CAREER: Adapting Flexible Display Technology for Optogenetic Peripheral Nerve Stimulation

提案标题：职业：将柔性显示技术应用于光遗传周围神经刺激项目目标：PI将研究使用柔性显示器的光包裹和刺激基因改造为光敏的神经。a)非技术摘要：生物电子医学是一种通过直接刺激特定神经来治疗疾病的新方法，该方法可以触发身体在不使用药物的情况下进行自我治疗。这一新兴研究领域对各种疾病显示出令人难以置信的前景，但目前刺激纤维内个别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，它使用光来刺激神经，而不是更传统的电极，从而彻底改变了与神经系统的接口。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破坏神经。然而，光刺激仅以低分辨率显示在二维图案上。这项研究利用了平板电视中使用的柔性显示技术；一个小阵列将环绕并刺激三维结构中的神经。目标是同时将几个像素照射到神经上，每个像素都太弱，无法刺激，以获得足够的光来激活光束交叉的神经。这将给予神经非常具体的目标。此外，这笔赠款将支持一个生物电子学研讨会的发展。研讨会将允许学生，特别是代表人数较少的少数族裔学生，通过细菌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技术如何实现治疗和假肢技术。B)技术摘要：生物电子医学是一种通过直接刺激特定神经来治疗疾病的新方法，它触发身体在不使用药物的情况下进行自我治疗。对神经系统的定向刺激可以上调人体对免疫缺陷的反应，下调其对自身免疫性疾病的反应。传统的神经刺激采用神经纤维外的电刺激来靶向单个或一组轴突，但这种技术的分辨率很低。挤压神经可以提高分辨率，但只能在表面附近。更具侵入性的技术切开神经和下层结构，在神经旁边放置极细的电线，以提高分辨率，但这是非常有侵入性的，可能会造成损害。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对特定波长遗传敏感的神经元。虽然这项技术彻底改变了神经接口，但实现的分辨率相当低，而且是二维的。这项工作使用包裹在坐骨神经上的超薄平板显示技术来刺激运动神经元。这使得一种非侵入性的神经刺激技术成为可能。此外，它还将提高刺激的分辨率，超越神经外的其他技术。多个发射器可以在光功率低于阈值的情况下同时用于光遗传刺激，因此每个像素发射的光的交集将足以刺激轴突。这应该会提高刺激在神经纤维中的靶向的分辨率。该系统的有效性将在转基因小鼠身上得到验证，转基因小鼠的运动神经元被特别转基因。一组发射器将缠绕在小鼠的坐骨神经上，肌电图(EMG)用于确认刺激。此外，这笔赠款将支持一个生物电子车间的发展。研讨会将允许学生，特别是未被充分代表的少数民族学生，制作他们自己的神经和肌电记录。学生们将学习这些生物电子接口如何实现治疗和假肢技术。

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.