利用CMOS-BioMEMS製程之微懸臂樑式蘭花病毒感測器

Abstract

本篇論文致力於開發蘭花病毒感測器；蘭花是我國農業重要精緻農業作物，每年約有數十億新台幣之出口貿易，故關於蘭花培養照護和出口前的品質把關相當地重要，因此快速而準確的蘭花病毒檢測一直是備受注目的課題。在本篇論文中所檢測之齒舌蘭輪斑病毒(ORSV)是感染蘭花最嚴重之病毒之一，是造成蘭花出口經濟影響最嚴重病毒之一，故能在田間快速檢測ORSV將對蘭花產業帶來極大助益。本論文將利用壓阻機制之微懸臂樑式生物感測器進行蘭花常見的病毒(例如：ORSV)之檢測。 在本研究當中先使用原子力顯微鏡(AFM)對感測器上之微懸臂樑進行特性分析(例如：剛性與壓阻特性)，以達到觀察生物分子結合時之表面應力變化現象，並為此感測器設計聚二甲基矽氧烷(PDMS)之流體腔室封裝，以隔離生物溶液與輸出電路並達到減低雜訊之效果；本研究中將ORSV-IgG為生物標定物，先固定在微懸臂樑表面隨後與ORSV 病毒結合，本感測器之ORSV檢測極限經實驗量測為1 ng/μl。 此微懸臂樑式生物感測器由是基於台積電CMOS之2P4M製程加上BioMEMS後製程所製造，相較於其他傳統的蘭花病毒檢測技術，例如ELISA或是RT-PCR大多在需要實驗室環境中進行，實驗步驟複雜大多需要有經驗之操作人員，或是需要昂貴之光辨識儀器進行辨識；微懸臂樑生物感測器配合簡單的電路設計可擁有不需額外標記、快速、和可攜式等優點，並具備成為即時現場照護(point-of-care)檢測平台之潛力。

This thesis is devoted to developing a portable sensor to detect orchid virus of Odontoglossum ringspot tobamovirus (ORSV) - one of the most prevalent viruses causing orchid diseases. Since orchid is the most important plant in Taiwan which accounts for billons-of-NT-dollars per year in floriculture exports, our proposed method resorts to a portable and fast detection device that can be operated on-site with a high accuracy. The device utilizes piezoresistive mechanism in c cantilevers to realize the specific bindings to pathogen molecules of interests (i.e. ORSV). Atom Force Microscope (AFM) system was employed to characterize the microcantilever sensor which provides a better understanding of the complex phenomenon of surface stress change induced by proteins absorption. The ORSV detection limit of the microcantilever biosensor was measured at 1 ng/μl. The device further adapts commercially-available TMSC 0.35 2P4M CMOS technology with BioMEMS post-processes, showing its potential as a low-cost, rapid, label-free and point-of-care (POC) device for orchid virus (ORSV) detection.