La nanoélectronique pour l'interfaçage neuronal : des nanofils de silicium à des dispositifs de carbone

In line with the technological progress of last decades a variety of adapted bioelectrical interfaces was developed to record electrical activity from the nervous system reaching from whole brain activity to single neuron signaling. Although neural interfaces have reached clinical utility and are commonly used in fundamental neuroscience, their performance is still limited. In this work we investigated alternative materials and techniques, which could improve the monitoring of neuronal activity of cultured networks, and the long-term performance of prospective neuroprosthetics. While silicon nanowire transistor arrays and diamond based microelectrodes are proposed for improving the spatial resolution and the electrode stability in biological environment respectively, the main focus of this thesis is set on the evaluation of graphene based field effect transistor arrays for bioelectronics. Due to its outstanding electrical, mechanical and chemical properties graphene appears as a promising candidate for the realization of chemically stable flexible electronics required for long-term neural interfacing. Here we demonstrate the outstanding neural affinity of pristine graphene and the realization of highly sensitive fast graphene transistors for neural interfaces.Dans la lignée des progrès technologiques récents en électronique, ces dernières décennies ont vu l’émergence d’une variété de systèmes permettant l’interface bioélectronique, allant de la mesure de l’activité électrique émise par l’ensemble du cerveau jusqu’à la mesure du signal émis par un neurone unique. Bien que des interfaces électroniques avec les neurones ont montré leur utilité pour des applications cliniques et sont communément utilisés par les neurosciences fondamentales, leurs performances sont encore très limitées, notamment en raison de l’incompatibilité relative entre les systèmes à l’état solide et le vivant. Dans ce travail de thèse, nous avons étudié des techniques et des matériaux nouveaux permettant une approche alternative et qui pourraient améliorer le suivi de l’activité de réseaux de neurones cultivés in situ et à terme la performance des neuroprothèses in vivo. Dans ce travail, des réseaux de nanofils de silicium et des microélectrodes en diamant sont élaborés pour respectivement améliorer la résolution spatiale et la stabilité des électrodes dans un environnement biologique. Un point important de cette thèse est également l’évaluation des performances de transistors à effet de champ en graphène pour la bio électronique. En raison des performances remarquables et combinées sur les aspects électrique, mécanique et chimique du graphène, ce matériau apparaît comme un candidat très prometteur pour la réalisation d’une électronique permettant une interface stable et sensible avec un réseau de neurones. Nous montrons dans ce travail l’affinité exceptionnelle des neurones avec une surface de graphène brut et la réalisation d’une électronique de détection rapide et sensible à base de transistor en graphène

Impact of crystalline quality on neuronal affinity of pristine graphene

International audienceDue to its outstanding mechanical and electrical properties as well as chemical inertness, graphene has attracted a growing interest in the field of bioelectric interfacing. Herein, we investigate the suitability of pristine, i.e. without a cell adhesive coating, chemical vapor deposition (CVD) grown monolayer graphene to act as a platform for neuronal growth. We study the development of primary hippocampal neurons grown on bare graphene (transferred on glass coverslip) for up to 5 days and show that pristine graphene significantly improves the neurons adhesion and outgrowth at the early stage of culture (1-2 days in vitro). At the later development stage, neurons grown on coating free graphene (untreated with poly-L-lysine) show remarkably well developed neuritic architecture similar to those cultured on conventional poly-L-lysine coated glass coverslips. This exceptional possibility to bypass the adhesive coating allows a direct electrical contact of graphene to the cells and reveals its great potential for chronic medical implants and tissue engineering. Moreover, regarding the controversial results obtained on the neuronal affinity of pristine graphene and its ability to support neuronal growth without the need of polymer or protein coating, we found that the crystallinity of CVD grown graphene play an important role in neuronal attachment, outgrowth and axonal growth. In particular, we show that the decreasing crystalline quality of graphene tunes the neuronal affinity from highly adhesive to fully repellent

Recording Spikes Activity in Cultured Hippocampal Neurons Using Flexible or Transparent Graphene Transistors

International audienceThe emergence of nanoelectronics applied to neural interfaces has started few decades ago, and aims to provide new tools for replacing or restoring disabled functions of the nervous systems as well as further understanding the evolution of such complex organization. As the same time, graphene and other 2D materials have offered new possibilities for integrating micro and nano-devices on flexible, transparent, and biocompatible substrates, promising for bio and neuro-electronics. In addition to many bio-suitable features of graphene interface, such as, chemical inertness and anti-corrosive properties, its optical transparency enables multimodal approach of neuronal based systems, the electrical layer being compatible with additional microfluidics and optical manipulation ports. The convergence of these fields will provide a next generation of neural interfaces for the reliable detection of single spike and record with high fidelity activity patterns of neural networks. Here, we report on the fabrication of graphene field effect transistors (G-FETs) on various substrates (silicon, sapphire, glass coverslips, and polyimide deposited onto Si/SiO 2 substrates), exhibiting high sensitivity (4 mS/V, close to the Dirac point at V LG < V D) and low noise level (10 −22 A 2 /Hz, at V LG = 0 V). We demonstrate the in vitro detection of the spontaneous activity of hippocampal neurons in-situ-grown on top of the graphene sensors during several weeks in a millimeter size PDMS fluidics chamber (8 mm wide). These results provide an advance toward the realization of biocompatible devices for reliable and high spatio-temporal sensing of neuronal activity for both in vitro and in vivo applications

Sensing ion channel in neuron networks with graphene field effect transistors

Graphene, the atomically-thin honeycomb carbon lattice, is a highly conducting 2D material whose exposed electronic structure offers an ideal platform for chemical and biological sensing. Its biocompatible, flexible and chemically inert nature associated with the lack of dangling bonds, offers novel perspectives for direct interfacing with biological molecules. Combined with its exceptional electronic and optical properties, this promotes graphene as a unique platform for bioelectronics. Among the successful bio-integrations of graphene, the detection of action potentials in numerous electrogenic cells including neurons has paved the road for the high spatio-temporal and wide-field mapping of neuronal activity. Ultimate resolution of sensing ion channel activity can be achieved with neural interfaces, and it was shown that macroscale electrodes can record extracellular current of individual ion channels in model systems, by charging the quantum capacitance of large graphene monolayer (mm). Here, we show the field effect detection of ion channel activity within neuron networks, cultured during several weeks above graphene transistor arrays. Dependences upon drugs, reference potential gating and device geometry confirm the field effect detection of individual ion channel and suggest a significant contribution of grain boundaries, which provide highly sensitive nanoscale-sized sensing sites. Our theoretical analysis and simulations demonstrate that the ion gating of a single grain boundary in liquid affects the electronic transmission of the whole transistor channel, resulting in significant conductance variations. Monitoring the ion channels activity is of great interest as most of neurodegenerative diseases relied on channelopathies, which rely on ion channel abnormal activity. Thus, such highly sensitive and biocompatible neuro-electronics which open the way to FET detection at the sub-cell precision should be useful for a wide range of fundamental and applied research areas, including brain-on-chip, pharmacology, and in vivo monitoring or diagnosis

Sensing ion channel in neuron networks with graphene field effect transistors

Graphene, the atomically-thin honeycomb carbon lattice, is a highly conducting 2D material whose exposed electronic structure offers an ideal platform for chemical and biological sensing. Its biocompatible, flexible and chemically inert nature associated with the lack of dangling bonds, offers novel perspectives for direct interfacing with biological molecules. Combined with its exceptional electronic and optical properties, this promotes graphene as a unique platform for bioelectronics. Among the successful bio-integrations of graphene, the detection of action potentials in numerous electrogenic cells including neurons has paved the road for the high spatio-temporal and wide-field mapping of neuronal activity. Ultimate resolution of sensing ion channel activity can be achieved with neural interfaces, and it was shown that macroscale electrodes can record extracellular current of individual ion channels in model systems, by charging the quantum capacitance of large graphene monolayer (mm2). Here, we show the field effect detection of ion channel activity within neuron networks, cultured during several weeks above graphene transistor arrays. Dependences upon drugs, reference potential gating and device geometry confirm the field effect detection of individual ion channel and suggest a significant contribution of grain boundaries, which provide highly sensitive nanoscale-sized sensing sites. Our theoretical analysis and simulations demonstrate that the ion gating of a single grain boundary in liquid affects the electronic transmission of the whole transistor channel, resulting in significant conductance variations. Monitoring the ion channels activity is of great interest as most of neurodegenerative diseases relied on channelopathies, which rely on ion channel abnormal activity. Thus, such highly sensitive and biocompatible neuro-electronics which open the way to FET detection at the sub-cell precision should be useful for a wide range of fundamental and applied research areas, including brain-on-chip, pharmacology, and in vivo monitoring or diagnosis.The authors gratefully acknowledge financial support from the University Joseph Fourrier (SMINGUE project), from la Région Rhône-Alpes (COOPERA project), and from the french Agence Nationale de la Recherche under the projects ANR-10-LABX-51-01 (Labex LANEF du Programme d'Investissements d'Avenir) the Lab Alliances on Nanosciences—Energies for the Future. ICN2 is supported by the CERCA programme/Generalitat de Catalunya. And the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (Project No. FIS2015-67767-P MINECO/FEDER), MINECO (Grant No. SEV-2013-0295) and funded by the CERCA Programme/Generalitat de Catalunya. The authors acknowledge the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (Project No. FIS2015-67767-P MINECO/FEDER).Peer reviewe

Graphene for sensing ion channels in neuron networks

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Introducing a biomimetic coating for graphene neuroelectronics: toward in-vivo applications

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