尿酸 (uric acid) 是人體內嘌呤代謝 (purine) 的最終產物，物質經由肝臟代謝後存在於血液及尿液中，若濃度過高易引發痛風 (gout)、高尿酸血症 (hyperuricemia) 等疾病。高尿酸血症也與許多疾病相關，例如：慢性腎病、代謝症候群、高血壓以及心臟病。因此監測血液或尿液中尿酸的濃度是掌握病況的重要方法。由於傳統尿酸分析方法繁複，所需時間也較長，且需要專業人員判讀。故近期朝著簡易輕便快速的方式檢測。因此本論文使用電化學中的電流式方式製備尿酸感測器，由於分析儀器的小巧靈敏，操作方式簡易，使用電化學方式測尿酸之研發也日新月異，逐漸成為市面上主要針測尿酸的方式。
本論文使用網印製程，配合濺鍍技術，在聚對苯二甲酸乙二酯 (polyethylene terephthalate, PET) 基材鍍上一層的金屬薄膜，再利用舉離製程，成功製備出二極式的金屬電極。接著各別濺鍍兩種金屬薄膜，鈦、鎳鉻作為導電材料。相較於傳統使用的貴金屬材料，例如：金、白金等，製備花費相對的低。在偵測尿酸方面是使用非酵素方式，利用電子傳遞物質 (ferricyanide) 會直接與尿酸產生電子轉移現象，接著電子傳送至金屬電極表面，達到訊號的偵測。除了比起傳統使用尿酸酶偵測尿酸，在製備上簡易且穩定外，使用電子傳遞物質也可有效的降低偵測電位，使得血液中的電活性物質的干擾訊號降低。例如：維他命C (ascorbic acid, AA)、對乙酰氨基酚 (acetaminophen, AAP) 。
本論文中利用循環伏安法以及計時安培法偵測尿酸，最佳化感測配方使用於金/鈦、金/鎳鉻金屬電極，得到靈敏度分別為60, 56 μA/(mM•cm2)；R-square分別為0.996、0.999；感測線性範圍分別為4-30, 4-40 mg/dL；變異係數分別為5.44, 4.52 %。實際運用人體血液的偵測，呈現高選擇性，且干擾物質訊號並不影響尿酸的偵測，室溫下保存時間可達至21天。

Uric acid (UA) is the primary end product of purine metabolism, and metabolized by liver present in blood and urine. High levels of UA in the blood (hyperuricemia) are linked with gout and other disease including renal disease, metabolic syndrome, high blood pressure and heart disease. The ability to monitor blood UA level would be helpful in the follow-up of hyperuricemic patients to give them adequate feedback and treatment guidelines. Due to the traditional method for dectecing UA is complicate and requires professional interpretation, the finding of portable UA sensors is important. Therefore, recently more methods were focused to develop using electrochemical method which provide advantages such as simple measurement, short response time, and high sensitivity.
In this thesis, a two-electrode strip was fabricated using thin films technology, followed by lift-off and screen-printing to pattern the electrodes. The titanium (Ti) and nickel-chromium (Ni-Cr) metal layers were sputtered on PET substrate. The electrodes cost less than those electrodes made by precious metals such as gold and platinum. The proposed method for detecting UA is direct electron transfer by ferricyanide. Therefore the prepared electrodes showed advantages of simple fabrication, high stability and reduction of the applied potential.
In this thesis, the UA was dectected using cyclic voltammetric and amperometric methods. The optimal sensing ink was applied in the two metal electrodes, Ti and Ni-Cr, respectively. The range of detected UA showed a linear relation between 4 to 30 and 4 to 40 mg/dL, which possess regression coefficient of R = 0.996, 0.999, respectively. The sensitivity of the UA biosensor was 60, 56 μA/(mM•cm2), and the average coefficient of variation was 5.44, 4.52 %, respectively on Ti and Ni-Cr coated electrodes. Furthermore, the detection of UA in human body has good selectivity, and the storage time can reach 21 days.

[1] Moriarity J. T., Folsom A. R., Iribarren C., Nieto F. J., Rosamond W. D. Serum uric acid and risk of coronary heart disease: Atherosclerosis risk in communities (ARIC) study. Annals of Epidemiology. 2000;10:136-43.
[2] Pan W. H., Kurpad A. V., Li D., Tanaka K. Asia pacific journal of clinical nutrition. The journal og the asia pacific clinical nutrition society. 2012.
[3] 蔡嘉哲, 余光輝, 梁統華, 蔡文展, 魏正宗, 謝祖怡. 台灣痛風與高尿酸血症診療指引. 中華民國風濕病醫學會 (Rheumatology Association of the Republic of China). 2007.
[4] 何敏夫. 臨床化學第二版. 合記圖書. 1999:pp.228-32.
[5] Singh B., Laffir F., Dickinson C., McCormac T., Dempsey E. Carbon supported cobalt and nickel based nanomaterials for direct uric acid determination. Electroanalysis. 2011;23:79-89.
[6] 黃谷臣. 痛風是種病，痛起來要人命--淺談GOUT. 淡江大學體育室. 2001.
[7] 陳清朗. 痛風與高尿酸血症. 台灣新生報出版部. 1995.
[8] Ramazzina I., Folli C., Secchi A., Berni R., Percudani R. Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes. Nature Chemical Biology. 2006;2:144-8.
[9] Kahn A. M., Weinman E. J. Urate transport in the proximal tubule: in vivo and vesicle studies. The American journal of physiology. 1985;249:F789-98.
[10] Chen Z., Fang C., Wang H., He J., Deng Z. A novel disposable amperometric UA strip. Sensors and Actuators, B: Chemical. 2008;129:710-5.
[11] 細谷龍男, 奈良昌治. 尿酸值健康診療. 大展出版社. 2004.
[12] 李信興, 廖桂聲. 中西醫會診：痛風. 書泉出版社. 2002.
[13] 一之瀨昇, 小林哲二, 陳克紹, 曹永偉. 感測器原理與應用技術. 全華科技圖書股份有限公司. 1988.
[14] 陳冠榮. 以奈米金修飾電極製備電流式免疫型感測器. 國立台灣科技大學化學工程研究所碩士論文. 2008.
[15] F. S., F. S. Preface. Techniques and Instrumentation in Analytical Chemistry. 1992;11:ix-x.
[16] 徐俊傑. 應用版式電極製作可攜式快速尿酸感測裝置. 私立中原大學醫 學 工 程 學 系碩士學位論文. 2003.
[17] 邱念華. 電化學. 文京圖書有限公司. 1996.
[18] A.J.Bard, L.F. Electrochemical Methods Fundaments and applications. New York: Wiley. 2001.
[19] 陳治誠. 生化感測器技術簡介. 科儀新知第十五卷第二期. 1993.
[20] Vetter K. J. Electrochemical kinetics-theoretical and experimental aspects. Academic Press Inc. 1961.
[21] Sawyer D. T., Sobkowaiak A. Electrochemistry for chemists. John wiley & Sons Inc. 1995.
[22] 李家逢. 新穎鉑鈀/多層壁奈米碳管之電化學觸媒於電流式葡萄糖感測器之製備與應用. 國立臺灣科技大學化學工程系碩士學位論文. 2011.
[23] 呂鋒洲, 林仁混. 基礎酵素學. 聯經出版社. 1991.
[24] Kano K., Morikage K., Uno B., Esaka Y., Goto M. Enzyme microelectrodes for choline and acetylcholine and their applications. Analytica Chimica Acta. 1994;299:69-74.
[25] Netchiporouk L. I., Shul'Ga A. A., Jaffrezic-Renault N., Martelet C., Olier R., Cespuglio R. Properties of carbon fibre microelectrodes as a basis for enzyme biosensors. Analytica Chimica Acta. 1995;303:275-83.
[26] Selvaraju T., Ramaraj R. Simultaneous detection of ascorbic acid, uric acid and homovanillic acid at copper modified electrode. Electrochimica Acta. 2007;52:2998-3005.
[27] M.A.Tehrani R., Ab Ghani S. Voltammetric analysis of uric acid by zinc-nickel nanoalloy coated composite graphite. Sensors and Actuators, B: Chemical. 2010;145:20-4.
[28] Marioli J. M., Kuwana T. Electrochemical detection of carbohydrates at nickel-copper and nickel-chromium-iron alloy electrodes. Electroanalysis. 1993;5:11-5.
[29] Wang J., Zhang W. D. Sputtering deposition of gold nanoparticles onto vertically aligned carbon nanotubes for electroanalysis of uric acid. Journal of Electroanalytical Chemistry. 2011;654:79-84.
[30] Thiagarajan S., Chen S. M. Preparation and characterization of PtAu hybrid film modified electrodes and their use in simultaneous determination of dopamine, ascorbic acid and uric acid. Talanta. 2007;74:212-22.
[31] Chaubey A., Malhotra B. D. Mediated biosensors. Biosensors and Bioelectronics. 2002;17:441-56.
[32] Khoo S. B., Chen F. Studies of sol-gel ceramic film incorporating methylene blue on glassy carbon: An electrocatalytic system for the simultaneous determination of ascorbic and uric acids. Analytical Chemistry. 2002;74:5734-41.
[33] Chen Z., Fang C., Qiu G., He J., Deng Z. Non-enzymatic disposable test strip for detecting uric acid in whole blood. Journal of Electroanalytical Chemistry. 2009;633:314-8.
[34] Kranz C., Wohlschläger H., Schmidt H. L., Schuhmann W. Controlled Electrochemical Preparation of Amperometric Biosensors Based on Conducting Polymer Multilayers. Electroanalysis. 1998;10:546-52.
[35] Nakaminami T., Ito S. I., Kuwabata S., Yoneyama H. Uricase-catalyzed oxidation of uric acid using an artificial electron acceptor and fabrication of amperometric uric acid sensors with use of a redox ladder polymer. Analytical Chemistry. 1999;71:1928-34.
[36] Nakaminami T., Ito S. I., Kuwabata S., Yoneyama H. A biomimetic phospholipid/alkanethiolate bilayer immobilizing uricase and an electron mediator on an Au electrode for amperometric determination of uric acid. Analytical Chemistry. 1999;71:4278-83.
[37] Zen J. M., Hsu C. T. A selective voltammetric method for uric acid detection at Nafion®-coated carbon paste electrodes. Talanta. 1998;46:1363-9.
[38] Zen J. M., Jou J. J., Ilangovan G. Selective voltammetric method for uric acid detection using pre-anodized Nation-coated glassy carbon electrodes. Analyst. 1998;123:1345-50.
[39] Sternberg R., Bindra D. S., Wilson G. S., Thévenot D. K. Covalent enzyme coupling on cellulose acetate membranes for glucose sensor development. Analytical Chemistry. 1988;60:2781-6.
[40] Kulys J., Hansen H. E. Long-term response of an integrated carbon paste based glucose biosensor. Analytica Chimica Acta. 1995;303:285-94.
[41] Liu L., Zhao Q., Liu T., Kong J., Long Z., Zhao M. Sodium caseinate/carboxymethylcellulose interactions at oil–water interface: Relationship to emulsion stability. Food Chemistry. 2012;132:1822-9.
[42] Koupantsis T., Kiosseoglou V. Whey protein-carboxymethylcellulose interaction in solution and in oil-in-water emulsion systems. Effect on emulsion stability. Food Hydrocolloids. 2009;23:1156-63.
[43] Ragheb A. A., Nassar S. H., Abd El-Thalouth I., Ibrahim M. A., Shahin A. A. Preparation, characterization and technological evaluation of CMC derived from rice-straw as thickening agents in discharge, discharge-resist and burn-out printing. Carbohydrate Polymers. 2012;89:1044-9.
[44] Greenawalt K. E., Corazzini R. L., Colt M. J., Holmdahl L. Adhesion formation to hemostatic agents and its reduction with a sodium hyaluronate/carboxymethylcellulose adhesion barrier. Journal of Biomedical Materials Research - Part A. 2012;100 A:1777-82.
[45] Varshney V. K., Gupta P. K., Naithani S., Khullar R., Bhatt A., Soni P. L. Carboxymethylation of α-cellulose isolated from Lantana camara with respect to degree of substitution and rheological behavior. Carbohydrate Polymers. 2006;63:40-5.
[46] Duteille F., Jeffery S. L. A. A phase II prospective, non-comparative assessment of a new silver sodium carboxymethylcellulose (AQUACEL ® Ag BURN) glove in the management of partial thickness hand burns. Burns. 2012.
[47] Mishima Y., Motonaka J., Maruyama K., Ikeda S. Determination of hydrogen peroxide using a potassium hexacyanoferrate(III) modified titanium dioxide electrode. Analytica Chimica Acta. 1998;358:291-6.
[48] Ensafi A. A., Khoddami E., Rezaei B., Karimi-Maleh H. P-Aminophenol-multiwall carbon nanotubes-TiO2 electrode as a sensor for simultaneous determination of penicillamine and uric acid. Colloids and Surfaces B: Biointerfaces. 2010;81:42-9.
[49] Liu A., Wei M., Honma I., Zhou H. Biosensing properties of titanate-nanotube films: Selective detection of dopamine in the presence of ascorbate and uric acid. Advanced Functional Materials. 2006;16:371-6.
[50] Marioli J. M., Luo P. F., Kuwana T. Nickel-chromium alloy electrode as a carbohydrate detector for liquid chromatography. Analytica Chimica Acta. 1993;282:571-80.
[51] Marioli J. M., Sereno L. E. The potentiodynamic behavior of nickel-chromium (80:20) alloy electrodes in 0.10 N sodium hydroxide. Electrochimica Acta. 1995;40:983-9.
[52] 古聖偉. 反應性濺鍍氮化鋯薄膜及其作為銅導線之阻障層的失效機制研究暨以鎳電極系統作為生物感測器. 國立臺灣科技大學化學工程系碩士學位論文. 2011.
[53] 潘扶民. 材料分析. 中國材料學會. 1988.
[54] 林麗娟. X光繞射原理及其應用. X光材料分析技術與應用專題. 1994.
[55] 行政院國家科學委員會精密儀器發展中心. 表面分析儀器原子力顯微鏡. 儀器總覽. 1998.
[56] Gamati S., Luong J. H. T., Mulchandani A. A microbial biosensor for trimethylamine using Pseudomonas aminovorans cells. Biosensors and Bioelectronics. 1991;6:125-31.
[57] R.Brian, E. Chemical Sensors and Biosensors. 2005.
[58] Chen Z., Jiang J., Shen G., Yu R. Impedance immunosensor based on receptor protein adsorbed directly on porous gold film. Analytica Chimica Acta. 2005;553:190-5.
[59] Park S. M., Yoo J. S. Electrochemical impedance spectroscopy for better electrochemical measurements. Analytical Chemistry. 2003;75:455A-61A.
[60] Abbott. Clinical Evaluation of a Faster, Smaller Volume Blood Glucose Test Strip Based on TrueMeasure™ Technology. Abbott Diabetes Care Inc. 2005.
[61] Miao Y., Tan S. N. Amperometric hydrogen peroxide biosensor with silica sol-gel/chitosan film as immobilization matrix. Analytica Chimica Acta. 2001;437:87-93.
[62] Kang X., Mai Z., Zou X., Cai P., Mo J. Glucose biosensors based on platinum nanoparticles-deposited carbon nanotubes in sol-gel chitosan/silica hybrid. Talanta. 2008;74:879-86.
[63] Lee S. H., Fang H. Y., Chen W. C. Amperometric glucose biosensor based on screen-printed carbon electrodes mediated with hexacyanoferrate-chitosan oligomers mixture. Sensors and Actuators, B: Chemical. 2006;117:236-43.