Optically-controlled neuromodulation with silicon carbide-based nanostructures

神经元和心脏细胞的细胞外电刺激是研究兴奋性的标准手段，是许多植入式疾病治疗设备的基础，包括帕金森病、抑郁症、癫痫和心律失常的设备。虽然这些神经调节装置改善了患者的生活质量，但由于体积庞大、侵入性强、复杂和昂贵，它们在许多动物研究中难以部署，从而限制了它们在基础神经科学研究中的应用。该项目的目标是展示灵活且经济高效的碳化硅（SiC）纳米结构，当被光触发时，可以调节单个神经元的行为。这些新的基于sic的接口将实现无线、非遗传、多尺度、精确的神经元调制，克服当前植入式电极的许多限制。这个项目将为学生在一个高度跨学科的领域提供学习机会。该研究员将以芝加哥大学现有的模式项目为基础，通过向高中生和本科生提供暑期研究机会，增加科学和工程领域的多样性。允许本科生和研究生访问以色列的国际暑期交流项目将继续进行，并将扩大为优秀高中生参加国家比赛（如再生科学人才）的特殊培训项目。研究和教育成果将通过同行评议的出版物、研讨会、会议报告和网站广泛传播。光遗传学已经成为神经调节的主要现代方法，但很难在许多动物模型系统中部署。最近开发的半导体和金属基生物材料界面具有相对容易地在非常广泛的动物模型系统中提供非遗传和多尺度神经活动的潜力。然而，这些材料和器件的大规模制造或合成方法通常非常复杂和昂贵。此外，缺乏来自同一类物质的兴奋性和抑制性神经调节的研究。该项目通过使用碳化硅（SiC）作为材料来构建用于光触发非遗传神经调节的神经接口，解决了这两个限制。工作流程计划分为三个连续的步骤：(1)创新大规模碳化硅合成和器件制造的合成方法，(2)使用培养的神经元研究兴奋性和抑制性反应，最后(3)在小鼠模型中部署和概念验证测试。本项目将汇集高效、多层次、跨学科的方法，实现大规模、稳定的大脑随机神经调节光电化学装置。该研究还将提供独特的知识和技能，可以在半导体或探测器行业开辟新的领域。在这项工作中研究的碳化硅基膜可能会产生用于转化研究的高效生物医学设备。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Extracellular electrical stimulation of neurons and heart cells, the standard means by which to study excitability, forms the basis for many implantable disease-treating devices including those for Parkinson's disease, depression, epilepsy, and cardiac arrhythmias. While these neural modulation devices have improved patients' quality of life, they are challenging to deploy in many animal studies due to being bulky, invasive, complex and expensive, thus limiting their use in basic neuroscience studies. The goal of this project is to demonstrate flexible and cost-effective silicon carbide (SiC)-based nanostructures that, when triggered by light, can modulate the behavior of single neurons. These new SiC-based interfaces will enable wireless, non-genetic, multiscale, precise modulation of neurons, overcoming many of the limitations of current implantable electrodes. This project will provide learning opportunities for students in a highly interdisciplinary area. The investigator will build on existing model programs at the University of Chicago to increase diversity in science and engineering by offering summer research opportunities to high school and undergraduate students. An international summer exchange program that allows undergraduate and graduate students to visit Israel will be continued and a special training program for outstanding high school students to compete in national competitions (e.g., Regeneron Science Talent) will be expanded. The research and education results will be disseminated broadly through peer-reviewed publications, seminars, conference presentations, and websites.Optogenetics has emerged as the leading modern approach for neuromodulation, but it is difficult to deploy in many animal model systems. Recently developed semiconductor and metal-based biomaterial interfaces have the potential to provide with relative ease the non-genetic and multiscale neural activities in a very broad range of animal model systems. However, the large-scale fabrication or synthesis methods for these materials and devices are usually very complex and expensive. Additionally, there is a lack of studies of both excitatory and inhibitory neuromodulation from the same class of materials. This project addresses these two limitations through use of silicon carbide (SiC) as a material to construct neural interfaces for optically triggered non-genetic neuromodulation. The Workflow Plan is presented as three consecutive steps: (1) innovation of synthetic methods for the large-scale silicon carbide synthesis and device fabrication, to (2) study both the excitatory and inhibitory responses using cultured neurons, and finally to (3) deployment and proof-of-concept testing in a mouse model. This project will bring together an efficient, multi-level, cross-disciplinary approach to achieve the large-scale and stable photoelectrochemical devices for random-access neuromodulation in the brain. The proposed study will also offer a unique knowledge and skill set that can open new areas of endeavor in the semiconductor or detector industry. The silicon carbide-based membranes studied in this work can potentially yield highly efficient biomedical devices for translational studies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.