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研究生： 葉庭善
Taufik - Poernomo
論文名稱： 利用網印式碳電極製造可拋棄式血糖測試片
Fabrication of a Disposable Glucose Biosensor on Screen-printed Carbon Electrodes
指導教授： 李嘉平
Chiapyng Lee
口試委員: 王孟菊
none
王文
Wen Wang
郭俞麟
none
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： 2008
畢業學年度： 96
語文別： 英文
論文頁數： 130
中文關鍵詞： 血糖測試片 、可拋棄式 、網印 、網印式碳電極
外文關鍵詞： glucose biosensor, disposable biosensor, screen printing, SPCEs
相關次數： 點閱：205  下載：4 
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    • 本研究是利用大量製造技術，即所謂的網印技術，來製造便宜且可拋棄式的安培式血糖測試片。本研究希望能夠建立一套標準程序用來製造有良好再現性且成本低的血糖測試片。本研究成功的利用網印技術製造血糖測試片。本實驗所製造的血糖測試片設計是兩電極式並且利用mediated enzymatic reaction system來偵測血糖濃度。實驗結果發現酵素反應產生的電流與所施加的葡萄糖濃度在50-600 mg/dL時呈良好的線性關係，靈敏度可以達到
    0.012uA/mg/dL，且平均誤差為6.4%左右。利用本研究所製造的血糖測試片來量測血糖只需1.5 uL的樣品量且可以在5秒鐘內就完成。

    The objective of this research is to use mass production compatible thick-film technology, namely, the screen printing and the stencil printing techniques to fabricate cost-effective, disposable, amperometric glucose biosensors. The scope of this study is to establish standard procedures of glucose biosensor fabrication with main focuses on low production cost and dependable reproducibility.
    A disposable glucose biosensor was successfully developed in this research using screen-printing technique. The glucose biosensor was designed to have two electrodes and employed a mediated enzymatic reaction system. The screen printing technique has demonstrated a capability of fabricating the biosensor rapidly, cheaply, and, quite precisely. The fabrication process began with a flat PVC substrate. Carbon electrodes, insulation layer, matrix layer, and adhesive layer were successively screen- (or stencil-) printed onto the substrate. Finally, following the inclusion of enzyme to the matrix layer, hydrophilic layer was applied to form fully functional glucose biosensor. Production parameters and materials were carefully selected and optimized in order to achieve best result while keeping the cost low.
    The fabricated biosensor was tested using relevant electrochemical methods such as cyclic voltammetry and amperometry. The biosensor responded linearly to samples with glucose concentrations of 50-600mg/dL (regression coefficient R=0.999). The sensitivity of the biosensor was 0.012uA/mg/dL and the average coefficient of variation was 6.4%. The biosensor only took as low as 1.5uL of sample and would complete the measurement in as fast as 5s. The most useful feature of the biosensor was its compatibility with LifeScan’s OneTouch® UltraTM meter. Additionally, low production cost of the glucose biosensor should open the possibility of commercialization.

    TABLE OF CONTENTS Abstract…....……………………………………………………………………………….I Table of Contents…....……………………………………………………………………II List of Figures…....…………………………………………………………………….....V List of Tables…....………………………………………………………………………VII Chapter 1. Introduction …………………………………………………………………...1 1.1. Biosensors and their applications………………………………………..........1 1.1.1. What is a biosensor? ………………………………………….…..1 1.1.2. Performance factors of biosensors………………………....…..….5 1.1.3. Applications of biosensors…………………….……………....…..6 1.1.3.1. Health care application of biosensors…………….……....6 1.1.3.2. Environmental monitoring application of biosensors…….8 1.1.3.3. Food and beverage analysis application of biosensors…...8 1.1.3.4. Defense and military applications of biosensors…...…….9 1.2. Transduction methods of biosensors………………………………………...10 1.2.1. Electrochemical biosensors………………………………………10 1.2.1.1. Potentiometric biosensor………………………….……..10 1.2.1.2. Amperometric and coulometric biosensor………..……..11 1.2.1.3. Conductometric biosensor…………………………........14 1.2.1.4. FET-based biosensors…………………………….……..15 1.2.2. Optical biosensors………………………………………....……..16 1.2.3. Thermal or calorimetric biosensors…………………….………..18 1.2.4. Piezoelectric biosensors…………………………………….........18 1.3. Types of commercial biosensors…………………………………..………...20 1.3.1. Single-use biosensors……………………………………….........20 1.3.2. Intermittent-use biosensors………………………………………20 1.3.3. Continuous-use biosensors………………………………….........21 1.4. Production technologies of biosensors……………………………….……...23 1.4.1. Thick film technology……………………………………………23 1.4.2. Thin film technology…………………………………..…………25 1.5. Importance of glucose biosensor...…………………………………....…….28 1.5.1. Status of diabetes……….………………………………………..28 1.5.2. Market of glucose biosensor…………………………….…….…31 1.6. Objective and scope of this research……………………………….…..…....35 1.7. Significance of this research…………………………………………….......36 . Chapter 2. Glucose biosensor technology…...……………………………………...…...38 2.1. Evolution of glucose biosensor……………………………………...………38 2.1.1. First generation glucose biosensor………………………...……..39 2.1.2. Second generation glucose biosensor……………………...…….41 2.1.3. Third generation glucose biosensor…………………………...…43 2.2. Current generation of glucose biosensor…………………………….………45 2.2.1. LifeScan…………………………….…………………...…….....46 2.2.2. Roche Diagnostics…..…………………………………………...47 2.2.3. Bayer Diagnostics…………………………….……………….…49 2.2.4. Abbot Diabetes Care………………………………………..........50 2.3. Future developments of glucose biosensor…………………………............52 2.3.1. Implantable glucose biosensor……………………………...........52 2.3.2. Minimally invasive glucose biosensor…………………..……….53 2.3.3. Non-invasive glucose biosensor………………………...……….55 2.4. LifeScan’s OneTouch® UltraTM glucose biosensor…………………………56 2.4.1. Mechanism of OneTouch® UltraTM system………………...........56 2.4.2. Fabrication process of OneTouch® UltraTM test strip……………59 Chapter 3. Experimental…………………………………………………………………63 3.1. Equipments………………………………………………………………….64 3.1.1. Semi-automatic screen printer, printing screens, and stencils…………………………………………….……………...64 3.1.2. Potentiostat……………………………………..………………...66 3.1.3. Other equipments…………………………………….…………..66 3.2. Materials………………………………………………….…………………67 3.2.1. Substrate and inks…………………………………………….….67 3.2.2. Matrix and enzyme………………………………………….…...67 3.2.2. Buffers and solvents…………………………………………..… 67 3.2.3. Other materials…………………………………………….….….68 3.3. Preparation of buffer solutions…………………………………………..…..69 3.4. Preparation of glucose solutions……………………………………….……69 3.5. Preparation of matrix ink………………………………………….……..….69 3.6. Preparation of enzyme solutions………………………………………....….70 3.7. Substrate handling and preconditioning……………………………......…....71 3.8. Carbon electrodes screen printing………………………………………..….72 3.9. Insulation layer screen printing…………………………………………..….72 3.10. Matrix layer screen printing……………………………………………......73 3.11. Adhesive layer screen printing……………………………………………..74 3.12. Enzyme solution drop-coating…………………………………….…….....75 3.13. Sensor strip finishing……………………………………………….….…..75 3.14. Testing the glucose biosensor’s characteristics…………………….……...76 3.14.1. Thickness and surface morphology.…………………….…..…..76 3.14.2. Cyclic Voltammetry…………………………………………......77 3.14.3. Amperometry…………………………………………….……...77 Chapter 4. Results and discussions…………………………………………….………...78 4.1. Glucose biosensor system…..……………………………………………...78 4.1.1. System mechanism…………………………………….…………78 4.1.1.1. Mediated enzymatic reaction……………………………78 4.1.1.2. Important features……………………………………….82 4.1.1.3. Compatibility with LifeScan’s OneTouch® UltraTM……84 4.1.2. Material selection, design, and fabrication process……………...86 4.1.2.1. Substrate………………………………………………....86 4.1.2.2. Electrodes………………………………………………..88 4.1.2.3. Insulation layer………………………………………......91 4.1.2.4. Matrix/enzyme layer…………………………………….92 4.1.2.5. Adhesive layer and hydrophilic film…………………….95 4.2. Thickness and surface morphology analysis…………………………….......96 4.3. Cyclic voltammetry analysis…………………………………………...........97 4.3.1. CV of the glucose biosensor………………………………………97 4.3.2. Effect of scan rate…………………………………………............99 4.4. Amperometry analysis….…………………………………………….........101 4.4.1. Effect of dissolved oxygen………………………………….........101 4.4.2. Effect of GOx loading………………………………………........102 4.4.3. Effect of applied potential…………………………………..........103 4.5. Construction of calibration curves………………………………................105 4.6. Cost analysis…………………………………………………….................108 Chapter 5. Conclusions and future work…………………………………......................110 5.1. Conclusions……………………………………………………...................110 5.2. Future work……………………………………………...............................111 References…………………………………………………………………………........112 Author……………...…………………………………………………………………...122

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