近年來，科技的發達使得人們壽命延長，疾病預防及病情監控已成為人們主要關心的話題，其中又以糖尿病及腎臟相關疾病最受到矚目，因此開發一良好的葡萄糖及尿素感測器已刻不容緩。在團隊先前的研究中，以氧化鎳薄膜製備的延伸式閘極場效電晶體具有極佳的酸鹼值感測特性包含良好的靈敏度、線性度、選擇性以及較小的遲滯變化與電壓偏移量。因此，吾人將酵素固定於氧化鎳薄膜之延伸式閘極，進一步將其製作成葡萄糖及尿素感測器。
首先，吾人將使用不同的材料和方法固定尿素酵素，並詳述各種固定化方法之流程及機制，並利用檢量線分析尿素感測元件之靈敏度。在本研究中，吾人使用玻璃和聚醯亞胺兩種基板，除了探討緩衝液之濃度及酸鹼值對尿素感測影響，亦量測尿素感測元件的暫態響應、操作次數及存放天數的穩定度。
接著，吾人將尿素感測器進行微小化，並結合自行設計的微流道系統，營造出一流動式並且可重複操作的測量環境。實驗結果顯示，尿素感測元件在靜態下量測擁有較寬廣的感測範圍及較長的壽命，而在動態下量測則具有較高的靈敏度與較高的抗干擾性。
最後，吾人使用兩種固定化方法完成葡萄糖感測元件，可發現將葡萄糖酵素固定在氧化鎳薄膜上亦擁有良好的感測特性。因此，氧化鎳薄膜極具開發尿素及葡萄糖生醫感測器之潛力。

In recent years, novel technologies are developed to make human life longer. Related topic about disease prevention and patient's condition monitoring are more concerned by human. Among them, diabetes and kidney disease are the most of attentive. Thus, to develop good glucose and urea sensors are very important. In previous studies, the NiO thin film based-extended gate field effect transistor (EGFET) shows good sensitivity, linearity, selectivity, and small hysteresis width and drift for pH sensing. Therefore, we used NiO thin film as our sensing membrane to fabricate glucose and urea sensors by immobilizing enzyme.
First, different methods are used to immobilize enzyme. Various processes and mechanisms of enzyme immobilization methods are detailedly described. Calibration curves are employed to analyze the urea sensing performance. In this study, the urea sensors are fabricated on glass and polyimide substrates, respectively. Influences of solute concentration, the pH value, buffer capacity, substrates on the sensing performance device are discussed and demonstrated. The reliability and storage stability are investigated as well.
Then, a miniaturized urea sensor is developed to integrate with a microfluidic system which is self-designed. The microchannel system is a dynamic sensing environment. Experimentally, the miniaturized urea sensor shows wide sensing linear region and a long life time in a static measurement. However, the miniaturized urea sensor shows a high sensitivity and a less interference by other ions.
Finally, glucose sensors are fabricated with two immobilized methods. Both of two devices demonstrate excellent glucose sensing performance. Therefore, the NiO thin film gives the promise for high-performance urea and glucose sensing applications.

Abstract iii
Table Captions 5
Figure Captions 6
Chapter 1 Introduction
1-1. Introduction to Semiconductor-Based pH Sensor 11
1-2. The Site-binding Model and Mechanism of EGFET pH Sensor 13
1-3. The Mechanisms of Urea and Glucose Sensors 16
1-4. Introduction to Michaelis-Menten Kinetics 17
1-5. The Debye–Hückel Theory 19
1-6. Introduction to the Microchannel System 20
1-7. Thesis Organization 21
Chapter 2 Experimental Details
2-1. Fabrication of NiO-Based Urea Biosensor 23
2-1-1. Preparation of Device Substrate 23
2-1-2. Fabrication of NiO-Based pH EGFET 24
2-1-3. Enzyme Immobilization of NiO-Based Urea Sensor 25
2-2. Fabrication of a NiO-Based Miniaturized Urea Sensor and a Microchannel System 25
2-2-1. Preparation of Device Substrate 26
2-2-2. Fabrication of NiO-Based Miniaturized pH Electrode (ME) 26
2-2-3. Enzyme Immobilization of a NiO-Based Miniaturized Urea Sensor 27
2-2-4. Fabrication of a Microchannel System 27
2-3. Fabrication of a NiO-Based Glucose Biosensor 28
2-4. Sensing Measurement 30
2-4-1. pH Sensing Measurement Setup 30
2-4-2. Urea and Glucose Sensing Measurement Setup 30
2-5. Material Analyses 32
2-5-1. Scanning Electron Microscopy (SEM) 32
2-5-2. Atomic Force Microscopy (AFM) 32

Chapter 3 Characteristics of NiO-Based Urea Sensors
3-1. Introduction 34
3-2. Device Fabrication 35
3-3. Experimental Results and Discussion 36
3-3-1. Urea Membrane Modified by PVC-COOH 36
3-3-2. Influence of Substrate 36
3-3-3. Influence of pH Value 37
3-3-4. Influence of Buffer Capacity 37
3-3-5. Response and Recovery Time 38
3-3-6. Interferences 39
3-3-7. Storage Stability of Urea Sensors 40
3-3-8. Repeatability of Urea Sensors 40
3-4. Summary 41
Chapter 4 Fabrication and Integration of NiO-Based Miniaturized Urea Sensors and a Microchannel System
4-1. Introduction 43
4-2. Device Fabrication 44
4-3. Experimental Results and Discussion 45
4-3-1. Influence of pH Sensing Area 45
4-3-2. Measurement of Microchannel System 46
4-3-3. Measuring within Microchannel System 46
4-3-4. Response Time and Recovery Time 47
4-3-5. Interferences 47
4-3-6. Storage Stability of Miniaturized Urea Sensors 48
4-3-7. Repeatability of a Miniaturized Urea Sensor 48
4-4. Summary 49
Chapter 5 Characteristics of NiO-Based Glucose Sensors
5-1. Introduction 50
5-2. Device Fabrication 51
5-3. Experimental Results and Discussion 52
5-3-1. Entrapment Method of Enzyme Membrane 52
5-3-2. Cross-linking Method of Enzyme Membrane 53
5-4. Summary 54
Chapter 6 Conclusion and Future Works
6-1. Conclusion 55
6-2. Future Works 57
References 59
Tables 74
Figures 83

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