Neurotransmitter Absolute Concentration Determination with Diamond Electrode

 描述(由申请人提供)：实时测定活脑中存在的神经递质水平是当前出于研究和临床原因而产生的科学兴趣。这些原因之一是需要了解和绘制大脑功能图，以及改进脑深部刺激(DBS)的临床应用。一种具有潜在应用前景的分析技术是快速扫描循环伏安法(FSCV)，但技术限制阻碍了其在体内的慢性应用。尤其困难的是构建一种可长期植入的FSCV电极，该电极既具有监测神经递质水平的适当化学特性，又具有足够的耐久性，可用于在人类或动物体内长期植入。碳纤维在某些情况下已被成功使用，特别是在低电压下，但在检测腺苷等神经递质所需的较高电压下(例如，高达1.5V)，其寿命非常有限。此外，目前的FSCV方法仅提供神经递质浓度或浓度变化的相对测量，但一旦电极被长期植入，在工作台上重新校准就变得不可能。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。因此，通过FSCV提取绝对浓度数据而只需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，当适当地掺杂到 提供导电性，产生足够灵敏和耐用的电极 长期在体内使用。为了构建这些金刚石涂层的FSCV电极，我们实验室已经完成了化学气相沉积反应器的建设，以制造基于聚晶金刚石薄膜的电极。初步结果是有希望的，但我们建议继续这项开发工作。我们还确定，对FSCV程序进行简单修改，结合更复杂的数据分析程序，似乎可以确定分析物的绝对浓度。这两项工作是相辅相成的，因为他们都专注于长期可植入的FSCV神经递质监测设备的目标，并最终实现闭环式DBS刺激器。

 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.