In vivo feasibility of epiretinal stimulation using ultrananocrystalline diamond electrodes.

OBJECTIVE: Due to their increased proximity to retinal ganglion cells (RGCs), epiretinal visual prostheses present the opportunity for eliciting phosphenes with low thresholds through direct RGC activation. This study characterised the in vivo performance of a novel prototype monolithic epiretinal prosthesis, containing Nitrogen incorporated ultrananocrystalline (N-UNCD) diamond electrodes. APPROACH: A prototype implant containing up to twenty-five 120 × 120 µm N-UNCD electrodes was implanted into 16 anaesthetised cats and attached to the retina either using a single tack or via magnetic coupling with a suprachoroidally placed magnet. Multiunit responses to retinal stimulation using charge-balanced biphasic current pulses were recorded acutely in the visual cortex using a multichannel planar array. Several stimulus parameters were varied including; the stimulating electrode, stimulus polarity, phase duration, return configuration and the number of electrodes stimulated simultaneously. MAIN RESULTS: The rigid nature of the device and its form factor necessitated complex surgical procedures. Surgeries were considered successful in 10/16 animals and cortical responses to single electrode stimulation obtained in eight animals. Clinical imaging and histological outcomes showed severe retinal trauma caused by the device in situ in many instances. Cortical measures were found to significantly depend on the surgical outcomes of individual experiments, phase duration, return configuration and the number of electrodes stimulated simultaneously, but not stimulus polarity. Cortical thresholds were also found to increase over time within an experiment. SIGNIFICANCE: The study successfully demonstrated that an epiretinal prosthesis containing diamond electrodes could produce cortical activity with high precision, albeit only in a small number of cases. Both surgical approaches were highly challenging in terms of reliable and consistent attachment to and stabilisation against the retina, and often resulted in severe retinal trauma. There are key challenges (device form factor and attachment technique) to be resolved for such a device to progress towards clinical application, as current surgical techniques are unable to address these issues.

3D Diamond Electrode Array for High-Acuity Stimulation in Neural Tissue.

Innovations in micro- and nanofabrication technologies enable the manufacture of multielectrode arrays for use in neuromodulation and neural recording. Multielectrode arrays make possible medical implants such as pacemakers, deep-brain stimulators, or visual and hearing aids, to treat numerous neural disorders. An optimal neural interface requires a high density of electrodes to precisely record from and stimulate the nervous system while minimizing the overall size of the array. For example, people with retinal degenerative diseases can benefit from retinal prostheses implanted inside the eye. However, at present the visual acuity provided by such implants is well below the threshold for functional vision, mainly due to the limited spatial resolution. In this work, we present a design of 3D nanostructured conductive diamond electrodes, integrated within a polycrystalline diamond housing, offering a high electrode density and count, which simultaneously satisfies spatial resolution and biocompatibility goals. The array is composed of height adjustable pillar electrodes that are 80 µm in diameter and separated by 150 µm. A holistic characterization of the electrodes was performed and the device tested for stimulation performance in a whole-mounted retina. Electrochemical testing showed impedance of 20 kΩ and a wide water window of 2.47 V. The pillar structure allows the distance between the electrodes and the retinal ganglion cells to be reduced which is key to more confined stimulation at lower current levels, leading to potentially higher-acuity stimulation without damaging retinal tissue.

Hybrid diamond/ carbon fiber microelectrodes enable multimodal electrical/chemical neural interfacing.

Implantable medical devices are now in regular use to treat or ameliorate medical conditions, including movement disorders, chronic pain, cardiac arrhythmias, and hearing or vision loss. Aside from offering alternatives to pharmaceuticals, one major advantage of device therapy is the potential to monitor treatment efficacy, disease progression, and perhaps begin to uncover elusive mechanisms of diseases pathology. In an ideal system, neural stimulation, neural recording, and electrochemical sensing would be conducted by the same electrode in the same anatomical region. Carbon fiber (CF) microelectrodes are the appropriate size to achieve this goal and have shown excellent performance, in vivo. Their electrochemical properties, however, are not suitable for neural stimulation and electrochemical sensing. Here, we present a method to deposit high surface area conducting diamond on CF microelectrodes. This unique hybrid microelectrode is capable of recording single-neuron action potentials, delivering effective electrical stimulation pulses, and exhibits excellent electrochemical dopamine detection. Such electrodes are needed for the next generation of miniaturized, closed-loop implants that can self-tune therapies by monitoring both electrophysiological and biochemical biomarkers.

Direct Electrohydrodynamic Patterning of High-Performance All Metal Oxide Thin-Film Electronics.

In this paper, we propose a scalable approach toward all-printed high-performance metal oxide thin-film transistors (TFTs), using a high-resolution electrohydrodynamic (EHD) printing process. Direct EHD micropatterning of metal oxide TFTs is based on diverse precursor solutions to form semiconducting materials (In2O3, In-Ga-ZnO (IGZO)), conductive metal oxide (Sn-doped In2O3 (ITO)), as well as aluminum oxide (Al2O3) gate dielectric at low temperatures. The fully printed TFT devices exhibit excellent electron transport characteristics (average electron mobilities of up to 117 cm2 V-1 s-1), negligible hysteresis, excellent uniformity, and stable operation at low-operating voltage. Furthermore, integrated logic gates such as NOT and NAND have been printed and demonstrated. All-printed logic with individual gating and symmetric input/output behavior, which is crucial for large-scale integration, is also demonstrated. The devices and fabrication process described in this paper enable high-performance and high-reliability transparent electronics.

Improved visual acuity using a retinal implant and an optimized stimulation strategy.

OBJECTIVE: Retinal prosthetic devices hold great promise for the treatment of retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Through electrical stimulation of the surviving retinal neurons, these devices evoke visual signals that are then relayed to the brain. Currently, the visual prostheses used in clinical trials have few electrodes, thus limiting visual acuity. Electrode arrays with high electrode densities have been developed using novel technologies, including diamond growth and laser machining, and these may provide a more promising route to achieve high visual acuity in blind patients. APPROACH: Here, we studied the potential spatial resolution of electrical stimulation using diamond electrodes. We did this by labeling retinal ganglion cells in whole mount retina with a calcium indicator in wild-type rats and those with retinal degeneration. We imaged the ganglion cell responses to a range of stimulation parameters, including pulse duration and return electrode configuration. MAIN RESULTS: With sub-retinal stimulation, in which electrodes were in contact with the intact or degenerated photoreceptor layer, we found that biphasic pulses of 0.1 ms phase duration and a local return configuration was the most effective in confining the retinal ganglion cell activation patterns, while also remaining within the safety limits of the materials and providing the best power efficiency. SIGNIFICANCE: These results provide an optimized stimulation strategy for retinal implants, which if implemented in a retinal prosthetic is expected to improve the achievable visual acuity.

Electrically conducting diamond films grown on platinum foil for neural stimulation.

OBJECTIVE: With the strong drive towards miniaturization of active implantable medical devices and the need to improve the resolution of neural stimulation arrays, there is keen interest in the manufacture of small electrodes capable of safe, continuous stimulation. Traditional materials such as platinum do not possess the necessary electrochemical properties to stimulate neurons safely when electrodes are very small (i.e. typically less than about 300 µm (78 400 µm2)). While there are several commercially viable alternative electrode materials such as titanium nitride and iridium oxide, an attractive approach is modification of existing Pt arrays via a high electrochemical capacitance material coating. Such a composite electrode could still take advantage of the wide range of fabrication techniques used to make platinum-based devices. The coating, however, must be biocompatible, exhibit good adhesion and ideally be long lasting when implanted in the body. APPROACH: Platinum foils were roughened to various degrees with regular arrays of laser milled pits. Conducting diamond films were grown on the foils by microwave plasma chemical vapor deposition. The adhesion strength of the films to the platinum was assessed by prolonged sonication and accelerated aging. Electrochemical properties were evaluated and compared to previous work. MAIN RESULTS: In line with previous results, diamond coatings increased the charge injection capacity of the platinum foil by more than 300% after functionalization within an oxygen plasma. Roughening of the underlying platinum substrate by laser milling was required to generate strong adhesion between the diamond and the Pt foil. Electrical stress testing, near the limits of safe operation, showed that the diamond films were more electrochemically stable than platinum controls. SIGNIFICANCE: The article describes a new method to protect platinum electrodes from degradation in vivo. A 300% increase in charge injection means that device designers can safely employ diamond coated platinum stimulation electrodes at much smaller sizes and greater density than is possible for platinum.

Fully Solution-Processed Transparent Artificial Neural Network Using Drop-On-Demand Electrohydrodynamic Printing.

Artificial neural networks (ANN), deep learning, and neuromorphic systems are exciting new processing architectures being used to implement a wide variety of intelligent and adaptive systems. To date, these architectures have been primarily realized using traditional complementary metal-oxide-semiconductor (CMOS) processes or otherwise conventional semiconductor fabrication processes. Thus, the high cost associated with the design and fabrication of these circuits has limited the broader scientific community from applying new ideas, and arguably, has slowed research progress in this exciting new area. Solution-processed electronics offer an attractive option for providing low-cost rapid prototyping of neuromorphic devices. This article proposes a novel, wholly solution-based process used to produce low-cost transparent synaptic transistors capable of emulating biological synaptic functioning and thus used to construct ANN. We have demonstrated the fabrication process by constructing an ANN that encodes and decodes a 100 × 100 pixel image. Here, the synaptic weights were configured to achieve the desired image processing functions.

Feasibility of Nitrogen Doped Ultrananocrystalline Diamond Microelectrodes for Electrophysiological Recording From Neural Tissue.

Neural prostheses that can monitor the physiological state of a subject are becoming clinically viable through improvements in the capacity to record from neural tissue. However, a significant limitation of current devices is that it is difficult to fabricate electrode arrays that have both high channel counts and the appropriate electrical properties required for neural recordings. In earlier work, we demonstrated nitrogen doped ultrananocrystalline diamond (N-UNCD) can provide efficacious electrical stimulation of neural tissue, with high charge injection capacity, surface stability and biocompatibility. In this work, we expand on this functionality to show that N-UNCD electrodes can also record from neural tissue owing to its low electrochemical impedance. We show that N-UNCD electrodes are highly flexible in their application, with successful recordings of action potentials from single neurons in an in vitro retina preparation, as well as local field potential responses from in vivo visual cortex tissue. Key properties of N-UNCD films, combined with scalability of electrode array fabrication with custom sizes for recording or stimulation along with integration through vertical interconnects to silicon based integrated circuits, may in future form the basis for the fabrication of versatile closed-loop neural prostheses that can both record and stimulate.

Single crystal diamond membranes for nanoelectronics.

Single crystal, nanoscale diamond membranes are highly sought after for a variety of applications including nanophotonics, nanoelectronics and quantum information science. However, so far, the availability of conductive diamond membranes has remained an unreachable goal. In this work we present a complete nanofabrication methodology for engineering high aspect ratio, electrically active single crystal diamond membranes. The membranes have large lateral directions, exceeding ∼500 × 500 µm2 and are only several hundreds of nanometers thick. We further realize vertical single crystal p-n junctions made from the diamond membranes that exhibit onset voltages of ∼10 V and a current of several mA. Moreover, we deterministically introduce optically active color centers into the membranes, and demonstrate for the first time a single crystal nanoscale diamond LED. The robust and scalable approach to engineer the electrically active single crystal diamond membranes offers new pathways for advanced nanophotonic, nanoelectronic and optomechanical devices employing diamond.

A Silk Fibroin Bio-Transient Solution Processable Memristor.

Today's electronic devices are fabricated using highly toxic materials and processes which limits their applications in environmental sensing applications and mandates complex encapsulation methods in biological and medical applications. This paper proposes a fully resorbable high density bio-compatible and environmentally friendly solution processable memristive crossbar arrays using silk fibroin protein which demonstrated bipolar resistive switching ratio of 104 and possesses programmable device lifetime characteristics before the device gracefully bio-degrades, minimizing impact to environment or to the implanted host. Lactate dehydrogenase assays revealed no cytotoxicity on direct exposure to the fabricated device and support their environmentally friendly and biocompatible claims. Moreover, the correlation between the oxidation state of the cations and their tendency in forming conductive filaments with respect to different active electrode materials has been investigated. The experimental results and the numerical model based on electro-thermal effect shows a tight correspondence in predicting the memristive switching process with various combinations of electrodes which provides insight into the morphological changes of conductive filaments in the silk fibroin films.

Wireless induction coils embedded in diamond for power transfer in medical implants.

Wireless power and data transfer to medical implants is a research area where improvements in current state-of-the-art technologies are needed owing to the continuing efforts for miniaturization. At present, lithographical patterning of evaporated metals is widely used for miniature coil fabrication. This method produces coils that are limited to low micron or nanometer thicknesses leading to high impedance values and thus limiting their potential quality. In the present work we describe a novel technique, whereby trenches were milled into a diamond substrate and filled with silver active braze alloy, enabling the manufacture of small, high cross-section, low impedance microcoils capable of transferring up to 10 mW of power up to a distance of 6 mm. As a substitute for a metallic braze line used for hermetic sealing, a continuous metal loop when placed parallel and close to the coil surface reduced power transfer efficiency by 43%, but not significantly, when placed perpendicular to the microcoil surface. Encapsulation of the coil by growth of a further layer of diamond reduced the quality factor by an average of 38%, which can be largely avoided by prior oxygen plasma treatment. Furthermore, an accelerated ageing test after encapsulation showed that these coils are long lasting. Our results thus collectively highlight the feasibility of fabricating a high-cross section, biocompatible and long lasting miniaturized microcoil that could be used in either a neural recording or neuromuscular stimulation device.

Nanomechanical Sensing Using Spins in Diamond.

Nanomechanical sensors and quantum nanosensors are two rapidly developing technologies that have diverse interdisciplinary applications in biological and chemical analysis and microscopy. For example, nanomechanical sensors based upon nanoelectromechanical systems (NEMS) have demonstrated chip-scale mass spectrometry capable of detecting single macromolecules, such as proteins. Quantum nanosensors based upon electron spins of negatively charged nitrogen-vacancy (NV) centers in diamond have demonstrated diverse modes of nanometrology, including single molecule magnetic resonance spectroscopy. Here, we report the first step toward combining these two complementary technologies in the form of diamond nanomechanical structures containing NV centers. We establish the principles for nanomechanical sensing using such nanospin-mechanical sensors (NSMS) and assess their potential for mass spectrometry and force microscopy. We predict that NSMS are able to provide unprecedented AC force images of cellular biomechanics and to not only detect the mass of a single macromolecule but also image its distribution. When combined with the other nanometrology modes of the NV center, NSMS potentially offer unparalleled analytical power at the nanoscale.

Diamond Devices for High Acuity Prosthetic Vision.

Retinal implants restore a sense of vision, for a growing number of users worldwide. Nevertheless, visual acuities provided by the current generation of devices are low. The quantity of information transferable to the retina using existing implant technologies is limited, far below receptor cells' capabilities. Many agree that increasing the information density deliverable by a retinal prosthesis requires devices with stimulation electrodes that are both dense and numerous. This work describes a new generation of retinal prostheses capable of upscaling the information density conveyable to the retina. Centered on engineered diamond materials, the implant is very well tolerated and long-term stable in the eye's unique physiological environment and capable of delivering highly versatile stimulation waveforms - both key attributes in providing useful vision. Delivery of high-density information, close to the retina with the flexibility to alter stimulation parameters in situ provides the best chance for success in providing high acuity prosthetic vision.

Optimizing growth and post treatment of diamond for high capacitance neural interfaces.

Electrochemical and biological properties are two crucial criteria in the selection of the materials to be used as electrodes for neural interfaces. For neural stimulation, materials are required to exhibit high capacitance and to form intimate contact with neurons for eliciting effective neural responses at acceptably low voltages. Here we report on a new high capacitance material fabricated using nitrogen included ultrananocrystalline diamond (N-UNCD). After exposure to oxygen plasma for 3 h, the activated N-UNCD exhibited extremely high electrochemical capacitance greater than 1 mF/cm(2), which originates from the special hybrid sp(2)/sp(3) structure of N-UNCD. The in vitro biocompatibility of the activated N-UNCD was then assessed using rat cortical neurons and surface roughness was found to be critical for healthy neuron growth, with best results observed on surfaces with a roughness of approximately 20 nm. Therefore, by using oxygen plasma activated N-UNCD with appropriate surface roughness, and considering the chemical and mechanical stability of diamond, the fabricated neural interfaces are expected to exhibit high efficacy, long-term stability and a healthy neuron/electrode interface.

Scalable Fabrication of Integrated Nanophotonic Circuits on Arrays of Thin Single Crystal Diamond Membrane Windows.

Diamond has emerged as a promising platform for nanophotonic, optical, and quantum technologies. High-quality, single crystalline substrates of acceptable size are a prerequisite to meet the demanding requirements on low-level impurities and low absorption loss when targeting large photonic circuits. Here, we describe a scalable fabrication method for single crystal diamond membrane windows that achieves three major goals with one fabrication method: providing high quality diamond, as confirmed by Raman spectroscopy; achieving homogeneously thin membranes, enabled by ion implantation; and providing compatibility with established planar fabrication via lithography and vertical etching. On such suspended diamond membranes we demonstrate a suite of photonic components as building blocks for nanophotonic circuits. Monolithic grating couplers are used to efficiently couple light between photonic circuits and optical fibers. In waveguide coupled optical ring resonators, we find loaded quality factors up to 66 000 at a wavelength of 1560 nm, corresponding to propagation loss below 7.2 dB/cm. Our approach holds promise for the scalable implementation of future diamond quantum photonic technologies and all-diamond photonic metrology tools.

Magneto-optical imaging of thin magnetic films using spins in diamond.

Imaging the fields of magnetic materials provides crucial insight into the physical and chemical processes surrounding magnetism, and has been a key ingredient in the spectacular development of magnetic data storage. Existing approaches using the magneto-optic Kerr effect, x-ray and electron microscopy have limitations that constrain further development, and there is increasing demand for imaging and characterisation of magnetic phenomena in real time with high spatial resolution. Here we show how the magneto-optical response of an array of negatively-charged nitrogen-vacancy spins in diamond can be used to image and map the sub-micron stray magnetic field patterns from thin ferromagnetic films. Using optically detected magnetic resonance, we demonstrate wide-field magnetic imaging over 100 × 100 µm(2) with sub-micron spatial resolution at video frame rates, under ambient conditions. We demonstrate an all-optical spin relaxation contrast imaging approach which can image magnetic structures in the absence of an applied microwave field. Straightforward extensions promise imaging with sub-µT sensitivity and sub-optical spatial and millisecond temporal resolution. This work establishes practical diamond-based wide-field microscopy for rapid high-sensitivity characterisation and imaging of magnetic samples, with the capability for investigating magnetic phenomena such as domain wall and skyrmion dynamics and the spin Hall effect in metals.

Scalable fabrication of high-quality, ultra-thin single crystal diamond membrane windows.

High quality, ultra-thin single crystal diamond (SCD) membranes that have a thickness in the sub-micron range are of extreme importance as a materials platform for photonics, quantum sensing, nano/micro electro-mechanical systems (N/MEMS) and other diverse applications. However, the scalable fabrication of such thin SCD membranes is a challenging process. In this paper, we demonstrate a new method which enables high quality, large size (∼4 × 4 mm) and low surface roughness, low strain, ultra-thin SCD membranes which can be fabricated without deformations such as breakage, bowing or bending. These membranes are easy to handle making them particularly suitable for fabrication of optical and mechanical devices. We demonstrate arrays of single crystal diamond membrane windows (SCDMW), each up to 1 × 1 mm in dimension and as thin as ∼300 nm, supported by a diamond frame as thick as ∼150 µm. The fabrication method is robust, reproducible, scalable and cost effective. Microwave plasma chemical vapour deposition is used for in situ creation of single nitrogen-vacancy (NV) centers into the thin SCDMW. We have also developed SCD drum head mechanical resonator composed of our fully clamped and freely suspended membranes.

Direct fabrication of 3D graphene on nanoporous anodic alumina by plasma-enhanced chemical vapor deposition.

High surface area electrode materials are of interest for a wide range of potential applications such as super-capacitors and electrochemical cells. This paper describes a fabrication method of three-dimensional (3D) graphene conformally coated on nanoporous insulating substrate with uniform nanopore size. 3D graphene films were formed by controlled graphitization of diamond-like amorphous carbon precursor films, deposited by plasma-enhanced chemical vapour deposition (PECVD). Plasma-assisted graphitization was found to produce better quality graphene than a simple thermal graphitization process. The resulting 3D graphene/amorphous carbon/alumina structure has a very high surface area, good electrical conductivity and exhibits excellent chemically stability, providing a good material platform for electrochemical applications. Consequently very large electrochemical capacitance values, as high as 2.1 mF for a sample of 10 mm(3), were achieved. The electrochemical capacitance of the material exhibits a dependence on bias voltage, a phenomenon observed by other groups when studying graphene quantum capacitance. The plasma-assisted graphitization, which dominates the graphitization process, is analyzed and discussed in detail.

Development of a Magnetic Attachment Method for Bionic Eye Applications.

Successful visual prostheses require stable, long-term attachment. Epiretinal prostheses, in particular, require attachment methods to fix the prosthesis onto the retina. The most common method is fixation with a retinal tack; however, tacks cause retinal trauma, and surgical proficiency is important to ensure optimal placement of the prosthesis near the macula. Accordingly, alternate attachment methods are required. In this study, we detail a novel method of magnetic attachment for an epiretinal prosthesis using two prostheses components positioned on opposing sides of the retina. The magnetic attachment technique was piloted in a feline animal model (chronic, nonrecovery implantation). We also detail a new method to reliably control the magnet coupling force using heat. It was found that the force exerted upon the tissue that separates the two components could be minimized as the measured force is proportionately smaller at the working distance. We thus detail, for the first time, a surgical method using customized magnets to position and affix an epiretinal prosthesis on the retina. The position of the epiretinal prosthesis is reliable, and its location on the retina is accurately controlled by the placement of a secondary magnet in the suprachoroidal location. The electrode position above the retina is less than 50 microns at the center of the device, although there were pressure points seen at the two edges due to curvature misalignment. The degree of retinal compression found in this study was unacceptably high; nevertheless, the normal structure of the retina remained intact under the electrodes.

In vivo biocompatibility of boron doped and nitrogen included conductive-diamond for use in medical implants.

Recently, there has been interest in investigating diamond as a material for use in biomedical implants. Diamond can be rendered electrically conducting by doping with boron or nitrogen. This has led to inclusion of boron doped and nitrogen included diamond elements as electrodes and/or feedthroughs for medical implants. As these conductive device elements are not encapsulated, there is a need to establish their clinical safety for use in implants. This article compares the biocompatibility of electrically conducting boron doped diamond (BDD) and nitrogen included diamond films and electrically insulating poly crystalline diamond films against a silicone negative control and a BDD sample treated with stannous octoate as a positive control. Samples were surgically implanted into the back muscle of a guinea pig for a period of 4-15 weeks, excised and the implant site sectioned and submitted for histological analysis. All forms of diamond exhibited a similar or lower thickness of fibrotic tissue encapsulating compared to the silicone negative control samples. All forms of diamond exhibited similar or lower levels of acute, chronic inflammatory, and foreign body responses compared to the silicone negative control indicating that the materials are well tolerated in vivo.