Optimization of pillar electrodes in subretinal prosthesis for enhanced proximity to target neurons

OBJECTIVE: High-resolution prosthetic vision requires dense stimulating arrays with small electrodes. However, such miniaturization reduces electrode capacitance and penetration of electric field into tissue. We evaluate potential solutions to these problems with subretinal implants based on utilization of pillar electrodes. APPROACH: To study integration of three-dimensional (3D) implants with retinal tissue, we fabricated arrays with varying pillar diameter, pitch, and height, and implanted beneath the degenerate retina in rats (Royal College of Surgeons, RCS). Tissue integration was evaluated six weeks post-op using histology and whole-mount confocal fluorescence imaging. The electric field generated by various electrode configurations was calculated in COMSOL, and stimulation thresholds assessed using a model of network-mediated retinal response. MAIN RESULTS: Retinal tissue migrated into the space between pillars with no visible gliosis in 90% of implanted arrays. Pillars with 10 μm height reached the middle of the inner nuclear layer (INL), while 22 μm pillars reached the upper portion of the INL. Electroplated pillars with dome-shaped caps increase the active electrode surface area. Selective deposition of sputtered iridium oxide onto the cap ensures localization of the current injection to the pillar top, obviating the need to insulate the pillar sidewall. According to computational model, pillars having a cathodic return electrode above the INL and active anodic ring electrode at the surface of the implant would enable six times lower stimulation threshold, compared to planar arrays with circumferential return, but suffer from greater cross-talk between the neighboring pixels. SIGNIFICANCE: 3D electrodes in subretinal prostheses help reduce electrode-tissue separation and decrease stimulation thresholds to enable smaller pixels, and thereby improve visual acuity of prosthetic vision

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

Optical Methods in Sensing and Imaging for Medical and Biological Applications

The recent advances in optical sources and detectors have opened up new opportunities for sensing and imaging techniques which can be successfully used in biomedical and healthcare applications. This book, entitled ‘Optical Methods in Sensing and Imaging for Medical and Biological Applications’, focuses on various aspects of the research and development related to these areas. The book will be a valuable source of information presenting the recent advances in optical methods and novel techniques, as well as their applications in the fields of biomedicine and healthcare, to anyone interested in this subject

Self-folding 3D micro antennas for implantable medical devices

Tese de Doutoramento em Engenharia Biomédica.Recent advances in device miniaturization have been enabling smart and small implantable medical devices. These are often powered by bulky batteries whose dimensions represent one of the major bottlenecks on further device miniaturization. However, alternative powering methods, such as electromagnetic waves, do not rely on stored energy and are capable of providing high energy densities per unit of area, thus increasing the potential for device miniaturization. Hence, we envision an implanted medical device with an integrated miniaturized antenna, capable of receiving a radiofrequency signal from an exterior source, and converting it to a DC signal, thus enabling remote powering. This thesis addresses the analysis, design, fabrication and characterization of novel 3D micro antennas that can be integrated on 500 × 500 × 500 μm3 cubic devices, and used for wireless power transfer purposes. The analysis is built upon the theory of electrically small antennas in lossy media, and the antenna design takes into consideration miniaturization techniques which are compatible with the antenna fabrication process. For the antenna fabrication, a methodology that combines conventional planar photolithography techniques and self-folding was used. While photolithography allows the easy patterning of virtually every desired planar antenna configuration with reproducible feature precision, and the flexibility to easily and precisely change the antenna geometry and size, self-folding allows assembly of the fabricated planar patterns into a 3D structure in a highly parallel and scalable manner. After fabrication, we characterized the fabricated antennas by measuring their S-parameters and radiation patterns, demonstrating their efficacy at 2 GHz when immersed in dispersive media such as water. This step required the development and test of multiple characterization setups based on connectors, RF probes and transmission lines and the use of an anechoic chamber. Moreover, we successfully show that the antennas can wireless transfer energy to power an LED, highlighting a proof of concept for practical applications. Our findings suggest that self-folding micro antennas could provide a viable solution for powering tiny micro devices.Os recentes avanços das tecnologias de miniaturização têm permitido o desenvolvimento de dispositivos médicos implantáveis inteligentes e mais pequenos. Estes são muitas vezes alimentados por baterias volumosas cujas dimensões limitam o nível de miniaturização alcançável por um micro dispositivo. No entanto, existem formas alternativas de alimentar estes dispositivos que não dependem de energia armazenada, tais como ondas eletromagnéticas, que são capazes de providenciar uma elevada densidade de energia por unidade de área, aumentando assim o potencial de miniaturização dos dispositivos. Desta forma, visionamos um dispositivo médico implantado, com uma antena miniaturizada e integrada, capaz de receber um sinal de rádio frequência a partir de uma fonte externa, e convertê-lo num sinal DC, permitindo assim a alimentação remota do aparelho. Esta tese apresenta a análise, desenho, fabrico e caracterização de micro antenas 3D, passíveis de serem integradas em micro dispositivos cúbicos (500 × 500 × 500 μm3), e utilizadas para fins de transferência de energia sem fios. A análise assenta na teoria das antenas eletricamente pequenas em meios com perdas, e o design da antena considera técnicas de miniaturização de antenas. Para o fabrico da antena foi utilizada uma metodologia que combina técnicas de fotolitografia planar e auto-dodragem (self-folding). Enquanto a fotolitografia permite a padronização de virtualmente todos os tipos de configurações planares de forma precisa, reprodutível, e com a flexibilidade para se mudar rapidamente a geometria e o tamanho da antena, o self-folding permite a assemblagem dos painéis planares fabricados numa estrutura 3D. Depois do fabrico, as antenas foram caracterizadas medindo os seus parâmetros S e diagramas de radiação, demonstrando a sua eficácia a 2 GHz quando imersas num meio dispersivo, tal como água. Esta etapa exigiu o desenvolvimento e teste de várias setups de caracterização com base em conectores, sondas de RF e linhas de transmissão, e ainda o uso de uma câmara anecóica. Além disso, mostramos com sucesso que as micro antenas podem receber e transferir o energia para um LED acendendo-o, destacando assim esta prova de conceito para aplicações práticas. Os nossos resultados sugerem que estas micro antenas auto-dobráveis podem fornecer uma solução viável para alimentar micro dispositivos implantáveis muito pequenos.Fundação para a Ciência e a Tecnologia (FCT) bolsa SFRH/BD/63737/2009

Novel CAD/CAM rapid prototyping of next-generation biomedical devices

An aging population with growing healthcare needs demands multifaceted tools for diagnosis and treatment of health conditions. In the near-future, drug-administration devices, implantable devices/sensors, enhanced prosthesis, artificial and unique functional tissue constructs will become increasingly significant. Conventional technologies for mass-produced implants do not adequately take individual patient anatomy into consideration. Development of novel CAD/CAM rapid prototyping techniques may significantly accelerate progress of these devices for next-generation patient-care. In this dissertation, several novel rapid prototyping techniques have been introduced for next-generation biomedical applications. Two-photon polymerization was developed to microfabricate scaffolds for tissue engineering, microneedles for drugdelivery and ossicular replacement prostheses. Various photoplymers were evaluated for feasibility, mechanical properties, cytotoxicity, and surface properties. Laser direct write using MDW was utilized for developing microstructures of bioceramics such as hydroxyapatite, and viable mammalian osteosarcoma cells. CAD/CAM laser micromachining (CLM) was developed to engineer biointerfaces as surface recognition regions for differential adherence of cells and growth into tissue-like networks. CLM was also developed for engineering multi-cellular vascular networks. Cytotoxic evaluations and growth studies demonstrated VEGF-induced proliferation of HAAE-1 human aortic endothelial cells with inhibition of HA-VSMC human aortic smooth muscle cells. Finally, piiezoelectric inkjet printing was developed for controlled administration of natural and synthetic adhesives to overcome several problems associated with conventional tissue bonding materials, and greatly improve wound repair in next generation eye repair, fracture fixation, organ fixation, wound closure, tissue engineering, and drug delivery devices

Antenna Systems

This book offers an up-to-date and comprehensive review of modern antenna systems and their applications in the fields of contemporary wireless systems. It constitutes a useful resource of new material, including stochastic versus ray tracing wireless channel modeling for 5G and V2X applications and implantable devices. Chapters discuss modern metalens antennas in microwaves, terahertz, and optical domain. Moreover, the book presents new material on antenna arrays for 5G massive MIMO beamforming. Finally, it discusses new methods, devices, and technologies to enhance the performance of antenna systems

NASA Tech Briefs, September 1993

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