FPGA design and implementation of a framework for optogenetic retinal prosthesis

PhD ThesisThere are 285 million people worldwide with a visual impairment, 39 million of whom are completely blind and 246 million partially blind, known as low vision patients. In the UK and other developed countries of the west, retinal dystrophy diseases represent the primary cause of blindness, especially Age Related Macular Degeneration (AMD), diabetic retinopathy and Retinitis Pigmentosa (RP). There are various treatments and aids that can help these visual disorders, such as low vision aids, gene therapy and retinal prosthesis. Retinal prostheses consist of four main stages: the input stage (Image Acquisition), the high level processing stage (Image preparation and retinal encoding), low level processing stage (Stimulation controller) and the output stage (Image displaying on the opto-electronic micro-LEDs array). Up to now, a limited number of full hardware implementations have been available for retinal prosthesis. In this work, a photonic stimulation controller was designed and implemented. The main rule of this controller is to enhance framework results in terms of power and time. It involves, first, an even power distributor, which was used to evenly distribute the power through image sub-frames, to avoid a large surge of power, especially with large arrays. Therefore, the overall framework power results are improved. Second, a pulse encoder was used to select different modes of operation for the opto-electronic micro-LEDs array, and as a result of this the overall time for the framework was improved. The implementation is completed using reconfigurable hardware devices, i.e. Field Programmable Gate Arrays (FPGAs), to achieve high performance at an economical price. Moreover, this FPGA-based framework for an optogenetic retinal prosthesis aims to control the opto-electronic micro-LED array in an efficient way, and to interface and link between the opto-electronic micro-LED array hardware architecture and the previously developed high level retinal prosthesis image processing algorithms.University of Jorda

Biomedical Engineering

Biomedical engineering is currently relatively wide scientific area which has been constantly bringing innovations with an objective to support and improve all areas of medicine such as therapy, diagnostics and rehabilitation. It holds a strong position also in natural and biological sciences. In the terms of application, biomedical engineering is present at almost all technical universities where some of them are targeted for the research and development in this area. The presented book brings chosen outputs and results of research and development tasks, often supported by important world or European framework programs or grant agencies. The knowledge and findings from the area of biomaterials, bioelectronics, bioinformatics, biomedical devices and tools or computer support in the processes of diagnostics and therapy are defined in a way that they bring both basic information to a reader and also specific outputs with a possible further use in research and development

Flexible Mems: A Novel Technology To Fabricate Flexible Sensors And Electronics

This dissertation presents the design and fabrication techniques used to fabricate flexible MEMS (Micro Electro Mechanical Systems) devices. MEMS devices and CMOS(Complementary Metal-Oxide-Semiconductor) circuits are traditionally fabricated on rigid substrates with inorganic semiconductor materials such as Silicon. However, it is highly desirable that functional elements like sensors, actuators or micro fluidic components to be fabricated on flexible substrates for a wide variety of applications. Due to the fact that flexible substrate is temperature sensitive, typically only low temperature materials, such as polymers, metals, and organic semiconductor materials, can be directly fabricated on flexible substrates. A novel technology based on XeF2(xenon difluoride) isotropic silicon etching and parylene conformal coating, which is able to monolithically incorporate high temperature materials and fluidic channels, was developed at Wayne State University. The technology was first implemented in the development of out-of-plane parylene microneedle arrays that can be individually addressed by integrated flexible micro-channels. These devices enable the delivery of chemicals with controlled temporal and spatial patterns and allow us to study neurotransmitter-based retinal prosthesis. The technology was further explored by adopting the conventional SOI-CMOS processes. High performance and high density CMOS circuits can be first fabricated on SOI wafers, and then be integrated into flexible substrates. Flexible p-channel MOSFETs (Metal-Oxide-Semiconductor Field-Effect-Transistors) were successfully integrated and tested. Integration of pressure sensors and flow sensors based on single crystal silicon has also been demonstrated. A novel smart yarn technology that enables the invisible integration of sensors and electronics into fabrics has been developed. The most significant advantage of this technology is its post-MEMS and post-CMOS compatibility. Various high-performance MEMS devices and electronics can be integrated into flexible substrates. The potential of our technology is enormous. Many wearable and implantable devices can be developed based on this technology

Microtacks for retinal implant applications.

Age-related macular degeneration (ARMD) and retinitis pigmentosa (RP) are the two leading causes of blindness in the world today. Despite enormous efforts and advances in clinical treatment of eye diseases, there is no established method or cure of degenerative processes in the eye, such as ARMD and RP. In these disorders, the primary cause of blindness is due to the loss of photoreceptors, however, the remaining conductive neural pathways in the inner retina are still intact and functional. As a result, the University of Louisville in collaboration with the Center of Innovative Visual Rehabilitation at the Eye and Ear Infirmary of Harvard University is currently developing a microelectrode array for direct stimulation of the epiretinal surface of the eye. A major problem associated with implantation of the microfabricated device is the inability to secure the implant to the epiretinal surface. To address this issue, our group designed retinal microtacks to attach the microelectrode arrays to the inner surface of the eye. Microtacks were successfully fabricated out of titanium and silicon using ultra-high-precision micromachining and microfabrication methods, respectively. Metrology was performed to verify the accuracy of both fabrication methods. Insertion and retention force experiments were performed on each tack design in fiber reinforced synthetic rubber and porcine eye tissue. Results show that the titanium microtack design required less insertion force and greater removal force than that of the other designs in the fiber reinforced synthetic rubber. The synthetic rubber experiments displayed repeatable results with minimal deviation. The porcine ocular tissue showed poor repeatability with high deviation across all microtack designs

Neuromorphic hardware for somatosensory neuroprostheses

In individuals with sensory-motor impairments, missing limb functions can be restored using neuroprosthetic devices that directly interface with the nervous system. However, restoring the natural tactile experience through electrical neural stimulation requires complex encoding strategies. Indeed, they are presently limited in effectively conveying or restoring tactile sensations by bandwidth constraints. Neuromorphic technology, which mimics the natural behavior of neurons and synapses, holds promise for replicating the encoding of natural touch, potentially informing neurostimulation design. In this perspective, we propose that incorporating neuromorphic technologies into neuroprostheses could be an effective approach for developing more natural human-machine interfaces, potentially leading to advancements in device performance, acceptability, and embeddability. We also highlight ongoing challenges and the required actions to facilitate the future integration of these advanced technologies

Next generation RFID telemetry design for biomedical implants.

The design and development of a Radio Frequency Identification (RFID) based pressure-sensing system to increase the range of current Intra-Ocular Pressure (IOP) sensing systems is described in this dissertation. A large number of current systems use near-field inductive coupling for the transfer of energy and data, which limits the operational range to only a few centimeters and does not allow for continuous monitoring of pressure. Increasing the powering range of the telemetry system will offer the possibility of continuous monitoring since the reader can be attached to a waist belt or put on a night stand when sleeping. The system developed as part of this research operates at Ultra-High Frequencies (UHF) and makes use of the electromagnetic far field to transfer energy and data, which increases the potential range of operation and allows for the use of smaller antennas. The system uses a novel electrically small antenna (ESA) to receive the incident RF signal. A four stage Schottky circuit rectifies and multiplies the received RF signal and provides DC power to a Colpitts oscillator. The oscillator is connected to a pressure sensor and provides an output signal frequency that is proportional to the change in pressure. The system was fabricated using a mature, inexpensive process. The performance of the system compares well with current state of the art, but uses a smaller antenna and a less expensive fabrication process. The system was able to operate over the desired range of 1 m using a half-wave dipole antenna. It was possible to power the system over a range of at least 6.4 cm when the electrically small antenna was used as the receiving antenna

A 16 x 16 CMOS amperometric microelectrode array for simultaneous electrochemical measurements

There is a requirement for an electrochemical sensor technology capable of making multivariate measurements in environmental, healthcare, and manufacturing applications. Here, we present a new device that is highly parallelized with an excellent bandwidth. For the first time, electrochemical cross-talk for a chip-based sensor is defined and characterized. The new CMOS electrochemical sensor chip is capable of simultaneously taking multiple, independent electroanalytical measurements. The chip is structured as an electrochemical cell microarray, comprised of a microelectrode array connected to embedded self-contained potentiostats. Speed and sensitivity are essential in dynamic variable electrochemical systems. Owing to the parallel function of the system, rapid data collection is possible while maintaining an appropriately low-scan rate. By performing multiple, simultaneous cyclic voltammetry scans in each of the electrochemical cells on the chip surface, we are able to show (with a cell-to-cell pitch of 456 μm) that the signal cross-talk is only 12% between nearest neighbors in a ferrocene rich solution. The system opens up the possibility to use multiple independently controlled electrochemical sensors on a single chip for applications in DNA sensing, medical diagnostics, environmental sensing, the food industry, neuronal sensing, and drug discovery

The potential of microelectrode arrays and microelectronics for biomedical research and diagnostics

Planar microelectrode arrays (MEAs) are devices that can be used in biomedical and basic in vitro research to provide extracellular electrophysiological information about biological systems at high spatial and temporal resolution. Complementary metal oxide semiconductor (CMOS) is a technology with which MEAs can be produced on a microscale featuring high spatial resolution and excellent signal-to-noise characteristics. CMOS MEAs are specialized for the analysis of complete electrogenic cellular networks at the cellular or subcellular level in dissociated cultures, organotypic cultures, and acute tissue slices; they can also function as biosensors to detect biochemical events. Models of disease or the response of cellular networks to pharmacological compounds can be studied in vitro, allowing one to investigate pathologies, such as cardiac arrhythmias, memory impairment due to Alzheimer's disease, or vision impairment caused by ganglion cell degeneration in the retin

Data analysis of retinal recordings from multi-electrode arrays under in situ electrical stimulation

The development of retinal implants has become an important field of study in recent years, with increasing numbers of people falling victim to legal or physical blindness as a result of retinal damage. Important weaknesses in current retinal implants include a lack of the resolution necessary to give a patient a viable level of visual acuity, question marks over the amount of power and energy required to deliver adequate stimulation, and the removal of eye movements from the analysis of the visual scene. This thesis documents investigations by the author into a new CMOS stimulation and imaging chip with the potential to overcome these difficulties. An overview is given of the testing and characterisation of the componments incorporated in the device to mimic the normal functioning of the human retina. Its application to in situ experimental studies of frog retina is also described, as well as how the data gathered from these experiments enables the optimisation of the geometry of the electrode array through which the device will interface with the retina. Such optimisation is important as the deposit of excess electrical charge and energy can lead to detrimental medical side effects. Avoidance of such side effects is crucial to the realisation of the next generation of retinal implants

Improving the mechanistic study of neuromuscular diseases through the development of a fully wireless and implantable recording device

Neuromuscular diseases manifest by a handful of known phenotypes affecting the peripheral nerves, skeletal muscle fibers, and neuromuscular junction. Common signs of these diseases include demyelination, myasthenia, atrophy, and aberrant muscle activity—all of which may be tracked over time using one or more electrophysiological markers. Mice, which are the predominant mammalian model for most human diseases, have been used to study congenital neuromuscular diseases for decades. However, our understanding of the mechanisms underlying these pathologies is still incomplete. This is in part due to the lack of instrumentation available to easily collect longitudinal, in vivo electrophysiological activity from mice. There remains a need for a fully wireless, batteryless, and implantable recording system that can be adapted for a variety of electrophysiological measurements and also enable long-term, continuous data collection in very small animals. To meet this need a miniature, chronically implantable device has been developed that is capable of wirelessly coupling energy from electromagnetic fields while implanted within a body. This device can both record and trigger bioelectric events and may be chronically implanted in rodents as small as mice. This grants investigators the ability to continuously observe electrophysiological changes corresponding to disease progression in a single, freely behaving, untethered animal. The fully wireless closed-loop system is an adaptable solution for a range of long-term mechanistic and diagnostic studies in rodent disease models. Its high level of functionality, adjustable parameters, accessible building blocks, reprogrammable firmware, and modular electrode interface offer flexibility that is distinctive among fully implantable recording or stimulating devices. The key significance of this work is that it has generated novel instrumentation in the form of a fully implantable bioelectric recording device having a much higher level of functionality than any other fully wireless system available for mouse work. This has incidentally led to contributions in the areas of wireless power transfer and neural interfaces for upper-limb prosthesis control. Herein the solution space for wireless power transfer is examined including a close inspection of far-field power transfer to implanted bioelectric sensors. Methods of design and characterization for the iterative development of the device are detailed. Furthermore, its performance and utility in remote bioelectric sensing applications is demonstrated with humans, rats, healthy mice, and mouse models for degenerative neuromuscular and motoneuron diseases