Evaluation of chronically implanted subdural boron doped diamond/CNT recording electrodes in miniature swine brain.

When implantable recording devices for brain or neural electrical activity are designed, the number of available materials for electrodes is quite limited. The material must be biocompatible with respect to ISO10993, its electrochemical properties must remain stable and the response of cells or tissues can be mitigated, especially on the glial scar. This involves electrode characterization pre- implantation and impedance spectroscopy during chronic implantation, in order to evaluate both electrode properties and performance. This study was aimed at a comparison of the long-term behavior of a nanostructured boron-doped diamond (BDD) with a nanostructured Platinum Iridium (PtIr) electrode. Firstly, a batch of cortical grids with bare and modified contacts (2 mm in diameter) was engineered for implantation. Secondly a miniature swine model was developed. This study highlighted the predominant role of electrode surface roughness on the quality of recordings. Rough PtIr contacts and BDD coated ones showed comparable behavior after three-month implantation with a slight increase of the modulus of the impedance and a tissue capsule. Nevertheless, immunohistochemistry analysis did not exhibit either a toxic or irritation reaction. With regard to biocompatibility, promising long term results are shown for both materials.

Monitoring the evolution of boron doped porous diamond electrode on flexible retinal implant by OCT and in vivo impedance spectroscopy.

Nanocrystalline Boron doped Diamond proved to be a very attractive material for neural interfacing, especially with the retina, where reduce glia growth is observed with respect to other materials, thus facilitating neuro-stimulation over long terms. In the present study, we integrated diamond microelectrodes on a polyimide substrate and investigated their performances for the development of neural prosthesis. A full description of the microfabrication of the implants is provided and their functionalities are assessed using cyclic voltammetry and electrochemical impedance spectroscopy. A porous structure of the electrode surface was thus revealed and showed promising properties for neural recording or stimulation. Using the flexible implant, we showed that is possible to follow in vivo the evolution of the electric contact between the diamond electrodes and the retina over 4months by using electrochemical impedance spectroscopy. The position of the implant was also monitored by optical coherence tomography to corroborate the information given by the impedance measurements. The results suggest that diamond microelectrodes are very good candidates for retinal prosthesis.

Biocompatibility of nanostructured boron doped diamond for the attachment and proliferation of human neural stem cells.

OBJECTIVE: We quantitatively investigate the biocompatibility of chemical vapour deposited (CVD) nanocrystalline diamond (NCD) after the inclusion of boron, with and without nanostructuring. The nanostructuring method involves a novel approach of growing NCD over carbon nanotubes (CNTs) that act as a 3D scaffold. This nanostructuring of BNCD leads to a material with increased capacitance, and this along with wide electrochemical window makes BNCD an ideal material for neural interface applications, and thus it is essential that their biocompatibility is investigated. APPROACH: Biocompatibility was assessed by observing the interaction of human neural stem cells (hNSCs) with a variety of NCD substrates including un-doped ones, and NCD doped with boron, which are both planar, and nanostructured. hNSCs were chosen due to their sensitivity, and various methods including cell population and confluency were used to quantify biocompatibility. MAIN RESULTS: Boron inclusion into NCD film was shown to have no observable effect on hNSC attachment, proliferation and viability. Furthermore, the biocompatibility of nanostructured boron-doped NCD is increased upon nanostructuring, potentially due to the increased surface area. SIGNIFICANCE: Diamond is an attractive material for supporting the attachment and development of cells as it can show exceptional biocompatibility. When boron is used as a dopant within diamond it becomes a p-type semiconductor, and at high concentrations the diamond becomes quasi-metallic, offering the prospect of a direct electrical device-cell interfacing system.

Synthetic 3D diamond-based electrodes for flexible retinal neuroprostheses: Model, production and in vivo biocompatibility.

Two retinal implants have recently received the CE mark and one has obtained FDA approval for the restoration of useful vision in blind patients. Since the spatial resolution of current vision prostheses is not sufficient for most patients to detect faces or perform activities of daily living, more electrodes with less crosstalk are needed to transfer complex images to the retina. In this study, we modelled planar and three-dimensional (3D) implants with a distant ground or a ground grid, to demonstrate greater spatial resolution with 3D structures. Using such flexible 3D implant prototypes, we showed that the degenerated retina could mould itself to the inside of the wells, thereby isolating bipolar neurons for specific, independent stimulation. To investigate the in vivo biocompatibility of diamond as an electrode or an isolating material, we developed a procedure for depositing diamond onto flexible 3D retinal implants. Taking polyimide 3D implants as a reference, we compared the number of neurones integrating the 3D diamond structures and their ratio to the numbers of all cells, including glial cells. Bipolar neurones were increased whereas there was no increase even a decrease in the total cell number. SEM examinations of implants confirmed the stability of the diamond after its implantation in vivo. This study further demonstrates the potential of 3D designs for increasing the resolution of retinal implants and validates the safety of diamond materials for retinal implants and neuroprostheses in general.

3D-nanostructured boron-doped diamond for microelectrode array neural interfacing.

The electrode material is a key element in the design of long-term neural implants and neuroprostheses. To date, the ideal electrode material offering high longevity, biocompatibility, low-noise recording and high stimulation capabilities remains to be found. We show that 3D-nanostructured boron doped diamond (BDD), an innovative material consisting in a chemically stable material with a high aspect ratio structure obtained by encapsulation of a carbon nanotube template within two BDD nanolayers, allows neural cell attachment, survival and neurite extension. Further, we developed arrays of 20-µm-diameter 3D-nanostructured BDD microelectrodes for neural interfacing. These microelectrodes exhibited low impedances and low intrinsic recording noise levels. In particular, they allowed the detection of low amplitude (10-20 µV) local-field potentials, single units and multiunit bursts neural activity in both acute whole embryonic hindbrain-spinal cord preparations and long-term hippocampal cell cultures. Also, cyclic voltammetry measurements showed a wide potential window of about 3 V and a charge storage capacity of 10 mC.cm(-2), showing high potentiality of this material for neural stimulation. These results demonstrate the attractiveness of 3D-nanostructured BDD as a novel material for neural interfacing, with potential applications for the design of biocompatible neural implants for the exploration and rehabilitation of the nervous system.

Distinctive glial and neuronal interfacing on nanocrystalline diamond.

Direct electrode/neuron interfacing is a key challenge to achieve high resolution of neuronal stimulation required for visual prostheses. Neuronal interfacing on biomaterials commonly requires the presence of glial cells and/or protein coating. Nanocrystalline diamond is a highly mechanically stable biomaterial with a remarkably large potential window for the electrical stimulation of tissues. Using adult retinal cell cultures from rats, we found that glial cells and retinal neurons grew equally well on glass and nanocrystalline diamond. The use of a protein coating increased cell survival, particularly for glial cells. However, bipolar neurons appeared to grow even in direct contact with bare diamond. We investigated whether the presence of glial cells contributed to this direct neuron/diamond interface, by using purified adult retinal ganglion cells to seed diamond and glass surfaces with and without protein coatings. Surprisingly, these fully differentiated spiking neurons survived better on nanocrystalline diamond without any protein coating. This greater survival was indicated by larger cell numbers and the presence of longer neurites. When a protein pattern was drawn on diamond, neurons did not grow preferentially on the coated area, by contrast to their behavior on a patterned glass. This study highlights the interesting biocompatibility properties of nanocrystalline diamond, allowing direct neuronal interfacing, whereas a protein coating was required for glial cell growth.

Tritium labeling of detonation nanodiamonds.

For the first time, the radioactive labeling of detonation nanodiamonds was efficiently achieved using a tritium microwave plasma. According to our measurements, the total radioactivity reaches 9120 ± 120 µCi mg(-1), with 93% of (3)H atoms tightly bonded to the surface and up to 7% embedded into the diamond core. Such (3)H doping will ensure highly stable radiolabeled nanodiamonds, on which surface functionalization is still allowed. This breakthrough opens the way to biodistribution and pharmacokinetics studies of nanodiamonds, while this approach can be scalable to easily treat bulk quantities of nanodiamonds at low cost.

Boron-doped nanocrystalline diamond microelectrode arrays monitor cardiac action potentials.

The expansion of diamond-based electronics in the area of biological interfacing has not been as thoroughly explored as applications in electrochemical sensing. However, the biocompatibility of diamond, large safe electrochemical window, stability, and tunable electronic properties provide opportunities to develop new devices for interfacing with electrogenic cells. Here, the fabrication of microelectrode arrays (MEAs) with boron-doped nanocrystalline diamond (BNCD) electrodes and their interfacing with cardiomyocyte-like HL-1 cells to detect cardiac action potentials are presented. A nonreductive means of structuring doped and undoped diamond on the same substrate is shown. The resulting BNCD electrodes show high stability under mechanical stress generated by the cells. It is shown that by fabricating the entire surface of the MEA with NCD, in patterns of conductive doped, and isolating undoped regions, signal detection may be improved up to four-fold over BNCD electrodes passivated with traditional isolators.

[Restoring vision in blind patients following photoreceptor degeneration: clinical results and future challenges]. / Restaurer la vision de patients aveugles avec des prothèses rétiniennes : Résultats cliniques et défis futurs.

Retinal prostheses aim at restoring vision in patients blind from photoreceptor degeneration by electrically stimulating the residual retinal tissue. Currently, the most efficient implants are either inserted in the subretinal space or on the vitreal side of the retina (epi-retinal). Although the residual tissue can partly degenerate, it was shown that acute stimulation of residual neurones can induce visual percepts. Recently, a clinical trial with the epiretinal Argus2 device (60 electrodes) from the company 2nd Sight enabled most patients to orient and find light targets, some even reading words. This device has received a CE mark. Surprisingly, when the subretinal implant from the company Retina Implant AG displaying many more electrodes (1500 electrodes) was evaluated in clinical trials, the patient visual performances were fairly similar. The restored visual performances of the patients demonstrate that blind patients can recover some visual function when their residual retina is properly stimulated. However, the resolution is not yet sufficient to perform complex tasks such as autonomous locomotion, face identification or text reading. Several challenges remain to generate an increase in pixel density corresponding to the increase in electrode number and density. These challenges include the stimulation modality, the tissue/implant interface design, the electrode materials, and the visual information encoder. This review will discuss these great challenges after introducing the major clinical results.

Surface transfer doping can mediate both colloidal stability and self-assembly of nanodiamonds.

Although undoped diamond is insulating, hydrogenated bulk diamond surfaces exhibit surface conductivity under air and are electrochemically active in aqueous solutions. Due to their large surface/volume ratio, similar surface effects may exhibit a dramatic impact on the properties of nanodiamonds. Here we show that plasma-hydrogenated detonation nanodiamonds (NDs-H) display a positive zeta potential in water due to charge transfer with a redox couple involving oxygen in water. The transfer doping of NDs-H in water can be modulated by pH. Surprisingly, after acid addition, strong Coulomb coupling between NDs-H and adsorbed counterions induces the self-assembly of NDs-H into organized macro-structures reaching millimeter scale.

Design of an electrochemically assisted radiation sensor for α-spectrometry of actinides traces in water.

We describe a new approach for the detection and identification of actinides at low activity levels directly in aqueous solution. The measurement consists initially, in immobilizing alpha emitters in the form of insoluble hydroxides onto the entrance window of an immersed alpha particles detector. For this, a boron doped diamond detector window is negatively polarized to produce a basic layer on its surface by water decomposition. Actinides elements that are known to be very sensitive to hydrolysis are precipitated as solid hydroxides onto the entrance window of the sensor. Due to the absence of an air layer between the radioactive source and the detector, there is no need for vacuum during the alpha spectrometry measurement. After analysis, the detector can be easily cleaned by anodization in the aqueous medium to be reused at once. The minimum detectable activity concentration (MDA) of the system has been evaluated with (241)Am at 0.5 Bq/L for a 0.33 cm(2) area Si PIN diode.

Quasi-real time quantification of uric acid in urine using boron doped diamond microelectrode with in situ cleaning.

We report herein an innovative electrochemical (EC) technique based on boron doped diamond (BDD) microelectrodes which enable the fast determination of uric acid (UA) concentrations in urine. On the basis of fast cyclic voltammetry (CV), the technique was assessed in human urine samples and compared successfully using routine spectrophotometric diagnosis. The approach relies on the use of BDD's superior properties such as low background current, low adsorption of species, long-term stability, and antifouling capabilities using electrochemical reactivation. Moreover, the article also describes an in situ activation technique, where the electrodes were reactivated within human urine, thereby opening the way toward automatic quantification of UA with in situ cleaning. The time taken to quantify UA concentration and cleaning remains below 0.5 s. Two analytic models were derived, based on different concentrations of ascorbic acid (AA) and uric acid, consisting of 2 s order calibration curves. Solving the second order equation enables the direct estimation of UA concentration, and values demonstrated good accuracy when compared with spectrophotometric measurements.

Oxygen hole doping of nanodiamond.

Surface-graphitized nanodiamonds (NDs) are promising hybrid nanomaterials which appear to combine core properties of diamond with surface properties of graphene-based materials. Here we demonstrate that NDs covered by graphene islands, so-called Fullerene-Like Reconstructions (FLRs), are sensitive to hole doping by molecular oxygen in water. NDs covered by FLRs (NDs-FLRs) are prepared by annealing under vacuum of detonation NDs at 750 °C. We propose that oxygen hole doping is promoted on FLRs due to a unique electronic interaction between the diamond core and the outer graphene layer. As a consequence, NDs-FLRs exhibit positive zeta potential in water, unlike NDs surrounded by several graphitic layers. Surface hole-doped NDs may be promising nanomaterials for new electronic and biomedical applications.

Multichannel boron doped nanocrystalline diamond ultramicroelectrode arrays: design, fabrication and characterization.

We report on the fabrication and characterization of an 8 × 8 multichannel Boron Doped Diamond (BDD) ultramicro-electrode array (UMEA). The device combines both the assets of microelectrodes, resulting from conditions in mass transport from the bulk solution toward the electrode, and of BDD's remarkable intrinsic electrochemical properties. The UMEAs were fabricated using an original approach relying on the selective growth of diamond over pre-processed 4 inches silicon substrates. The prepared UMEAs were characterized by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The results demonstrated that the electrodes have exhibited a very fast electrode transfer rate (k(0)) up to 0.05 cm·s(-1) (in a fast redox couple) and on average, a steady state limiting current (in a 0.5 M potassium chloride aqueous solution containing 1 mM Fe(CN)(6)(4-) ion at 100 mV·s(-1)) of 1.8 nA. The UMEAs are targeted for electrophysiological as well as analytical applications.

High sensitivity of diamond resonant microcantilevers for direct detection in liquids as probed by molecular electrostatic surface interactions.

Resonant microcantilevers have demonstrated that they can play an important role in the detection of chemical and biological agents. Molecular interactions with target species on the mechanical microtransducers surface generally induce a change of the beam's bending stiffness, resulting in a shift of the resonance frequency. In most biochemical sensor applications, cantilevers must operate in liquid, even though damping deteriorates the vibrational performances of the transducers. Here we focus on diamond-based microcantilevers since their transducing properties surpass those of other materials. In fact, among a wide range of remarkable features, diamond possesses exceptional mechanical properties enabling the fabrication of cantilever beams with higher resonant frequencies and Q-factors than when made from other conventional materials. Therefore, they appear as one of the top-ranked materials for designing cantilevers operating in liquid media. In this study, we evaluate the resonator sensitivity performances of our diamond microcantilevers using grafted carboxylated alkyl chains as a tool to investigate the subtle changes of surface stiffness as induced by electrostatic interactions. Here, caproic acid was immobilized on the hydrogen-terminated surface of resonant polycrystalline diamond cantilevers using a novel one-step grafting technique that could be also adapted to several other functionalizations. By varying the pH of the solution one could tune the -COO(-)/-COOH ratio of carboxylic acid moieties immobilized on the surface, thus enabling fine variations of the surface stress. We were able to probe the cantilevers resonance frequency evolution and correlate it with the ratio of -COO(-)/-COOH terminations on the functionalized diamond surface and consequently the evolution of the electrostatic potential over the cantilever surface. The approach successfully enabled one to probe variations in cantilevers bending stiffness from several tens to hundreds of millinewtons/meter, thus opening the way for diamond microcantilevers to direct sensing applications in liquids. The evolution of the diamond surface chemistry was also investigated using X-ray photoelectron spectroscopy.

Electrostatic grafting of diamond nanoparticles: a versatile route to nanocrystalline diamond thin films.

Nanodiamond (ND) seeding is a well-established route toward the CVD (chemical vapor deposition) synthesis of diamond ultrathin films. This method is based on the deposition onto a substrate of diamond nanoparticles which act as pre-existing sp(3) seeds. Here, we report on a straightforward method to disperse diamond nanoparticles on a substrate by taking advantage of the electrostatic interactions between the nanodiamonds and the substrate surface coated with a cationic polymer. This layer-by-layer deposition technique leads to reproducible and homogeneous large-scale nanoparticle deposits independent of the substrate's nature and shape. No specific functionalization of the nanoparticles is required, and low concentrated solutions can be used. The density of NDs on the substrate can be controlled, as shown by in situ ATR-FTIR (attenuated total reflection Fourier transform infrared) analysis and QCM (quartz crystal microbalance) measurements. Highly dense and compact ND deposits can be obtained, allowing CVD growth of nanocrystalline diamond ultrathin films (70 nm) on various substrates. The synthesis of 3D structured and patterned diamond thin films has also been demonstrated with this method.

Effect of diamond nucleation process on propagation losses of AlN/diamond SAW filter.

In this work, the effect of a diamond nucleation process on freestanding aluminium nitride (AlN)/diamond surface acoustic wave (SAW) device performances was studied. Before diamond deposition, silicon (Si) substrates have been mechanically nucleated, using an ultrasonic vibration table with submicron diamond slurry, and bias-enhanced nucleated (BEN). Freestanding diamond layers obtained on mechanically scratched Si substrates exhibit a surface roughness of R(MS) = 13 nm, whereas very low surface roughness (as low as R(MS) < or = 1 nm) can be achieved on a freestanding BEN diamond layer. Propagation losses have been measured as a function of the operating frequency for the two nucleation techniques. Dispersion curves of phase velocities and electromechanical coupling coefficient (K2) were determined experimentally and by calculation as a function of normalized thickness AlN film (kh(AlN) = 2pi h(AlN)/lambda). Experimental results show that the propagation losses strongly depend on the nucleation technique, and that these losses are weakly increased with frequency when the BEN technique is used.