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

可卡因是一种高度成瘾的精神兴奋剂，在整个大脑中表现出特定区域的活动。 人们普遍认为，青少年比成年人更容易对可卡因上瘾。最近 有证据表明，这种脆弱性的增加是生物起源，因此提出了一个问题， 这种年龄效应是否是由于神经回路的差异或大脑中局部可卡因浓度的差异。在 为了研究这个和其他重要的神经科学问题，毫无疑问，有必要发展 可卡因传感技术能够直接测量多个离散点的实时瞬时事件 大脑的各个区域。目前用于体内可卡因定量的惯例（微透析， 均质化的组织组合物等）缺乏必要的空间和时间分辨率。我们最近 开发了一种基于硅基微电极阵列的电化学适体体内可卡因传感器 (MEA)该平台能够直接测量来自离散大脑位置的可卡因。该传感器具有 检测限为1 µM，具有出色的空间和时间分辨率，可保持可重复检测 在三个小时的过程中。3小时后，观察到性能下降，可能是由于生物结垢， 适体脱离。 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两性离子聚合物， 高度抗生物污垢。为了提高适体结合效率和稳定性，使用了一种新的电 将开发能够与硫醇化适体生物缀合的导电聚合物。我们假设 这些聚合物涂层的结合将改善可卡因传感器的长期性能 置入本项目的具体目标是开发方法来图案化这些聚合物 膜电极上的涂层，以获得最佳的传感能力和抗污染能力，然后测试聚合物的能力， 改进的可卡因传感器，以在72周的时间内可重复地直接测量体内可卡因浓度 小时将在成人和成人之间比较重复IV注射后可卡因的局部脑浓度。 青春期大鼠，以确定年龄效应的起源。 该传感器将成为有史以来第一个能够测量体内可卡因的技术 浓度超过数小时和数天。这项技术有可能彻底改变我们的 了解可卡因滥用和成瘾。此外，修饰的微电极还能够 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，基于适体的电化学传感平台可以被推广到 广泛的重要分析物，而高度官能化和防污涂层可以 应用于遍及广泛的生物研究领域和医学领域的其他可植入生物传感器。 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.