Neurotransmitter Absolute Concentration Determination with Diamond Electrode

用金刚石电极测定神经递质绝对浓度

• 批准号: 8826512
• 负责人: Kendall H. Lee
• 金额: $ 80.09万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8826512
• 关键词: Acute; Adenosine; Adoption; Algorithms; Animals; Area; Biocompatible Coated Materials; Brain; Brain Chemistry; Brain Mapping; Buffers; Calibration; Carbon; Chemicals; Chronic; Clinical; Data; Data Analyses; Deep Brain Stimulation; Deposition; Detection; Development; Devices; Diamond; Disease; Dopamine; Electric Conductivity; Electrodes; Endogenous depression; Essential Tremor; FDA approved; Family suidae; Film; Goals; Human; Implant; In Situ; In Vitro; Intervention; Life; Measures; Mediating; Methodology; Microscopy; Modeling; Modification; Monitor; Mood Disorders; Motor; Neurotransmitters; Operative Surgical Procedures; Parkinson Disease; Patients; Physiologic pulse; Procedures; Property; Rattus; Relative (related person); Research; Scanning; Series; Solutions; Stress Tests; Techniques; Testing; Time; Work; awake; base; carbon fiber; chemical property; clinical application; design; functional improvement; implantation; in vitro testing; in vivo; interest; monitoring device; neurochemistry; neurotransmitter release; public health relevance; vapor; voltage

 DESCRIPTION (provided by applicant): Determining the levels of neurotransmitters present in the living brain in real time is a matter of current scientific interest for research and clinicl reasons. Among these reasons is the need for understanding and mapping brain function and for improvement in the clinical application of deep brain stimulation (DBS). One analytical technique that holds potential promise in this application is fast-scan cyclic voltammetry (FSCV), however technical limitations have hindered its adoption for chronic in vivo use. Of particular difficulty has been the construction of a chronically-implantable FSCV electrode that possesses both the proper chemical properties for the monitoring of neurotransmitter levels as well as sufficient durability for chronic implantation in humans or animals. Carbon fiber has been used successfully under some circumstances, particularly at low voltage potentials, but at the higher voltages required for detection of neurotransmitters such as adenosine (e.g., up to +1.5V), its lifetime is very limited. Additionally, current FSCV methodology provides only a relative measure of neurotransmitter concentration or concentration change, but once an electrode is implanted chronically, recalibrating it on the bench becomes impossible. Due to buffer effects, proper bench calibration of a FSCV electrode intended for implantation is impossible in any case. Therefore, a means to extract absolute concentration data via FSCV with only in situ calibration would prove extremely valuable. Our work in these areas has been ongoing for several years, and initial results indicate that a coating of polycrystalline diamond film, when properly doped to provide electrical conductivity, yields electrodes that are both sufficiently sensitive and durable for chronic in vivo use. To construct these diamond-coated FSCV electrodes, our lab has already completed the construction of a chemical vapor deposition reactor to create polycrystalline diamond film-based electrodes. Initial results have been promising, but we propose to continue this development work. We have also determined that simple modifications to the FSCV procedure, combined with more sophisticated data analysis procedures, appear to allow for the determination of absolute analyte concentration. These two lines of work are mutually-reinforcing insofar as they are both focused on the goal of a long-term implantable FSCV neurotransmitter-monitoring device and, ultimately, a closed-loop DBS stimulator.

 描述（应用程序提供）：确定实时生存大脑中存在的神经递质的水平是目前出于研究和临床原因的科学兴趣。这些原因包括需要理解和映射大脑功能，并改善深脑刺激（DBS）的临床应用。在此应用中具有潜在希望的一种分析技术是快速扫描的循环伏安法（FSCV），但是技术限制阻碍了其用于体内慢性使用的采用。特别困难的是构建长期植入的FSCV电极，该电极既具有用于监测神经递质水平的适当化学特性，又假定了人类或动物中慢性植入的足够耐用性。在某些情况下，尤其是在低压电势下成功使用了碳纤维，但是在检测神经递质（例如腺苷（例如，高达 +1.5V））所需的较高电压下，其寿命非常有限。此外，当前的FSCV方法仅提供了神经递质浓度或浓度变化的相对度量，但是一旦将电极长期植入，将其重新校准了，将其重新校准。由于缓冲效果，在任何情况下都不可能对旨在植入的FSCV电极进行适当的台式校准。因此，仅通过原位校准通过FSCV提取绝对浓度数据的手段将被证明非常有价值。我们在这些领域的工作已经进行了几年，最初的结果表明，正确掺杂到多晶钻石膜的涂层 提供电导率，产生足够敏感且耐用的电子 用于慢性体内使用。为了构建这些钻石涂层的FSCV电极，我们的实验室已经完成了化学蒸气沉积反应器的构建，以创建基于多晶钻石膜的电极。已承诺最初的结果，但我们建议继续这项开发工作。我们还确定，对FSCV程序的简单修改与更复杂的数据分析程序相结合，似乎可以确定绝对分析浓度。这两条工作是相互强化的，因为它们都集中在长期可植入的FSCV神经递质监测设备上，并最终是闭环DBS刺激器。