Carbon nanotube fiber and yarn microelectrodes for high temporal resolution measu

描述(由申请人提供)：神经递质的实时测量对于了解大脑中化学信号是如何控制的以及在神经疾病期间它是如何发生故障的至关重要。神经传递的调节发生在毫秒的时间尺度上，但监测神经递质浓度一直被仪器限制在秒到分钟的时间尺度上。神经递质测量需要高时间分辨率和高灵敏度，因为纳摩尔浓度变化是预期的。这项研究的目标是开发高灵敏度、高时间分辨率的电化学传感器，以了解在毫秒级时间尺度上多巴胺浓度的调节。该方法是制作高灵敏度的碳纳米管丝和碳纳米管纤维微电极，用于快速扫描循环伏安法(FSCV)的高时间分辨率测量。FSCV既提供了用于识别被检测物种的指纹，也提供了高时间分辨率。然而，对于传统的碳纤维微电极，扫描通常以100ms的间隔重复进行，因为灵敏度随着重复频率的增加而降低。初步数据表明，碳纳米管纱线和碳纳米管纤维微电极不存在这一缺陷，可以快速重复使用。碳纳米管微电极有望提供1纳米的检测极限和2毫秒的时间分辨率，这足以 首次在体内表征单一刺激脉冲后的多巴胺释放。首次对碳纳米管纤维作为微电极材料进行了研究。这些纤维是通过湿法纺丝技术制成的，方法是将碳纳米管挤出到聚乙烯亚胺等凝固剂中。第二个目标是测试碳纳米管纱线作为微电极传感器。碳纳米管纱线是一种商业材料，它是通过将排列好的碳纳米管阵列扭曲成排列好的碳纳米管纱线而制成的。对于碳纳米管纱线和碳纳米管纤维微电极，将研究氧化物官能化对吸附和电化学性能的影响。最好的传感器将用于表征体内多巴胺的释放，以表明它们对于生物样本的高时间分辨率测量是有用的。从单个刺激脉冲测量释放的能力将支持这样的假设，即在脉冲激发期间，单个刺激之间的间隔调节要测试的多巴胺的释放量。这项工作意义重大，因为它将克服监测多巴胺释放的关键仪器障碍，并允许首次在毫秒时间尺度上表征多巴胺，速度比目前可能的速度快50倍。这将为未来研究多巴胺的毫秒级调节如何影响成瘾等疾病打开大门。这些传感器还可以用来监测其他电活性化合物，包括腺苷、5-羟色胺、去甲肾上腺素、组胺、抗坏血酸和过氧化氢。因此，潜在的影响是更好地理解许多神经递质和神经调节剂的毫秒调节。

DESCRIPTION (provided by applicant): Real-time measurements of neurotransmitters are critical for understanding how chemical signaling is controlled in the brain and how it malfunctions during neurological diseases. Regulation of neurotransmission occurs on a millisecond time scale but monitoring neurotransmitter concentrations has been instrumentally limited to the second to minute time scale. Neurotransmitter measurements require both high temporal resolution and high sensitivity, as nanomolar concentration changes are expected. The goal of this research is to develop high sensitivity, high temporal resolution electrochemical sensors to understand the regulation of dopamine concentrations on a millisecond time scale. The strategy is to fabricate high sensitivity carbon nanotube (CNT) yarn and CNT fiber microelectrodes for high temporal resolution measurements with fast-scan cyclic voltammetry (FSCV). FSCV provides both a fingerprint for identification of the species being detected and high temporal resolution. However, the scan is usually repeated at 100 ms intervals with traditional carbon-fiber microelectrodes because sensitivity decreases with increasing repetition rate. Preliminary data show that CNT yarn and CNT fiber microelectrodes do not suffer from this drawback and can be used with rapid repetition rates. The CNT microelectrodes are expected to provide a 1 nM limit of detection with 2 ms temporal resolution, which is sufficient to characterize dopamine release after single stimulation pulses in vivo for the first time. The firs aim is to study CNT fibers as microelectrode materials. The fibers are made by wet spinning techniques, by extruding CNTs into a coagulant such as polyethyleneimine. The second aim is to test CNT yarns as microelectrode sensors. CNT yarns are a commercial material that is made by twisting aligned CNT arrays into aligned CNT yarns. For both CNT yarn and CNT fiber microelectrodes, the effects of oxide functionalization on adsorption and electrochemical properties will be studied. The best sensors will be used to characterize dopamine release in vivo to show that they are useful for high temporal resolution measurements in a biological sample. The ability to measure release from a single stimulation pulse will enable the hypothesis that the interval between single stimulations during burst firing regulates the amount of dopamine release to be tested. This work is significant because it will overcome a critical instrumentation barrier for monitoring dopamine release and allow the first characterization of dopamine on the millisecond time scale, 50-times faster than currently possible. This will open the door for future studies of how millisecond regulation of dopamine impacts diseases, such as addiction. These sensors could also be implemented to monitor other electroactive compounds including adenosine, serotonin, norepinephrine, histamine, ascorbic acid, and hydrogen peroxide. Thus, the potential impact is a better understanding of the millisecond regulation of many neurotransmitters and neuromodulators.