David J. Garrett

Electrical stimulation of retinal ganglion cells with diamond and the development of an all diamond retinal prosthesis

Electronic retinal implants for the blind are already a market reality. A world wide effort is underway to find the technology that offers the best combination of performance and safety for potential patients. Our approach is to construct an epi-retinally targeted device entirely encapsulated in diamond to maximise longevity and biocompatibility. The stimulating array of our device comprises a monolith of electrically insulating diamond with thousands of hermetic, microscale nitrogen doped ultra-nanocrystalline diamond (N-UNCD) feedthroughs. Here we seek to establish whether the conducting diamond feedthroughs of the array can be used as stimulating electrodes without further modification with a more traditional neural stimulation material. Efficacious stimulation of retinal ganglion cells was established using single N-UNCD microelectrodes in contact with perfused, explanted, rat retina. Evoked rat retinal ganglion cell action potentials were recorded by patch clamp recording from single ganglion cells, adjacent to the N-UNCD stimulating electrode. Separately, excellent electrochemical stability of N-UNCD was established by prolonged pulsing in phosphate buffered saline at increasing charge density up to the measured charge injection limit for the material.

Ultra-nanocrystalline diamond electrodes: optimization towards neural stimulation applications

Diamond is well known to possess many favourable qualities for implantation into living tissue including biocompatibility, biostability, and for some applications hardness. However, conducting diamond has not, to date, been exploited in neural stimulation electrodes due to very low electrochemical double layer capacitance values that have been previously reported. Here we present electrochemical characterization of ultra-nanocrystalline diamond electrodes grown in the presence of nitrogen (N-UNCD) that exhibit charge injection capacity values as high as 163 µC cm(-2) indicating that N-UNCD is a viable material for microelectrode fabrication. Furthermore, we show that the maximum charge injection of N-UNCD can be increased by tailoring growth conditions and by subsequent electrochemical activation. For applications requiring yet higher charge injection, we show that N-UNCD electrodes can be readily metalized with platinum or iridium, further increasing charge injection capacity. Using such materials an implantable neural stimulation device fabricated from a single piece of bio-permanent material becomes feasible. This has significant advantages in terms of the physical stability and hermeticity of a long-term bionic implant.

A Simple Approach to Patterned Protein Immobilization on Silicon via Electrografting from Diazonium Salt Solutions

A highly versatile method utilizing diazonium salt chemistry has been developed for the fabrication of protein arrays. Conventional ultraviolet mask lithography was used to pattern micrometer sized regions into a commercial photoresist on a highly doped p-type silicon (100) substrate. These patterned regions were used as a template for the electrochemical grafting of the in situ generated p-aminobenzenediazonium cation to form patterns of aminophenyl film on silicon. Immobilization of biomolecules was demonstrated by coupling biotin to the aminophenyl regions followed by reaction with fluorescently labeled avidin and visualization with fluorescence microscopy. This simple patterning strategy is promising for future application in biosensor devices.

Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity

High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions.

Patterning of metal, carbon, and semiconductor substrates with thin organic films by microcontact printing with aryldiazonium salt inks.

Surface modification through reduction of aryldiazonium salts to give covalently attached layers is a widely investigated procedure. However, realization of potential applications of the layers requires development of patterning methods. Here, we demonstrate that microcontact printing with poly(dimethylsiloxane) stamps inked with aqueous acid solutions of aryldiazonium salts gives stable organic layers on gold, copper, silicon, and graphitic carbon surfaces. Depending on the substrate-diazonium salt combination, the layers range from relatively irregular multilayers to smooth films with close to monolayer thickness. After printing, surface attached aminophenyl and carboxyphenyl groups retain their usual reactivity toward amide bond formation with solution species, and hence, the method is a simple route to patterned, covalently attached, reactive tether layers. Multicomponent patterned films can be prepared by printing a second modifier onto a film-coated surface. Microcontact printing using aryldiazonium salt inks is experimentally very simple and is applicable to the broad range of substrates capable of spontaneously reducing aryldiazonium salts.

Electron transfer from Proteus vulgaris to a covalently assembled, single walled carbon nanotube electrode functionalised with osmium bipyridine complex: application to a whole cell biosensor.

We report the fabrication and use of electrodes constructed from single walled carbon nanotubes (SWCNTs) chemically assembled on a carbon surface and functionalised with an osmium(II) bipyridine complex (Osbpy). The ability of the electrodes to transduce biologically generated currents from Proteus vulgaris has been established. Our investigations show that there are two contributions to the current: one from electroactive species secreted into solution and another from cell redox sites. The modified electrode can be used to monitor cell metabolism, thereby acting as a whole cell biosensor. The biosensor was used in a 1-h assay to investigate the toxicity of ethanol, sodium azide and the antibiotic ampicillin and gave quantitative data that were closely correlated with standard cell plate viability assays. The results provide proof of principle that the whole cell biosensor could be used for high throughput screening of antimicrobial activity. One of the modified electrodes was used for approximately 1000 measurements over four months demonstrating the robustness of the system.

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.

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 mm3, 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.

Optimizing the Electrical Stimulation of Retinal Ganglion Cells

Epiretinal prostheses aim to restore visual perception in the blind through electrical stimulation of surviving retinal ganglion cells (RGCs). While the effects of several waveform parameters (e.g., phase duration) on stimulation efficacy have been described, their relative influence remains unclear. Further, morphological differences between RGC classes represent a key source of variability that has not been accounted for in previous studies. Here we investigate the effect of electrical stimulus waveform parameters on activation of an anatomically homogenous RGC population and describe a technique for identifying optimal stimulus parameters to minimize the required stimulus charge. Responses of rat A2-type RGCs to a broad array of biphasic stimulation parameters, delivered via an epiretinal stimulating electrode (200 × 200 μm) were recorded using whole-cell current clamp techniques. The data demonstrate that for rectangular charge-balanced stimuli, phase duration and polarity have the largest effect on threshold current amplitude-cells were most responsive to cathodic-first pulses of short phase duration. Waveform asymmetry and increases in interphase interval further reduced thresholds. Using optimal waveform parameters, we observed a drop in stimulus efficacy with increasing stimulation frequency. This was more pronounced for large cells. Our results demonstrate that careful choice of electrical waveform parameters can significantly improve the efficacy of electrical stimulation and the efficacy of implantable neurostimulators for the retina.

Crystal structure and magnetism of a well isolated 2D-quantum Heisenberg antiferromagnet, (Quinolinium)(2)CuBr(4).2H(2)O, and its anhydrous form.

Reaction of quinoline with HBr and CuBr(2) generates a mixture of two compounds, (quinolinium)(2)CuBr(4).2H(2)O (1) and (quinolinium)(2)CuBr(4) (2) for which single-crystal X-ray structures have been solved. Compound 1 crystallizes in the monoclinic space group C2/c as layers of tetrabromocuprate ions which are separated by intervening layers of quinolinium ions. Compound 2 crystallizes in the triclinic space group P1. Magnetic data analysis reveals that 1 behaves as a 2D-quantum Heisenberg antiferromagnet with 2J/k(B) = -6.17(3) K within the layers. High field magnetization data at low temperatures suggests that T(N) must be less than 1.8 K for 1, yielding a figure of merit |k(B)T(N)/2J| < 0.29, which indicates excellent isolation between the layers. Magnetic exchange in compound 2 was much weaker and was fit to a linear chain antiferromagnet with 2J/k(B) = -1.59(3) K.