臺灣博碩士論文加值系統

電噴灑噴嘴與質譜儀的結合，可有效的分辨出待測物種的成分，亦即電噴灑噴嘴影響解析程度的好壞扮演著辨識是否精確的關鍵角色。
目前廣泛使用的電噴灑頭大體上可分為晶片管道出口直接噴灑與外植毛細管式噴嘴二大體系。前者之缺點乃是管道出口側表面的面積太大，造成管道出口端的濕潤以及產生大液滴，使得泰勒錐的穩定性下降。外植式噴嘴即是為了縮減管道出口側表面的面積，但往往伴隨惰性停滯區的產生，使樣本無法自管道淨空而造成樣本分離度的下降。
為解決以上問題，本研究嘗試以微機械加工製作出二種新型電噴灑頭。高效能泰勒錐晶片選用疏水性高的聚合材質，並以縮小噴口側緣的方式來抑制管道出口的濕潤程度以及出口邊緣的液體擴散。無惰性停滯區之微流道晶片的設計是將針狀體植入晶片管道內，使針狀體貫穿整個管道，讓微流道中不存在任何接合點，以清除一般外植式噴嘴頭可能發生的體積滯留現象。在管道內已分離的樣本因為不需通過任何接合點，所以不會再次混合而造成分離效果與解析度的下降。為更提升晶片之解析度與靈敏度，本研究進一步以改良噴口的形狀來達到泰勒錐之尖銳化。
相較於廣泛使用於生化檢測的元件，諸如以延拉毛細管當噴口的晶片，或是一般的平口型晶片，在相同尺寸與控制條件的前提下，本研究研發出的高效能泰勒錐晶片與無惰性停滯區之微管道晶片經實驗證實在解析效果與靈敏度上與延拉毛細管晶片之效能相去無幾，可取代延拉毛細管晶片而大大降低成本，且確實優於一般的平口型晶片。為精確分析電噴灑頭之動態噴灑特性，本研究亦以流體動力學理論模擬電噴灑頭之動態模式，並從實驗得到與模擬一致的結果。
結合以上種種優勢，以及無需更改檢測機制或新增額外之輔助元件的前提下，本研究之成果對相關研究與產業技術之提升有相當助益。

The combination of electro-spray tip and mass spectrometry can effectively distinguishing the compositions of the examining sample. The analytical capability of the electro-spray tip plays the key role to the quality of the distinguishing results.
In general, the electro-spray tip in use can be categorized into two groups, the fused-silica capillary chip and the planar-edge chip. The main drawback of the planar-edge chip is that the side area of the channel exit is large enough such that the stability of the Taylor cone is affected by the moist at the channel exit and its inducing big droplet. The fused-silica capillary chip was developed to reduce the area at the side surface of the planar-edge chip. However, the dead volume will decrease the separating resolution.
In order to solve these problems, two new types of electro-spray tips are designed and fabricated by precisely mechanical micro machining. The first type is the high efficiency Taylor cone chip that is made of the hydrophobic poly-material. In this new chip, the degree of moist and the edge diffusion problems are suppressed through the scale down of the side surface. While the design concept of the dead volume free micro-channel chip is to insert a needle-like bar into the micro channel such that there is no redundant area inside the channel and the dead volume problem can be eliminated. Since the sample does not need to pass any redundant junction, the separating quality and resolution decline problems can be reduced.
Experimental results demonstrate that the proposed two new electro-spray tips possess the similar resolution and sensitivity as the conventional fused-silica capillary chip. However, the cost of our new chips is much lower than the conventional ones.
To precisely understand the dynamic spray characteristics of the electro-spray tip, the micro-fluidics theory is adopted to model the behavior of the tip. The dynamic model is verified through experiments.
In addition to the advantages aforementioned, the proposed chips require no extra modification of the equipment. It can be helpful to the researches and industry in the bio-chemical society.

中文摘要……………………………………………………………… Ⅰ
英文摘要………………………………………………………………..Ⅲ
致謝……………………………………………………………………..Ⅴ
目錄……………………………………………………………………. Ⅵ
圖目錄…………………………………………………………………. Ⅷ
表目錄……………………………………………………………….. ⅩⅡ
第一章 緒論…………………………………………………………….. 1
1.1 研究動機與目標……………………………………………….. 1
1.2 論文大綱……………………………………………………….. 6
第二章 高效能泰勒錐晶片設計製作……..……………………………7
2.1 高效能泰勒錐晶片設計……………………………………….. 7
2.2 高效能泰勒錐晶片製作………………………………………10
2.3流體動力學模型建置…………………………………………. 20
第三章 無惰性停滯區之微管道晶片設計製作….……………….......30
3.1無惰性停滯區之微管道晶片設計……………………………. 30
3.2無惰性停滯區之微管道晶片製作……………………………. 35
3.3流體動力學模型建置………………………..…………………38
第四章 實驗設計與驗證………………………………………………40
4.1 實驗設計……………………………………………………… 40
4.2實驗驗證………………………………………………………..45
4.2.1高效能泰勒錐晶片……………………………………………45
4.2.2無惰性停滯區之微管道晶片…………………………………50
4.2.3 實驗結果與改進方式的探討………………………………..54
第五章 結論與未來展望…………………………………………........59
參考文獻………………………………………………………………..62

[1] Qifeng Xue, Frantisek Foret, Yuriy M. Dunayevskiy, Paul M. Zavracky, Nicol E. McGruer, and Barry L. Karger, “Multichannel Microchip Electrospray Mass Spectrometry”, Anal. Chem., vol. 69, pp. 426-430, 1997.
[2] Jianjun Li, Pierre Thibault, Nicolas H. Bings, Cameron D. Skinner, Can Wang, Christa Colyer, and Jed Harrison,“Integration of Microfabricated Devices to Capillary Electrophoresis-Electrospray Mass Spectrometry Using a Low Dead Volume Connection: Application to Rapid Analyses of Proteolytic Digests”, Anal. Chem., vol. 71, pp. 3036-3045, 1999.
[3] R. S. Ramsey and J. M. Ramsey,“Generating Electrospray from Microchip Devices Using Electroosmotic Pumping”, Anal. Chem., vol. 69, pp. 1174-1178, 1997.
[4] Cheng-Hui Yuan and Jentaie Shiea,“Sequential Electrospray Analysis Using Sharp-Tip Channels Fabricated on a Plastic Chip”, Anal. Chem., vol. 73, pp. 1080-1083, 2001.
[5] Nicolas H. Bings, Can Wang, Cameron D. Skinner, Christa L. Colyer, Pierre Thibault, and D. Jed Harrison, “Microfluidic Devices Connected to Fused-Silica Capillaries with Minimal Dead Volume”, Anal. Chem., vol. 71, pp. 3292-3296, 1999.
[6] Iulia M. Lazar, Roswitha S. Ramsey, Steven Sundberg, and J. Michael Ramsey, “Subattomole-Sensitivity Microchip Nano-electrospray Source with Time-of-Flight Mass Spectrometry Detection”, Anal. Chem., vol. 71, pp. 3627-3631, 1999.
[7] Johannes N. van der Moolen, Hans Poppe, and Her C. Smit,“A Micromachined Injection Device for CZE: Application to Correlation CZE”, Anal. Chem., vol. 69, pp. 4220-4225, 1997.
[8] Daniel Figeys and Ruedi Aebersold,“Nanoflow Solvent Gradient Delivery from a Micro-fabricated Device for Protein Identifications by Electrospray Ionization Mass Spectrometry”, Anal. Chem., vol. 70, pp. 3721-3727, 1998.
[9] Daniel Figeys, Yuebin Ning, and Ruedi Aebersold,“A Microfabricated Device for Rapid Protein Identification by Micro-electrospray Ion Trap Mass Spectrometry”, Anal. Chem., vol. 69, pp. 3153-3160, 1997.
[10] 陳邦維, 李國賓, 林中源, 陳淑慧, 宋旺洲, 廖寶琦,“微流體晶片連結質譜儀偵測在蛋白質分析上的應用”,微系統科技協會季刊第5期, pp. 44-51, 2001.
[11] Larry Licklider, Xuan-Qi Wang, Amish Desai, Yu-Chong Tai, and Terry D. Lee, “A Micromachined Chip-Based Electrospray Source for Mass Spectrometry”, Anal. Chem., vol. 72, pp. 367-375, 2000.
[12] Wolfgang Schuetzner and Ernst Kenndler, “Electrophoresis in synthetic organic polymer capillaries: variation of electro-osmotic velocity and .zeta. potential with pH and solvent composition”, Anal. Chem., vol. 64, pp. 1991-1995, 1992.
[13] Yu-Hung Chen, Shu-Hui Chen, “Analysis of DNA fragments by microchip electrophoresis fabricated on poly(methyl methacrylate) substrates using a wire-imprinting method”, Electrophoresis, vol. 21, pp. 165-170, 2000.
[14] Bruce R. Munson, Donald F. Young, Theodore H. Okiishi, “Fundamentals of Fluid Mechanics 2/e”, John Wiley & Sons, 1994.
[15] David N. Heiger, “High Performance Capillary Electrophoresis-Analysis Introduction”, 1992.
[16] 陳國祥, “毛細管電泳微晶片之彎道最佳化研究”, 國立成功大學機械工程研究所碩士論文, 2002.
[17] Birendra N. Pramanik, A. K. Ganguly, Michael L. Gross, “Applied Electrospray Mass Spectrometry”, Copyright by Marcel Dekker, Inc. USA, 2002.
[18] Jenny Wen, Yuehe Lin, Fan Xiang, Dean W. Matson, Harold R. Udseth, Richard D. Smith, “Microfabricated Isoelectric Focusing Device for Direct Electospray Ionization-Mass Spectrometry”, Electrophoresis, vol. 21, pp. 191-197, 2000.
[19] Jin-Sung Kim and Daniel R. Knapp, “Microfabricated PDMS Multichannel Emitter for Electrospray Ionization Mass Spectrometry”, American Society for Mass Spectrometry, vol. 12, pp. 463-469, 2001.
[20] Arthur T. Blades, Michael G. Ikonomou, and Paul Kebarle, “Mechanism of Electro-spray Mass Spectrometry. Electro-spray as an Electrolysis Cell”, Anal. Chem., vol. 63, pp. 2109-2114, 1991.
[21] Yuzhong Deng, Jack Henion, Jianjun Li, Pierre Thibault, Can Wang, and D. Jed Harrison, “Chip-Based Capillary Electro-phoresis / Mass Spectrometry Determination of Carnitines in Human Urine”, Anal. Chem., vol. 73, pp. 639-646, 2001.
[22] B. Zhang, H. Liu, B. L. Karger, and F. Foret, “Micro-fabricated Devices for Capillary Electrophoresis —Electro-spray Mass Spectometry”, Anal. Chem., vol. 71, pp. 3258-3264, 1999.