3-Dimensional Intracortical Neural Interface For The Study Of Epilepsy

Epilepsy is a chronic disease characterized by recurrent, unprovoked seizures, where seizures are described as storms of uncontrollable neuro-electrical activity within the brain. Seizures are therefore identified by observation of electrical spiking observed through electrical contacts (electrodes) placed on the scalp or the cortex above the epileptic regions. Current epilepsy research is identifying several specific molecular markers that appear at specific layers of the epilepsy-affected cortex. However, technology is limited in allowing for live observation of electrical spiking across these layers. The underlying hypothesis of this project is that electrical interictal activity is generated in a layer- and lateral-specific pattern. This work reports a novel neural probe technology for the manufacturing of 3D arrays of electrodes with integrated microchannels. This new technology is based on a silicon island structure and a simple folding procedure. This method simplifies the assembly or packaging process of 3D neural probes, leading to higher yield and lower cost. Various types of 3D arrays of electrodes, including acute and chronic devices, have been successfully developed. Microchannels have been successfully integrated into the 3D neural probes via isotropic XeF2 gas phase etching and a parylene resealing process. This work describes in detail the development of neural devices targeted towards the study of layer-specific interictal discharges in an animal model of epilepsy. Devices were designed utilizing parameters derived from the rat model of epilepsy. The progression of device design is described from 1st prototype to final chronic device. The fabrication process and potential pitfall are described in detail. Devices have been characterized by SEM (scanning electron microscope) imaging, optical imaging, various types of impedance analysis, and AFM (atomic force microscopy) characterization of the electrode surface. Flow characteristics of the microchannels were also analyzed. Various animal tests have been carried out to demonstrate the recording functionality of the probes, preliminary biocompatibility studies, and the reliability of the final chronic device package. These devices are expected to be of great use to the study of epilepsy as well as various other neurological diseases

Ono: an open platform for social robotics

In recent times, the focal point of research in robotics has shifted from industrial ro- bots toward robots that interact with humans in an intuitive and safe manner. This evolution has resulted in the subfield of social robotics, which pertains to robots that function in a human environment and that can communicate with humans in an int- uitive way, e.g. with facial expressions. Social robots have the potential to impact many different aspects of our lives, but one particularly promising application is the use of robots in therapy, such as the treatment of children with autism. Unfortunately, many of the existing social robots are neither suited for practical use in therapy nor for large scale studies, mainly because they are expensive, one-of-a-kind robots that are hard to modify to suit a specific need. We created Ono, a social robotics platform, to tackle these issues. Ono is composed entirely from off-the-shelf components and cheap materials, and can be built at a local FabLab at the fraction of the cost of other robots. Ono is also entirely open source and the modular design further encourages modification and reuse of parts of the platform

Roadmap on semiconductor-cell biointerfaces.

This roadmap outlines the role semiconductor-based materials play in understanding the complex biophysical dynamics at multiple length scales, as well as the design and implementation of next-generation electronic, optoelectronic, and mechanical devices for biointerfaces. The roadmap emphasizes the advantages of semiconductor building blocks in interfacing, monitoring, and manipulating the activity of biological components, and discusses the possibility of using active semiconductor-cell interfaces for discovering new signaling processes in the biological world

The rise of flexible electronics in neuroscience, from materials selection to in vitro and in vivo applications

Neuroscience deals with one of the most complicate system we can study: the brain. The huge amount of connections among the cells and the different phenomena occurring at different scale give rise to a continuous flow of data that have to be collected, analyzed and interpreted. Neuroscientists try to interrogate this complexity to find basic principles underlying brain electrochemical signalling and human/animal behaviour to disclose the mechanisms that trigger neurodegenerative diseases and to understand how restoring damaged brain circuits. The main tool to perform these tasks is a neural interface, a system able to interact with brain tissue at different levels to provide a uni/bidirectional communication path. Recently, breakthroughs coming from various disciplines have been combined to enforce features and potentialities of neural interfaces. Among the different findings, flexible electronics is playing a pivotal role in revolutionizing neural interfaces. In this work, we review the most recent advances in the fabrication of neural interfaces based on flexible electronics. We define challenges and issues to be solved for the application of such platforms and we discuss the different parts of the system regarding improvements in materials selection and breakthrough in applications both for in vitro and in vivo tests

MEMS-based Lab-on-chip platform with integrated 3D and planar microelectrodes for organotypic and cell cultures

La presente tesis doctoral se centra en el desarrollo y la validación de plataformas lab on chip (LOC) para su aplicación en el campo de la Biología, la Medicina y la Biomedicina, particularmente relacionados con el cultivo de células y tejidos, así como su tratamiento mediante electroestimulación y su actividad eléctrica. Actualmente, las investigaciones centradas en el desarrollo de LOCs han experimentado un crecimiento considerable, gracias, en gran medida, a la versatilidad que ofrecen. Dicha versatilidad se traduce en numerosas aplicaciones, de las cuales, aquellas relacionadas con la Biología y la Medicina, están alcanzando especial relevancia. La integración de sensores, actuadores, circuitos microfluídicos y circuitos electrónicos en la misma plataforma, permite fabricar sistemas con múltiples aplicaciones. Esta tesis se centra fundamentalmente en el desarrollo de plataformas para el cultivo in vitro de tejidos y células, así como para la monitorización y la interacción con dicho cultivo. Los cultivos in vitro resultan de vital importancia para realizar estudios en células o tejidos, experimentar con medicamentos o estudiar su proliferación y morfología. De esta manera, se cubriría la creciente necesidad de encontrar una alternativa para replicar modelos humanos de enfermedades in vitro para poder desarrollar nuevos fármacos y avanzar en la medicina personalizada. Por tanto, la posibilidad de realizar cultivos de media o larga duración en plataformas que no precisen de un equipamiento costoso como las incubadoras de CO2 y que puedan ser monitorizadas mediante aplicaciones ópticas, supone un salto cualitativo en el desarrollo de los cultivos in vitro. En este contexto, se presenta el trabajo relacionado con esta tesis que ha sido desarrollada dentro del grupo de Microsistemas de la Escuela Superior de Ingeniería de la Universidad de Sevilla. La tesis está estructurada de manera que a lo largo de este escrito se da respuesta a los distintos aspectos anteriormente descritos. En primer lugar, se hace una breve introducción a la tecnología MEMS y a los principios básicos de la microfluídica. Dado que este trabajo se ha desarrollado en un ambiente multidisciplinar, esta sección resulta necesaria para dar una visión general a aquellos no familiarizados con esta disciplina. Tras esa introducción se realiza una descripción del estado del arte en el que se encuadra este trabajo, incluyendo los sistemas LoCs, y sus principales aplicaciones en el campo de la Biología, Medicina y Biomedicina, prestando especial atención a las aplicaciones de los LoCs relacionadas con cultivos organotípicos y de células. Tras la introducción y el estado del arte en el que se enmarca la tesis, se explican los resultados obtenidos durante este trabajo. Durante la primera parte, se describe el desarrollo, fabricación y caracterización de un sistema autónomo para el cultivo y electroestimulación de tejidos que integra un lab on PCB (LOP) formado por un array de microelectrodos en 3D (MEA) formado por hilos de oro de 25 µm en sustrato transparente, sensores y actuadores, junto con una plataforma microfluídica fabricada en metacrilato (PMMA) y polidimetilsiloxano (PDMS). El LOP permite mantener las condiciones de temperatura idóneas para llevar a cabo cultivos de media-larga duración sin necesidad de usar incubadoras deCO2 , así como su seguimiento de forma continua a través de un microscopio, gracias al uso de materiales transparentes. Este sistema también incluye una electrónica suplementaria y un programa que permite la monitorización del sistema y la electrostimulación de la muestra biológica. Tras explicar detalladamente el diseño y el novedoso proceso de fabricación del LOP, se presentan los resultados experimentales. En primer lugar, se ha demostrado que es posible desarrollar cultivos organotípicos de retinas de ratón durante más de 7 días, obteniendo resultados muy similares a los conseguidos para las mismas muestras biológicas, pero mediante métodos de cultivo tradicionales. Además, se ha logrado la neuro-protección mediante la electroestimulación de retinas de ratón con la enfermedad de la retinosis pigmentaria, logrando de esta manera ralentizar la degeneración de la muestra debido a la enfermedad. Otra de las aplicaciones que se quiere conseguir con el desarrollo del LOP anteriormente descrito se centra en la adquisición de señales eléctricas procedentes de las muestras biológicas cultivadas en el dispositivo, así como extrapolar su uso a cultivos celulares. Para la adquisición de señales procedentes del cultivo, la impedancia de los electrodos fabricados con hilos de oro de 25 µm ha resultado ser demasiado alta como para discernir entre el ruido base y la actividad eléctrica del cultivo. Por ello, la segunda parte de esta tesis doctoral se centra en la mejora de la MEA para la adquisición de actividad eléctrica. Dado el objetivo marcado en esta segunda parte, durante esta tesis se ha realizado una estancia en la Universidad de Bath. En dicha estancia, se ha caracterizado la actividad eléctrica de células del cáncer de próstata (PC-3), que fueron cultivadas en chips de silicio con electrodos de oro. La experiencia obtenida durante la estancia ha permitido avanzar en el desarrollo y la fabricación de nuevas MEAs para la adquisción de señales eléctricas de cultivos celulares. La primera aproximación para mejorar la MEA se ha realizado sobre PCB. Se trata de un dispositivo compuesto por pilares de oro en 3D fabricados mediante la técnica de Resumen XXV electroplating. Estos electrodos tienen 100 µm de diámetro y una altura de 25 µm que aseguran el contacto en el caso de cultivos de tejidos. Se ha demostrado una mejora significativa, traducida tanto en una impedancia más baja, como en una línea base de ruido menor con respecto a la MEA con hilos de oro. Asimismo, se han obtenido patrones de actividad eléctrica en las células PC-3 muy similares a los obtenidos con el chip de silicio y oro empleado en la estancia. Como mejora de la MEA 3D se ha cambiado el sustrato por otro transparente, como vidrio o PMMA, para permitir su uso en aplicaciones ópticas. Dichas MEAs integran electrodos planares fabricados mediante la técnica de sputtering de oro sobre su superficie. Estas MEAs están en una fase preliminar de desarrollo, y se está probando en primer lugar su biocompatibilidad y viabilidad para el desarrollo de cultivos celulares. Para finalizar, se exponen las conclusiones de esta tesis doctoral, entre las que destacan: el proceso de fabricación del LOP con electrodos de oro y la aplicación del sistema completo para desarrollar cultivos organotípicos, monitorizarlos y aplicar electroestimulación, logrando la neuro-protección de retinas de ratón con la retinosis pigmentaria; la transición hacia el desarrollo de una plataforma para cultivos celulares mejorando la MEA y su fabricación usando diferentes sustratos; la caracterización de la actividad eléctrica de las células PC-3. También se incluyen las líneas de investigación abiertas para continuar lo que se ha empezado en esta tesis doctoral. Para facilitar la comprensión del lector, se adjuntan los apéndices complementarios a esta tesis doctoral.The presented thesis is focused on the development and validation of lab on chip (LOC) platforms for their application on Biology, Medicine and Biomedicine, particularly those related with cells and tissues cultures, as well as their treatment through electrostimulation and their electrical behavior. Nowadays, research works focused on the development of LOCs have significantly increased, mostly thanks to its high versatility, which involves countless applications. Among all this applications, those related with Biology and Medicine are becoming more and more important. The integration of sensors, actuators, microfluidic circuits and electronic circuits in the same platform allows the fabrication of systems with lots of applications. This thesis is focused on the development of platforms for in vitro cultures of cells and tissues, to monitor their behavior and interact with the biological samples. The importance of in vitro cultures lies on the study of cells and tissues proliferation and morphology or performing drug delivery experiments. In this respect, through LOC technologies, it would be possible to model human diseases in vitro, in order to improve the development of new drugs and advance personalized medicine. Thus, the possibility of carrying out medium-long term cultures on platforms without the need of any expensive equipment, such as CO2 incubators, with software and monitoring, implies a qualitative step forward in the development of in vitro cultures. Within this framework, the work related to this thesis is presented. This PhD has been undertaken in the Microsystem group of the High School Engineering of the University of Seville. The structure of this thesis is organized in such a way that, all along the text, the different aspects previously described are explained in detail. Firstly, a brief introduction about MEMS technology and the basic principles of Microfluidics is presented. Due to this work has been developed in a multidisciplinary environment, this section becomes necessary in order to give a wide view to those non XXVII XXVIII Abstract directly familiarized with these fields. Subsequently, a description of the state of the art is presented, including LOC systems and their applications in Biology, Medicine and Biomedicine, taking special attention to those applications related to organotypic and cell cultures. After the introduction and the state of the art of the framework of this thesis, the results obtained are presented. In the first part of this PhD, the development, fabrication and characterization of the autonomous system for culture and electrostimulation of tissues is described. This system includes a lab on PCB (LOP) composed of a 3D microelectrode array (MEA), with gold wires of 25 µm on transparent substrate, sensors and actuators, together with a microfluidic platform made of PMMA and PDMS. This LOP allows to maintain the appropriate temperature conditions to carry out medium-long term cultures without using a CO2 incubator, as well as its continuous monitoring through an inverted microscope, thanks to the transparent materials used for its fabrication. This system is connected to an external electronic circuit and a software to control the whole system, including the electrostimulation of the biological sample. After explaining the design and the innovative fabrication process of the LOP, the experimental results are presented. Firstly, it has been demonstrated the suitability of this system to perform organotypic cultures of mice retinas for longer than 7 days, obtaining similar results to the same samples, but cultured through traditional methods. In addition, it has been provided neuroprotection to mice retinal explants with the retinitis pigmentosa (RP) disease through the electrostimulation of the samples, being able to slowdown the degeneration of the retinas caused by RP

SU-8 microprobes for biomedical applications

152 p. : il.[ES]La presente tesis doctoral aborda el diseño, fabricación, encapsulado, y caracterización de microagujas de SU-8 para aplicaciones médicas. En la actualidad existe una amplia variedad de agujas para el registro, estimulación y dispensado de drogas, pero se han observado algunas limitaciones en relación a su diseño y material estructural utilizados. En este trabajo se han desarrollado microagujas basadas en la tecnología de SU-8 como alternativa a las agujas actuales. Primeramente se diseñan las agujas para cada tipo de aplicación, después se determinan los procedimientos de fabricación y finalmente se desarrollan los encapsulados para conectar la aguja miniaturizada con el exterior macroscópico. La aplicación de las agujas se ha centrado en dos campos biomédicos: 1) la monitorización de órganos tal como el riñón, y 2) el registro de la actividad neuronal, añadiendo la posibilidad de realizar dispensado de drogas de forma simultánea. El primer objetivo es crear microagujas que causen el menor daño posible en el tejido biológico. Las mediciones eléctricas que se llevan a cabo para conocer el estado real del tejido pueden resultar modificadas, debilitadas o destruidas si las células que constituyen el tejido han sido previamente dañadas. En este trabajo, se desarrollan microagujas basadas en la tecnología MEMS (micro electromechanical systems) para evitar daños profundos en el tejido y poder así realizar mediciones fidedignas. La tecnología MEMS integra elementos y dispositivos eléctricos, mecánicos y electrónicos miniaturizados, los cuales están basados en la industria consolidada de los Circuitos Integrados (IC). Generalmente, las dimensiones de los elementos basados en MEMS son de entre 1 y 100 micras y los dispositivos pueden variar entre 20 micras y 1 milímetro. Las técnicas base de esta tecnología son la deposición de materiales en láminas, la fotolitografía y el grabado. El silicio es el material más utilizado para crear los múltiples dispositivos MEMS, sin embargo, su rigidez y fragilidad ha motivado el estudio de otros materiales tales como los polímeros. En esta tesis se ha utilizado el polímero SU-8 como material estructural debido a sus propiedades favorables para la fabricación de microagujas. Además, la fabricación de microagujas con este polímero permite el uso de procesos de bajo coste. Esta fotoresina presenta una baja absorción a la luz UV, posibilitando exposiciones uniformes en función del espesor del polímero. Así, se obtienen perfiles verticales y un buen control dimensional para toda la estructura. Además, estudios recientes muestran una adecuada biocompatibilidad del polímero SU-8. El segundo objetivo es obtener la más alta relación señal-ruido posible en las mediciones eléctricas. Para ello se han integrado microelectrodos en las agujas y se ha estudiado la constitución física, la configuración espacial y los tratamientos superficiales de los mismos. Un determinado diseño para cada aplicación y la modificación de las técnicas de fabricación han dado como resultado una óptima capacidad sensora de los electrodos. Así, se ha demostrado su uso a través de la monitorización de episodios de isquemia y reperfusión en riñón de rata. En cuanto a las aplicaciones neuronales, se han registrado potenciales de acción con una amplitud de hasta 400-500 ¿V en hipocampo de rata. Además, se ha demostrado que los microelectrodos son capaces de discriminar diferentes fuentes neuronales. Todos estos resultados han demostrado la versatilidad del polímero para crear dispositivos sensores con aplicación en diversas áreas biomédicas. El último objetivo de esta tesis ha sido integrar canales microfluídicos en la aguja para poder dispensar drogas en aplicaciones neuronales y como resultado, detectar cambios en la actividad neuronal. Finalmente, se han llevado a cabo los primeros experimentos fluídicos in vivo en hipocampo de rata como prueba de concepto. Se dispensan 0.5 ¿l de una disolución de kainato y a continuación se registra un incremento en la actividad neuronal. Los resultados preliminares han demostrado la funcionalidad de la aguja para dispensar y monitorizar de forma simultánea aunque se tienen que realizar más experimentos y optimizar el protocolo experimental para verificar el buen funcionamiento de la aguja. En estos momentos, se están realizando más experimentos neuronales para llegar a establecer la tecnología desarrollada en esta tesis

소형동물의 뇌신경 자극을 위한 완전 이식형 신경자극기

학위논문(박사)--서울대학교 대학원 :공과대학 전기·정보공학부,2020. 2. 김성준.In this study, a fully implantable neural stimulator that is designed to stimulate the brain in the small animal is described. Electrical stimulation of the small animal is applicable to pre-clinical study, and behavior study for neuroscience research, etc. Especially, behavior study of the freely moving animal is useful to observe the modulation of sensory and motor functions by the stimulation. It involves conditioning animal's movement response through directional neural stimulation on the region of interest. The main technique that enables such applications is the development of an implantable neural stimulator. Implantable neural stimulator is used to modulate the behavior of the animal, while it ensures the free movement of the animals. Therefore, stable operation in vivo and device size are important issues in the design of implantable neural stimulators. Conventional neural stimulators for brain stimulation of small animal are comprised of electrodes implanted in the brain and a pulse generation circuit mounted on the back of the animal. The electrical stimulation generated from the circuit is conveyed to the target region by the electrodes wire-connected with the circuit. The devices are powered by a large battery, and controlled by a microcontroller unit. While it represents a simple approach, it is subject to various potential risks including short operation time, infection at the wound, mechanical failure of the device, and animals being hindered to move naturally, etc. A neural stimulator that is miniaturized, fully implantable, low-powered, and capable of wireless communication is required. In this dissertation, a fully implantable stimulator with remote controllability, compact size, and minimal power consumption is suggested for freely moving animal application. The stimulator consists of modular units of surface-type and depth-type arrays for accessing target brain area, package for accommodating the stimulating electronics all of which are assembled after independent fabrication and implantation using customized flat cables and connectors. The electronics in the package contains ZigBee telemetry for low-power wireless communication, inductive link for recharging lithium battery, and an ASIC that generates biphasic pulse for neural stimulation. A dual-mode power-saving scheme with a duty cycling was applied to minimize the power consumption. All modules were packaged using liquid crystal polymer (LCP) to avoid any chemical reaction after implantation. To evaluate the fabricated stimulator, wireless operation test was conducted. Signal-to-Noise Ratio (SNR) of the ZigBee telemetry were measured, and its communication range and data streaming capacity were tested. The amount of power delivered during the charging session depending on the coil distance was measured. After the evaluation of the device functionality, the stimulator was implanted into rats to train the animals to turn to the left (or right) following a directional cue applied to the barrel cortex. Functionality of the device was also demonstrated in a three-dimensional maze structure, by guiding the rats to navigate better in the maze. Finally, several aspects of the fabricated device were discussed further.본 연구에서는 소형 동물의 두뇌를 자극하기 위한 완전 이식형 신경자극기가 개발되었다. 소형 동물의 전기자극은 전임상 연구, 신경과학 연구를 위한 행동연구 등에 활용된다. 특히, 자유롭게 움직이는 동물을 대상으로 한 행동 연구는 자극에 의한 감각 및 운동 기능의 조절을 관찰하는 데 유용하게 활용된다. 행동 연구는 두뇌의 특정 관심 영역을 직접적으로 자극하여 동물의 행동반응을 조건화하는 방식으로 수행된다. 이러한 적용을 가능케 하는 핵심기술은 이식형 신경자극기의 개발이다. 이식형 신경자극기는 동물의 움직임을 방해하지 않으면서도 그 행동을 조절하기 위해 사용된다. 따라서 동물 내에서의 안정적인 동작과 장치의 크기가 이식형 신경자극기를 설계함에 있어 중요한 문제이다. 기존의 신경자극기는 두뇌에 이식되는 전극 부분과, 동물의 등 부분에 위치한 회로부분으로 구성된다. 회로에서 생산된 전기자극은 회로와 전선으로 연결된 전극을 통해 목표 지점으로 전달된다. 장치는 배터리에 의해 구동되며, 내장된 마이크로 컨트롤러에 의해 제어된다. 이는 쉽고 간단한 접근방식이지만, 짧은 동작시간, 이식부위의 감염이나 장치의 기계적 결함, 그리고 동물의 자연스러운 움직임 방해 등 여러 문제점을 야기할 수 있다. 이러한 문제의 개선을 위해 무선통신이 가능하고, 저전력, 소형화된 완전 이식형 신경자극기의 설계가 필요하다. 본 연구에서는 자유롭게 움직이는 동물에 적용하기 위하여 원격 제어가 가능하며, 크기가 작고, 소모전력이 최소화된 완전이식형 자극기를 제시한다. 설계된 신경자극기는 목표로 하는 두뇌 영역에 접근할 수 있는 표면형 전극과 탐침형 전극, 그리고 자극 펄스 생성 회로를 포함하는 패키지 등의 모듈들로 구성되며, 각각의 모듈은 독립적으로 제작되어 동물에 이식된 뒤 케이블과 커넥터로 연결된다. 패키지 내부의 회로는 저전력 무선통신을 위한 지그비 트랜시버, 리튬 배터리의 재충전을 위한 인덕티브 링크, 그리고 신경자극을 위한 이상성 자극파형을 생성하는 ASIC으로 구성된다. 전력 절감을 위해 두 개의 모드를 통해 사용률을 조절하는 방식이 장치에 적용된다. 모든 모듈들은 이식 후의 생물학적, 화학적 안정성을 위해 액정 폴리머로 패키징되었다. 제작된 신경자극기를 평가하기 위해 무선 동작 테스트가 수행되었다. 지그비 통신의 신호 대 잡음비가 측정되었으며, 해당 통신의 동작거리 및 데이터 스트리밍 성능이 검사되었고, 장치의 충전이 수행될 때 코일간의 거리에 따라 전송되는 전력의 크기가 측정되었다. 장치의 평가 이후, 신경자극기는 쥐에 이식되었으며, 해당 동물은 이식된 장치를 이용해 방향 신호에 따라 좌우로 이동하도록 훈련되었다. 또한, 3차원 미로 구조에서 쥐의 이동방향을 유도하는 실험을 통하여 장치의 기능성을 추가적으로 검증하였다. 마지막으로, 제작된 장치의 특징이 여러 측면에서 심층적으로 논의되었다.Chapter 1 : Introduction 1 1.1. Neural Interface 2 1.1.1. Concept 2 1.1.2. Major Approaches 3 1.2. Neural Stimulator for Animal Brain Stimulation 5 1.2.1. Concept 5 1.2.2. Neural Stimulator for Freely Moving Small Animal 7 1.3. Suggested Approaches 8 1.3.1. Wireless Communication 8 1.3.2. Power Management 9 1.3.2.1. Wireless Power Transmission 10 1.3.2.2. Energy Harvesting 11 1.3.3. Full implantation 14 1.3.3.1. Polymer Packaging 14 1.3.3.2. Modular Configuration 16 1.4. Objectives of This Dissertation 16 Chapter 2 : Methods 18 2.1. Overview 19 2.1.1. Circuit Description 20 2.1.1.1. Pulse Generator ASIC 21 2.1.1.2. ZigBee Transceiver 23 2.1.1.3. Inductive Link 24 2.1.1.4. Energy Harvester 25 2.1.1.5. Surrounding Circuitries 26 2.1.2. Software Description 27 2.2. Antenna Design 29 2.2.1. RF Antenna 30 2.2.1.1. Design of Monopole Antenna 31 2.2.1.2. FEM Simulation 31 2.2.2. Inductive Link 36 2.2.2.1. Design of Coil Antenna 36 2.2.2.2. FEM Simulation 38 2.3. Device Fabrication 41 2.3.1. Circuit Assembly 41 2.3.2. Packaging 42 2.3.3. Electrode, Feedthrough, Cable, and Connector 43 2.4. Evaluations 45 2.4.1. Wireless Operation Test 46 2.4.1.1. Signal-to-Noise Ratio (SNR) Measurement 46 2.4.1.2. Communication Range Test 47 2.4.1.3. Device Operation Monitoring Test 48 2.4.2. Wireless Power Transmission 49 2.4.3. Electrochemical Measurements In Vitro 50 2.4.4. Animal Testing In Vivo 52 Chapter 3 : Results 57 3.1. Fabricated System 58 3.2. Wireless Operation Test 59 3.2.1. Signal-to-Noise Ratio Measurement 59 3.2.2. Communication Range Test 61 3.2.3. Device Operation Monitoring Test 62 3.3. Wireless Power Transmission 64 3.4. Electrochemical Measurements In Vitro 65 3.5. Animal Testing In Vivo 67 Chapter 4 : Discussion 73 4.1. Comparison with Conventional Devices 74 4.2. Safety of Device Operation 76 4.2.1. Safe Electrical Stimulation 76 4.2.2. Safe Wireless Power Transmission 80 4.3. Potential Applications 84 4.4. Opportunities for Further Improvements 86 4.4.1. Weight and Size 86 4.4.2. Long-Term Reliability 93 Chapter 5 : Conclusion 96 Reference 98 Appendix - Liquid Crystal Polymer (LCP) -Based Spinal Cord Stimulator 107 국문 초록 138 감사의 글 140Docto