reach two main goals: enlarging the visual field of the patient and improving its visual acuity. From the engineering point of view, these needs demand the overcoming of two major issues: implanting a prosthesis (i) large enough to cover the retinal surface and (ii) embedding a high number of highly dense stimulatory elements. Our goal is the development of an injectable, self-opening, and freestanding retinal prosthesis restoring at least 40° of visual field, therefore covering at least a retinal surface of 12 mm in diameter. Moreover, the prosthesis must have a hemispherical shape in order to minimize the distance from the targeted cells over its entire surface, it should operate according to a photovoltaic stimulation principle and it must be injected trough a minimal scleral incision. Methods:Using solution processes and micro-fabrication techniques, we designed a retinal prosthesis based on polydimethylsiloxane (PDMS) as shell material, embedding photovoltaic pixels made of conjugated polymers. The prosthesis is shaped with a molding technique. Results:The prosthesis consists in a photovoltaic PDMS-interface, embedding 2345 organic stimulating pixels (100 µm and 150 µm in diameter, density 54.34 px/mm2) with a biomimetic distribution in an active area of 13 mm (44° of visual field). Our results indicate that those photovoltaic pixels can deliver up to 54.22±10.55 mA/cm2 and generate an electrode potential of 182.22±6.72 mV when illuminated with a pulse light of 10 ms, 32.47 µW/mm2, at 530 nm. Sample tested n = 20. Accelerated aging tests and experiments with explanted retinas are currently under evaluation. Conclusions:These preliminary results show the potential of organic photovoltaic technology in the fabrication of a retinal prosthesis with large surface area and high stimulation efficiency. The biocompatibility and mechanical compliance of the materials represent an additional step forward in building advanced photovoltaic retinal prostheses.

A polymer-based optoelectronic interface comprises an elastomeric substrate (10) and a plurality of discrete photovoltaic pixel elements (20) disposed on top of the substrate. Each pixel element comprises at least one active layer comprising a semiconducting polymer or polymer mixture. The pixel elements are excitable by light to generate an electric signal via a photovoltaic process. For mechanically protecting the pixel elements, an elastomeric encapsulation layer (30) can be disposed on top of the substrate, the encapsulation layer defining access openings (31) for the pixel elements (20). Pillar-like structures (40) can be disposed on the pixel elements. Methods for fabricating such an optoelectronic interface are also disclosed. The optoelectronic interface can be used as a retinal prosthesis.

© 2015 American Chemical Society. Thin films of organic semiconductors have been widely studied at different length scales for improving the electrical response of devices based on them. Hitherto, a lot of knowledge has been gained about how molecular packing, morphology, grain boundaries, and defects affect the charge transport in organic thin film transistors. However, little is known about the impact of an electric field on the organic semiconductor microstructure and the consequent effect on the device performances. To fill this gap, we investigated the evolution of the structure of pentacene thin film transistors during device operation by in situ real time X-ray diffraction measurements and theoretical calculations. We observed for the first time the occurrence of a reversible structural strain taking place during the bias application mainly due to reorientation at the terrace edges of monolayer islands under the effect of electrical field. Strain exhibits the same trend of the threshold voltage hinting to the existence of a direct correlation between the phenomenon of bias stress and the structural modification., The authors acknowledge A. Shehu for his collaboration at the early stage of the project, F. Borgatti for the fruitful discussion, J. R. Plaisier, G. Zerauschek and A. Lausi for optimizing the experimental setup at the MCX-ELETTRA beamline, and V. L.R. Jacques and P. Evans for technical support at the ID01-ESRF beamline. Financial support for this research was by the National Project N−CHEM, Flagship NANOMAX, by the DGI (Spain) with Project BE-WELL CTQ2013-40480-R, Generalitat de Catalunya (2014-SGR-17), the ERC StG 2012-306826, and by the Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBERBBN).