簡易檢索 / 詳目顯示

研究生: 許富翔
Fu-hsiang Hsu
論文名稱: 高靈敏度糖化血紅素電流式感測器之製備研究
Fabrication of amperometric glycated hemoglobin biosensor with high sensitivity
指導教授: 李振綱
Cheng-kang Lee
口試委員: 王孟菊
Meng-jiy Wang
王文
Wen Wang
楊佩芬
Pei-fen Yang
學位類別: 碩士
Master
系所名稱: 工程學院 - 化學工程系
Department of Chemical Engineering
論文出版年: 2012
畢業學年度: 100
語文別: 中文
論文頁數: 102
中文關鍵詞: 糖化血紅素電流式感測器
外文關鍵詞: glycated hemoglobin, amperometric biosensor
相關次數: 點閱:229下載:1
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 糖化纈草胺酸 (fructosyl valine, FV) 為糖化血紅素 (HbA1c) 的末端糖化官能基,糖化血紅素在血液中濃度可以反應出體內二至三個月的平均血糖濃度。因此糖化纈草胺酸之濃度可作為糖尿病之指標。
      本研究是以電化學方法,偵測由糖化胺基酸氧化酶 (fructosyl amino acid oxidase,FAO) 氧化糖化纈草胺酸,所產生之過氧化氫。在旋轉式碳電極表面塗佈一層含鉑-多層壁奈米碳管觸媒催化過氧化氫,以增強電流訊號,於施加電位0.6V時,偵測過氧化氫之線性範圍為0.00125-6.05 mM,靈敏度為1027.34 μA mM-1 cm-2,最低偵測極限為0.00125 mM;在觸媒層上再固定化一層FAO酵素固定層,此層主要是以覆有約10 nm奈米金之奈米纖維素為載體以利FAO酵素之固定。製作出高靈敏度糖化血紅素感測器,其對糖化纈草酸靈敏度為135.44 μA mM-1 cm-2 ,線性範圍為0.01-1.92 mM,最低偵測極限為0.01 mM。
    將觸媒及酵素修飾層移至微型感測器電極上 (工作電極面積為0.0018cm2),其過氧化氫靈敏度為177.02 μA mM-1 cm-2,糖化纈草胺酸靈敏度為47.65μA mM-1 cm-2,線性範圍0.05-1.19 mM,且測試時間只需5秒,成功製備出偵測快速且具高靈敏度之糖化血紅素感測器。


    Fructosyl valine (FV) is the glycated functional end group of glycosylated hemoglobin (HbA1c). In human body, the level of HbA1c can reflect the average blood sugar level within the recent 2 to 3 months. Consequently, the measurement of the concentration of HbA1c can be used to obtain the concentration of sugar which is important for the long-term control of the glycemic state of diabetic patients.
       In this study, FV was catalyzed by fructosyl amino oxidase (FAO) to produce hydrogen peroxide, which could be detected electrochemically. Platinum-Carbon nano tube (Pt-CNT) catalyst was coated on glassy carbon rotating disk electrode (GCRDE) to enhance the current signal by catalyzing hydrogen peroxide. The working potential was fixed at +0.25 V versus the reference electrode(Ag/AgCl), the range of hydrogen peroxide detection ranged from 0.00125 to 6.05 mM, with the sensitivity of 1027.34 μA mM-1 cm-2,and the limit of detection (LOD) at 0.00125 mM. FAO was coated on 10 nm Au particles of Au-BC and further coated onto the catalyst layer to obtain HbA1c sensor. The results showed that the fabricated HbA1c sensor possessed sensitivity of 135.44 μA mM-1 cm-2 with linear detection range between 0.01 and 1.92 mM, and with the limit of detection of 0.01 mM.
       By applying the optimized experimental parameters on the disposable electrodes (with working area of 0.0018 cm2), the results exhibited sensitivity of 177.02 μA mM-1 cm-2 and 47.65μA mM-1 cm-2 for detecting H2O2 and FV in the range of 0.05 and 1.19 mM, respectively. A fast response time of less than 5 seconds was obtained. In conclusion, we demonstrated that a highly sensitive HbA1c sensor was successfully prepared not only on glassy carbon electrode but also on portable microelectrode which can be applied for diabetes patients.

    摘要 I Abstract II 誌謝 III 目錄 IV 圖索引 VIII 表索引 XI 第一章、緒論 1 1-1、前言 1 1-2、研究動機 2 1-3、糖尿病簡介 3 1-3-1、糖尿病的定義與分類 3 1-3-2、糖尿病的臨床診斷標準 4 1-4、糖化血紅素簡介 5 1-4-1、血紅素介紹 5 1-4-2、糖化血紅素 6 第二章、理論基礎與文獻回顧 9 2-1、感測器簡介 9 2-2、生物感測器簡介 9 2-2-1、生物感測器定義 9 2-2-2、生物感測器之基本結構與原理 10 2-2-3、生物感測器種類 11 2-2-4、訊號換能器分類 12 2-3、電化學式生物感測器(Bard and Faulkner, 2001, 汪玉銘, 2003, 陳冠榮, 2008) 13 2-3-1、電位式(Potentiometric)生物感測器 13 2-3-2、電流式(Amperometry)生物感測器 14 2-3-3、電導式 (Conductometric)生物感測器(Shen, 2007) 15 2-4生物分子固定化技術(汪玉銘, 2003, 陳冠榮, 2008) 15 2-4-1吸附法 (Adsorption) 16 2-4-2 包埋法 (Entrapment) 16 2-4-3 共價鍵結法 (Covalent attachment) 17 2-4-4 交聯架橋法 (Cross-linking) 17 2-5、酵素簡介 17 2-5-1、酵素特性 17 2-5-2、酵素的分類 18 2-5-3、酵素專一性反應 18 2-6、奈米金屬粒子 19 2-6-1、奈米粒子之簡介(王世敏 et al., 2004, 馬振基, 2005) 19 2-6-2、奈米粒子之製備方法(王世敏 et al., 2004) 20 2-6-3、奈米粒子於生物感測器之文獻回顧 22 2-7、細菌纖維素 23 2-7-1、纖維素(cellulose) 23 2-7-2、細菌纖維素(bacterial cellulose, BC) 23 2-8、糖化血紅素量測技術 24 2-8-1、市面上糖化血紅素量測系統 24 2-8-2、酵素量測系統(Ferri et al., 2009) 25 2-8-3、電流式糖化纈草胺酸感測器文獻回顧 26 2-8-3-1 酵素型 26 2-8-3-2 非酵素型 29 第三章 實驗方法 35 3-1、實驗藥品 35 3-2、樣品配製 36 3-3、實驗儀器 36 3-4、實驗方法 37 3-4-1、糖化纈草胺酸合成方法 38 3-4-2、金屬複合觸媒合成方法 38 3-4-2-1、載體前處理 39 3-4-2-1-1、硝酸改質 39 3-4-2-1-2、硝酸與硫酸改質 39 3-4-2-1-3、修改之Watanabe膠體化還原法合成Pt-CNT觸媒 39 3-4-3、酵素固定層(Au-BC)之合成方法 40 3-4-3-1、奈米纖維素均質化步驟 40 3-4-3-2、Au-BC之合成方法 40 3-4-4、糖化纈草胺酸酵素感測器之修飾層製備 41 3-4-5、電化學實驗流程 42 3-4-6、微型感測器試片(Mini sensor) 43 3-5、分析儀器與方法 44 3-5-1、X 光繞射分析(XRD) 44 3-5-2、感應偶合電漿放射光譜儀分析(ICP-AES) 44 3-5-3、穿透式電子顯微鏡分析(TEM) 45 3-5-4、掃描式電子顯微鏡分析(SEM) 45 3-5-5、傅立葉轉換紅外線光譜儀(FT-IR) 45 3-5-6、紫外線/可見光分光光譜儀(UV-vis) 45 3-5-7、化學分析電子能譜 (ESCA) 46 3-6、電化學分析原理 46 3-6-1、循環伏安法 (Cyclic Voltammetry) 46 3-6-2、電流應答法 (Amperometric Method) 49 第四章、結果與討論 50 4-1、糖化纈草胺酸之特性分析 50 4-1-1、酵素反應呈色試驗 50 4-1-2、糖化纈草胺酸之純度分析 52 4-1-2-1、紫外線/可見光分光光譜儀之分析 52 4-1-2-2、高壓液相層析儀分析 53 4-2、奈米複合觸媒之電化學鑑定與材料結構分析 54 4-2-1、多層壁奈米碳管之活化改質 54 4-2-1-1、硝酸及硝酸與硫酸混合液之改質程度影響 54 4-2-2、奈米複合觸媒之特性分析 56 4-2-2-1、奈米複合觸媒之表面形態分析 56 4-2-2-2、奈米複合觸媒之X-ray繞射晶格分析 58 4-2-2-3、電化學硫酸前處理之電化學反應探討 58 4-2-2-4、奈米複合觸媒之活性表面積分析 60 4-2-2-5、硫酸前處理對於觸媒催化雙氧水之影響 61 4-3、奈米金屬觸媒於雙氧水感測器上之實驗參數與電化學分析 63 4-3-1、奈米複合觸媒之雙氧水催化能力與機制探討 63 4-3-2、溶氧干擾 65 4-3-3、施加電位對雙氧水偵測影響 66 4-4、利用吸附法固定糖化纈草胺酸氧化酶之修飾電極之實驗參數與電化學特性分析 70 4-4-1、Au-BC之材料結構分析 70 4-4-1-1、表面形態分析 70 4-4-1-2、X-ray光電子能譜 72 4-4-2、固定糖化纈草胺酸氧化酶於修飾電極上之製程參數 73 4-4-2-1、電極各修飾層之形態分析與探討 73 4-4-2-2、酵素活性量乘載最適化 76 4-4-2-3、酵素動力學 79 4-5、微型感測器 81 4-5-1、雙氧水定電位滴定測試分析 81 4-5-1、糖化纈草胺酸定電位滴定測試分析 84 4-6、抗干擾之探討 87 4-6-1、Nafion之抗干擾探討 88 4-6-2、施加電位之抗干擾探討 90 4-6-3、醋酸纖維素之抗干擾探討 91 第五章、結論與未來方向 93 第六章、參考文獻 95

    (1993) 'The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus', New England Journal of Medicine, 329, 977-86.
    Akazawa, S.-I., Karino, T., Yoshida, N., Katsuragi, T. & Tani, Y. (2004) 'Functional Analysis of Fructosyl-Amino Acid Oxidases of Aspergillus oryzae', Applied and Environmental Microbiology, 70, 5882-90.
    Alexander, C., Andersson, H. S., Andersson, L. I., Ansell, R. J., Kirsch, N., Nicholls, I. A., O'mahony, J. & Whitcombe, M. J. (2006) 'Molecular imprinting science and technology: A survey of the literature for the years up to and including 2003', Journal of Molecular Recognition, 19, 106-80.
    Antolini, E. & Cardellini, F. (2001) 'Formation of carbon supported PtRu alloys: An XRD analysis', Journal of Alloys and Compounds, 315, 118-22.
    Association, A. D. (2008) 'Diagnosis and Classification of Diabetes Mellitus', Diabetes Care, 31, S55-S60.
    Azizi Samir, M. a. S., Alloin, F. & Dufresne, A. (2005) 'Review of Recent Research into Cellulosic Whiskers, Their Properties and Their Application in Nanocomposite Field', Biomacromolecules, 6, 612-26.
    Bard, A. J. & Faulkner, L. R. (2001) Electrochemical Methods: Fundamentals and Applications.
    Biegler, T., Rand, D. a. J. & Woods, R. (1971) 'Limiting oxygen coverage on platinized platinum; Relevance to determination of real platinum area by hydrogen adsorption', Journal of Electroanalytical Chemistry and Interfacial Electrochemistry, 29, 269-77.
    Bishop, M. L., Fody, E. P. & Schoeff, L. E. (2005) Clinical Chemistry: Principles, Procedures, Correlations, Lippincott Williams & Wilkins.
    Bry, L., Chen, P. C. & Sacks, D. B. (2001) 'Effects of Hemoglobin Variants and Chemically Modified Derivatives on Assays for Glycohemoglobin', Clinical Chemistry, 47, 153-63.
    Cabral, J. M. & Kennedy, J. F. (1991) 'Covalent and coordination immobilization of proteins', Bioprocess technology, 14, 73-138.
    Castillo, J., Gaspar, S., Leth, S., Niculescu, M., Mortari, A., Bontidean, I., Soukharev, V., Dorneanu, S. A., Ryabov, A. D. & Csoregi, E. (2004) 'Biosensors for life quality: Design, development and applications', Sensors and Actuators B: Chemical, 102, 179-94.
    Chartarrayawadee, W., Moulton, S. E., Li, D., Too, C. O. & Wallace, G. G. (2012) 'Novel composite graphene/platinum electro-catalytic electrodes prepared by electrophoretic deposition from colloidal solutions', Electrochimica Acta, 60, 213-23.
    Chen, K.-J., Lee, C.-F., Rick, J., Wang, S.-H., Liu, C.-C. & Hwang, B.-J. (2012) 'Fabrication and application of amperometric glucose biosensor based on a novel PtPd bimetallic nanoparticle decorated multi-walled carbon nanotube catalyst', Biosensors and Bioelectronics, 33, 75-81.
    Chen, P., Cho, S. & Jin, H.-J. (2010) 'Modification and applications of bacterial celluloses in polymer science', Macromolecular Research, 18, 309-20.
    Chien, H.-C. & Chou , T.-C. (2011) 'A Nonenzymatic Amperometric Method for Fructosyl-Valine Sensing Using Ferroceneboronic Acid', Electroanalysis, 23, 402-08.
    Chien, H. C. & Chou, T. C. (2010) 'Glassy carbon paste electrodes for the determination of fructosyl valine', Electroanalysis, 22, 688-93.
    Choi, S. W., Shin, M. H., Yun, W. J., Kim, H. Y., Lee, Y. H., Kweon, S. S., Rhee, J. A. & Choi, J. S. (2011) 'Association between hemoglobin A 1c, carotid atherosclerosis, arterial stiffness, and peripheral arterial disease in Korean type 2 diabetic patients', Journal of Diabetes and its Complications, 25, 7-13.
    Conway, B. E. & Gottesfeld, S. (1973) 'Real condition of oxidized platinum electrodes. Part 2. - Resolution of reversible and irreversible processes by optical and impedance studies', Journal of the Chemical Society, Faraday Transactions 1: Physical Chemistry in Condensed Phases, 69, 1090-107.
    D'orazio, P. (2003) 'Biosensors in clinical chemistry', Clinica Chimica Acta, 334, 41-69.
    Diamond, D. & De Saez Viteri, F. J. (1998) 'Ion-selective electrodes and optodes'.
    Eggins, B. R. (2002) 'Chemical Sensors and Biosensors'.
    Fang, L., Li, W., Zhou, Y. & Liu, C. C. (2009) 'A single-use, disposable iridium-modified electrochemical biosensor for fructosyl valine for the glycoslated hemoglobin detection', Sensors and Actuators, B: Chemical, 137, 235-38.
    Ferri, S., Kim, S., Tsugawa, W. & Sode, K. (2009) 'Review of fructosyl amino acid oxidase engineering research: a glimpse into the future of hemoglobin A1c biosensing', Journal of diabetes science and technology, 3, 585-92.
    Ferri, S., Sakaguchi, A., Goto, H., Tsugawa, W. & Sode, K. (2005) 'Isolation and characterization of a fructosyl-amine oxidase from an <i>Arthrobacter sp', Biotechnology Letters, 27, 27-32.
    Gamati, S., Luong, J. H. T. & Mulchandani, A. (1991) 'A microbial biosensor for trimethylamine using Pseudomonas aminovorans cells', Biosensors and Bioelectronics, 6, 125-31.
    Gavin, J. R., Alberti, K. G. M. M., Davidson, M. B., Defronzo, R. A., Drash, A., Gabbe, S. G., Genuth, S., Harris, M. I., Kahn, R., Keen, H., Knowler, W. C., Lebovitz, H., Maclaren, N. K., Palmer, J. P., Raskin, P., Rizza, R. A. & Stern, M. P. (2003) 'Report of the expert committee on the diagnosis and classification of diabetes mellitus', Diabetes Care, 26, S5-S20.
    Gill, I. & Ballesteros, A. (1998) 'Encapsulation of Biologicals within Silicate, Siloxane, and Hybrid Sol−Gel Polymers:  An Efficient and Generic Approach', Journal of the American Chemical Society, 120, 8587-98.
    Haffner, S. M. (1998) 'The Importance of Hyperglycemia in the Nonfasting State to the Development of Cardiovascular Disease', Endocrine Reviews, 19, 583-92.
    Hamnett, A., Kennedy, B. J. & Wagner, F. E. (1990) 'PtRu anodes for methanol electrooxidation: A ruthenium-99 Mossbauer study', Journal of Catalysis, 124, 30-40.
    Hirokawa, K., Gomi, K., Bakke, M. & Kajiyama, N. (2003) 'Distribution and properties of novel deglycating enzymes for fructosyl peptide in fungi', Archives of Microbiology, 180, 227-31.
    Hirokawa, K., Nakamura, K. & Kajiyama, N. (2004) 'Enzymes used for the determination of HbA1C', FEMS Microbiology Letters, 235, 157-62.
    Hou, J. N., Bi, Y. F., Xu, M., Huang, Y., Li, X. Y., Wang, W. Q., Chen, Y. H. & Ning, G. (2011) 'The change points of HbA 1C for detection of retinopathy in Chinese type 2 diabetic patients', Diabetes Research and Clinical Practice, 91, 401-05.
    Huang, J., Wang, D., Hou, H. & You, T. (2008) 'Electrospun palladium nanoparticle-loaded carbon nanofibers and their electrocatalytic activities towards hydrogen peroxide and NADH', Advanced Functional Materials, 18, 441-48.
    John F. Moulder, William F. Stickle, Peter E. Sobol & Bomben., K. D. (1995) Handbook of X-ray Photoelectron Spectroscopy, Physical Electronics, Inc. 6509 Flying Cloud Drive Eden Prairie, Minnesota 55344 United States of America.
    Jones, T. P. & Porter, M. D. (1988) 'Optical pH sensor based on the chemical modification of a porous polymer film', Analytical Chemistry, 60, 404-06.
    Keil, P., Mortensen, H. B. & Christophersen, C. (1985) 'Fructosylvaline. A simple model of the N-terminal residue of human haemoglobin A1c', Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry, 39, 191-93.
    Khudaish, E. A. (1999) 'The electrochemical oxidation of hydrogen peroxide on platinum electrodes at phosphate buffer solutions'.
    Klemm, D., Heublein, B., Fink, H.-P. & Bohn, A. (2005) 'Cellulose: Fascinating Biopolymer and Sustainable Raw Material', Angewandte Chemie International Edition, 44, 3358-93.
    Liu, L., Hood, S., Wang, Y., Bezverkov, R., Dou, C., Datta, A. & Yuan, C. (2008) 'Direct enzymatic assay for %HbA1c in human whole blood samples', Clinical Biochemistry, 41, 576-83.
    Liu, Z., Lee, J. Y., Chen, W., Han, M. & Gan, L. M. (2003) 'Physical and Electrochemical Characterizations of Microwave-Assisted Polyol Preparation of Carbon-Supported PtRu Nanoparticles', Langmuir, 20, 181-87.
    Mehrvar, M. & Abdi, M. (2004) 'Recent developments, characteristics, and potential applications of electrochemical biosensors', Analytical Sciences, 20, 1113-26.
    Ming, L., Xi, X. & Liu, J. (2006) 'Electrochemically platinized carbon paste enzyme electrodes: A new design of amperometric glucose biosensors', Biotechnology Letters, 28, 1341-45.
    Miscoria, S. A., Barrera, G. D. & Rivas, G. A. (2002) 'Analytical Performance of a Glucose Biosensor Prepared by Immobilization of Glucose Oxidase and Different Metals into a Carbon Paste Electrode', Electroanalysis, 14, 981-87.
    Nanjo, Y., Hayashi, R. & Yao, T. (2007) 'An enzymatic method for the rapid measurement of the hemoglobin A1c by a flow-injection system comprised of an electrochemical detector with a specific enzyme-reactor and a spectrophotometer', Analytica Chimica Acta, 583, 45-54.
    Ngsp (2012) 'College of American Pathologists (CAP) GH2 Survey Data:'.
    Ogawa, K., Stollner, D., Scheller, F., Warsinke, A., Ishimura, F., Tsugawa, W., Ferri, S. & Sode, K. (2002) 'Development of a flow-injection analysis (FIA) enzyme sensor for fructosyl amine monitoring', Analytical and Bioanalytical Chemistry, 373, 211-14.
    Okitsu, K., Bandow, H., Maeda, Y. & Nagata, Y. (1996) 'Sonochemical Preparation of Ultrafine Palladium Particles', Chemistry of Materials, 8, 315-17.
    Petersen, N. & Gatenholm, P. (2011) 'Bacterial cellulose-based materials and medical devices: current state and perspectives', Applied Microbiology and Biotechnology, 91, 1277-86.
    Reetz, M. T., Helbig, W. & Quaiser, S. A. (1995) 'Electrochemical preparation of nanostructured bimetallic clusters', Journal Name: Chemistry of Materials; Journal Volume: 7; Journal Issue: 12; Other Information: PBD: Dec 1995, Medium: X; Size: pp. 2227-28.
    Roberts, N. B., Green, B. N. & Morris, M. (1997) 'Potential of electrospray mass spectrometry for quantifying glycohemoglobin', Clinical Chemistry, 43, 771-78.
    Rodriguez-Segade, S., Rodriguez, J., Paz, J. M. & Camina, F. (2009) 'Translating the A1C assay into estimated average glucose values', Diabetes Care, 32.
    Ross, P., Mayer, R. & Benziman, M. (1991) 'Cellulose biosynthesis and function in bacteria', Microbiological Reviews, 55, 35-58.
    Sacks, D. B. (2003) 'Hemoglobin Variants and Hemoglobin A1c Analysis: Problem Solved?', Clinical Chemistry, 49, 1245-47.
    Sakaguchi, A., Tsugawa, W., Ferri, S. & Sode, K. (2003) 'Development of highly-sensitive fructosyl-valine enzyme sensor employing recombinant fructosyl amine oxidase', Electrochemistry, 71, 442-45.
    Sakurabayashi, I., Watano, T., Yonehara, S., Ishimaru, K., Hirai, K., Komori, T. & Yagi, M. (2003) 'New Enzymatic Assay for Glycohemoglobin', Clinical Chemistry, 49, 269-74.
    Schnedl, W. J., Lahousen, T., Lang, T., Lipp, R. W., Yonehara, S., Fukunaga, S., Imai, T. & Little, R. R. (2004) 'Determination of glycated hemoglobin in clinically silent hemoglobin variants', Diabetes/Metabolism Research and Reviews, 20, 460-65.
    Shen, J. (2007) Development and Characterization of Thick-film Printed Electrochemical Biosensors.
    Shen, J., Dudik, L. & Liu, C. C. (2007) 'An iridium nanoparticles dispersed carbon based thick film electrochemical biosensor and its application for a single use, disposable glucose biosensor', Sensors and Actuators, B: Chemical, 125, 106-13.
    Shimazu, K., Weisshaar, D. & Kuwana, T. (1987) 'Electrochemical dispersion of Pt microparticles on glassy carbon electrodes', Journal of Electroanalytical Chemistry, 223, 223-34.
    Siro, I. & Plackett, D. (2010) 'Microfibrillated cellulose and new nanocomposite materials: a review', Cellulose, 17, 459-94.
    Skoog Dah, F. J. & Nieman, T. A. (1998) Principles of Instrumental Analysis.
    Sode, K., Ishimura, F. & Tsugawa, W. (2001a) 'Screening and Characterization of Fructosyl-Valine–Utilizing Marine Microorganisms', Marine Biotechnology, 3, 126-32.
    Sode, K., Ohta, S., Yanai, Y. & Yamazaki, T. (2003) 'Construction of a molecular imprinting catalyst using target analogue template and its application for an amperometric fructosylamine sensor', Biosensors and Bioelectronics, 18, 1485-90.
    Sode, K., Takahashi, Y., Ohta, S., Tsugawa, W. & Yamazaki, T. (2001b) 'A new concept for the construction of an artificial dehydrogenase for fructosylamine compounds and its application for an amperometric fructosylamine sensor', Analytica Chimica Acta, 435, 151-56.
    Takahashi, M., Pischetsrieder, M. & Monnier, V. M. (1997) 'Isolation, Purification, and Characterization of Amadoriase Isoenzymes (Fructosyl Amine-oxygen Oxidoreductase EC 1.5.3) from Aspergillus sp', Journal of Biological Chemistry, 272, 3437-43.
    Tatsuo, H. & Toshiko, K. (1991) 'Purification and properties of fructosylamine oxidase from Aspergillus sp. 1005', Agric Biol Chem, 55, 333-38.
    Tsugawa, W., Ishimura, F., Ogawa, K. & Sode, K. (2000) 'Development of an Enzyme Sensor Utilizing a Novel Fructosyl Amine Oxidase from a Marine Yeast', Electrochemistry, 68, 869-71.
    Tsugawa, W., Ogawa, K., Ishimura, F. & Sode, K. (2001) 'Fructosyl amine sensing based on Prussian blue modified enzyme electrode', Electrochemistry, 69, 973-75.
    Wang, J., Fang, L., Lopez, D. & Tobias, H. (1993) 'Highly Selective and Sensitive Amperometric Biosensing of Glucose at Ruthenium-Dispersed Carbon Paste Enzyme Electrodes', Analytical Letters, 26, 1819-30.
    Wang, J., Rivas, G. & Chicharro, M. (1996) 'Iridium-Dispersed Carbon Paste Enzyme Electrodes', Electroanalysis, 8, 434-37.
    Wang, X. & Hsing, I. M. (2002) 'Surfactant stabilized Pt and Pt alloy electrocatalyst for polymer electrolyte fuel cells', Electrochimica Acta, 47, 2981-87.
    Watanabe, M., Uchida, M. & Motoo, S. (1987) 'Preparation of highly dispersed Pt + Ru alloy clusters and the activity for the electrooxidation of methanol', Journal of Electroanalytical Chemistry, 229, 395-406.
    Whiting, D. R., Guariguata, L., Weil, C. & Shaw, J. (2011) 'IDF Diabetes Atlas: Global estimates of the prevalence of diabetes for 2011 and 2030', Diabetes Research and Clinical Practice, 94, 311-21.
    Who (1999) 'Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications'.
    Who (2011) 'Use of Glycated Haemoglobin (HbA1c) in the Diagnosis of Diabetes Mellitus'.
    Wilson, D. H., Bogacz, J. P., Forsythe, C. M., Turk, P. J., Lane, T. L., Gates, R. C. & Brandt, D. R. (1993) 'Fully automated assay of glycohemoglobin with the Abbott IMxR analyzer: Novel approaches for separation and detection', Clinical Chemistry, 39, 2090-97.
    Yalcinkaya, F. & Powner, E. T. (1996) 'Intelligent structures', Sensor Review, 16, 32-37.
    Yamazaki, T. (2012) 'An amperometric sensor based on gold electrode modified by soluble molecularly imprinted catalyst for fructosyl valine', Electrochemistry, 80, 353-57.
    Yamazaki, T., Ohta, S. & Sode, K. (2008) 'Operational condition of a molecular imprinting catalyst-based fructosyl-valine sensor', Electrochemistry, 76, 590-93.
    Yonezawa, Y., Sato, T., Kuroda, S. & Kuge, K.-I. (1991) 'Photochemical formation of colloidal silver: peptizing action of acetone ketyl radical', Journal of the Chemical Society, Faraday Transactions, 87, 1905-10.
    Yoshida, N., Sakai, Y., Isogai, A., Fukuya, H., Yagi, M., Tani, Y. & Kato, N. (1996) 'Primary structures of fungal fructosyl amino acid oxidases and their application to the measurement of glycated proteins', European Journal of Biochemistry, 242, 499-505.
    Yoshida, N., Sakai, Y., Serata, M., Tani, Y. & Kato, N. (1995) 'Distribution and properties of fructosyl amino acid oxidase in fungi', Applied and Environmental Microbiology, 61, 4487-89.
    Zhang, P., Zhang, X., Brown, J., Vistisen, D., Sicree, R., Shaw, J. & Nichols, G. (2010a) 'Global healthcare expenditure on diabetes for 2010 and 2030', Diabetes Research and Clinical Practice, 87, 293-301.
    Zhang, T., Wang, W., Zhang, D., Zhang, X., Ma, Y., Zhou, Y. & Qi, L. (2010b) 'Biotemplated Synthesis of Gold Nanoparticle–Bacteria Cellulose Nanofiber Nanocomposites and Their Application in Biosensing', Advanced Functional Materials, 20, 1152-60.
    Zhang, X. & Chan, K. Y. (2003) 'Water-in-oil microemulsion synthesis of platinum-ruthenium nanoparticles, their characterization and electrocatalytic properties', Chemistry of Materials, 15, 451-59.
    Zhang, X., Medzihradszky, K. F., Cunningham, J., Lee, P. D. K., Rognerud, C. L., Ou, C.-N., Harmatz, P. & Witkowska, H. E. (2001) 'Characterization of glycated hemoglobin in diabetic patients: usefulness of electrospray mass spectrometry in monitoring the extent and distribution of glycation', Journal of Chromatography B: Biomedical Sciences and Applications, 759, 1-15.
    Zhujun, Z. & Seitz, W. R. (1986) 'Optical sensor for oxygen based on immobilized hemoglobin', Analytical Chemistry, 58, 220-22.
    Zou, Y., Xiang, C., Sun, L.-X. & Xu, F. (2008) 'Glucose biosensor based on electrodeposition of platinum nanoparticles onto carbon nanotubes and immobilizing enzyme with chitosan-SiO2 sol–gel', Biosensors and Bioelectronics, 23, 1010-16.
    王世敏, 許祖勛 & 傅晶 (2004) 奈米材料原理與製備, 五南出版社.
    田蔚城 (1998) 生物技術的發展與應用.
    呂鋒洲 & 林仁混 (1991) 基礎酵素學, 聯經出版社.
    汪玉銘 (2003) '定電流聚合導電性高分子法製備葡萄糖生物感測器之研究', 國立成功大學.
    花雀惠, 李弘元, 林怡如, 洪玉鳳, 周自賢 & 簡毓芬 (2006) '糖化血色素對於篩檢葡萄糖耐量異常高血糖其敏感性與特異性之分析', Journal of Biomedical & Laboratory Sciences 18, 1-4.
    邱宗鴻 (2009) '妊娠性糖尿病', 中華明國糖尿病衛教學會12月會迅.
    馬振基 (2005) 奈米材料科技原理與應用.
    張義泉 (2005) '具界面活性擬樹枝狀聚乙烯亞胺之合成與製備燃料電池觸媒之應用', 國立成功大學.
    郭家宏 (2009) '纖維素之溶解對其酵素醣化及發酵應用之研究', 台灣科技大學.
    陳冠榮 (2008) '以奈米金修飾電極製備電流式免疫型感測器', 國立台灣科技大學.
    陳春吉 (2002) '自主性單層薄膜電極之阻抗分析與其在內毒素檢測上之應用', 國立成功大學.
    彭文權 (1997) '以沉積法製備甲醇燃料電池用之Pt-Ru雙金屬觸媒', 元智大學.
    黃炳照 & 莊睦賢 (1999) '電化學感測器', 化工技術, 第七卷.
    楊于萱 '淺談糖尿病監控指標'.
    劉英俊 (1995) 酵素工程, 中央圖書出版社.
    蔡佳珊 (2008) '氣體擴散層之稱PtW/WO3奈米線陽極觸媒', 台灣科技大學.

    無法下載圖示 全文公開日期 2017/08/01 (校內網路)
    全文公開日期 本全文未授權公開 (校外網路)
    全文公開日期 本全文未授權公開 (國家圖書館:臺灣博碩士論文系統)
    QR CODE