Gupta Bhavna, Kepros Brandon, Landgraf Jann B, Becker Michael F, Li Wen, Purcell Erin K, Siegenthaler James R
bioRxiv. 2024 Aug 9:2024.08.07.606919. doi: 10.1101/2024.08.07.606919.
Neurochemical sensing with implantable devices has gained remarkable attention over the last few decades. A promising area of this research is the progress of novel electrodes as electrochemical tools for neurotransmitter detection in the brain. The boron-doped diamond (BDD) electrode is one such candidate that previously has been reported for its excellent electrochemical properties, including a wide working potential, superior chemical inertness and mechanical stability, good biocompatibility and resistance to fouling. Meanwhile, limited research has been conducted on the BDD as a microelectrode for neurochemical detection. Our team has developed a freestanding, all diamond microelectrode consisting of a boron-doped polycrystalline diamond core, encapsulated in an insulating polycrystalline diamond shell, with a cleaved planar tip for electrochemical sensing. This all-diamond electrode is advantageous due to its - (1) batch fabrication using wafer technology that eliminates traditional hand fabrication errors and inconsistencies, (2) absence of metal-based wires, or foundations, to improve biocompatibility and flexibility, and (3) sp carbon surface with resistance to biofouling, i.e. adsorption of proteins or unwanted molecules at the electrode surface in a biological environment that impedes overall electrode performance. Here, we provide findings on further in vitro testing and development of the freestanding boron-doped diamond microelectrode (BDDME) for neurotransmitter detection using fast scan cyclic voltammetry (FSCV). In this report, we elaborate on - 1) an updated fabrication scheme and work flow to generate all diamond BDDMEs, 2) slow scan cyclic voltammetry measurements of reference and target analytes to understand basic electrochemical behavior of the electrode, and 3) FSCV characterization of common neurotransmitters, and overall favorability of serotonin (5-HT) detection. The BDDME showed a 2-fold increased FSCV response for 5-HT in comparison to dopamine (DA), with a limit of detection of 0.16 µM for 5-HT and 0.26 µM for DA. These results are intended to expand on the development of the next generation BDDME and guide future in vivo experiments, adding to the growing body of literature on implantable devices for neurochemical sensing.
在过去几十年里,利用可植入设备进行神经化学传感受到了极大关注。该研究中一个有前景的领域是新型电极作为用于检测大脑中神经递质的电化学工具的进展。硼掺杂金刚石(BDD)电极就是这样一种候选电极,此前已有报道称其具有优异的电化学性能,包括宽工作电位、卓越的化学惰性和机械稳定性、良好的生物相容性以及抗污染能力。与此同时,关于BDD作为用于神经化学检测的微电极的研究有限。我们的团队开发了一种独立式全金刚石微电极,它由硼掺杂多晶金刚石芯组成,封装在绝缘多晶金刚石壳中,具有用于电化学传感的劈开平面尖端。这种全金刚石电极具有以下优势:(1)采用晶圆技术进行批量制造,消除了传统手工制造的误差和不一致性;(2)不存在金属基导线或基底,以提高生物相容性和灵活性;(3)具有抗生物污染的sp碳表面,即在生物环境中电极表面蛋白质或不需要分子的吸附会阻碍整体电极性能。在此,我们提供了关于使用快速扫描循环伏安法(FSCV)对独立式硼掺杂金刚石微电极(BDDME)进行神经递质检测的进一步体外测试和开发的研究结果。在本报告中,我们详细阐述了:1)生成全金刚石BDDME的更新制造方案和工作流程;2)对参考和目标分析物进行慢扫描循环伏安法测量,以了解电极的基本电化学行为;3)常见神经递质的FSCV表征以及血清素(5-HT)检测的总体适宜性。与多巴胺(DA)相比,BDDME对5-HT的FSCV响应提高了2倍,5-HT的检测限为0.1 µM,DA的检测限为0.26 µM。这些结果旨在扩展下一代BDDME的开发,并指导未来的体内实验,为关于用于神经化学传感的可植入设备的不断增长的文献增添内容。