以磷脂質修飾之石墨烯場效電晶體量測乙型類澱粉蛋白聚集

Abstract

阿茲海默症(Alzheimer’s disease, AD)是最常見的神經退化性疾病之一，主要病理特徵為神經細胞外的乙型類澱粉蛋白斑塊(β-amyloid plaque)，斑塊中主要成分乙型類澱粉蛋白(β-amyloid, Aβ)是一段由40到42個胺基酸組合成的胜肽(Aβ40, Aβ42)。阿茲海默症的真正成因至今未明，也沒有治療的藥物，因此乙型類澱粉蛋白是阿茲海默症的研究焦點之一。本研究利用單層石墨烯(graphene)製成場效電晶體生物感測器(field-effect transistor biosensor)來研究乙型類澱粉蛋白單體在脂雙層膜上的聚集現象(aggregation)。 石墨烯的高化學穩定性、高載子遷移率、高導熱、高導電性、高機械強度、可撓性，以及高透光率，讓其應用受到許多領域的關注與研究，石墨烯的二維結構亦可以提供磷脂雙層穩定支撐，因此本研究以單層石墨烯在透明石英基板表面製成場效電晶體，接著在元件表面上以囊泡融合法(vesicle fusion method)鋪上含有神經節苷脂GM1之支撐性磷脂雙層(supported lipid bilayer, SLB)，並透過液相閘極(solution gate)量測到乙型類澱粉蛋白聚集現象，並使用Thioflavin T做為螢光探針驗證脂雙層膜上形成之纖維狀聚集。此「膜修飾石墨烯場效電晶體」提供了一個新的生物感測平台，未來可應用來進一步了解乙型類澱粉蛋白聚集機制、篩檢乙型類澱粉蛋白聚集抑制藥物。

Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by neurofibrillary tangles and amyloid plaques. As the main component of the amyloid plagues, amyloid beta (Aβ), a peptide consisting of 40-42 amino acids, are crucially involved in Alzheimer’s disease. However, the knowledge around the disease pathogenesis is poorly understood and there is no effective cure for AD. Hence, a great deal of attention has focused on the study of Aβ. This research uses a lipid-modified graphene-based field-effect transistor (G-FET) as a biosensor to study the aggregation of Aβ on the supported lipid bilayer. Graphene has shown a great potential for research and applications because of its high chemical stability, high carrier mobility, high thermal conduction, high conductivity, flexibility, and high transmittance. Due to its two-dimensional (2D) nature, graphene possesses a large and stable interface with lipid membranes. We fabricated G-FET on a transparent quartz substrate, then modified a supported lipid bilayer containing GM1 on the G-FET by the vesicle fusion method. The as-fabricated G-FET biosensor is able to detect the aggregation of Aβ on the GM1 containing SLB. This aggregation is also verified by using Thioflavin T as a fluorescence indicator. With the capability of sensitively detecting the Aβ aggregation, this lipid-modified G-FET can be employed as a highly sensitive biosensing platform for further investigation of the mechanism of Aβ aggregation.