Massively Parallel Optoacoustic Retinal Stimulation at Micrometer-Resolution

微米分辨率的大规模并行光声视网膜刺激

• 批准号: 10731795
• 负责人: Chen Yang
• 金额: $ 26.52万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10731795
• 关键词: Blindness; Brain; Cells; Chemicals; Cicatrix; Clinical Trials; Complex; Coupled; Data; Development; Device Designs; Devices; Electrodes; Electrons; Electrophysiology (science); Elements; Esthesia; Eye; Fiber; Film; Focused Ultrasound; Foundations; General Hospitals; Genetic; Human; Image; Implant; Individual; Intervention; Label; Lasers; Legal; Lighting; Magnetism; Measurement; Medical; Methods; Mus; Natural regeneration; Neurons; Pattern; Penetration; Performance; Physiologic pulse; Prosthesis; Resolution; Retina; Retinal Degeneration; Retinal Ganglion Cells; Scheme; Source; Technology; Testing; Tissues; United States; Vision; biomaterial compatibility; clinical translation; cranium; density; design; digital; electric impedance; flexibility; implant design; implantable device; improved; in vivo; lens; medical schools; meter; multi-electrode arrays; multidisciplinary; nanomaterials; neural; neural circuit; neuroregulation; new technology; non-genetic; noninvasive brain stimulation; patch clamp; response; retina implantation; retinal prosthesis; retinal stimulation; scale up; sight restoration; technology platform; tissue culture; translational potential; ultrasound

Project Summary Retinal degenerative diseases are the leading cause of irreversible vision loss. There is no approved medical intervention that could cure or reverse the courses of retinal degenerative diseases. Retina prosthesis are implantable devices designed to stimulate sensation of vision in the eyes of individuals with these significant conditions. Yet, due to the current spreading, resolution and pixel density are limited in the existing electrical based devices. New technologies and methods are still being sought for precise and non-genetic implantable retinal stimulation with an improved pixel density. In this application, we aim to develop an optoacoustic micro- lens array (OAA). This array can generate a desired pattern of focus ultrasound for massively parallel retinal stimulation with a focus size of 40-50 microns and pixel density up to 178 pixels per mm2. Such ultra-high spatial precision, variable penetration and massive parallel capabilities enabled our focused optoacoustic technology while incorporated in the soft implant design will offer clear advantages over existing methods. A multi- disciplinary team with complementary expertise is assembled to perform the proposed activities. Prof. Chen Yang (PI) is an expert in nanomaterials and development of new neural interface for modulation and regeneration. Prof. Fried (Co-I, Mass General Hospital/Harvard Medical School) has considerable expertise studying the responses of retinal and other CNS neurons to electric, magnetic, and other forms of artificial stimulation. Prof. Ji-Xin Cheng (collaborator) is an expert in label-free chemical imaging and photoacoustic devices. Our team has pioneered ultra-high precision optoacoustic neuromodulation. We have successfully shown the retina can directly be stimulated by optoacoustic. These feasibility data led to our central hypothesis that via the design of the optoacoustic lens arrays, optoacoustic is able to deliver massively parallel retinal stimulation at an unprecedented 50 micro-meter spatial precision, serving a foundation for retinal prothesis. To test this central hypothesis, the following specific aims are proposed. In Aim 1, we will demonstrate direct retinal stimulation of four subtypes alpha RGC at micrometer-resolution by TFOE validated by patch clamp. In Aim 2, we will demonstrate massively parallel retinal stimulation at micrometer resolution by OAA using multi-electron array measurements. These efforts are expected to generate an implant design offering massively parallel and high precision optoacoustic stimulation as genetics-free retinal prosthesis with translational potential to human.

项目摘要 视网膜退行性疾病是视力丧失的主要原因。没有批准的医疗 可以治愈或扭转视网膜退行性疾病的干预措施。视网膜假体是 旨在刺激具有这些意义的个体眼中的视觉感觉的植入式设备 状况。但是，由于当前的扩展，分辨率和像素密度在现有电气中受到限制 基于设备。仍在寻求新技术和方法，以确切和非遗传植入 视网膜刺激具有改善的像素密度。在此应用中，我们旨在开发光声微观 - 镜头阵列（OAA）。该阵列可以生成所需的焦点超声模式，以进行大规模平行的视网膜 刺激量为40-50微米，像素密度高达178像素。这样的超高空间 精度，可变渗透和庞大的并行功能使我们专注的光声技术 虽然在软植入物设计中合并将提供明显的优势，而不是现有方法。多 具有互补专业知识的纪律团队将组装以执行拟议的活动。陈教授 杨（PI）是纳米材料的专家，并开发了调制和 再生。 Fried教授（Co-I，Mass General Hospital/Harvard Medical School）具有相当大的专业知识 研究视网膜和其他中枢神经系统神经元对电气，磁和其他形式的人工的反应 刺激。 Ji-Xin Cheng教授（合作者）是无标签化学成像和光声的专家 设备。我们的团队开创了超高精度光声神经调节。我们已经成功 显示的视网膜可以通过光声直接刺激。这些可行性数据导致了我们的中心假设 通过光声晶状体阵列的设计，光声能够提供大量平行的视网膜 在前所未有的50微米空间精度下刺激，为视网膜原状奠定了基础。到 检验此中心假设，提出了以下特定目标。在AIM 1中，我们将展示直接视网膜 通过贴片夹验证的TFOE在微米分辨率下以微米分辨率刺激四个亚型alpha rgc。在AIM 2中， 我们将使用多电子在OAA分辨率下在微米分辨率下进行大量平行的视网膜刺激 阵列测量。预计这些努力将产生一种植入物设计，可提供巨大的平行性和 高精度光声刺激是无遗传学的视网膜假体，对人的转化潜力。