Optometry and Vision Sciences - Research Publications
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ItemHigh Fidelity Bidirectional Neural Interfacing with Carbon Fiber Microelectrodes Coated with Boron-Doped Carbon Nanowalls: An Acute Study(WILEY-V C H VERLAG GMBH, 2020-12)Abstract Implantable electrodes that can communicate with a small, selective group of neurons via both neural stimulation and recording are critical for the development of advanced neuroprosthetic devices. Microfiber electrodes with neuron‐scale cross‐sections have the potential to improve the spatial resolution for both stimulation and recording, while minimizing the chronic inflammation response after implantation. In this work, glass insulated microfiber electrodes are fabricated by coating carbon fibers with boron‐doped carbon nanowalls. The coating significantly improves the electrochemical properties of carbon fibers, leading to a charge injection capacity of 7.82 ± 0.35 mC cm−2, while retaining good flexibility, stability and biocompatibility. When used for neural interfacing, the coated microelectrodes successfully elicit localized stimulation responses in explanted retina, and are also able to detect signals from single neurons, in vivo with a signal‐to‐noise ratio as high as 6.7 in an acute study. This is the first report of using carbon nanowall coated carbon fibers for neural interfacing.
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ItemHybrid diamond/ carbon fiber microelectrodes enable multimodal electrical/chemical neural interfacing(Elsevier, 2020-02-01)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.
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ItemStimulation Strategies for Improving the Resolution of Retinal Prostheses.(Frontiers Media, 2020-03-26)Electrical stimulation using implantable devices with arrays of stimulating electrodes is an emerging therapy for neurological diseases. The performance of these devices depends greatly on their ability to activate populations of neurons with high spatiotemporal resolution. To study electrical stimulation of populations of neurons, retina serves as a useful model because the neural network is arranged in a planar array that is easy to access. Moreover, retinal prostheses are under development to restore vision by replacing the function of damaged light sensitive photoreceptors, which makes retinal research directly relevant for curing blindness. Here we provide a progress review on stimulation strategies developed in recent years to improve the resolution of electrical stimulation in retinal prostheses. We focus on studies performed with explanted retinas, in which electrophysiological techniques are the most advanced. We summarize achievements in improving the spatial and temporal resolution of electrical stimulation of the retina and methods to selectively stimulate neurons with different visual functions. Future directions for retinal prostheses development are also discussed, which could provide insights for other types of neuromodulatory devices in which high-resolution electrical stimulation is required.
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ItemElectrical receptive fields of retinal ganglion cells: Influence of presynaptic neurons(PUBLIC LIBRARY SCIENCE, 2018-02)Implantable retinal stimulators activate surviving neurons to restore a sense of vision in people who have lost their photoreceptors through degenerative diseases. Complex spatial and temporal interactions occur in the retina during multi-electrode stimulation. Due to these complexities, most existing implants activate only a few electrodes at a time, limiting the repertoire of available stimulation patterns. Measuring the spatiotemporal interactions between electrodes and retinal cells, and incorporating them into a model may lead to improved stimulation algorithms that exploit the interactions. Here, we present a computational model that accurately predicts both the spatial and temporal nonlinear interactions of multi-electrode stimulation of rat retinal ganglion cells (RGCs). The model was verified using in vitro recordings of ON, OFF, and ON-OFF RGCs in response to subretinal multi-electrode stimulation with biphasic pulses at three stimulation frequencies (10, 20, 30 Hz). The model gives an estimate of each cell's spatiotemporal electrical receptive fields (ERFs); i.e., the pattern of stimulation leading to excitation or suppression in the neuron. All cells had excitatory ERFs and many also had suppressive sub-regions of their ERFs. We show that the nonlinearities in observed responses arise largely from activation of presynaptic interneurons. When synaptic transmission was blocked, the number of sub-regions of the ERF was reduced, usually to a single excitatory ERF. This suggests that direct cell activation can be modeled accurately by a one-dimensional model with linear interactions between electrodes, whereas indirect stimulation due to summated presynaptic responses is nonlinear.
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ItemTechniques for Processing Eyes Implanted with a Retinal Prosthesis for Localized Histopathological Analysis: Part 2 Epiretinal Implants with Retinal Tacks(JOURNAL OF VISUALIZED EXPERIMENTS, 2015-02)Retinal prostheses for the treatment of certain forms of blindness are gaining traction in clinical trials around the world with commercial devices currently entering the market. In order to evaluate the safety of these devices, in preclinical studies, reliable techniques are needed. However, the hard metal components utilised in some retinal implants are not compatible with traditional histological processes, particularly in consideration for the delicate nature of the surrounding tissue. Here we describe techniques for assessing the health of the eye directly adjacent to a retinal implant secured epiretinally with a metal tack. Retinal prostheses feature electrode arrays in contact with eye tissue. The most commonly used location for implantation is the epiretinal location (posterior chamber of the eye), where the implant is secured to the retina with a metal tack that penetrates all the layers of the eye. Previous methods have not been able to assess the proximal ocular tissue with the tack in situ, due to the inability of traditional histological techniques to cut metal objects. Consequently, it has been difficult to assess localized damage, if present, caused by tack insertion. Therefore, we developed a technique for visualizing the tissue around a retinal tack and implant. We have modified an established technique, used for processing and visualizing hard bony tissue around a cochlear implant, for the soft delicate tissues of the eye. We orientated and embedded the fixed eye tissue, including the implant and retinal tack, in epoxy resin, to stabilise and protect the structure of the sample. Embedded samples were then ground, polished, stained, and imaged under various magnifications at incremental depths through the sample. This technique allowed the reliable assessment of eye tissue integrity and cytoarchitecture adjacent to the metal tack.
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ItemIn vivo biocompatibility of boron doped and nitrogen included conductive-diamond for use in medical implants(WILEY, 2016-01)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.