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研究生:何政達
研究生(外文):Chen-Ta Ho
論文名稱:新型生醫應用之微T形開關細胞分類裝置
論文名稱(外文):Novel Micro T-Switches for Cell Sorting Applications
指導教授:劉承賢劉承賢引用關係
指導教授(外文):Cheng-Hsien Liu
學位類別:碩士
校院名稱:國立清華大學
系所名稱:動力機械工程學系
學門:工程學門
學類:機械工程學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:中文
論文頁數:60
中文關鍵詞:生醫微機電系統生醫晶片微流體電解氣泡細胞分類生物分離
外文關鍵詞:BioMEMSBiochipMicrofluidicsElectrolysis BubbleCell SortingBioseparation
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摘要
在生物醫學的領域裡,疾病檢驗一直是此領域中重要的一環,但是傳統的疾病檢驗工作一般需在實驗室經過各種儀器繁複的處理步驟,而且需長時間及耗費大量人力才能獲得檢測結果。近年來由於生醫微機電系統的蓬勃發展,其微小化、快速、低價等優點更大大加快人類對於疾病檢驗的速度。本論文計畫根據螢光活化細胞分類儀(Fluorescence-activated cell sorter----FACS)的需求,配合微機電系統(MEMS)的製造技術,研發新型生醫應用之微T形開關細胞分類裝置(Novel Micro T-Switches for Cell Sorting Applications)。有別於螢光活化細胞分類儀利用在流道兩端加上一高電壓電場,讓通過電場的帶測物依帶電量、電性的不同而達到分離、分類的功能,本論文驅動機制是利用電化學電解(electrolysis)產生氣泡(bubble),藉氣泡的推力來推動T形微開關機械結構,產生順時或逆時針的轉動,以達到將特定細胞分類的功能。電解反應可在室溫下操作,避免傳統FACS利用高電位差的分離機制而殺死活生物檢體的缺點發生。此微T形開關分類裝置將可結合樣品注入機制、驅動機制、化學反應機制、混和機制、聚合脢連鎖反應(PCR)、光學檢測系統等各種不同功能而整合成一可攜式(portable)、用完即丟(disposable)的微多工生醫晶片(micro biochips)。

Abstract
The diagnosis of diseases is an important field in bio-medical science. Traditional diagnosis of disease must be proceeded with a variety of complicated instruments and complex steps. The results of diagnosis also need long-time waiting and heavy manpower. With the development of flourishing and BioMEMS technologies, the advantages of BioMEMS, such as miniaturization, fast response, low cost et al., greatly improve the diagnosis period of diseases.
Flow Cytometry is an instrument with functions of biological cell detection, counting, and sorting. It can provide fast and high-precision results for medical diagnosis. It is widely used for all kind of medical research applications. It also can be applied to bacteria detection and embryonic stem cells including both fundamental researches and applications. It has also become an important diagnostic tool for hematology and oncology in clinical medical researches. The latest and main fields of Flow Cytometry include cancer detection, HIV recognition, embryonic stem cells, medicine discovery and genetic therapy.
According to the application demands of Flow Cytometry and taking advantage of MEMS technology, this thesis proposes a novel micro T-switches for cell sorting applications. The sorting principle for Flow Cytometry is based on high-electric field between the sample outlet. The cells go through the high-electric field region and can be separated and sorted based on their dielectric properties and size. The driving mechanism for our research takes advantage of electrochemistry electrolyze electrolytic solution to generate micro-bubbles. We uses the micro-bubbles to push our micro T-switch structure either clockwise or counterclockwise by the surface tension of micro-bubbles. We can utilize these micro T-switch to sort out specific Cell.
Electrolysis can be operated at room temperature. The usage of this diving mechanism can avoid the potential of cell-damage that happens for conventional electric-separation design. This micro T-Switch cell sorter potentially can be integrated into a portable and disposable Micro- Bio-chip. People can even finish self-disease detection at home to achieve the goal of homecare.

目錄
摘要………………………………………………………………..…. i
abstract…………………………………………………………….…. ii
致謝…………………………………………………………………. iii 目錄………………………………………………………………….. vi
圖目錄………………………………………………………………. ix
表目錄……………………………………………………………… xiii
第一章 序論……………………………………………………… 1
1.1 微機電系統………………………………………………... 1
1.2 生醫晶片簡介……………………….…………………….. 2
1.2.1 微陣列型晶片………………………………………. 3
1.2.2微處理型晶片…………………….…………………. 4
1.2.3 檢驗方式…………………………………………….. 7
1.2.3.1 傳統檢驗試劑…………………...……..….. 7
1.2.3.2 檢驗試劑標示方式……………………...… 8
1.2.3.3 生物晶片檢驗標示方式……………...…… 9
1.2.4 螢光偵測與應用..………………...………………. 10
1.3 文獻回顧………………………………………..…………. 13
1.3.1 微制動器回顧…………………………...…………. 13
1.3.2 氣泡式制動器………………………………...……. 16
1.3.3 電化學式制動器……………...……………………. 18
1.4 研究動機與論文大綱…………………………………..…. 22
第二章 理論分析………………………………………………… 24
2.1 電化學電解氣泡………………………………..…………. 24
2.1.1 電解……………………………...…………………. 24
2.1.2 法拉第電解定律……………...……………………. 24
2.1.3 水的電解…………..……………………………….. 26
2.2 氣泡的表面張力………….……………………………….. 27
2.3 微T型開關制動原理……………………………..……….. 29
第三章 結構尺寸設計與製程規劃……………………………… 32
3.1 結構尺寸設計……………………………………………... 32
3.2 製程規劃…………………………………………………... 36
3.2.1 製程簡介…………………………………………… 36
3.2.2 製程步驟…………………………………………… 39
第四章 製程結果與實驗量測…………….…………………… 45
4.1 矽基材SCREAM製程……………………………………. 45
4.1.1 RIE蝕刻選擇比…………………………..……… 45
4.1.2 ICP(感應耦合電漿蝕刻)深蝕刻與負載效應……. 46
4.1.3 微T形開關之釋放……………………………….. 48
4.1.4 矽基材微流道流體入口開口製程………….…….. 49
4.2 玻璃基材製程…………………………………….…….…. 50
4.2.1 玻璃基材微流道流體出口開口製程…..………… 50
4.2.2 電解氣泡微電極Lift-off製程…………….……… 51
4.3 陽極接合製程(Anodic Bonding) ………….……………... 54
4.4 量測實驗.…………………………………………………. 55
4.4.1 電解氣泡生成實驗…………………………….…… 55
第五章 結論、未來工作與展望…………….…………………. 57
5.1 結論………………..…………………………………… 57
5.2 論文貢獻..……..………..…………………………….. 57
5.3 完成進度與未來工作…………………………………… 58
5.4 展望………………………..…….……………………….. 58
參考文獻…………………………………………………………… 59

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