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研究生:盧武德
研究生(外文):Ude Lu
論文名稱:發展以互補式金氧半導體為基礎之偵測與定量生物冷光之儀器
論文名稱(外文):Development of CMOS base instruments for the quantification of biological luminescence
指導教授:楊裕雄
指導教授(外文):Yuh-Shyong Yang
學位類別:碩士
校院名稱:國立交通大學
系所名稱:生物科技研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2002
畢業學年度:90
語文別:英文
論文頁數:108
中文關鍵詞:互補式金氧半導體化學冷光
外文關鍵詞:CMOSChemiluminescence
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  在二十一世紀中,生物科技與電機資訊的結合是必然的趨勢。生物晶片就是生物科技與電機資訊結合下的產物,它有潛力成為一項大量、快速、準確的檢測與篩選工具,對於醫學診斷、藥物篩選、病體檢測,以及後基因時代對於蛋白質體的研究,它將提供一項嶄新的視野。我們利用標準CMOS(Complementary Metal Oxide Semiconductor)製程所製造的感光二極體(N+/Pwell photo diode),來定量酵素冷光反應,並且作酵素活性分析。我們的目的是能夠利用CMOS photodiodes chip建立一項平台技術來建構出一個掌上型、可攜式的光譜儀。在研究的過程中,我們設計了第一代的CMOS化學冷光感測晶片,並利用HP 4145 Semiconductor Parameter Analyzer來偵測並定量其訊號,並證實可行之後;為了將整個化學冷光感測晶片偵測系統微小化,我們又設計了第二代的晶片,並搭配上一台商品化的萬用電表(Agilent 34401A multimeter)來偵測並定量晶片的訊號,這樣的設計使我們將整個儀器架構縮減至桌上型的大小;而最後我們設計了一台掌上型的電壓顯示器來偵測並定量第二代晶片的訊號,這樣的設計使的整個儀器架構大幅縮小至手掌般的大小。這樣的平台技術可以提供傳統生化儀器冷光儀的功能,並且不論在體積、價格、耗電量上,擁有遠優於傳統儀器的特性,非常適合作為可攜式或野外用儀器。我們在此篇報告中所提出的技術若經過稍加修改,就可以提供傳統螢光儀、或可見光譜吸收儀的功能,將可以在各種場合做各樣的生化檢測。

In 21st century, the combination of biotechnology and electrical engineering is the main trend in worldwide research revolution. Biochip is the product of this kind of combination, and it has the potential to become a high throughput, fast response, and high accuracy screening tool for medical diagnosis, drug targeting, and proteomics in post genome era. This new technique will bring us a whole new version of research and healthy care industry. In this report, we use the N+/Pwell photo diode, which is produced by CMOS (Complementary Metal Oxide Semiconductor) standard process to quantify and assay the biological enzymatic luminescent reaction. Our purpose is to develop a portable handheld spectrometer with the CMOS photodiodes chip. In our report, we designed 1st generation CMOS chemiluminescence sensing chip, and we use HP 4145 semiconductor parameter analyzer to detect and measure the chemiluminescence induced signal of the chip. After the verification of the feasibility of the system, we designed the 2nd generation CMOS chemiluminescence sensing chip, and we utilize a common commercial multimeter (Agilent 34401A) to quantify the signal of the chip. This improvement helps us to reduce the whole instrument into desktop size. Finally, we designed a handheld voltage monitor to substitute the commercial multimeter, and this design reduces the whole instrument into handheld size. The platform technique described in our report could carry the functions of the traditional luminescence meter, and have great improvements in reducing size, cost down, and lowering the power consumption compare to traditional instrument. These advantages make this novel CMOS base instrument very suitable to be a portable field use instrument. Conveniently, with some suitable modification, this instrument could carry the functions of traditional fluorescence and UV-Vis absorption spectrum meters, it will be able to quantify and assay variant biochemical reactions in variant environment.

Abstract (Chinese)…………………………………………………..…………..i
Abstract (English)…………………………………………………………….……...ii
Contents……………………………………………………………………….…….iii
Abbreviation and Symbol……………………………………………………..…….iv
Chapter 1. Introduction…………………………………………………..…….1
Chapter 2. Review of Lab-on-Chip…………………….……………………14
Chapter 3. 1st Generation CMOS Chemiluminescence Sensing Chip with Hp 4145 Semiconductor Analyzer System
I. Sub Abstract………………………………………………………….……..28
II. Experimental……………………………………………………… … …….29
III. Result and Discussion………………………………………………..… ...33
IV. Conclusion………………………………………………………..…..……..37
V. Reference………………………………………………………………..…..38
Chapter 4. 2nd Generation CMOS Chemiluminescence Sensing Chip with Agilent 34401A Multimeter Detection System
I. Sub Abstract…………………………………………………………..…....50
II. Material and Method………………………………………………………..51
III. Result and Discussion…………………………………………………… ...58
IV. Conclusion………………………………………………………….….…...63
V. Reference…………………………………………………………...………64
Chapter 5. 2nd Generation CMOS Chemiluminescence Sensing Chip with Handheld Voltage Monitor Detector System
I. Sub Abstract……………………………………………………………..…75
II. Material and Method………………………………………………….…....76
III. Result and Discussion……………………………………………….…..…81
IV. Conclusion………………………………………………………..……...…85
V. Acknowledgments…………………………………………………….……87
Appendix A: HP 4145B Standard Operation Procedure…………………………..96
Appendix B: Agilent 34401A Multimeter Setup Standard Operation Procedure…99
Appendix C: Portable Display System Setup Standard Operation Procedure…....105

1. Yuh-Shyong Yang, Ude Lu, and Ben C.P.Hu. Toward the development of enzyme and the CMOS chips. 2002.
Ref Type: Unpublished Work
2. A.J.Cunningham (1998) Introduction to Bioanalytical Sensors, John Wiley & Sons, New York
3. Denise Michele Wilson, Sean Hoyt, Jiri Janata, Karl Booksh, and Louis Obando (2001) IEEE sensors Journal 1, 256-273
4. S.M.Sze (1985) Semiconductor Devices (physics and technology), 1st Ed., John Wiley & Sons, New York
5. Marlene A.Deluca (1978) Preface. In Marlene A.Deluca, editor. Methods in Enzymology: Bioluminescence and Chemiluminescence, Academic Press
6. Larry J.Kricka and Gary H.G.Thorpe (1990) Bioluminescent and Chemiluminescent Detection of Horseradish Peroxidase Labels in Ligand Binder Assay. In Knox Van Dyke and Richard Van Dyke, editors. Luminescence Immunoassay and Molecular Applications, CRC press
7. Larry J.Kricka, Irena Bronstein, and Jhon C.Voyta (2000) Chemiiluminescence Methods for Detecting and Quantitating Enzyme Activity. In Mirian M.Ziegler and Thomas O.Baldwin, editors. Methods in Enzymology: Bioluminescence and Chemiluminescence, Acadamic Press

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