臺灣博碩士論文加值系統

根據醫學報導，糖尿病患者呼出氣體中所含的丙酮濃度高於一般正常值，故可將丙酮視為糖尿病診斷的指標，取代侵入式傳統抽血方法。因此，本研究利用厚膜印刷及電鍍方法製備工作電極，配合固態高分子電解質防止液態電解質漏液問題。並將之與微小型恆電位儀整合，發展一套可攜式丙酮氣體感測器。此感測器系統可區別糖尿病患者與正常人呼氣成份中之丙酮濃度，並找出糖尿病患者呼氣丙酮濃度與血糖濃度之間的關係，即時監控糖尿病患者的病情。
本研究以電鍍鉛為工作電極、改良式銀/氯化銀為參考電極、網印金為輔助電極，含有離子液體BMIPF6之PVdF(HFP)高分子當作固態電解質組合而成。於室溫下，對此感測器施加電壓-1.1V(vs. modified Ag/AgCl)進行感測，對丙酮氣體之感測靈敏度為0.52μAcm-2ppm-1，偵測極限可達1ppm。在工作電極對感測結果的探討中，發現電鍍鉛是感測丙酮氣體最佳電極，電鍍條件中，電鍍溫度及電流密度皆為影響感測的因素；而在高分子電解質薄膜對感測的結果探討，奈米級二氧化矽為添加物時其靈敏度最高，添加量為20wt%有最大之感測電流；其他感測特性方面，發現相對濕度提高至58及100%時，雖會使電流密度增大，但雜訊增加且靈敏度下降。感測器之選擇性測試方面，二氧化碳、氨氣及異戊二烯氣體對丙酮感測並不會造成干擾；與微小型恆電位儀整合後，此感測系統所得之靈敏度0.58μAcm-2ppm-1，且與商用恆電位儀所測得之電流相關係數高達0.997；臨床應用上，不管是商用或微小型恆電位儀感測器系統皆可明確的將患者及健康者作一區別。並利用商用及微小型恆電位儀測量糖尿病患者之呼氣丙酮值，發現丙酮氣體與血糖之相關係數為0.501及0.521，顯示糖尿病患者中之呼氣丙酮值與血糖確實呈現正相關，使此套可攜式丙酮感測器系統對於應用於糖尿病診斷更具有潛力。

According to medical reports, diabetes have higher acetone concentration in their expired air; thus, the determination of acetone in expired air is useful for diagnosis of diabetes. It would be possible to substitute traditional blood test method. The screen-printing and electroplating method were used to prepare working electrode. And the solid polymer electrolyte could prevent leakage. It developed one portable acetone sensing system by integrating home-made potentiostat. By using the sensing system, the difference of acetone responses between diabetic patients and healthy person were obtained. The possibility exists to use an acetone sensor system as a means of monitoring the diabetic patient’s condition.

In this study, the sensing system included electroplating lead working electrode, modified Ag/AgCl reference electrode, screen-printing gold counter electrode and solid polymer electrolyte PVdF(HFP) with ionic liquid BMIPF6. At applied potential -1.1V vs. modified Ag/AgCl, the sensitivity of sensing system was 0.52μAcm-2ppm-1, and the detection limit attained to 1ppm. The effects of working electrode materials on sensing, electroplating lead was found to be the best one. It prepared under 25℃ and 40mA/cm2. The solid polymer electrolyte with 20% nano SiO2 were the best preparing conditions. Furthermore, the sensor selectivity was tested. It indicated that carbon dioxide, ammonia and isoprene did not affect the acetone detection. The results of integrating home-made mini portable potentiostat show the good sensitivity to 0.58μAcm-2ppm-1, and the correlation coefficient of measured current between commercial and home-made potentiostat was 0.997. In clinical application, the sensor could clearly distinguish the normal expired air from the diabetic ones. We also measured the expired air of diabetic patients to find out the relationship between concentration of blood sugar and acetone using commercial and home-made potentiostat. The correlation coefficient was 0.501 and 0.521. These values showed that the relationship between blood sugar and concentration of acetone was correlative. The developed acetone sensing system is potential for diagnosis of diabetes.

中文摘要………………………………………………………... I
英文摘要………………………………………………………... III
致謝……………………………………………………………... V
目錄……………………………………………………………... VI
表目錄.………………………………………………………….. X
圖目錄…………………………………………………………... XII
符號說明………………………………………………………... XIX
第一章 緒論……………………………………………………. 1
1-1 糖尿病之呼氣檢驗……………………. 1
1-1-1 糖尿病之簡介………………………………… 1
1-1-2 目前糖尿病檢測方法………………………... 3
1-1-3 呼氣檢測與疾病關係…….………………....... 5
1-1-4 呼氣丙酮與糖尿病診斷……………………… 11
1-2 感測器簡介……………………………………………. 15
1-2-1 感測器的主要特性…………………………… 16
1-2-2 感測器相較於目前一般呼氣分析儀器之優勢 17
1-2-3 丙酮氣體感測器……………………………… 18
1-3 丙酮感測器的研究動機與目的………………………. 23
第二章 理論分析………………………………………………. 24
2-1 電鍍鉛工作電極簡介…...…………………………….. 24
2-1-1 電鍍的基本原理……….……………………... 24
2-1-2 鍍層的影響因素……………………………... 26
2-1-3 常用的鍍液配方……....………………….…... 28
2-2 固態高分子電解質簡介………………………………. 29
2-2-1 離子液體-固態高分子電解質...……………... 33
2-2-2 添加奈米粒子之影響.………………………... 36
2-3 丙酮感測器機制探討………………….............43
2-3-1 丙酮氣體之還原反應機構…….............43
2-3-2 感測系統之動力及質傳模式探討……….…... 44
2-3-2-1 動力控制模式...……………….…... 46
2-3-2-2 質傳控制模式...……………….…... 47
第三章 實驗儀器與步驟………………………………………. 53
3-1 藥品……………………………..……….…………….. 53
3-2 儀器設備……………..………………………………... 54
3-3 電極之製作.……………………..…………………….. 55
3-3-1 電鍍鉛工作電極之製作……………………… 55
3-3-1-1 網印金電極的製備………………... 55
3-3-1-2 電鍍鉛電極的製備………………... 56
3-3-2 鉛箔工作電極之製作………………………… 58
3-3-3 輔助電極之製作……………………………… 58
3-3-4 改良式固體參考電極之製作………………… 58
3-4 參考電極之穩定性測試………………………………. 59
3-5 固態高分子電解質之製備……………………………. 59
3-6 丙酮電化學感測分析…………………………………. 60
3-6-1 以循環伏安法求取電位窗…………………… 64
3-6-2 線性伏安法…………………………………… 64
3-6-3 應答曲線及校正曲線………………………… 64
3-6-3-1 流動式系統……………………….. 65
3-6-3-2 封閉式系統……………………….. 65
3-7 自製感測器之臨床應用……………………………… 68
3-8 掃描式電子顯微鏡分析……………………………… 68
第四章 結果與討論……………………………………………. 69
4-1 銀/氯化銀參考電極穩定度測試……….…………….. 69
4-2 工作電極對感測行為的影響.………….…………….. 71
4-2-1 循環伏安法及線性伏安法探討電位窗區域... 71
4-2-2 電鍍鉛及鉛箔之感測行為探討………….…... 74
4-2-3 不同電鍍條件下對感測的影響………..…..... 78
4-2-3-1 電鍍溫度對感測的影響.………...... 78
4-2-3-2 電流密度對感測的影翔….……...... 82
4-3 固態電解質對感測行為的探討..……….…………….. 86
4-3-1 添加離子液體對感測的影響………………… 86
4-3-2 不同添加物對感測的影響…………………… 89
4-3-3 不同添加物比例對感測的影響……………… 94
4-4 其他感測特性之探討…..……………….…………….. 98
4-4-1 溼度對感測行為之影響……………………… 98
4-4-2 選擇性感測…………………………………… 101
4-4-3 穩定性測試…………………………………… 108
4-5 商用恆電位儀與微小型恆電位儀..…….…………….. 112
4-5-1 丙酮感測器之應答曲線及濃度校正曲線…… 112
4-5-2 糖尿病患者臨床生醫感測……...……….…… 115
4-5-2-1 糖尿病患者血糖值與呼氣丙酮值 關係……………115
4-5-2-2 糖尿病患者與健康者之呼氣結果... 124
第五章 綜合討論………………………………………………. 127
5-1 理論與實驗結果之綜合討論..……….……………….. 127
5-2 微小型恆電位儀…….……………………..………….. 128
5-3 臨床上應用的探討…….…………………..………….. 129
第六章 結論與建議……………………………………………. 132
6-1 結論……………………………………………………. 132
6-2 建議……………………………………………………. 133
參考文獻………………………………………………………... 134
附錄……………………………………………………………... 141
A 碳工作電極對丙酮氣體感測…………………………… 141
A-1 網印碳片工作電極之製作……………………….. 141
A-2 固態高分子電解質之製備……………………….. 141
A-3 線性伏安法探討電位窗區域…………………….. 141
A-4 應答曲線及濃度校正曲線……………………….. 142
B 不同條件下之循環伏安法……………………………… 146
C 電鍍鉛工作電極對高濃度丙酮氣體之感測行為……..152
D 封閉式感測方法………………………………………... 154
E 微小恆電位儀實際外觀………………………………... 155
F 真實氣體實驗數據……………………………………… 156
自述……………………………………………………………... 158

[1] World Health Organization, http://www.who.int/diabetes/facts/en, 2004
[2] Mayo Clinic, “Mayo clinic on managing diabetes-糖尿病”, 天下生活, pp. 207-209, 2002
[3] M. Phillips, “Method for the Collection and Assay of Volatile Organic Compounds in Breath”, Analytical Biochemistry, 247, issue 2, pp. 272-278, 1997
[4] B. Buszewski, M. Kesy , T. Ligor, A. Amann, “Human exhaled air analytics: biomarkers of diseases”, Biomedical Chromatography, 21, issue 6, pp. 553-566, 2007
[5] M. Phillips, J. Herrera, S. Krishnan, M. Zain, J. Greenberg, R. N. Cataneo, “Variation in volatile organic compounds in the breath of normal humans”, Journal of chromatography. B, Biomedical sciences and applications, 729, pp. 75-88, 1999
[6] A. Manolis, “The diagnostic potential of breath analysis”, Clin. Chem., 29, issue 1, pp. 5-15, 1983
[7] W. Miekisch, J. K. Schubert, G. F. E. Noeldge-Schomburg, “Diagnostic potential of breath analysis-focus on volatile organic compounds”, Clinica. Chimica. Acta., 347, pp. 25-39, 2004
[8] L. Laffel, “Ketone bodies: a review of physiology,pathophysiology, and application of monitoring to diabetes/metabolism research and reviews”, Diabetes/Metabolism Research and Reviews, 15, pp. 412-426, 1999
[9] M. Fleischer, E. Simon, E. Rumpel, H. Ulmer, M. Harbeck, M. Wandel, C. Fietzek, U. Weimar, H. Meixner, “Detection of volatile compounds correlated to human disease through breath analysis with chemical sensors”, Sensors and Actuators. B, 83, pp. 245-249, 2002
[10] Y. L. Lin, H. R. Guo, Y. H. Chang, M .T. Kao, H. H. Wang, R. I. Hong, “Application of the electronic nose for uremia diagnosis”, Sensors and Actuators B: Chemical, 76, issue 1-3, pp. 177-180, 2001
[11] C. Di Natale, A. Macagnano, E. Martinelli, R. Paolesse, G. D’Arcangelo , C. Roscioni, A. Finazzi-Agro, A. D’Amico, “Lung cancer identification by the analysis of breath by means of an array of non-selective gas sensor”, Biosensors and Bioelectronics, 18, pp. 1209-1218, 2003
[12] J. Romagnuolo, D. Schiller, R. J. Bailey, “Using breath tests wisely in a gastroenterology pratice: an evidance based review of indications and pitfalls in interpretation”, Am. J. Gastroenterol., 97, pp. 1113-1126, 2002
[13] S. K. Rossana, Cashman Kevin D, “Potential applications of breath isoprene as a biomarker in modern medicine: a concise overview”, Wiener klinische Wochenschrift, 117, pp. 180-186, 2005
[14] G. D. Bell, “Clinical practice-breath tests”, Br. med. bull., 54, pp. 187-193, 1998
[15] 陳錦順, “內分泌與代謝”, 臺北市藝軒出版社, 923頁, 1992
[16] N. Makisimovich, V. Vorotyntsev, N. Nikitina, O. Kaskevich, P. Karabun, F. Martynenko, “Adsorption semiconductor sensor for diabetic ketoacidosis diagnosis”, Sensors and Actuators B, 35-36, pp. 419-421, 1996
[17] F. Di Francesco, R. Fuoco, M. G. Trivella, A. Ceccarini, “Breath analysis: trends in techniques and clinical applications”, Microchemical Journal, 79, issue 1-2, pp. 405-410, 2005
[18] P. P. Janate, “Principle of chemical sensor”, New York, 1998
[19] W. H. Cheng, W. J. Lee, “Technology development in breath microanalysis for clinical diagnosis”, J. Lab. Clin. Med., 133, pp. 218-228, 1999
[20] W. Miekisch, J.K. Schubert, “From highly sophisticated analytical techniques to life-saving diagnostics: Technical developments in breath analysis”, Trends in Analytical Chemistry, 25, pp. 665-673, 2006
[21] B. L. Zhu, C. S. Xie, W. Y. Wang, K. J. Huang, J. H. Hu, “Improvement in gas sensitivity of ZnO thick film to volatile organic compounds (VOCs) by adding TiO2”, Materials Letters, 58, pp. 624-629, 2004
[22] S.V. Ryabtsev, A.V. Shaposhnick, A.N. Lukin, E.P. Domashevskaya, “Application of semiconductor gas sensors for medical diagnosis”, Sensors and Actuators B, 59, pp. 26-29, 1999
[23] X. Liu, H. Ji, Y. Gu, M. Xu, “Preparation and acetone sensitive characteristics of nano-LaFeO3 semiconductor thin films by polymerization complex method”, Materials Science and Engineering B, 133, pp. 98-101, 2006
[24] J. N. Barisci, C. Conn, G. G. Wallace, “Reviews: Conducting Polymer Sensors”, TRIP, 4, pp. 307-311, 1996
[25] J. B. Yu, H. G. Byun, M. S. So, J. S. Huh, “Analysis of diabetic patient's breath with conducting polymer sensor array”, Sensors and Actuators B, 108, pp. 305-308, 2005
[26] G. Mensitieri, V. Venditto, G. Guerra, “Polymer sensing films absorbing organic guests into a nanoporous host crystalline phase”, Sensors & Actuators B, 92, pp. 255-261, 2003
[27] H. Huang, J. Zhou, S. Chen, L. Zeng, Y. Huang, “A highly sensitive QCM sensor coated with Ag+-ZSM-5 film foe medical diagnosis”, Sensors and Actuators B, 101, pp. 316-321, 2004
[28] Q. Zhang, P. Wang, J. Li, X. Gao, “Diagnosis of diabetes by image detection of breath using gas-sensitive laps”, Biosensors & Bioelectronics, 15, pp. 249-256, 2000
[29] D. S. Ballantine. H. Wohltjen, “Surface acoustic wave devices for chemical analysis”, Analytical Chemistry, 61, 704A, 1989
[30] D. Q. Li, M. Ma, “Surface acoustic wave microsensors based on cyclodextrin coatings”, Sensors & Actuators B, 69, pp. 72, 2000
[31] 蘇癸陽, “實用電鍍理論與實際”, 復文書局, Chap. 4，1994
[32] H. Lund , M. M. Baizer, “Organic electrochemistry: an introduction and a guide”, 435, 1991
[33] F. A. Lowenheim, “Modern electrpplating”, Wiley, New York, 266, 1974
[34] C. C. Yang, S. J. Lin, S. T. Hsu, “Synthesis and characterization of alkaline polyvinyl alcohol and poly(epichlorohydrin) blend polymer electrolytes and performance in electrochemical cells”, Journal of Power Sources, 122, pp. 210-218, 2003
[35] B. Adhikari, S. Majumdar, “Polymers in sensor applications”, Prog. Polym. Sci., 29, pp. 699-766, 2004
[36] C. Berthier, W. Gorecki, M. Minier, M. B. Armand, J. M. Chabagno, P. Rigaud, “Microscopic investigation of ionic conductivity in alkali metal salts-poly(ethylene oxide) adducts”, Solid State Ionics, 11, pp. 91, 1983
[37] P. P. Chu, H. P. Jen, F. R. Lo, and C. L. Lang, “Exceedingly High Lithium Conductivity in Novolac Type Phenolic Resin/PEO Blends”, Macromolecules, 32, pp. 4738-4740, 1999
[38] L. Z. Fan, X. L. Wang, F. Long, X. Wang, “Enhanced ionic conductivities in composite polymer electrolytes by using succinonitrile as a plasticizer”, Solid State Ionics, 179, pp. 1772-1775, 2008
[39] A. Lewandowski, A. Swiderska, “Electrochemical capacitors with polymer electrolytes based on ionic liquids”, Solid State Ionics, 161, pp. 243-249, 2003
[40] S. S. Sekhon, B. S. Lalia, C. S. Kim, W. Y. Lee, “Polymer Electrolyte Membranes Based on Room Temperature Ionic Liquid: 2,3-Dimethyl-1-octyl imidazolium hexafluorophosphate (DMOImPF6)”, Macromolecular symposia, 249, pp. 216-220, 2007
[41] P. Wasserscheid, T. Welton, “Ionic liquids in Synthesis”, Wiley-VCH, 2003
[42] R. Wang, T. Okajima, F. Kitamura, T. Ohsaka, “A novel amperometric O2 gas sensor based on supported room-temperature ionic liquid porous polyethylene membrane-coated electrodes”, Electroanalysis, 16, pp. 66-72, 2003
[43] R. Wang, S. Hoyano, T. Ohsaka, “O2 Gas Sensor Using Supported Hydrophobic Room-Temperature Ionic Liquid Membrane-coated electrode”, Chemistry Letters, 33, 2004
[44] J. Fuller, A. C. Breda, R. Carlin, “Ionic liquid-polymer gel electrolytes from hydrophilic and hydrophobic ionic liquids”, Journal of Electroanalytical Chemical, 459, pp. 29-34, 1998
[45] K. S. Kim, S. Y. Park, S. Choi, H. Lee, “Ionic liquid-polymer gel electrolytes based on morpholinium salt and PVdF(HFP) copolymer”, Journal of Power Sources, 155, pp. 385-390, 2006
[46] K. S. Kim, S. Y. Park, S. H. Yeon, H. Lee, “N-Butyl-N-methylmorpholinium bis(trifluoromethanesulfonyl) imide–PVdF(HFP) gel electrolytes imide–PVdF(HFP) gel electrolytes”, Electrochimica Acta, 50, pp. 5673-5678, 2005
[47] K. M. Kim, N. G. Park, K. S. Ryu, S. H. Chang, “Characteristics of PVdF-HFP/TiO2 composite membrane electrolytes prepared by phase inversion and conventional casting methods”, Electrochimica Acta, 51, pp. 5636-5644, 2006
[48] Z. Li, G. Su, D. Gao, X. Wang, X. Li, “Effect of Al2O3 nanoparticles on the electrochemical characteristics of P(VDF-HFP)-based polymer electrolyte”, Electrochimica Acta, 49, pp. 4633-4639, 2004
[49] Z. Li, G. Su, X. Wang, D. Gao, “Micro-porous P(VdF-HFP)-based polymer electrolyte filled with Al2O3 nanoparticles”, Solid State Ionics, 176, pp. 1903-1908, 2005
[50] S. H. Chung, Y. Wang, L. Persi, F. Croce, S. G. Greenbaum, B. Scrosati, E. Plichta, “Enhancement of ion transport in polymer electrolytes by addition of nanoscale inorganic oxides”, Journal of power sources, 97, pp. 644-648, 2001
[51] T. Itoh, Y. Ichikawa, T. Uno, M. Kubo, O. Yamamoto, “Thermal, electrical, and mechanical properties of composite polymer electrolytes based on cross-linked poly(ethylene oxide-co-propylene oxide) and ceramic filler”, Solid State Ionics, 156, pp. 393-399, 2003
[52] C.C. Wang, Y.C. Weng, T.C. Chou, “Acetone sensor using lead foil as working electrode”, Sensors and Actuators B, pp. 591-595, 2007
[53] W. Y. Liao, T. C. Chou, “Fabrication of a planar-form screen-printed solid electrolyte modified Ag/AgCl reference electrode for application in a potentiometric biosensor”, Anal. Chem., 78, pp. 4219-4223, 2006
[54] H. Suzuki, A. Hiratsuka, S. Ssaki, I. Karube, “Problems associated with the thin-film Ag/AgCl reference electrode and a novel structure with improved durability”, Sensors and Actuators B, 46, pp. 104-113, 1998
[55] Davidson, “Diabetes Mellitus: Diagnosis and Treatment”, 南山堂, pp. 25-46，1986