CAREER: Adapting Flexible Display Technology for Optogenetic Peripheral Nerve Stimulation

项目目标：PI将研究使用来自柔性显示器的光包裹和刺激基因修饰的光敏神经。摘要：生物电子医学是在不使用药物的情况下，通过直接刺激特定的神经来触发身体自我治疗的一种治疗疾病的新方法。这一新兴研究领域对多种疾病显示出令人难以置信的前景，但目前刺激纤维内单个神经的方法是不准确的，并且/或会对神经造成损害。光遗传学是一项新技术，它通过光来刺激神经而不是传统的电极，彻底改变了与神经系统的界面。光可以刺激神经，而不像许多电刺激技术那样物理地穿透和损害神经。然而，光刺激只在低分辨率的二维模式下显示出来。这项工作利用了平板电视的柔性显示技术；一个小阵列将环绕并以三维结构刺激神经。目标是同时照射几个像素，每个像素都太弱而无法刺激神经，以获得足够的光线来激活光束相交的神经。这将给神经提供非常具体的目标。此外，这笔拨款将支持生物电子学研讨会的发展。该研讨会将允许学生，特别是代表性不足的少数民族学生，根据虫子的大脑和自己的肌肉进行自己的测量。学生们将学习这些生物电子学如何使治疗和假肢技术成为可能。技术摘要：生物电子医学是一种新的治疗疾病的方法，通过直接刺激特定的神经，触发身体自我治疗，而不使用药物。有针对性地刺激神经系统可以上调机体对免疫缺陷的反应，下调机体对自身免疫性疾病的反应。传统的神经刺激是利用神经纤维外的电刺激来针对单个轴突或轴突群，但这种技术的分辨率很差。挤压神经可以提高分辨率，但仅限于表面。更有侵入性的技术是切开神经和亚结构，在神经旁边放置极细的导线来提高分辨率，但这是非常有侵入性的，可能会造成损伤。这项工作利用了一种新的神经刺激技术，光遗传学。光遗传学是利用光来刺激基因上对特定波长敏感的神经元。虽然这种技术已经彻底改变了神经接口，但它的实现是相当低的分辨率和二维的。这项工作使用超薄平板显示技术包裹坐骨神经来刺激运动神经元。这使得一种非侵入性刺激技术成为可能。此外，它将比神经外的其他技术提高刺激的分辨率。多个发射器可以在低于光遗传刺激阈值的光功率下同时使用，因此每个像素发出的光的交集将足以刺激轴突。这将提高神经纤维内刺激的分辨率。该系统的功效将在运动神经元特异性转染的转基因小鼠中得到验证。一组发射器将被包裹在小鼠坐骨神经周围，肌电图（EMG）用于确认刺激。此外，这笔拨款将支持生物电子学研讨会的发展。该研讨会将允许学生，特别是少数族裔学生，制作他们自己的神经和肌电图记录。学生将学习这些生物电子接口如何使治疗和假肢技术成为可能。

Proposal Title: CAREER: Adapting Flexible Display Technology for Optogenetic Peripheral Nerve StimulationProject Goals: The PI will investigate using light from flexible displays to wrap around and stimulate nerves genetically modified to be light sensitive.a) Nontechnical Abstract: Biolelectronic medicine is a new approach to treating diseases by direct stimulation of specific nerves which triggers the body to treat itself without the use of pharmaceuticals. This emerging area of research shows incredible promise for a variety of diseases, but current methods of stimulating individual nerves within a fiber are inaccurate and/or cause damage to the nerve. Optogenetics is a new technique has revolutionized interface with the nervous system by using light to stimulate nerves rather than more traditional electrodes. Light can stimulate a nerve without physically penetrating and damaging the nerve like many electrical stimulation techniques. However the optical stimulation has only been shown with low resolution in two dimensional patterns. This work exploit flexible display technology used in flat panel televisions; a small array will wrap around and stimulate the nerve in a three dimensional configuration. The goal is to simultaneously shine several pixels, each too weak to stimulate, on the nerve to get enough light to activate the nerve where the beams cross. This will give very specific targeting of nerves.In addition, this grant will support the development of a bioelectronics workshop. The workshop will allow students, especially underrepresented minority students, to make their own measurements from the brain of a bug and their own muscles. The students will learn about how these bioelectronics can enable therapeutic and prosthetic technology. b) Technical Abstract:Bioelectronic medicine is a new approach to treating disease by direct stimulation of specific nerves which triggers the body to treat itself without the use of pharmaceuticals. Targeted stimulation of the nervous system can upregulate the body's response to immune deficiency and downregulate its response to autoimmune disease. Traditional nerve stimulation uses electrical stimulation outside of the nerve fiber to target individual axons or groups of axons, but the resolution of this technique is very poor. Squeezing the nerve can improve this resolution but only near the surface. More invasive techniques cut open the nerve and substructures to place extremely fine wires next to the nerves to improve resolution, but this is very invasive and can cause damage. This work leverages a new technique for neural stimulation, optogenetics. Optogenetics is the use of light to stimulate neurons that have been genetically sensitized to specific wavelengths. While this technique has revolutionized neural interface, the implementation has been fairly low resolution and two dimensional.This work uses ultra-thin flat panel display technology wrapped around the sciatic nerve to stimulate motor neurons. This enables a stimulation technique that is non-invasive to the nerve. In addition, it will increase the resolution of stimulation beyond other techniques external to the nerve. Multiple emitters can be used with optical power below the threshold for optogenetic stimulation simultaneously, so the intersection of the emitted light from each of the pixels will be sufficient to stimulate the axon. This should increase the resolution with which stimulation can be targeted within a nerve fiber. The efficacy of the system will be demonstrated using transgenic mice with motor neurons specifically transfected. An arrays of emitters will be wrapped around a mouse sciatic nerve with electromyography (EMG) used to confirm the stimulation.In addition, this grant will support the development of a bioelectronics workshop. The workshop will allow students, especially underrepresented minority students, to make their own neural and EMG recordings. The students will learn about how these bioelectronics interfaces can enable therapeutic and prosthetic technology.