高性能视网膜修复芯片的研究
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摘要
全球因视网膜色素变异(RP:retinitis pigmentosa)或老年黄斑(AMD:age-related macular degeration)而致盲的人,数以百万计。这类患者中,尽管视网膜内的光感受器完全受损,但与光感受器相连的神经细胞存活率较高,视觉传送的通路依然完好。研究发现,用适当的电信号刺激这些存活的神经细胞,这类盲人能在一定程度上获得视觉感知。随着集成电路技术、微系统加工工艺技术、射频无线技术和生物医学技术等的进步,基于神经电刺激的人工视觉功能修复技术已成为当前人工器官领域的研究热点之一。本文在国家自然科学基金项目(No.30470469)资助下,旨在从电路层面上研究一种适用于自然光照条件的、替代盲人视网膜中受损光感受器的CMOS视网膜修复芯片。
利用国际上已有的研究成果和相关文献,论文首先介绍了人工视觉功能修复技术的概念、分类及特点。从视网膜的多层细胞结构及其信号传导过程出发,阐述了神经细胞电刺激产生动作电位的原理;在分析神经电刺激视觉修复技术所涉及的几个重要因素之后,得出了开展本论文研究的理论与实验依据。从电路层面综述了国际上在这一领域内的研究现状,在比较这些主流方案的优点与不足之后,提出了本论文拟研制的视网膜修复芯片的功能要求和结构组成。
提出了一种适用于自然光照条件下的视网膜修复电路:光电脉冲频率调制像元电路。每一个像元都是一个独立的振荡器,其输出信号的正脉冲宽度(高电平持续时间)在其动态工作范围内基本保持恒定、频率受入射光强度调制并与入射光强度成比例。对影响像元电路性能的因素做了深入的研究,对像元电路的关键指标进行了优化设计。实验结果表明,较之相似视网膜修复电路,本文提出的的像元电路具有一系列较高的性能:动态范围大、脉冲宽度基本恒定、功耗低、像元面积小等优点。
一般采用射频无线感应传输技术为植入体内的器件提供电源。论文利用相关文献对无线感应能源传输技术进行了阐述和总结。提出了一种可以片上集成的射频电源电路,对其各组成部分:整流滤波单元、参考电压源和单位增益缓冲器等进行了设计和验证。仿真结果表明,输入射频信号的幅值在一个比较大的变化范围内,设计的射频电源电路都能为光电脉冲频率调制像元阵列提供稳定的直流电压。
结合所选的0.5μm 2P3M CMOS加工工艺,进行了视网膜修复芯片的版图设计。所设计的样片上包含了一个8×8的光电脉冲频率调制像元阵列、5个光电二极管面积不同的测试像元及片上射频电源电路。单个像元的尺寸约为50μm×50μm。
作者在标准色温灯和自然光照条件下,分别对加工的视网膜修复芯片进行了测试。测试包含3个方面的内容:直流电压驱动下光电脉冲频率调制像元电路的性能、射频电源电路的性能以及射频电源电路提供驱动电压下像元电路的性能。测试结果表明,射频电源电路能为像元阵列提供稳定的电压和所需的驱动电流,适用于为体内植入器件提供电源;光电脉冲频率调制像元电路在几个关键指标上都表现出了较高的性能,基本达到了设计目标。整个电路设计符合视网膜修复芯片高密度、低功耗的发展方向,在电路层次上已经达到了视网膜视觉功能修复的应用要求。
本文从“视网膜-电极界面模型”对视网膜电刺激信号的特殊要求出发,从电路的层次上研究了一种模仿视网膜内光感受器工作机理的高性能视网膜修复电路及片上射频电源电路。本论文的研究工作处于人工视网膜工程的最前端,后续还有诸多工作亟待完成。本文的研究工作和后续配套的研究工作,有望为视网膜病变患者重拾光明带来福音!
Millions of people suffering from diseases such as RP (Retinitis Pigmentosa) and AMD (Age-related Macular Degeneration) are legally blind due to the loss of photoreceptor function. Fortunately, a large percentage of the neural cells connected to the photoreceptors remain viable, and electrical stimulation of these cells has been shown to result in visual perception. With advance in microfabrication, integrated circuits, wireless technologies, and biomedicine, much attention in the field of artificial organs has been attracted by artificial visual functions recovery based on electrical stimulation of the neural cells. Under the supports of NSFC (No.30470469), this dissertation aims to develope a CMOS retinal prosthesis microchip with high perfermance at the circuit level for natural light illumination.
Ultilizing the existed research achievements and related documents, this dissertation introduces the concept, classification and characteristics of artificial visual functions recovery technology. The theoretic and experimental foundations for designing a CMOS retinal prosthesis microchip are constructed after such key techeniques in the fields are analyzed as the generation principles of action potential by neuronal electrical stimulation and signal transmission process based on the multilayer structure of retina. The research progress in artifical retina is reviewed and advantage and disadvange of some mainstream schemes at the circuit level for visual recovery are also summarized. Then, a CMOS retinal prosthesis microchip with the satisfying fuction and structure is proposed in this dissertation.
An OPFM (Optoelectronic Pulse Frequency Modulation) circuit for nature light illumilation is proposed. Each pixel is an independent oscillator whose frequency is proportional to the intensity of incident light while its pulsewidth holds constant. The factors effecting performance of the pixel are analyzed and some pivotal indexes of the pixel are optimized. The simulation results showed this proposed OPFM circuit possessed high dynamic range of more than 70dB and power consumtion of less than 1.46μA per pixel.
A wireless inductive link is employed to power the implanted devices. The key technology in this field is summerized. And a monilithic radio frequency energy recovery circuit is presented, which consists of a full-wave rectifier, a voltage reference and a unity gain buffer. It exhibits an excellent supply independency and it can output a stable DC voltage for OPFM array in a wide range of input supply voltage.
The layout of the retinal prosthesis microchip on 0.5μm 2P3M standard CMOS process is designed. The designed prototype contains an 8×8 pixels array, five independent pixels for test and a radio frequency energy recovery circuit. The pixel size is 50μm×50μm approximately.
The fabricated retina prosthesis microchip is tested under tungsten lamp illumination at standard color temperature and natural light illumination, respectively. The tests involve three parts: the performance test of OPFM circuit powered by DC voltage, the performance test of the radio frequency energy recovery circuit and the performance test of OPFM circuit powered by the radio frequency energy recovery circuit. The tested rerults showed the fabricated chip possessed desired fuctions. And the results also demonstrate the potential of the integration for retinal implants.
This dissertation aims at presenting a high performance CMOS microchip for visual fuction recovery at the circuitry level. Consequent researches need to be done, including electrode package, surgical implantation, physiology tests of the device, and so on, which requires interdiscipline collabrations of researcher in the fields of eye surgery medicine, neurobiology, material science and micro machine process. The author hope the dissertation can provide some help for further research in this field.
利用国际上已有的研究成果和相关文献,论文首先介绍了人工视觉功能修复技术的概念、分类及特点。从视网膜的多层细胞结构及其信号传导过程出发,阐述了神经细胞电刺激产生动作电位的原理;在分析神经电刺激视觉修复技术所涉及的几个重要因素之后,得出了开展本论文研究的理论与实验依据。从电路层面综述了国际上在这一领域内的研究现状,在比较这些主流方案的优点与不足之后,提出了本论文拟研制的视网膜修复芯片的功能要求和结构组成。
提出了一种适用于自然光照条件下的视网膜修复电路:光电脉冲频率调制像元电路。每一个像元都是一个独立的振荡器,其输出信号的正脉冲宽度(高电平持续时间)在其动态工作范围内基本保持恒定、频率受入射光强度调制并与入射光强度成比例。对影响像元电路性能的因素做了深入的研究,对像元电路的关键指标进行了优化设计。实验结果表明,较之相似视网膜修复电路,本文提出的的像元电路具有一系列较高的性能:动态范围大、脉冲宽度基本恒定、功耗低、像元面积小等优点。
一般采用射频无线感应传输技术为植入体内的器件提供电源。论文利用相关文献对无线感应能源传输技术进行了阐述和总结。提出了一种可以片上集成的射频电源电路,对其各组成部分:整流滤波单元、参考电压源和单位增益缓冲器等进行了设计和验证。仿真结果表明,输入射频信号的幅值在一个比较大的变化范围内,设计的射频电源电路都能为光电脉冲频率调制像元阵列提供稳定的直流电压。
结合所选的0.5μm 2P3M CMOS加工工艺,进行了视网膜修复芯片的版图设计。所设计的样片上包含了一个8×8的光电脉冲频率调制像元阵列、5个光电二极管面积不同的测试像元及片上射频电源电路。单个像元的尺寸约为50μm×50μm。
作者在标准色温灯和自然光照条件下,分别对加工的视网膜修复芯片进行了测试。测试包含3个方面的内容:直流电压驱动下光电脉冲频率调制像元电路的性能、射频电源电路的性能以及射频电源电路提供驱动电压下像元电路的性能。测试结果表明,射频电源电路能为像元阵列提供稳定的电压和所需的驱动电流,适用于为体内植入器件提供电源;光电脉冲频率调制像元电路在几个关键指标上都表现出了较高的性能,基本达到了设计目标。整个电路设计符合视网膜修复芯片高密度、低功耗的发展方向,在电路层次上已经达到了视网膜视觉功能修复的应用要求。
本文从“视网膜-电极界面模型”对视网膜电刺激信号的特殊要求出发,从电路的层次上研究了一种模仿视网膜内光感受器工作机理的高性能视网膜修复电路及片上射频电源电路。本论文的研究工作处于人工视网膜工程的最前端,后续还有诸多工作亟待完成。本文的研究工作和后续配套的研究工作,有望为视网膜病变患者重拾光明带来福音!
Millions of people suffering from diseases such as RP (Retinitis Pigmentosa) and AMD (Age-related Macular Degeneration) are legally blind due to the loss of photoreceptor function. Fortunately, a large percentage of the neural cells connected to the photoreceptors remain viable, and electrical stimulation of these cells has been shown to result in visual perception. With advance in microfabrication, integrated circuits, wireless technologies, and biomedicine, much attention in the field of artificial organs has been attracted by artificial visual functions recovery based on electrical stimulation of the neural cells. Under the supports of NSFC (No.30470469), this dissertation aims to develope a CMOS retinal prosthesis microchip with high perfermance at the circuit level for natural light illumination.
Ultilizing the existed research achievements and related documents, this dissertation introduces the concept, classification and characteristics of artificial visual functions recovery technology. The theoretic and experimental foundations for designing a CMOS retinal prosthesis microchip are constructed after such key techeniques in the fields are analyzed as the generation principles of action potential by neuronal electrical stimulation and signal transmission process based on the multilayer structure of retina. The research progress in artifical retina is reviewed and advantage and disadvange of some mainstream schemes at the circuit level for visual recovery are also summarized. Then, a CMOS retinal prosthesis microchip with the satisfying fuction and structure is proposed in this dissertation.
An OPFM (Optoelectronic Pulse Frequency Modulation) circuit for nature light illumilation is proposed. Each pixel is an independent oscillator whose frequency is proportional to the intensity of incident light while its pulsewidth holds constant. The factors effecting performance of the pixel are analyzed and some pivotal indexes of the pixel are optimized. The simulation results showed this proposed OPFM circuit possessed high dynamic range of more than 70dB and power consumtion of less than 1.46μA per pixel.
A wireless inductive link is employed to power the implanted devices. The key technology in this field is summerized. And a monilithic radio frequency energy recovery circuit is presented, which consists of a full-wave rectifier, a voltage reference and a unity gain buffer. It exhibits an excellent supply independency and it can output a stable DC voltage for OPFM array in a wide range of input supply voltage.
The layout of the retinal prosthesis microchip on 0.5μm 2P3M standard CMOS process is designed. The designed prototype contains an 8×8 pixels array, five independent pixels for test and a radio frequency energy recovery circuit. The pixel size is 50μm×50μm approximately.
The fabricated retina prosthesis microchip is tested under tungsten lamp illumination at standard color temperature and natural light illumination, respectively. The tests involve three parts: the performance test of OPFM circuit powered by DC voltage, the performance test of the radio frequency energy recovery circuit and the performance test of OPFM circuit powered by the radio frequency energy recovery circuit. The tested rerults showed the fabricated chip possessed desired fuctions. And the results also demonstrate the potential of the integration for retinal implants.
This dissertation aims at presenting a high performance CMOS microchip for visual fuction recovery at the circuitry level. Consequent researches need to be done, including electrode package, surgical implantation, physiology tests of the device, and so on, which requires interdiscipline collabrations of researcher in the fields of eye surgery medicine, neurobiology, material science and micro machine process. The author hope the dissertation can provide some help for further research in this field.
引文
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