Flexible Graphene Solution-Gated Field-Effect Transistors : Efficient Transducers for Micro-Electrocorticography

Brain-computer interfaces and neural prostheses based on the detection of electrocorticography (ECoG) signals are rapidly growing fields of research. Several technologies are currently competing to be the first to reach the market; however, none of them fulfill yet all the requirements of the ideal interface with neurons. Thanks to its biocompatibility, low dimensionality, mechanical flexibility, and electronic properties, graphene is one of the most promising material candidates for neural interfacing. After discussing the operation of graphene solution-gated field-effect transistors (SGFET) and characterizing their performance in saline solution, it is reported here that this technology is suitable for μ-ECoG recordings through studies of spontaneous slow-wave activity, sensory-evoked responses on the visual and auditory cortices, and synchronous activity in a rat model of epilepsy. An in-depth comparison of the signal-to-noise ratio of graphene SGFETs with that of platinum black electrodes confirms that graphene SGFET technology is approaching the performance of state-of-the art neural technologies

Flexible Graphene Solution-Gated Field-Effect Transistors : Efficient Transducers for Micro-Electrocorticography

Brain-computer interfaces and neural prostheses based on the detection of electrocorticography (ECoG) signals are rapidly growing fields of research. Several technologies are currently competing to be the first to reach the market; however, none of them fulfill yet all the requirements of the ideal interface with neurons. Thanks to its biocompatibility, low dimensionality, mechanical flexibility, and electronic properties, graphene is one of the most promising material candidates for neural interfacing. After discussing the operation of graphene solution-gated field-effect transistors (SGFET) and characterizing their performance in saline solution, it is reported here that this technology is suitable for μ-ECoG recordings through studies of spontaneous slow-wave activity, sensory-evoked responses on the visual and auditory cortices, and synchronous activity in a rat model of epilepsy. An in-depth comparison of the signal-to-noise ratio of graphene SGFETs with that of platinum black electrodes confirms that graphene SGFET technology is approaching the performance of state-of-the art neural technologies

Transfer of vertical nanowire arrays on polycaprolactone substrates for biological applications

We used two methods, namely stamping and printing, to transfer arrays of epitaxial gallium phosphide (Gap) nanowires from their growth substrate to a soft, biodegradable layer of polycaprolactone (PCL). Using the stamping method resulted in a very inhomogeneous surface topography with a wide distribution of transferred nanowire lengths, whereas using the printing method resulted in an homogeneous substrate topography over several mm(2). PC12 cells were cultured on the hybrid nanowire-PCL substrates realized using the printing method and exhibited an increased attachment on these substrates, compared to the original nanowire-semiconductor substrate. Transferring nanowires on PCL substrates is promising for implanting nanowires in-vivo with a possible reduced inflammation compared to when hard semi-conductor substrates are implanted together with the nanowires. The nanowire-PCL hybrid substrates could also be used as biocompatible cell culture substrates. Finally, using nanowires on PCL substrates would enable to recycle the expensive GaP substrate and repeatedly grow nanowires on the same substrate. (C) 2015 The Authors. Published by Elsevier B.V

Substrate porosity induces phenotypic alterations in retinal cells cultured on silicon nanowires

Arrays of silicon nanowires (Si NW) may be used in the development of implantable drug delivery systems. Here, we performed short-and long-term cultures of mouse retinal cells on substrates consisting of high aspect ratio Si NW, which confers high porosity to the surface. As controls, cells were grown on flat silicon substrates. The cell phenotype was assessed using immunocytochemistry, fluorescence microscopy and scanning electron microscopy. We observed that, despite good adhesion and long-term survival on Si NW (for at least 18 days in vitro), cells underwent striking phenotypic changes, characterized by the absence of neurites and an underexpression of most retinal cell markers. These alterations could, however, be prevented by functionalizing the surface using perfluorosilane molecules. The study also provides evidence that the altered cell behavior on Si NW can be attributed to contaminants entrapped in the nanowire array. Our data thus indicate that creating high aspect ratio pores, while increasing porosity in order to increase the loading capacity of the substrate, results in neurotoxicity. The functionalized substrates, while allowing for cell growth, would not be suitable for drug delivery. The findings are important for the design of porous silicon-based cell scaffolds and drug delivery systems, in particular when aimed at interfacing CNS cells

Neurite outgrowth and synaptophysin expression of postnatal CNS neurons on GaP nanowire arrays in long-term retinal cell culture.

We have established long-term cultures of postnatal retinal cells on arrays of gallium phosphide nanowires of different geometries. Rod and cone photoreceptors, ganglion cells and bipolar cells survived on the substrates for at least 18 days in vitro. Glial cells were also observed, but these did not overgrow the neuronal population. On nanowires, neurons extended numerous long and branched neurites that expressed the synaptic vesicle marker synaptophysin. The longest nanowires (4 μm long) allowed a greater attachment and neurite elongation and our analysis suggests that the length of the nanowire per se and/or the adsorption of biomolecules on the nanowires may have been important factors regulating the observed cell behavior. The study thus shows that CNS neurons are amenable to gallium phosphide nanowires, probably as they create conditions that more closely resemble those encountered in the in vivo environment. These findings suggest that gallium phosphide nanowires may be considered as a material of interest when improving existing or designing the next generation of implantable devices. The features of gallium phosphide nanowires can be precisely controlled, making them suitable for this purpose

Support of Neuronal Growth Over Glial Growth and Guidance of Optic Nerve Axons by Vertical Nanowire Arrays.

Neural cultures are very useful in neuroscience, providing simpler and better controlled systems than the in vivo situation. Neural tissue contains two main cell types, neurons and glia, and interactions between these are essential for appropriate neuronal development. In neural cultures, glial cells tend to overgrow neurons, limiting the access to neuronal interrogation. There is therefore a pressing need for improved systems that enable a good separation when coculturing neurons and glial cells simultaneously, allowing one to address the neurons unequivocally. Here, we used substrates consisting of dense arrays of vertical nanowires intercalated by flat regions to separate retinal neurons and glial cells in distinct, but neighboring, compartments. We also generated a nanowire patterning capable of guiding optic nerve axons. The results will facilitate the design of surfaces aimed at studying and controlling neuronal networks

Surface nanostructures for fluorescence probing of supported lipid bilayers on reflective substrates.

The fluorescence interference contrast (FLIC) effect prevents the use of fluorescence techniques to probe the continuity and fluidity of supported lipid bilayers on reflective materials due to a lack of detectable fluorescence. Here we show that adding nanostructures onto reflective surfaces to locally confer a certain distance between the deposited fluorophores and the reflecting surface enables fluorescence detection on the nanostuctures. The nanostructures consist of either deposited nanoparticles or epitaxial nanowires directly grown on the substrate and are designed such that they can support a lipid bilayer. This simple method increases the fluorescence signal sufficiently to enable bilayer fluorescence detection and to observe the recovery of fluorescence after photobleaching in order to assess lipid bilayer formation on any reflective surface

Fluid and Highly Curved Model Membranes on Vertical Nanowire Arrays

Sensing and manipulating living cells using vertical nanowire devices requires a complete understanding of cell behavior on these substrates. Changes in cell function and phenotype are often triggered by events taking place at the plasma membrane, the properties of which are influenced by local curvature. The nanowire topography can therefore be expected to greatly affect the cell membrane, emphasizing the importance of studying membranes on vertical nanowire arrays. Here, we used supported phospholipid bilayers as a model for biomembranes. We demonstrate the formation of fluid supported bilayers on vertical nanowire forests using self-assembly from vesicles in solution. The bilayers were found to follow the contours of the nanowires to form continuous and locally highly curved model membranes. Distinct from standard flat supported lipid bilayers, the high aspect ratio of the nanowires results in a large bilayer surface available for the immobilization and study of biomolecules. We used these bilayers to bind a membrane-anchored protein as well as tethered vesicles on the nanowire substrate. The nanowire-bilayer platform shown here can be expanded from fundamental studies of lipid membranes on controlled curvature substrates to the development of innovative membrane-based nanosensors