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: 9136231
• 负责人: Kendall H. Lee
• 金额: $ 79.44万
• 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 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9136231
• 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; Research; Scanning; Series; 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）：出于研究和临床原因，实时确定活体大脑中存在的神经递质水平是当前科学兴趣的一个问题，其中一个原因是需要了解和绘制大脑功能以及改善大脑功能。深部脑刺激（DBS）的临床应用是快速扫描循环伏安法（FSCV），但技术限制阻碍了其在体内长期使用。已经构建了一种可长期植入的 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，又具有足够的耐久性，可在人类或动物体内长期植入。碳纤维已在某些情况下得到成功使用，特别是在低浓度情况下。电压电位，但在检测神经递质（例如腺苷）所需的较高电压（例如高达+1.​​5V）下，其寿命非常有限。此外，当前的 FSCV 方法仅提供相对测量。神经递质浓度或浓度变化，但一旦电极被长期植入，由于缓冲效应，在任何情况下都不可能对用于植入的 FSCV 电极进行适当的台架校准。仅通过原位校准通过 FSCV 获得的浓度数据将被证明是非常有价值的，我们在这些领域的工作已经持续了好几年，初步结果表明，当适当掺杂时，多晶金刚石薄膜涂层可以达到最佳效果。 提供导电性，产生足够灵敏且耐用的电极 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建造，以制造基于多晶金刚石薄膜的电极。初步结果令人鼓舞，但我们建议继续这一开发。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物浓度，就目前而言，这两项工作是相辅相成的。因为他们都专注于长期植入 FSCV 神经递质监测设备以及最终的闭环 DBS 刺激器的目标。

项目成果

Tracking tonic dopamine levels in vivo using multiple cyclic square wave voltammetry.

• DOI: 10.1016/j.bios.2018.08.034
• 发表时间: 2018-12-15
• 期刊: Biosensors & bioelectronics
• 影响因子: 12.6
• 作者: Oh Y;Heien ML;Park C;Kang YM;Kim J;Boschen SL;Shin H;Cho HU;Blaha CD;Bennet KE;Lee HK;Jung SJ;Kim IY;Lee KH;Jang DP
• 通讯作者: Jang DP

Sensitive and Selective Measurement of Serotonin in Vivo Using Fast Cyclic Square-Wave Voltammetry.

使用快速循环方波伏安法灵敏、选择性地测量体内血清素。

• DOI: 10.1021/acs.analchem.9b03164
• 发表时间: 2020
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Shin,Hojin;Oh,Yoonbae;Park,Cheonho;Kang,Yumin;Cho,HyunU;Blaha,CharlesD;Bennet,KevinE;Heien,MichaelL;Kim,InYoung;Lee,KendallH;Jang,DongPyo
• 通讯作者: Jang,DongPyo

Instrumentation for electrochemical performance characterization of neural electrodes.

用于神经电极电化学性能表征的仪器。

• DOI: 10.1063/1.4993796
• 发表时间: 2017
• 期刊: The Review of scientific instruments
• 作者: Marsh,MichaelP;Kruchowski,JamesN;Hara,SethA;McIntosh,MalcomB;Forsman,RenaeM;Reed,TerryL;Kimble,Christopher;Lee,KendallH;Bennet,KevinE;Tomshine,JonathanR
• 通讯作者: Tomshine,JonathanR

On the surface tension and Zeta potential of electrolyte solutions.

• DOI: 10.1016/j.cis.2016.06.006
• 发表时间: 2017-06
• 期刊: Advances in colloid and interface science
• 影响因子: 15.6
• 作者: M. Manciu;F. Manciu;E. Ruckenstein