Four-Wire Interface ASIC for a Multi-Implant Link

This paper describes an on-chip interface for recovering power and providing full-duplex communication over an AC-coupled 4-wire lead between active implantable devices. The target application requires two modules to be implanted in the brain (cortex) and upper chest; connected via a subcutaneous lead. The brain implant consists of multiple identical “optrodes” that facilitate a bidirectional neural interface (electrical recording and optical stimulation), and the chest implant contains the power source (battery) and processor module. The proposed interface is integrated within each optrode ASIC allowing full-duplex and fully-differential communication based on Manchester encoding. The system features a head-to-chest uplink data rate (up to 1.6 Mbps) that is higher than that of the chest-to-head downlink (100 kbps), which is superimposed on a power carrier. On-chip power management provides an unregulated 5-V dc supply with up to 2.5-mA output current for stimulation, and two regulated voltages (3.3 and 3 V) with 60-dB power supply rejection ratio for recording and logic circuits. The 4-wire ASIC has been implemented in a 0.35-μm CMOS technology, occupying a 1.5-mm 2 silicon area, and consumes a quiescent current of 91.2 μA. The system allows power transmission with measured efficiency of up to 66% from the chest to the brain implant. The downlink and uplink communication are successfully tested in a system with two optrodes and through a 4-wire implantable lead

A Versatile Hermetically Sealed Microelectronic Implant for Peripheral Nerve Stimulation Applications

This article presents a versatile neurostimulation platform featuring a fully implantable multi-channel neural stimulator for chronic experimental studies with freely moving large animal models involving peripheral nerves. The implant is hermetically sealed in a ceramic enclosure and encapsulated in medical grade silicone rubber, and then underwent active tests at accelerated aging conditions at 100°C for 15 consecutive days. The stimulator microelectronics are implemented in a 0.6-μm CMOS technology, with a crosstalk reduction scheme to minimize cross-channel interference, and high-speed power and data telemetry for battery-less operation. A wearable transmitter equipped with a Bluetooth Low Energy radio link, and a custom graphical user interface provide real-time, remotely controlled stimulation. Three parallel stimulators provide independent stimulation on three channels, where each stimulator supports six stimulating sites and two return sites through multiplexing, hence the implant can facilitate stimulation at up to 36 different electrode pairs. The design of the electronics, method of hermetic packaging and electrical performance as well as in vitro testing with electrodes in saline are presented

In-body wireline interfacing platform for multi-module implantable microsystems

The recent evolution of implantable medical devicesfrom single-unit stimulators to modern implantable microsys-tems, has driven the need for distributed technologies, in whichboth the implant system and functions are partitioned across mul-tiple active devices. This multi-module approach is made possiblethanks to novel network architectures, allowing for in-body powerand data communications to be performed using implantableleads. This paper discusses the challenges in implementing suchinterfacing system and presents a platform based on one centralimplant (CI) and multiple peripheral implants (PIs) using a cus-tom 4WiCS communication protocol. This is implemented in PCBtechnology and tested to demonstrate intrabody communicationcapabilities and power transfer within the network. Measuredresults show CI-to-PI power delivery achieves 70%efficiency inexpected load condition, while establishing full-duplex data linkwith up to 4 PIs simultaneously

An Implantable Wireless Multi-Channel Neural Prosthesis for Epidural Stimulation

This paper presents a fully implantable multi-channel neural prosthesis for epidural stimulation. The prosthesis features three telemetry-operated independent stimulators providing in total eighteen stimulation channels. The stimulator circuits were implemented in a 0.6-μm CMOS technology. The prosthesis is protected in a hermetically sealed ceramic enclosure and encapsulated in medical grade silicone rubber. In-vitro measured results with electrodes in saline are presented

SenseBack - An implantable system for bidirectional neural interfacing

Chronic in-vivo neurophysiology experiments require highly miniaturized, remotely powered multi-channel neural interfaces which are currently lacking in power or flexibility post implantation. In this article, to resolve this problem we present the SenseBack system, a post-implantation reprogrammable wireless 32-channel bidirectional neural interfacing that can enable chronic peripheral electrophysiology experiments in freely behaving small animals. The large number of channels for a peripheral neural interface, coupled with fully implantable hardware and complete software flexibility enable complex in-vivo studies where the system can adapt to evolving study needs as they arise. In complementary ex-vivo and in-vivo preparations, we demonstrate that this system can record neural signals and perform high-voltage, bipolar stimulation on any channel. In addition, we demonstrate transcutaneous power delivery and Bluetooth 5 data communication with a PC. The SenseBack system is capable of stimulation on any channel with ±20 V of compliance and up to 315 μA of current, and highly configurable recording with per-channel adjustable gain and filtering with 8 sets of 10-bit ADCs to sample data at 20 kHz for each channel. To the best of our knowledge this is the first such implantable research platform offering this level of performance and flexibility post-implantation (including complete reprogramming even after encapsulation) for small animal electrophysiology. Here we present initial acute trials, demonstrations and progress towards a system that we expect to enable a wide range of electrophysiology experiments in freely behaving animals

A Fully Implantable Opto-Electro Closed-Loop Neural Interface for Motor Neuron Disease Studies

This paper presents a fully implantable closed-loop device for use in freely moving rodents to investigate new treatments for motor neuron disease. The 0.18 µm CMOS integrated circuit comprises 4 stimulators, each featuring 16 channels for optical and electrical stimulation using arbitrary current waveforms at frequencies from 1.5 Hz to 50 kHz, and a bandwidth programmable front-end for neural recording. The implant uses a Qi wireless inductive link which can deliver >100 mW power at a maximum distance of 2 cm for a freely moving rodent. A backup rechargeable battery can support 10 mA continuous stimulation currents for 2.5 hours in the absence of an inductive power link. The implant is controlled by a graphic user interface with broad programmable parameters via a Bluetooth low energy bidirectional data telemetry link. The encapsulated implant is 40 mm × 20 mm × 10 mm. Measured results are presented showing the electrical performance of the electronics and the packaging method

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

Key Considerations for Power Management in Active Implantable Medical Devices

Within the rapidly advancing field of active implantable medical devices, power management is a major consideration. Devices that provide life critical (or avoiding life threatening) function require a dependable, always-on power source, for example pacemakers. There is then a trade-off with battery lifetime as to whether such devices employ a primary cell or rechargeable battery. With new applications requiring multi-module implants, there is now also a need for transmitting within the body from one device to another. This paper outlines the key considerations and the process to define and optimise the power management strategy. We then apply this to a case study application – developing an implanted, multi-module closed-loop neuromodulation device for the treatment of focal epilepsy

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

완전 이식형 시각 보철 시스템을 위한 연구

학위논문(박사)--서울대학교 대학원 :공과대학 전기·정보공학부,2020. 2. 김성준.A visual prosthetic system typically consists of a neural stimulator, which is a surgically implantable device for electrical stimulation intended to restore the partial vision of blind patients, and peripheral external devices including an image sensor, a controller, and a processor. Although several visual prosthetic systems, such as retinal prostheses or retinal implants, have already been commercialized, there are still many issues on them (e.g., substrate materials for implantable units, electrode configurations, the use of external hardware, power supply and data transmission methods, design and fabrication approaches, etc.) to be dealt with for an improved visual prosthetic system. In this dissertation, a totally implantable visual prosthetic system is suggested with four motivations, which are thought to be important, as in the following: 1) simple fabrication of implantable parts, such as micro-sized electrodes and a case, for a neural stimulator based on polymer without semiconductor techniques, 2) multi-polar stimulation for virtual channel generation to overcome a limited number of physical electrodes in a confined space, 3) a new image acquisition strategy using an implantable camera, and 4) power supply as well as data transmission to a neural stimulator without hindering patients various activities. First, polymer materials have been widely used to develop various implantable devices for visual prosthetic systems because of their outstanding advantages including flexibility and applicability to microfabrication, compared with metal, silicon, or ceramic. Most polymer-based implantable devices have been fabricated by the semiconductor technology based on metal deposition and photolithography. This technology provides high accuracy and precision for metal patterning on a polymer substrate. However, the technology is also complicated and time-consuming as it requires masks for photolithography and vacuum for metal deposition as well as huge fabrication facilities. This is the reason why biocompatible cyclic olefin polymer (COP) with low water absorption (<0.01 %) and high light transmission (92 %) was chosen as a new substrate material of an implantable device in this study. Based on COP, simple fabrication process of an implantable device was developed without masks, vacuum, and huge fabrication facilities. COP is characterized by strong adhesion to gold and high ultraviolet (UV) transparency as well. Because of such adhesion and UV transparency, a gold thin film can be thermally laminated on a COP substrate with no adhesion layer and micromachined by a UV laser without damaging the substrate. Using the developed COP-based process, a depth-type microprobe was fabricated first, and its electrochemical and mechanical properties as well as functionality were evaluated by impedance measurements, buckling tests, and in vivo neural signal recording, respectively. Furthermore, the long-term reliability of COP encapsulation formed by the developed process was estimated through leakage current measurements during accelerated aging in saline solution, to show the feasibility of the encapsulation using COP as well. Second, even if stimulation electrodes become sufficiently small, it is demanding to arrange them for precise stimulation on individual neurons due to electrical crosstalk, which is the spatial superposition of electric fields generated by simultaneous stimuli. Hence, an adequate spacing between adjacent electrodes is required, and this causes a limited number of physical electrodes in a confined space such as in the brain or in the retina. To overcome this limitation, many researchers have proposed stimulation strategies using virtual channels, which are intermediate areas with large magnitudes of electric fields between physical electrodes. Such virtual channels can be created by multi-polar stimulation that can combine stimuli output from two or more electrodes at the same time. To produce more delicate stimulation patterns using virtual channels herein, penta-polar stimulation with a grid-shaped arrangement of electrodes was leveraged specially to generate them in two dimensions. This penta-polar stimulation was realized using a custom-designed integrated circuit with five different current sources and surface-type electrodes fabricated by the developed COP-based process. The effectiveness of the penta-polar stimulation was firstly evaluated by focusing electric fields in comparison to mono-polar stimulation. In addition, the distribution of electric fields changed by the penta-polar stimulation, which indicated virtual channel generation, was estimated in accordance with an amplitude ratio between stimuli of the two adjacent electrodes and a distance from them, through both finite element analysis and in vitro evaluation. Third, an implantable camera is herein proposed as a new image acquisition approach capturing real-time images while implanted in the eye, to construct a totally implantable visual prosthetic system. This implantable camera has distinct advantages in that it can provide blind patients with benefits to perform several ordinary activities, such as sleep, shower, or running, while focusing on objects in accordance with natural eye movements. These advantages are impossible to be achieved using a wearing unit such as a glasses-mounted camera used in a conventional partially implantable visual prosthetic system. Moreover, the implantable camera also has a merit of garnering a variety of image information using the complete structure of a camera, compared with a micro-photodiode array of a retinal implant. To fulfill these advantageous features, after having been coated with a biocompatible epoxy to prevent moisture penetration and sealed using a medical-grade silicone elastomer to gain biocompatibility as well as flexibility, the implantable camera was fabricated enough to be inserted into the eye. Its operation was assessed by wireless image acquisition that displayed a processed black and white image. In addition, to estimate reliable wireless communication ranges of the implantable camera in the body, signal-to-noise ratio measurements were conducted while it was covered by an 8-mm-thick biological medium that mimicked an in vivo environment. Lastly, external hardware attached on the body has been generally used in conventional visual prosthetic systems to stably deliver power and data to implanted units and to acquire image signals outside the body. However, there are common problems caused by this external hardware, including functional failure due to external damages, unavailability during sleep, in the shower, or while running or swimming, and cosmetic issues. Especially, an external coil for power and data transmission in a conventional visual prosthetic system is connected to a controller and processor through a wire, which makes the coil more vulnerable to the problems. To solve this issue, a totally implantable neural stimulation system controlled by a handheld remote controller is presented. This handheld remote controller can control a totally implantable stimulator powered by a rechargeable battery through low-power but relatively long-range ZigBee wireless communication. Moreover, two more functions can be performed by the handheld controller for expanded applications; one is percutaneous stimulation, and the other is inductive charging of the rechargeable battery. Additionally, simple switches on the handheld controller enable users to modulate parameters of stimuli like a gamepad. These handheld and user-friendly interfaces can make it easy to use the controller under various circumstances. The functionality of the controller was evaluated in vivo, through percutaneous stimulation and remote control especially for avian navigation, as well as in vitro. Results of both in vivo experiments were compared in order to verify the feasibility of remote control of neural stimulation using the controller. In conclusion, several discussions on results of this study, including the COP-based simple fabrication process, the penta-polar stimulation, the implantable camera, and the multi-functional handheld remote controller, are addressed. Based on these findings and discussions, how the researches in this thesis can be applied to the realization of a totally implantable visual prosthetic system is elucidated at the end of this dissertation.시각 보철 시스템은 일반적으로 실명 환자들의 부분 시력을 전기 자극으로 회복시키기 위하여 수술적으로 이식될 수 있는 장치인 신경 자극기와 이미지 센서 또는 컨트롤러, 프로세서를 포함하는 외부의 주변 장치들로 구성된다. 망막 보철 장치 또는 망막 임플란트와 같이 몇몇 시각 보철 시스템은 이미 상용화 되었지만, 여전히 더 나은 시각 보철 시스템을 위하여 다뤄져야 할 많은 이슈들 (예를 들어, 이식형 장치의 기판 물질, 전극의 배열, 외부 하드웨어의 사용, 전력 공급 및 데이터 전송 방법, 설계 및 제작 방식 등)이 있다. 본 학위논문은 완전 이식형 시각 보철 시스템을 제안하며, 이를 위하여 다음과 같이 중요하다고 생각되는 총 네 가지의 이슈들과 관련된 연구 내용을 다룬다. 1) 폴리머를 기반으로 한 신경 자극기의 미세 전극 및 패키지와 같은 이식 가능한 부분을 반도체 기술 없이 간단하게 제작하는 방법과 2) 제한된 공간에서 전극 개수의 물리적인 한계를 극복하기 위하여 가상 채널을 형성하는 다극성 자극 방식, 3) 이식형 카메라를 사용하는 새로운 이미지 획득 전략, 4) 환자의 다양한 활동을 방해하지 않으면서 신경 자극기에 전력을 공급하고 데이터를 전송하는 방법. 첫째로, 금속이나 실리콘, 세라믹에 비하여 폴리머는 유연성 및 미세 제작에의 적용 가능성을 포함하는 두드러진 이점들이 있기 때문에 시각 보철 시스템을 구성하는 다양한 이식 가능한 부분들에 널리 이용되었다. 대부분의 폴리머 기반 이식형 장치들은 금속 증착과 사진 식각을 기반으로 하는 반도체 공정으로 제작되었다. 이 공정은 폴리머 기판 위에 금속을 패터닝 하는 데에 있어서 높은 정확성과 정밀도를 제공한다. 하지만 그 공정은 또한, 사진 식각에 쓰이는 마스크와 금속 증착을 위한 진공뿐만 아니라 아주 큰 공정 설비를 요구하기 때문에 시간 소모가 심하고 복잡하다. 이는 본 연구에서 낮은 수분 흡수 (<0.01 %)와 높은 빛 투과 (92 %)를 특징으로 하는 생체적합한 고리형 올레핀 폴리머 (cyclic olefin polymer, COP)가 이식형 장치를 위한 새로운 기판 물질로써 선택된 이유이다. COP를 기반으로 하여, 마스크와 진공, 큰 공정 설비가 필요 없이 이식 가능한 장치를 간단하게 제작하는 공정이 개발되었다. COP는 금과의 강한 접합과 자외선에 대한 높은 투명성을 또 다른 특징으로 한다. 이와 같은 접합 특성과 자외선 투명성 덕분에, 금박은 COP 기판에 별도의 접합층 없이 열로 접합될 수 있을 뿐만 아니라 그 기판에 손상을 주지 않으면서 자외선 레이저를 통하여 미세하게 가공될 수 있다. 개발된 COP 기반의 공정을 처음으로 사용하여 침습형 미세 프로브가 제작되었고, 그 전기화학적, 기계적 특성과 기능성이 각각 임피던스 측정과 버클링 테스트, 생체 내 신경신호 기록으로 평가되었다. 그리고 COP를 사용한 밀봉의 가능성도 알아보기 위하여, 개발된 공정을 사용하여 형성된 COP 밀봉의 장기 안정성이 생리식염수에서의 가속 노화 중 누설 전류 측정을 통하여 추정되었다. 둘째로, 자극 전극의 크기가 충분히 작아진다고 하더라도, 동시에 출력되는 자극에 의해 형성되는 전기장의 중첩인 크로스 토크 때문에 개개의 신경세포를 정밀하게 자극하기 위하여 전극을 배열하는 것은 아주 어렵다. 따라서 인접한 전극 사이에 적당한 간격이 필요하게 되고, 이는 특히 뇌 또는 망막과 같은 제한된 공간에서 전극 개수의 물리적인 한계를 야기한다. 이 한계를 극복하기 위하여, 많은 연구자들은 실제 전극 사이에서 큰 전기장 세기를 갖는 중간 영역을 나타내는 가상 채널을 이용한 자극 전략을 제안하였다. 이러한 가상 채널은 둘 이상의 전극에서 동시에 출력되는 자극 파형을 합칠 수 있는 다극성 자극에 의하여 형성이 가능하다. 본 연구에서는 가상 채널을 이용하여 더 정교한 자극 패턴을 만들기 위하여, 특히 2차원에서의 가상 채널을 생성하고자 격자형 배열의 전극과 함께 5극성 자극이 사용되었다. 이 5극성 자극은 다섯 개의 서로 다른 전류원을 갖도록 맞춤 설계된 집적회로와 개발된 COP 기반 공정으로 제작된 평면형 전극을 사용하여 구현되었다. 먼저, 5극성 자극의 효과를 확인하고자 이 자극으로 전기장을 한 곳에 더 집중된 형태로 만들 수 있음이 단극성 자극과의 비교를 통하여 검증되었다. 그리고 유한 요소 분석과 생체 외 평가 둘 모두를 통하여, 5극성 자극으로 인한 가상 채널 형성을 뜻하는 전기장 분포가 인접한 두 전극에서 나오는 자극의 진폭비와 그 전극으로부터 떨어진 거리에 따라 변화됨이 추정되었다. 셋째로, 본 연구에서는 눈에 이식된 채로 실시간 이미지를 얻음으로써 완전 이식형 시각 보철 시스템을 구성하는 이식형 카메라를 새로운 이미지 획득 방식으로써 제안한다. 이 이식형 카메라는 실명 환자들이 자연스러운 눈의 움직임을 따라서 물체를 볼 수 있으며 잠이나 샤워, 달리기와 같은 일상적인 활동들을 방해 받지 않고 수행할 수 있도록 돕는다는 점에서 독특한 장점을 갖는다. 기존의 부분 이식형 시각 보철 시스템에서 쓰이는 안경 부착형 카메라와 같은 착용 장비로는 이러한 장점들을 얻을 수 없다. 게다가, 이식형 카메라는 망막 임플란트의 미세 포토다이오드 어레이와 달리 완전한 카메라 구조를 이용하여 다양한 이미지 정보를 획득할 수 있다는 장점을 갖는다. 이러한 이점들을 달성하기 위하여, 그 이식형 카메라는 수분 침투를 막고자 생체적합한 에폭시로 코팅되었고 생체적합성과 유연성을 얻기 위하여 의료용 실리콘 엘라스토머로 밀봉된 후에 눈에 충분히 삽입될 수 있는 형태 및 크기로 제작되었다. 이 장치의 동작은 흑백으로 처리된 이미지를 표시하는 무선 이미지 획득으로 시험되었다. 그리고 몸 안에서 이식형 카메라 갖는 안정적인 통신 거리를 측정하기 위하여, 장치가 생체 내 환경을 모사하기 위한 8 mm 두께의 생체 물질로 덮인 상태에서 그 장치의 신호 대 잡음비가 측정되었다. 마지막으로, 기존의 시각 보철 시스템에서 몸에 부착된 형태의 외부 하드웨어는 이식된 장치에 전력과 데이터를 안정적으로 전달하고 이미지 신호를 수집하기 위하여 일반적으로 사용되었다. 그럼에도 불구하고, 이러한 하드웨어는 외부로부터의 손상으로 인한 기능적인 결함과 수면 및 샤워, 달리기, 수영 활동 중 이용 불가능성, 외형적인 이슈 등을 포함하는 공통적인 문제들을 야기한다. 전력 및 데이터 전송을 위한 외부 코일은 시각 보철 시스템에서 컨트롤러와 프로세서에 유선으로 연결되고, 이러한 연결은 그 코일이 앞서 언급된 문제들에 특히 취약하게 만든다. 이러한 이슈를 해결하고자, 휴대용 무선 컨트롤러로 제어되는 완전 이식형 신경 자극 시스템이 제안된다. 이 휴대용 무선 컨트롤러는 저전력이지만 비교적 장거리 통신이 가능한 직비 (ZigBee) 무선 통신을 통하여 재충전 가능한 배터리로 동작하는 완전 이식형 자극기를 제어할 수 있다. 이 외에도, 이 휴대용 컨트롤러를 사용하면 폭넓은 응용을 위한 두 가지 기능을 추가로 수행할 수 있다. 하나는 유선 경피 자극이며, 다른 하나는 재충전 가능한 배터리의 유도 충전 기능이다. 또한, 이 휴대용 컨트롤러의 간단한 스위치를 사용하면 사용자는 게임패드와 같이 자극 파라미터를 쉽게 조절할 수 있다. 이러한 휴대 가능하고 사용자 친화적인 인터페이스를 통해 다양한 상황에서 그 컨트롤러를 쉽게 사용할 수 있다. 그 컨트롤러의 기능은 생체 외 평가뿐만 아니라 조류의 움직임 제어를 위한 유선 경피 자극 및 원격 제어를 통해 생체 내에서도 평가되었다. 또한, 그 컨트롤러를 사용한 원격 신경 자극 제어의 수행 가능성을 검증하기 위하여 두 생체 내 실험의 결과가 서로 비교되었다. 결론적으로, COP 기반의 간단한 제작 공정과 5극성 자극, 이식형 카메라, 휴대용 다기능 무선 컨트롤러를 포함하는 연구 결과에 대한 여러 논의가 이루어진다. 그리고 이러한 결과와 고찰에 기초하여, 본 학위논문의 연구가 완전 이식형 시각 보철 시스템의 구현에 어떻게 적용될 수 있는 지가 이 논문의 끝에서 상세히 설명된다.Abstract ------------------------------------------------------------------ i Contents ---------------------------------------------------------------- vi List of Figures ---------------------------------------------------------- xi List of Tables ----------------------------------------------------------- xx List of Abbreviations ------------------------------------------------ xxii Chapter 1. Introduction --------------------------------------------- 1 1.1. Visual Prosthetic System --------------------------------------- 2 1.1.1. Current Issues ------------------------------------------------- 2 1.1.1.1. Substrate Materials ---------------------------------------- 3 1.1.1.2. Electrode Configurations --------------------------------- 5 1.1.1.3. External Hardware ----------------------------------------- 6 1.1.1.4. Other Issues ------------------------------------------------- 7 1.2. Suggested Visual Prosthetic System ------------------------ 8 1.3. Four Motivations ---------------------------------------------- 10 1.4. Proposed Approaches ---------------------------------------- 11 1.4.1. Cyclic Olefin Polymer (COP) ------------------------------ 11 1.4.2. Penta-Polar Stimulation ----------------------------------- 13 1.4.3. Implantable Camera --------------------------------------- 16 1.4.4. Handheld Remote Controller ---------------------------- 18 1.5. Objectives of this Dissertation ------------------------------ 20 Chapter 2. Materials and Methods ----------------------------- 23 2.1. COP-Based Fabrication and Encapsulation -------------- 24 2.1.1. Overview ----------------------------------------------------- 24 2.1.2. Simple Fabrication Process ------------------------------- 24 2.1.3. Depth-Type Microprobe ---------------------------------- 26 2.1.3.1. Design ----------------------------------------------------- 26 2.1.3.2. Characterization ----------------------------------------- 27 2.1.3.3. In Vivo Neural Signal Recording ---------------------- 30 2.1.4. COP Encapsulation ---------------------------------------- 31 2.1.4.1. In Vitro Reliability Test ---------------------------------- 33 2.2. Penta-Polar Stimulation ------------------------------------- 34 2.2.1. Overview ---------------------------------------------------- 34 2.2.2. Design and Fabrication ----------------------------------- 35 2.2.2.1. Integrated Circuit (IC) Design ------------------------- 35 2.2.2.2. Surface-Type Electrode Fabrication ------------------ 38 2.2.3. Evaluations -------------------------------------------------- 39 2.2.3.1. Focused Electric Field Measurement ---------------- 42 2.2.3.2. Steered Electric Field Measurement ----------------- 42 2.3. Implantable Camera ----------------------------------------- 43 2.3.1. Overview ---------------------------------------------------- 43 2.3.2. Design and Fabrication ----------------------------------- 43 2.3.2.1. Circuit Design -------------------------------------------- 43 2.3.2.2. Wireless Communication Program ------------------ 46 2.3.2.3. Epoxy Coating and Elastomer Sealing -------------- 47 2.3.3. Evaluations ------------------------------------------------- 50 2.3.3.1. Wireless Image Acquisition --------------------------- 50 2.3.3.2. Signal-to-Noise Ratio (SNR) Measurement -------- 52 2.4. Multi-Functional Handheld Remote Controller --------- 53 2.4.1. Overview ---------------------------------------------------- 53 2.4.2. Design and Fabrication ----------------------------------- 53 2.4.2.1. Hardware Description ---------------------------------- 53 2.4.2.2. Software Description ----------------------------------- 57 2.4.3. Evaluations -------------------------------------------------- 57 2.4.3.1. In Vitro Evaluation -------------------------------------- 57 2.4.3.2. In Vivo Evaluation --------------------------------------- 59 Chapter 3. Results ------------------------------------------------- 61 3.1. COP-Based Fabrication and Encapsulation ------------- 62 3.1.1. Fabricated Depth-Type Microprobe ------------------- 62 3.1.1.1. Electrochemical Impedance -------------------------- 63 3.1.1.2. Mechanical Characteristics --------------------------- 64 3.1.1.3. In Vivo Neural Signal Recording --------------------- 66 3.1.2. COP Encapsulation --------------------------------------- 68 3.1.2.1. In Vitro Reliability Test --------------------------------- 68 3.2. Penta-Polar Stimulation ------------------------------------ 70 3.2.1. Fabricated IC and Surface-Type Electrodes ---------- 70 3.2.2. Evaluations ------------------------------------------------- 73 3.2.2.1. Focused Electric Field Measurement --------------- 73 3.2.2.2. Steered Electric Field Measurement ---------------- 75 3.3. Implantable Camera ---------------------------------------- 76 3.3.1. Fabricated Implantable Camera ----------------------- 76 3.3.2. Evaluations ------------------------------------------------ 77 3.3.2.1. Wireless Image Acquisition -------------------------- 77 3.3.2.2. SNR Measurement ------------------------------------ 78 3.4. Multi-Functional Handheld Remote Controller ------- 80 3.4.1. Fabricated Remote Controller ------------------------- 80 3.4.2. Evaluations ------------------------------------------------ 81 3.4.2.1. In Vitro Evaluation ------------------------------------ 81 3.4.2.2. In Vivo Evaluation ------------------------------------- 83 Chapter 4. Discussions ------------------------------------------ 86 4.1. COP-Based Fabrication and Encapsulation ------------ 87 4.1.1. Fabrication Process and Fabricated Devices -------- 87 4.1.2. Encapsulation and Optical Transparency ------------ 89 4.2. Penta-Polar Stimulation------------------------------------ 99 4.2.1. Designed IC and Electrode Configurations --------- 99 4.2.2. Virtual Channels in Two Dimensions ---------------- 101 4.3. Implantable Camera -------------------------------------- 102 4.3.1. Enhanced Reliability by Epoxy Coating ------------- 106 4.4. Multi-Functional Handheld Remote Controller ------ 107 4.4.1. Brief Discussions of the Two Extra Functions ------ 108 4.5. Totally Implantable Visual Prosthetic System --------- 113 Chapter 5. Conclusion ------------------------------------------ 117 References -------------------------------------------------------- 121 Supplements ------------------------------------------------------ 133 국문 초록 ----------------------------------------------------------- 143Docto