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研究生: 申憲樺
Shen, Hsien-Hua
論文名稱: 白金微型加熱線圈整合共平面式介電濕潤晶片並將其應用於生醫檢測
Coplanar-Type Electrode of EWOD chip with Micro Heater in Biomedical Application
指導教授: 饒達仁
Yao, Da-Jeng
口試委員: 王玉麟
Wang, Yu-Lin
施文彬
Shih, Wen-Pin
學位類別: 碩士
Master
系所名稱: 工學院 - 奈米工程與微系統研究所
Institute of NanoEngineering and MicroSystems
論文出版年: 2011
畢業學年度: 99
語文別: 中文
論文頁數: 89
中文關鍵詞: 微型加熱線圈介電濕潤單一核苷酸多型性磁球去氧核醣核酸接合酶
外文關鍵詞: Electrowetting on Dielectric, Micro-heater, Nano-magnetic bead, Single-nucleotide Polymorphism, DNA ligase
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  • 本研究主要探討設計電阻式微型加熱線圈(Micro-Heater)於介電濕潤(Electrowetting on dielectric, EWOD)晶片上蓋之方法做為操控液珠的平台,用以檢測生物單一核苷酸多型性(Single-nucleotide Polymorphism, SNP)是否發生於特定的基因片段。此設計提供EWOD晶片在操控液珠時達到預設之溫度環境,使特定生化反應足以發生,搭配EWOD系統能夠有效率的產生、移動、混合與分離DNA、磁球與緩衝液等檢體液滴之功能,目標是在EWOD晶片上完整呈現SNP檢測實驗,達到Lab on a chip之目標。
    電阻式微型加熱線圈之設計是利用透明玻璃為基板,在其上沉積金屬導線並沉積絕緣層後可製作出加熱線圈晶片,再經由紅外線熱像儀(IR Scope)量測,可得知不同施加功率對於溫度變化之關係。並將其整合於EWOD晶片之上蓋結構,並透過特殊的線路設計使得微加熱線圈能夠符合EWOD晶片上所需的加熱位置,經由對準封裝後完成微型加熱器晶片與EWOD晶片之整合。本研究設計之微加熱線圈將在SNP檢測之核心步驟提供去氧核醣核酸接合酶(DNA Ligase)反應的適當溫度環境,最終將在晶片上完成SNP檢測實驗。


    This study bases on the technique, “Electrowetting on Dielectric (EWOD),” and we design micro-heaters on the cover of a EWOD chip as proper temperature sources for biomedical detection. Droplets in a EWOD chip are actuated by addressable electrodes. Multiple bio-reagents such as DNA, nano-magnetic beads and buffer droplets have been manipulated by the EWOD system already. Due to the nano-magnetic beads property that can be collected and purified, it can use to detect a single-nucleotide polymorphism (SNP) in specific gene sequence. Above these, the final goal of this research is efficiently using temperature-controllable EWOD digital microfluidics system for SNP detection in specific gene sequence.
    The micro-heaters are fabricated on glass substrate by Pt deposition. After the heater circuit design, they are constructed with bottom chip to complete the packaging of temperature-controllable EWOD system. In this study, micro-heaters in a EWOD system can provide proper temperature for DNA ligase in SNP detection experiments. In the end, we successfully use temperature-controllable EWOD digital microfluidics system to detect SNP code in specific gene sequence, and this research will contribute to biomedical diagnosis.

    第一章 緒論 8 1.1前言 8 1.2研究目的 9 第二章 文獻回顧 11 2.1 介電濕潤現象與微液珠操控 11 2.2 介電濕潤共平面電極系統 15 2.3介電濕潤系統於生醫檢測之應用 17 2.4微型加熱線圈之應用文獻 22 2.5 文獻總結 29 第三章 研究方法 30 3.1實驗原理 30 3.1.1 介電濕潤原理 30 3.1.2 介電濕潤晶片製程 31 3.1.3 介電濕潤晶片系統架設 37 3.1.4 白金加熱晶片設計與製程 38 3.2 DNA生醫檢體配置設計 42 3.2.1 單一核酸多型性(SNP)檢測實驗設計 42 第四章 初步實驗成果 48 4.1 共平面式介電濕潤晶片製程結果 48 4.2 EWOD晶片之微液滴操控 51 4.2.1 介電濕潤晶片之微液珠產生(Creating) 51 4.2.2 介電濕潤晶片之微液珠傳輸(Transporting) 52 4.2.3 介電濕潤晶片之微液珠合併(Merging) 53 4.2.4 介電濕潤晶片之微液珠分離(Cutting) 54 4.2.5 利用磁球檢測時之清潔步驟(Washing) 55 4.3 SNP檢測結果 56 4.3 利用紅外線熱像儀量測白金加熱測試晶片 58 4.3 EWOD白金加熱上蓋晶片製作 66 4.4 EWOD加熱上蓋晶片量測與作圖方法 68 4.5 利用加熱上蓋晶片加熱液珠並量測溫度 71 4.6 EWOD晶片整合加熱上蓋並進行SNP檢測 74 4.7 磁球螢光訊號檢測 80 第五章 結論與未來工作 82 5.1 結論 82 5.2 未來工作 83 5.2.1 利用EWOD系統進行完整的SNP檢測 83 5.2.2 EWOD介電層品質改善 83 5.2.3 將溫控EWOD晶片應用於其他生醫檢測反應 85 第六章 參考文獻 87

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