A Bidirectional ASIC for Active Microchannel Neural Interfaces

Closed-loop neural prostheses have been widely used as a therapeutic strategy for a range of neurological, inflammatory, and cardiac disorders. Vagus nerve stimulation has shown promising results for the monitoring and treatment of post-operation symptoms of heart transplant recipients. A prime candidate for selective control of vagal fibres is the microchannel neural interface (MNI), which provides a suitable environment for neural growth and enables effective control of the neural activity in a bidirectional system. This paper presents the design and simulation of an ASIC in 180-nm high-voltage CMOS technology, capable of concurrent stimulation and neural recording with artifact reduction in a seven-channel MNI. The analog front-end amplifies action potentials with a gain of 40 dB, presenting a common-mode rejection ratio of 81 dB at 1 kHz and a noise efficiency factor of 5.13 over the 300 Hz to 5 kHz recording bandwidth. A 42-V-compliant stimulation module operates concurrently and independently across the seven channels

Novel methods and circuits for field shaping in deep brain stimulation

Deep Brain Stimulation (DBS) is a clinical tool used to treat various neurological disorders, including tremor, Parkinson’s disease (PD) and dystonia. Today’s routine use of this therapy is a result of the pioneering work of Benabid and colleagues, who assessed the benefits of applying high-frequency stimulation to the ventral intermediate nucleus and reported substantial long-term improvements in PD patients. Clinical applications of DBS, however, have preceded research and left a number of challenges to optimise this therapeutic technique in terms of quality, therapy costs and understanding of its underlying mechanisms. DBS is based on monopolar or bipolar stimulation techniques, which are characterised by a limited control over the effects of stimulation and, in particular, over the shape and direction of the electric field propagating around the electrode. This thesis proposes two approaches to achieve dynamic electric field control during deep brain stimulation. The first method is based on the use of current-steering multipolar electrode drive, adopted to split the stimulation current between 2 or more contacts, in order to shift the stimulation field to a desired location. The work included the design, development and testing of an integrated circuit current-steering tripolar current source, developed in AMS 0.35μm technology. The second method is based on the use of phased arrays (PAs) in order to create an electromagnetic beam, which can be steered to a desired location. Computational models have shown the ability to steer and focus the electromagnetic fields in brain tissue by varying the phase and frequency of stimulation. Modelling simulations have shown that the use of multipolar electrode configurations is essential to achieve dynamic control over the shape and area of tissue stimulated. Configurations with larger number of cathodes allow for several stimulation patterns, making this stimulation approach beneficial in a clinical environment. Tests on the performance of the integrated tripolar current source have shown its capability to generate stimulation currents up to 1.86mA, to linearly steer the stimulation current to one of the anodes and to generate biphasic square and exponential current pulses, with time constant up to 28ms. In vitro experiments, carried out to map the electric potential generated by a dynamic tripolar current source, validated the model results, by showing the ability to shape the potential distribution around the electrode during stimulation. Finally, models of the behaviour of PA fields in brain tissue have shown that PAs could be introduced to DBS to allow for more accurate field steering and shaping in DBS. This thesis presents methods and implementations to achieve dynamic field shaping in DBS, which can greatly ameliorate the efficacy of clinical DBS

VLSI Circuits for Bidirectional Neural Interfaces

Medical devices that deliver electrical stimulation to neural tissue are important clinical tools that can augment or replace pharmacological therapies. The success of such devices has led to an explosion of interest in the field, termed neuromodulation, with a diverse set of disorders being targeted for device-based treatment. Nevertheless, a large degree of uncertainty surrounds how and why these devices are effective. This uncertainty limits the ability to optimize therapy and gives rise to deleterious side effects. An emerging approach to improve neuromodulation efficacy and to better understand its mechanisms is to record bioelectric activity during stimulation. Understanding how stimulation affects electrophysiology can provide insights into disease, and also provides a feedback signal to autonomously tune stimulation parameters to improve efficacy or decrease side-effects. The aims of this work were taken up to advance the state-of-the-art in neuro-interface technology to enable closed-loop neuromodulation therapies. Long term monitoring of neuronal activity in awake and behaving subjects can provide critical insights into brain dynamics that can inform system-level design of closed-loop neuromodulation systems. Thus, first we designed a system that wirelessly telemetered electrocorticography signals from awake-behaving rats. We hypothesized that such a system could be useful for detecting sporadic but clinically relevant electrophysiological events. In an 18-hour, overnight recording, seizure activity was detected in a pre-clinical rodent model of global ischemic brain injury. We subsequently turned to the design of neurostimulation circuits. Three critical features of neurostimulation devices are safety, programmability, and specificity. We conceived and implemented a neurostimulator architecture that utilizes a compact on-chip circuit for charge balancing (safety), digital-to-analog converter calibration (programmability) and current steering (specificity). Charge balancing accuracy was measured at better than 0.3%, the digital-to-analog converters achieved 8-bit resolution, and physiological effects of current steering stimulation were demonstrated in an anesthetized rat. Lastly, to implement a bidirectional neural interface, both the recording and stimulation circuits were fabricated on a single chip. In doing so, we implemented a low noise, ultra-low power recording front end with a high dynamic range. The recording circuits achieved a signal-to-noise ratio of 58 dB and a spurious-free dynamic range of better than 70 dB, while consuming 5.5 μW per channel. We demonstrated bidirectional operation of the chip by recording cardiac modulation induced through vagus nerve stimulation, and demonstrated closed-loop control of cardiac rhythm

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

A fully-programmable neural interface for multi-polar, multi-channel stimulation strategies

Accepted versio

Advances in Microelectronics for Implantable Medical Devices

Implantable medical devices provide therapy to treat numerous health conditions as well as monitoring and diagnosis. Over the years, the development of these devices has seen remarkable progress thanks to tremendous advances in microelectronics, electrode technology, packaging and signal processing techniques. Many of today’s implantable devices use wireless technology to supply power and provide communication. There are many challenges when creating an implantable device. Issues such as reliable and fast bidirectional data communication, efficient power delivery to the implantable circuits, low noise and low power for the recording part of the system, and delivery of safe stimulation to avoid tissue and electrode damage are some of the challenges faced by the microelectronics circuit designer. This paper provides a review of advances in microelectronics over the last decade or so for implantable medical devices and systems. The focus is on neural recording and stimulation circuits suitable for fabrication in modern silicon process technologies and biotelemetry methods for power and data transfer, with particular emphasis on methods employing radio frequency inductive coupling. The paper concludes by highlighting some of the issues that will drive future research in the field

광 다이오드 기반 인공 망막 시스템을 위한 저전력 설계 및 LCP 패키징에 대한 연구

학위논문 (박사)-- 서울대학교 대학원 : 전기·컴퓨터공학부, 2017. 2. 김성준.The retinal prosthesis is an implantable electronic device that delivers electrical stimuli containing visual information to the retina for the visual restoration of the blinds. The currently available retinal prostheses have several problems in the number of pixels. They are limited in the number of pixels, which restricts the amount of visual information they can deliver. Many research groups are trying to improve their device in this aspect. In order to achieve a significant number of pixels, retinal prosthesis needs large stimulus power dissipation. A typical device consumes more than 20 mW of power to drive 1000 channels. Some of this power can lead to temperature rise which is a safety issue. As the power dissipation scales up with the increase in the number of channels, it is desired to minimize the power per channel as much as possible. Another problem is the absence of a suitable packaging material for the long-term reliable optical window. Due to the curved and narrow implant space available for this kind of device, as well as the transparency required for the incoming wavelengths of lights, it is quite difficult to choose a material that satisfies all requirements of long-term hermetic packaging with optically transparent window. Sapphire glass with titanium metal package are too bulky and rigid, and flexible transparent polymers such as polyimide and parylene-C have high moisture absorption for the implant. This dissertation proposes strategies and methods to solve the problems mentioned above. Two stimulation strategies are proposed. One strategy is to confine the stimulus level with a threshold that cell is activated. Thus we coin it as thresholding strategy.' The other strategy is to reduce the number of stimulation channels by using only outlines of images (outline extraction strategy). Prototype ICs were designed and fabricated for the verification of the effects of these strategies. The simulation and the measurement agree to show that retinal implant with the thresholding and outline extraction strategies consumes below one-third of the stimulus power of the conventional photodiode-based devices. Area-efficient designs of the voltage-controlled current source are also adopted to increase the number of channels. The unit pixel area of the fabricated prototype IC was 0.0072 mm2, expanding up to 1200-channels in the macular area. Liquid crystal polymer (LCP) is proposed as the long-term implantable packaging material with an optical window. It is an inert, biocompatible, and flexible polymer material that has a moisture absorption rate similar to Pyrex glass. We showed that an LCP film with a thickness less than 10 μm allows transmission of the lights in the visible wavelengths by more than 10 %, as the rate increases with thinner films. Thus a thinning process was developed. O2 DRIE was shown effective in reducing the roughness of the film, and the corresponding light scattering. The spatial resolution of LCP with 8.28 μm thickness showed a minimum distinguishable pitch of 90 μm, allowing a 1200 channel integration within a macular area.Chapter 1: Introduction 1 1.1. Retinal Prosthesis – State of the Arts 2 1.1.1. Retinal Prosthesis with External Camera 3 1.1.2. Retinal Prosthesis with Internal Photodiode Array 5 1.2. Photodiode-based Retinal Prosthesis 8 1.2.1. Problems 8 1.2.2. Possible Solutions 12 Chapter 2: Methods 17 2.1. Thresholding 17 2.1.1. Concept 17 2.1.2. Circuit Descriptions 19 2.2. Outline Extraction 28 2.2.1. Concept 28 2.2.2. Circuit Descriptions 30 2.3. Average Stimulus Power Estimation 40 2.3.1. Stimulus Patterns Generation of Conventional and Proposed Strategies 40 2.3.2. Minimum Distinguishable Channels to Recognize 41 2.4. Virtual Channel 43 2.4.1. Concept 43 2.4.2. Circuit Descriptions 44 2.5. Polymer Packaging 51 2.5.1. LCP as a Long-term Reliable Packaging Material 51 2.5.2. Test Methods 53 Chapter 3: Results 58 3.1. Thresholding 58 3.1.1. Fabricated IC 58 3.1.2. Test Setup 60 3.1.3. Test Results 61 3.2. Outline Extraction 65 3.2.1. Simulation Results 65 3.2.2. Fabricated IC 67 3.2.3. Test Setup 68 3.2.4. Test Results 72 3.3. Average Stimulus Power Estimation 76 3.4. Virtual Channels 79 3.4.1. Fabricated IC 79 3.4.2. Test Setup 80 3.4.3. Test Results 81 3.4.4. Two-dimensional Virtual Channel Generator– Test setup and Its Result 84 3.5. Polymer Packaging 87 3.5.1. Light Transmittance according to LCP Thickness 87 3.5.2. Thickness Control of LCP 89 3.5.3. Spatial Resolution of LCP 89 Chapter 4: Discussion 92 4.1. Average Stimulus Power 92 4.2. Visual Acuity 95 4.3. Hermeticity of the Thinned LCP Film 97 Chapter 5: Conclusion and Future Directions 99 References 103 Appendix – Generated Stimulus Patterns of Various the Number of Channels 112 국 문 초 록 139Docto

MiniVStimA: A miniaturized easy to use implantable electrical stimulator for small laboratory animals

According to PubMed, roughly 10% of the annually added publications are describing findings from the small animal model (mice and rats), including investigations in the field of muscle physiology and training. A subset of this research requires neural stimulation with flexible adjustments of stimulation parameters, highlighting the need for reliable implantable electrical stimulators, small enough (~1 cm3), that even mice can tolerate them without impairing their movement. The MiniVStimA is a battery-powered implant for nerve stimulation with an outer diameter of 15 mm and an encapsulated volume of 1.2 cm3 in its smallest variation. It can be pre-programmed according to the experimental protocol and controlled after implantation with a magnet. It delivers constant current charge-balanced monophasic rectangular pulses up to 2 mA and 1 ms phase width (1 kΩ load). The circuitry is optimized for small volume and energy efficiency. Due to the variation of the internal oscillator (31 kHz ± 10%), calibration measures must be implemented during the manufacturing process, which can reduce the deviation of the frequency related parameters down to ± 1%. The expected lifetime of the smaller (larger) version is 100 (480) days for stimulation with 7 Hz all day and 10 (48) days for stimulation with 100 Hz. Devices with complex stimulation patterns for nerve stimulation have been successfully used in two in-vivo studies, lasting up to nine weeks. The implant worked fully self-contained while the animal stayed in its familiar environment. External components are not required during the entire time