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

双聚合物涂层可实现 MEA 体内可卡因的高保真度和稳定感测

• 批准号: 9453776
• 负责人: XINYAN Tracy CUI
• 金额: $ 19.05万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9453776
• 关键词: Adolescent; Adult; Albumins; Autopsy; Binding; Biological; Biosensor; Brain; Brain region; Calibration; Chemistry; Cocaine; Cocaine Abuse; Cocaine Dependence; Corpus striatum structure; Deoxyribonucleases; Deposition; Detection; Diagnosis; Dorsal; Drug Kinetics; Effectiveness; Electrodes; Environment; Event; Exhibits; Gold; Hour; Hydration status; Implant; In Vitro; Infusion procedures; Injection of therapeutic agent; Location; Longevity; Measurement; Measures; Medical; Methacrylates; Methodology; Microdialysis; Microelectrodes; Monitor; Nature; Neurosciences; Neurosciences Research; Pattern; Performance; Physiological; Polymers; Proteins; Rattus; Reproducibility; Resistance; Signal Transduction; Silanes; Silicon; Site; Sulfhydryl Compounds; Surface; Technology; Testing; Time; Tissues; addiction; age effect; age related; aptamer; base; biological research; biomaterial compatibility; brain tissue; cocaine use; design; electric impedance; experimental study; hydrophilicity; implantation; implanted sensor; improved; in vivo; monomer; neural circuit; neuropathology; neurophysiology; novel; polymerization; psychostimulant; response; sensor; symposium; temporal measurement

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.

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上瘾。最近的 有证据表明，这种脆弱性的增加源于生物学，因此提出了以下问题： 这种年龄效应是否是由于神经回路或大脑中局部可卡因浓度的差异造成的。在 为了研究这个问题和其他重要的神经科学问题，毫无疑问有必要开发 可卡因传感技术能够直接测量多个离散的实时瞬态事件 整个大脑的区域。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。我们最近有 在硅基微电极阵列上开发了基于电化学适体的体内可卡因传感器 （MEA）平台能够直接从离散的大脑位置测量可卡因。该传感器表现出 检测限为 1 µM，具有出色的空间和时间分辨率，并且可以保持可重复的检测 3个小时的时间里。 3 小时后，观察到性能下降，可能是由于生物污垢和 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 对生物污垢具有高度抵抗力。为了提高适配体的结合效率和稳定性，一种新型的电适配体 将开发能够与硫醇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对这些聚合物进行图案化的方法 MEA 上的涂层以获得最佳的传感能力和防污性，然后测试聚合物的能力 改进的可卡因传感器可在 72 年内重复地直接测量体内可卡因浓度 小时。将比较成人和成人重复静脉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。 所提出的传感器将成为第一个能够测量体内可卡因的技术 数小时和数天的浓度。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，改进的微电极还能够 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，基于适配体的电化学传感平台可以推广到 广泛的重要分析物，同时高度功能化和防污涂层可以 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。