Biosubstance Delivery and Detection Platform based on Nanoparticle Robots

单细胞研究中一个很大程度上尚未解决的挑战是提供准确的分子剂量，并以规定的速率将它们释放到许多活细胞中的指定单个活细胞，或特定的亚细胞位置。克服这一挑战将对单细胞生物科学和有针对性的医疗干预产生深远影响，特别是对许多重要的脑部疾病。在这项工作中，提出了一种基于智能和可控纳米颗粒机器人的创新平台，以在所需的单个/亚细胞位置以可编程的释放速率递送所需剂量的生物物质。这种装置将允许在细胞培养和组织设置中进行前所未有的水平的操作。特别是，该平台将用于将药物分子递送到血脑屏障，血脑屏障是大脑结构中保护神经元免受毒素，抗体，免疫细胞循环损伤的重要组成部分。如果成功，将揭示单个/亚细胞水平上对血脑屏障调节的理解，这将为寻找许多神经系统疾病的解决方案提供关键的新知识。该项目还将为本科生和研究生提供纳米机器人，纳米机电系统和纳米传感跨学科领域的难得机会。将推出一个教育网站，及时突出最近的成就，并激发公众对尖端科学进展的认识和兴趣。这款基于纳米粒子的智能生物物质输送和传感机器人平台将利用战略性设计的等离子体活性纳米结构，以亚细胞分辨率精确地将生物物质输送和可编程地释放到单个活细胞中，并同时通过光学光谱监测分子释放过程。为了实现这样一个系统，拟议的研究将解决材料，设备和系统水平上的挑战，并展示该平台在操纵和理解局部血脑屏障药物渗透性和递送方面的应用。它有望在理解和解决血脑屏障破坏及其药物刺激动力学的长期谜团方面取得巨大飞跃，这是许多关键神经系统疾病（如阿尔茨海默病）的标志。不限于拟议的血脑屏障研究，纳米棒平台将提供一个具有前所未有的空间分辨率，时间精度和分子释放可控性的变革性工具，以促进其他单细胞研究学科，包括细胞-细胞通信，信号通路，干细胞和生物物质递送。预计它将对多个领域产生重大影响，包括纳米机器人，纳米传感，纳米机电系统，单细胞研究和药物输送。

A largely unmet challenge in single-cell study is to deliver accurate molecular doses and release them with prescribed rates to a designated single living cell in the midst of many, or to a specific sub-cellular location. The overcoming of this challenge will have profound impact on single-cell bioscience and targeted medical interventions, particularly for many important brain diseases. In this work, an innovative platform based on intelligent and controllable nanoparticle robots is proposed to deliver desired dose of biosubstances at programmable release rates at desired single/sub-cellular locations. Such device will allow unprecedented levels of manipulation in both cell culture and tissue setting. Particularly, the platform will be employed to deliver drug molecules to blood-brain barrier, a vital component in the brain structures that protect the neurons from circulating insults of toxins, antibodies, immune cells. If successful, the understanding of blood-brain barrier regulation on the single/subcellular level will be unveiled, which will add new knowledges critical for finding solutions for many neurologic diseases. The project will also provide undergraduate and graduate students rarely available opportunities in the interdisciplinary field of nanorobotics, nanoelectromechanical systems, and nanosensing. An educational website will be launched to timely highlight the recent achievements and to intrigue the awareness and interest of the public in cutting-edge scientific advances. A professional symposium will be organized to bring researchers to this emerging field and to foster collaborations.The innovative nanoparticle based robotic platform for smart biosubstance delivery and sensing will utilize strategically designed plasmonic-active nanostructures to precisely transport and programmably release biosubstances to a single live cell amidst many with sub-cellular resolution, and simultaneously monitor the molecule release process by optical spectroscopy. To realize such a system, the proposed research will address challenges on the material, device, and system levels and demonstrate the applications of the platform in manipulating and understanding localized blood-brain barrier drug permeability and delivery. It is expected to make a giant leap towards understanding and resolving the long-standing mystery of blood-brain barrier breakdown and its drug stimulated dynamics, a hallmark of many critical neurologic diseases, such as Alzheimer's disease. Not limited to the proposed blood-brain barrier study, the nanorobtic platform will provide a transformative tool with unprecedented spatial resolution, temporal precision, and molecule release controllability to facilitate other single-cell research disciplines, including cell-cell communications, signal pathways, stem cells, and biosubstance delivery. It is expected to significantly impact multiple fields, including nanorobotics, nanosensing, nanoelectromechanical systems, single-cell research, and drug delivery.