CAREER: Scalable Nano-integrated 3D Fibers for Multifunctional Neural Interfacing

世界上近六分之一的人口患有神经系统疾病，包括癫痫、帕金森氏病、自闭症、阿尔茨海默病、抑郁症等，他们的生活质量受到严重影响。为了以最小的副作用有效地治疗这些与大脑相关的疾病，我们需要充分了解大脑中的功能网络。然而，这一努力在很大程度上受到了制造与大脑功能复杂性和机械顺应性相匹配的大脑深部接口设备的工程挑战的阻碍。仍然迫切需要创造一种多功能设备，可以与大脑无缝连接，而不会造成重大损害。这项研究计划开发具有高度灵活性、生物兼容性、可扩展性和临床可转译的具有多部位多功能功能的新型神经接口设备。开发的工具包还将用于解决生物应用中的一些关键挑战，重点是癫痫发作、肿瘤和视觉系统。为了实现这些目标，拟议的研究计划将建立在多个领域的前沿研究基础上，包括纳米材料、光学、电子学、表面化学、微制造和神经科学，旨在显著促进对这些领域的基础理解。这项拟议的研究为社会提供了许多潜在的好处，包括改善神经疾病患者生活的可能性。这项研究将与面向K12学生和教师、本科生和研究生的多层次教育组成部分高度整合，重点关注代表性不足的学生群体。例如，从幼儿园到大学的计划针对弗吉尼亚州十多所第一标题学校的五年级学生，以及弗吉尼亚理工大学的计算机和技术计划针对弗吉尼亚州和其他州的高中女孩。PI还将积极参与国家科学基金会的革命性工程部门拨款，用于改革弗吉尼亚理工大学电气和计算机工程系的本科生教育。拟议研究计划的目标是解决利用非传统纤维拉伸和图案化平台开发生物友好和多功能神经接口的关键挑战。将采用的方法包括纳米材料的加工和建模、多功能纤维的制造和图案化、电化学表征和电路建模、光学表征和建模以及体外和体内神经刺激和记录。该项目将实现灵活的、生物兼容的、纳米电极集成的、双向的、多部位的三维神经接口。它可以促进对复杂大脑功能的理解以及神经疾病的治疗。该计划的具体目标是(1)可伸缩地制造纳米集成电极。通过彻底的表征以及机械和电学建模，将获得对材料性质和电荷转移的基本了解。(2)多功能集成与建模相结合，了解材料和结构的局限性。(3)用于神经科学应用的体外和体内神经刺激和记录，包括癫痫发作、肿瘤治疗和视觉回路。这项拟议研究的智力价值包括理解(1)纳米材料如何在细胞或亚细胞水平上与神经元相互作用；(2)神经电极尺寸和光学通道的基本限制；(3)纳米材料在极端物理条件下的特性。此外，这一开发的工具包将通过跨多个领域的跨学科研究，对各种神经科学应用提供重要的新见解。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Nearly one-sixth of the world's population suffer from neurological diseases, including epilepsy, Parkinson's disease, autism, Alzheimer's disease, depression, etc., and their life qualities are severely compromised. In order to effectively treat these brain-related diseases with minimal side effects, we need to fully understand the functional networks in the brain. However, this endeavor has been largely hindered by the engineering challenges of making deep brain interface devices that match the functional complexity and mechanical compliance of the brain. There remains an urgent need to create a multifunctional device that can seamlessly interface with the brain without causing significant damage. This research program proposes to develop novel neural interface devices which are highly flexible, biocompatible, scalable, and clinically translatable, with multisite multifunctional capabilities. The developed toolset will also be utilized to address some of the key challenges in biological applications, with a focus on the seizure, tumor, and the visual system. To achieve these goals, the proposed research program will build upon the leading edge research across multiple fields, including nanomaterials, optics, electronics, surface chemistry, microfabrication, and neuroscience, and aims to significantly advance the fundamental understanding in these fields. The proposed research offers many potential benefits to society, including the possibility of improving the lives of patients with neurological disorders. The research will be highly integrated with multilevel educational components towards K12 students and teachers, undergraduate, and graduate students, with a focus on underrepresented student groups. Examples include the Kindergarten-to-College program targeting fifth graders from more than ten title I schools across Virginia, and the Computers and Technology at Virginia Tech program targeting high school girls from Virginia and out of state. The PI will also actively participate in the National Science Foundation's Revolutionizing Engineering Departments grant for transforming undergraduate education in the Electrical and Computer Engineering department at Virginia Tech. The objective of the proposed research program is to address a key challenge in developing bio-friendly and multifunctional neural interfaces utilizing a non-conventional fiber drawing and patterning platform. The methods to be employed include nanomaterials processing and modeling, multimaterial multifunctional fiber fabrication and patterning, electrochemical characterization and circuit modeling, optical characterization and modeling, and in vitro and in vivo neural stimulation and recording. This project will enable flexible and biocompatible, nanoelectrodes-integrated, bidirectional, and multisite three-dimensional neural interfaces. It can facilitate the understanding of complex brain functions as well as the treatment of neurological diseases. The specific goals of this program are (1) Scalable fabrication of nano-integrated electrodes. Fundamental understanding of the material properties and charge transfer will be obtained through thorough characterization as well as mechanical and electrical modeling. (2) Multifunctional integration combined with modeling to understand the material and structural limitations. (3) In vitro and in vivo neural stimulation and recording for neuroscience applications including seizure, tumor treatment, and visual circuitry. The intellectual merit of this proposed research includes the understanding of (1) how nanomaterials interface with neurons at the cellular or subcellular level; (2) the fundamental limitations to neural electrode sizes and optical channels; (3) nanomaterials properties under extreme physical conditions. Besides, this developed toolset will enable significant new insights into various neuroscience applications through interdisciplinary research across multiple fields.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.