Enhanced Vision Restoration for Blind People: High-Density Electrodes with Ultrasensitive Graphene Photodetectors to Realize Novel Biomimetic Neuroretinal Stimulation Paradigms

背景：电视网膜植入物可以帮助患有导致视网膜变性的疾病的盲人恢复视力。尽管在临床试验中取得了开创性的成功，但该技术仍然面临两个主要的瓶颈挑战：1）由于使用宏电极一次激活太多细胞而导致的空间和时间分辨率差，以及与视网膜神经元密度相比较低的技术像素密度，以及2）与视网膜光感受器相比，光电探测器的灵敏度低且动态范围有限。愿景：为了实现适合日常视觉任务的人工视觉，两个项目合作伙伴自2020年以来一直在合作，通过协同先进的技术和神经生物学解决方案，开发具有前所未有的空间和时间分辨率的新型视网膜植入物。该项目的核心特征是一个自然灵感和高密度的花像素架构，允许以仿生方式刺激神经元：由六个电极包围的中央光电探测器。图像单元收集、调整和丰富从光电探测器获得的光信息，并将其提供给刺激单元，刺激单元将其转换为图像编码的电刺激。具体而言，对于下一代视网膜植入物，目标如下：目标1 -传感器：基于增强型2D材料的光电探测器阵列：目前研究的基于仿生2D材料的光电探测器的增强将被开发，目的是将光电探测器的灵敏度和动态范围扩展到至少1到104勒克斯，这是单个视觉场景中典型的视网膜照度范围。放大将提供一个256像素的光电探测器阵列作为图像传感器。目标2 -图像单元：将传感器图像转换为电子信号：将开发一种图像单元，包括用于新型光电探测器的专用并行读出电路和仿真实时信号处理单元，使图像信息能够适应神经刺激和像素富集技术的要求。目标3 -刺激单元：基于图像特征的电刺激：刺激单元作为定制的高密度1536电极（10 µm）阵列芯片的驱动器，以实现高空间分辨率（分辨两个相距<60 µm的光幻视）。为了唤起高级神经元反应，将利用图像特征来调制电脉冲。此外，为了进一步提高时间和空间分辨率，电极将以仿生方式激活，减少视觉衰退并促进持续的细胞反应。目标4 -半组装e-Retina：四个独立的单元-光电探测器阵列、图像单元、刺激单元和电极阵列-将在功能上连接起来，形成完整的e-Retina演示器。

Background: Electrical retinal implants can aid vision of blind people suffering from diseases leading to retinal degeneration. Despite the pioneering success in clinical trials, the technology still faces two main bottleneck challenges: 1) poor spatial and temporal resolution due to the use of macroelectrodes activating too many cells at once and the lower technical pixel density in comparison to retinal neuron density, and 2) the low sensitivity and limited dynamic range of the photodetectors in comparison to retinal photoreceptors. Vision: To realize artificial vision suited for daily vision tasks, the two project partners have been collaborating since 2020 by synergizing advanced technical and neuro-biological solutions towards a new retinal implant type with an unprecedented spatial and temporal resolution. The core feature of this project is a nature-inspired and high-density flower pixel architecture allowing neuronal stimulation in biomimetic fashion: a central photodetector surrounded by six electrodes. An image unit collects, adapts and enriches the light information obtained from the photodetectors and provides it to the stimulation unit, which translates it into image-encoded electrical stimuli. Specifically, for the next generation of retinal implants the following objectives are targeted: Objective 1 – Sensor: Enhanced 2D-material Based Photodetector Arrays: Enhancements for currently studied biomimetic 2D-material-based photodetectors will be developed with the aim to extend the sensitivity and the dynamic range of the photodetectors to at least 1 to 104 lux, which is the typical retinal illuminance range in a single visual scene. The upscaling will provide a 256-pixel photodetector array acting as the image sensor. Objective 2 – Image Unit: Transforming Sensor Images into Electronic Signals: An image unit consisting of a dedicated parallelized readout circuit for the novel photodetectors and an emulated real-time signal processing unit will be developed, enabling the adaptation of the image information to the requirements of the neural stimulation and pixel enrichment techniques. Objective 3 – Stimulation Unit: Image-Feature Based Electrical Stimulation: The stimulation unit acts as the driver for a custom-fabricated high-density 1536-electrode (10 µm) array chip to achieve high spatial resolution (resolving two <60 µm apart phosphenes). To evoke advanced neuronal responses, image-features will be utilized to modulate the electrical pulses. Moreover, to enhance the temporal and spatial resolution further, electrodes will be activated in biomimetic fashion reducing vision-fading and promoting sustained cell responses. Objective 4 – Semi-Assembled e-Retina: The four independent units – the photodetector array, image unit, stimulation unit and the electrode array – will be connected functionally, forming the complete e-Retina demonstrator.