CAREER: Functionalized Diamond Surfaces for Neuro-Sensing and Stimulation

基于钻石的电极是一个令人兴奋的最新发展，它有望比目前用于生物医学研究的电极传感器技术具有重大优势。该项目的主要研究目标是开发导电的、表面功能化的纳米级金刚石基材料，作为神经传感和刺激的优良电极。新奇之处在于，钻石提供了一个独特的机会，可以在同一设备中集成刺激和感知。这项研究是PI在生物电化学材料工程方面长期努力的基础。这也将是纳入拟议教育计划的几个重点领域之一：一个面向研究的中心(明天的化学工程-体验研究)计划，使本科生和研究生都受益。通过该中心计划，本科生将接触到一套以研究为导向的课程和实验模块；选定的研究生将教授这些课程块作为指导教学经验，为他们提供专业发展。拟议活动的智力价值。(1)基于金刚石的电极将提供实时的神经传感能力，大大提高了灵敏度、选择性和稳定性，并扩大了现有材料的潜在操作范围。这些优势将通过对多巴胺和腺苷的体外传感来证明。(2)明确定义的钻石表面化学允许功能化可能提供特定的化学相互作用，从而区分生物分析物。(3)钻石的高度稳定的反应也为动作电位的测量提供了有利条件。(4)钻石电极可以通过避免导致组织损伤的水的水解和提供长期的稳定性来扩展神经刺激能力。这些能力，如果实现，将适用于广泛的神经系统。(5)通过使用基于钻石的传感器，可以更多地了解多巴胺作为调节性神经递质在控制加州海兔摄食行为的神经电路中的作用。最后，(6)在体外实时检测腺苷的能力是新颖的，将有助于阐明其在调节负责启动呼吸节律的神经元中的作用。研究影响：(1)拟议的项目应该为神经应用提供一整套坚固的、基于钻石的设备的基础，这些设备可以扩展到更广泛的生物医学研究领域。(2)纳米功能化的金刚石表面可以在包括催化在内的各种领域中得到应用。(3)钻石的高灵敏度可能为研究人员提供了一种监测自然神经动力学行为的工具，而不是电刺激放大的神经动力学行为。(4)钻石长期持续监测多巴胺的能力最终可能导致为这些疾病的患者开发可植入的多巴胺传感器。(5)新的、实时的体外腺苷水平测量可以为理解腺苷的调节机制提供许多未来的方向。(6)同时测量多巴胺和腺苷的能力可以深入了解它们在帕金森病中的共同作用。(7)更好、更稳定的钻石基神经刺激装置可能会导致健壮的神经假体的发展。最后，(8)集成传感和刺激装置的钻石将能够操纵特定的神经活动，并实时监测对空间中其他神经元的影响，提供一种多功能、可植入的神经控制装置。教育影响：(1)该中心计划将加强PI实验室和化学工程系的研究和教学的整合。(2)这种指导教学经验可以为凯斯大学的研究生专业发展计划提供一个基石，并可作为其他大学的典范。(3)该计划将产生更强大的未来新教师队伍，他们将成为更好的教师，更好地关注教师生活。最后，(4)通过中心计划，本科生应该为研究或工业职业做好更好的准备。

ABSTRACTDiamond-based electrodes are an exciting, recent development that promises major advantages over present electrode sensor technologies used in biomedical research. The main research objective of this project is to develop conductive, surface-functionalized at the nano-scale, diamond-based materials as superior electrodes for neurological sensing and stimulation. The novelty is that diamond provides a unique opportunity to integrate stimulation and sensing in the same device. This research is the basis of the PI's long-term efforts in engineering of bio-electrochemical materials. It will also be one of several focus areas incorporated into the proposed educational program: a research-oriented CENTER (Chemical ENgineering of Tomorrow - Experience Research) program benefiting both undergraduate and graduate students. Through the CENTER program, undergraduates will be exposed to a set of research-oriented courses and lab modules; select graduate students will teach the course blocks as mentored teaching experiences, providing them with professional development.Intellectual Merit of Proposed Activities. (1) Diamond-based electrodes will provide real-time neurological sensing capability, with greatly improved sensitivity, selectivity and stability, as well as an expanded potential range of operation over present materials. These advantages will be demonstrated through in vitro sensing of dopamine and adenosine. (2) The well-defined surface chemistry of diamond permits functionalization to likely provide specific chemical interactions that can discriminate between bioanalytes. (3) The highly stable response of diamond should also provide advantage for measurement of action potentials. (4) Diamond electrodes may expand neural stimulation capabilities by avoiding water hydrolysis that leads to tissue damage and by providing long-term stability. These capabilities, if achieved, will be applicable to a broad variety of neurological systems. (5) Through use of diamond-based sensors, much may be learned of the role of dopamine as a modulatory neurotransmitter in the neural circuitry that controls feeding behaviors in the Aplysia Californica (sea slug). Lastly, (6) the ability to detect adenosine in vitro in real-time is novel and will help elucidate its role in modulating the neurons responsible for the initiation of respiratory rhythm.Broader Impacts of Proposed Activities. Research impacts: (1) The proposed project should provide the basis of a whole class of robust, diamond-based devices for neurological applications, which could be extended into broader areas of biomedical research. (2) Nano-Functionalized diamond surfaces may provide application in a variety of areas including catalysis. (3) Diamond's higher sensitivity may provide researchers with a tool to monitor natural neurodynamic behaviors instead of those amplified by electrical stimulation. (4) Diamond's capability for long-term continuous monitoring of dopamine could eventually lead to development of implantable dopamine sensors for patients with these illnesses. (5) Novel, realtime measurement of adenosine levels in vitro could provide many future directions in understanding adenosine modulatory mechanisms. (6) The ability to simultaneously measure dopamine and adenosine could provide insight into their coupled roles in Parkinson's disease. (7) Superior, stable diamond-based neural stimulation devices may lead to development of robust neural prostheses. Lastly, (8) Diamond in an integrated sensing and stimulation device would be capable of both manipulating specific neural activity and monitoring the effects on other neurons in space and in real-time, providing a versatile, implantable neural control device. Educational Impacts: (1) The CENTER program will strengthen the integration of research and teaching in the PI's laboratory and the chemical engineering department. (2) This mentored teaching experience could provide a cornerstone for a graduate professional development program at Case, to use as a model at other universities. (3) The program will generate a stronger pool of future new faculty who will be better teachers and better oriented about faculty life. Finally, (4) through the CENTER program, undergraduates should be better prepared for research or industrial careers.