Antibody Encapsulated Electrochemical Biosensor for GABA

描述（申请人提供）：γ -氨基丁酸（GABA）是哺乳动物神经系统主要的抑制性神经递质，在神经功能和功能障碍中起重要作用。GABA的精确实时测量将极大地加速发现GABA在运动障碍（包括亨廷顿氏病和帕金森病）、癫痫、肌阵挛性放电和酒精成瘾中的关键作用。目前GABA的细胞外测量技术主要集中在脑脊液的微透析，然后是液相色谱法结合柱前/柱后衍生化。基于液相色谱的测量不是连续的，而微透析是一种侵入性手术，导致神经元死亡和反应性胶质瘤，且时空分辨率差。INFRAMAT提出利用功能化生物材料的可行性，通过“竞争性酶免疫测定”策略，电化学测量非电活性GABA神经递质，显着提高生物传感器在高灵敏度GABA检测中的性能。该技术将采用IMC的湿式化学合成技术生产抗体连接纳米颗粒，将功能化纳米颗粒固定在传感器上，获得高灵敏度的生物传感器，用于实时监测GABA浓度，并能够在人工脑脊液中对基于功能化纳米颗粒的生物传感器进行体外测试。这种纳米工程方法将使生物传感器能够连续和直接测量GABA浓度，并且可以扩展到多个通道，以获得脑切片和细胞培养制剂中的时空分布。

DESCRIPTION (provided by applicant): Gamma-aminobutyric acid ("GABA") is a main mammalian nervous system inhibitory neurotransmitter, playing important roles in neural function and dysfunction. Accurate real time measurement of GABA will greatly accelerate discoveries on the key role of GABA in motor disorders including Huntington's disease and Parkinson's, seizures, myoclonic discharges, and alcohol addiction. Current technology for extracellular measurement of GABA focuses on microdialysis of the cerebro-spinal fluid, followed by liquid chromatography combined with pre-/post column derivatization. Liquid chromatography-based measurements are not continuous, while microdialysis is an invasive procedure causing neuronal death and reactive gliosis with poor spatial-temporal resolution. INFRAMAT proposes to demonstrate feasibility of exploiting functionalized biomaterials to dramatically improve biosensor performance in high sensitivity GABA detection, via a "competitive enzyme immunoassay" strategy, electrochemically measuring non-electroactive GABA neurotransmitters. The proposed technology will adopt IMC's wet chemical synthesis to produce antibody-linked nanoparticles, immobilize functionalized nanoparticles onto transducers to obtain high sensitivity biosensors for real time monitoring GABA concentrations, and enable in-vitro testing of the biosensor based functionalized nanoparticles in artificial cerebro-spinal fluid. This nano-engineered approach will enable biosensors for continuous and direct measurement of GABA concentrations, and can be extended to multiple channels to obtain a spatial-temporal distribution in brain slice and cell culture preparations.