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: 8935968
• 负责人: Kendall H. Lee
• 金额: $ 79.25万
• 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/8935968
• 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; Essential Tremor; FDA approved; Family suidae; Film; Goals; Health; Human; Implant; In Situ; In Vitro; Intervention; Life; Major Depressive Disorder; 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; 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（由申请人提供）：确定在真实的时间内存在于活脑中的神经递质的水平是当前出于研究和临床原因的科学兴趣的问题。这些原因之一是需要理解和映射脑功能，并改善脑深部电刺激（DBS）的临床应用。在该应用中具有潜在前景的一种分析技术是快速扫描循环伏安法（FSCV），然而技术限制阻碍了其用于长期体内使用。特别困难的是长期植入的FSCV电极的构造，其具有用于监测神经递质水平的适当化学性质以及用于长期植入人或动物的足够耐久性。碳纤维已经在某些情况下成功地使用，特别是在低电压电势下，但是在检测神经递质如腺苷（例如，高达+1.5V），其寿命非常有限。此外，目前的FSCV方法仅提供了神经递质浓度或浓度变化的相对测量，但是一旦电极被长期植入，在工作台上重新校准它就变得不可能。由于缓冲效应，在任何情况下都不可能对预期用于植入的FSCV电极进行适当的工作台校准。因此，一种通过FSCV提取绝对浓度数据并仅进行现场校准的方法将被证明是非常有价值的。 我们在这些领域的工作已经进行了几年，初步结果表明，当适当掺杂时， 提供导电性，产生既足够灵敏又耐用的电极 用于长期体内使用。为了构建这些金刚石涂层FSCV电极，我们的实验室已经完成了化学气相沉积反应器的构建，以创建基于多晶金刚石膜的电极。初步结果是有希望的，但我们建议继续这项发展工作。 我们还确定，FSCV程序的简单修改，结合更复杂的数据分析程序，似乎允许绝对分析物浓度的测定。这两条工作线是相互加强的，因为它们都专注于长期植入式FSCV神经递质监测装置的目标，并最终成为闭环DBS刺激器。