Dual Polymer Coatings for High Fidelity and Stable In Vivo Cocaine Sensing From MEAs

可卡因是一种高度上瘾的精神刺激剂，在整个大脑中表现出特定的区域活动。 人们普遍认为，青少年比成年人更容易染上可卡因成瘾。近期 有证据表明，这种增加的脆弱性源于生物，因此提出了一个问题 无论这种年龄效应是由于神经回路的差异还是大脑中局部可卡因浓度的差异。在……里面 为了研究这个和其他重要的神经科学问题，毫无疑问有必要开发 一种可直接测量多离散实时瞬变事件的可卡因传感技术 大脑的各个区域。目前体内可卡因定量的惯例(微透析， 均质化的组织成分等)缺乏必要的空间和时间分辨率。我们最近做了 基于硅基微电极阵列的体内可卡因电化学适配子传感器的研制 (MEA)能够从离散的大脑位置直接测量可卡因的平台。该传感器表现出 检测下限为1微米，具有良好的空间和时间分辨率，并可保持检测的重复性 在3个小时的过程中。3小时后，观察到性能可能由于生物污垢和 适体分离。 我们建议开发和应用先进的双聚合物涂层策略来提高灵敏度 和传感器的稳定性。涂层包括非导电和导电的两性离子聚合物 高度抵抗生物污垢。为了提高核酸适体结合效率和稳定性，一种新型的电子 将开发能够与硫代化适配子生物偶联的导电聚合物。我们假设 这些聚合物涂层的加入将长期改善可卡因传感器的性能 植入。该项目的具体目标是开发设计这些聚合物的方法。 在MEAS上涂覆以获得最佳的传感能力和防污垢性能，然后测试聚合物的能力- 改装的可卡因传感器可直接测量体内可卡因浓度，可在72小时内重复测量 几个小时。重复静脉注射可卡因的局部脑浓度将在成人和成人之间进行比较 确定青春期大鼠年龄来源的影响。 该传感器将成为首个能够在体内测量可卡因的技术。 注意力集中在几个小时和几天。这项技术有可能使我们的 对可卡因滥用和成瘾的了解。此外，修饰后的微电极还能够 记录神经生理信号。具有双重功能的植入式传感器将对 神经科学研究。最后，基于适配子的电化学传感平台可以推广到 范围广泛的重要分析物，而高度功能化和防污染的涂层可以 应用于广泛的生物研究领域和医学领域的其他植入式生物传感器 诊断。

Cocaine is a highly addictive psychostimulant that exhibits region-specific activity throughout the brain. It is widely accepted that adolescents present a higher vulnerability to cocaine addiction than adults. Recent evidence has suggested that this increased vulnerability is biological in origin, thus raising the question of whether this age effect is due to differences in neural circuitry or local cocaine concentration in the brain. In order to investigate this and other important neuroscience questions, it is unequivocally necessary to develop cocaine sensing technology capable of directly measuring real-time transient events at multiple discrete regions throughout the brain. Current conventions for in vivo cocaine quantification (microdialysis, homogenized tissue composition, etc.) lack the necessary spatial and temporal resolution. We have recently developed an electrochemical aptamer-based in vivo cocaine sensor on a silicon based microelectrode array (MEA) platform capable of directly measuring cocaine from discrete brain locations. The sensor exhibits a detection limit of 1 µM with excellent spatial and temporal resolution and can maintain a reproducible detection over the course of 3 hours. After 3 hours, performance degradation was observed likely due to biofouling and aptamer detachment. We propose to develop and apply advanced dual polymer coating strategy to improve the sensitivity and stability of the sensor. The coatings include non-conductive and conductive zwitterionic polymers that are highly resistant to biofouling. To improve the aptamer binding efficiency and stability, a novel electrically conducting polymer will be developed capable of bio-conjugation with thiolated aptamers. We hypothesize that the incorporation of these polymer coatings will improve cocaine sensor performance over long-term implantation. The specific objectives of this project are to develop the methodology to pattern these polymer coatings on MEAs for the best sensing capability and fouling resistance and then test the ability of the polymer- modifed cocaine sensor to directly measure in vivo cocaine concentration reproducibly over a period of 72 hours. The local brain concentration of cocaine upon repeated IV injection will be compared between adult and adolescent rats to determine the origin of the age effect. The proposed sensor will serve as the first ever technology capable of measuring in vivo cocaine concentration over multiple hours and days. This technology has the potential to revolutionize our understanding of cocaine abuse and addiction. Additionally, the modified microelectrodes are also able to recording neurophysiological signals. Implantable sensors with dual functionality will have a broad impact on neuroscience research. Finally, the aptamer based electrochemical sensing platform can be generalized to a broad range of important analytes, while the highly functionalizable and fouling resistant coatings can be applied to other implantable biosensors throughout a broad range of biological research fields and medical diagnosis.