臺灣博碩士論文加值系統

葡萄糖是人體血液中重要物質，由於人體內葡萄糖水平是衡量糖尿病的重要指標，所以它一直是生醫檢測研究的焦點。本論文以電壓式量測技術的方式研究氧化鎂(MgO)薄膜氫離子感測器，並以此為基礎進一步開發基於酶修飾的MgO薄膜葡萄糖感測器，且使用電壓回授型儀表放大器組成量測電路。又因微型化是生醫感測器的發展重點，本論文將感測器以及量測電路整合成微型化架構之多感測器系統。本多感測器系統分為兩部份，一為感測電極之研究開發，二為下線晶片與量測電路板之整合開發，兩者皆採用柔軟、輕便且低成本的柔性印刷電路板製成。在感測電極的方面藉由射頻濺鍍工藝並在實驗出的穩定濺鍍參數下沉積MgO在感測薄膜工作電極上。為了增強感測器對葡萄糖的感測能力，本論文採用了葡萄糖氧化酶(GOD)增強感測器的性能。本論文使用了多項儀器對MgO薄膜進行了分析和驗證，包括X光光電子能譜儀、場發射掃描電子顯微鏡、原子力顯微鏡和能量色散X光譜儀。研究及實驗結果表明，在2 mM至10 mM範圍內，基於酶修飾MgO葡萄糖感測器在各項指標上皆具有出色的表現，其中感測度為17.45 mV/mM並且線性度可達到0.998。在儀表放大器的方面，藉由電路的設計、結構、佈局以及下線。本碩士論文成功實現下線晶片整合感測器之微型化多工感測器的開發並且將感測器之面積從11.52 cm2縮小至3.3 cm2。

Glucose is an important substance in the human blood, and it has always been the focus of biomedical testing and research because the glucose level in the human body is an important indicator for measuring diabetes. In this thesis, the magnesium oxide (MgO) film hydrogen ion sensor was studied by potentiometric measurement technology, and the MgO film glucose sensor based on enzyme modification was further developed on this basis, and the measurement circuit was composed by using a voltage-feedback instrumentation amplifier. Since miniaturization is the focus of the development of biosensors, this paper integrates sensors and measurement circuits into a multi-sensor system with a miniaturized architecture. The multi-sensor system is divided into two parts, one is the research and development of sensing electrodes, and the other is the integration and development of tape-out chips and measurement circuit boards, both of which are made of flexible, lightweight and low-cost flexible printed circuit boards. In terms of the sensing electrode, MgO is deposited on the working electrode of the sensing film by the RF sputtering process and under the stable sputtering parameters of the experiment. To enhance the sensor's ability to sense glucose, glucose oxidase (GOD) was used to enhance the performance of the sensor. In this paper, MgO thin films were analyzed and validated using several instruments, including X-ray photoelectron spectroscopy, field emission scanning electron microscopy, atomic force microscopy, and energy dispersive X-ray spectroscopy. The results show that the enzyme-modified MgO glucose sensor has an excellent performance in all indexes in the range of 2 mM to 10 mM, the sensitivity is 17.45 mV/mM and the linearity can reach 0.998. In terms of instrumentation amplifiers, the design, structure, layout, and tape-out circuits are introduced. In this master's thesis, we successfully developed a miniaturized multi-task sensor with integrated sensors on the tape-out chip and reduced the sensor area from 11.52 cm2 to 3.3 cm2.

摘要 i
Abstract ii
Acknowledgments iii
Table of Contents iv
List of Tables viii
List of Figures x
Chapter 1 Background 1
1.1 Development 1
1.2 Motivations and Purposes 4
1.3 Outline 7
Chapter 2 Introduction 10
2.1 Materials of the pH Sensor, Glucose Biosensor, and Multi-Sensor 10
2.1.1 Magnesium Oxide, MgO 10
2.1.2 Glucose Oxidase, GOD 11
2.1.3 Flexible Printed Circuit Board, FPCB 12
2.2 Measurement Principles and Characteristics of the pH Sensor and Glucose Biosensor 14
2.2.1 Measurement Principle of the pH Sensor 14
2.2.2 Measurement Principles of the Glucose Biosensor 17
2.2.3 Sensing Characteristics of the pH Sensor and Biosensor 18
2.3 Measurement System of the pH Sensor and Glucose Biosensor 23
2.3.1 Potentiometric Measurement System 23
2.3.2 Operational Amplifier, OPA 26
2.3.3 Instrumentation Amplifier, INA 27
Chapter 3 Experimental 28
3.1 Materials and Instruments 28
3.1.1 Source of Materials 28
3.1.2 Experiment and Analysis Instruments 31
3.1.2.1 Radio Frequency (RF) Sputtering System 31
3.1.2.2 Field-emission Scanning Electron Microscope, FE-SEM 33
3.1.2.3 X-ray photoelectron spectroscopy, XPS 35
3.1.2.4 Atomic Force Microscopy, AFM 37
3.1.2.5 Analysis Instruments 39
3.2 Fabrication Process and Structure of the pH Sensor, Glucose Biosensor, and Multi-Sensor 40
3.2.1 Structure of the pH Sensor, Glucose Biosensor and Multi-Sensor 40
3.2.2 Fabrication Process of the pH Sensor 44
3.2.3 Fabrication Process of the Glucose Biosensor 46
3.2.4 Fabrication Process of the Multi-Sensor 48
3.3 Fabrication Process of the Test Solution 50
3.3.1 Fabrication Process of the pH Solution 50
3.3.2 Fabrication Process of the Glucose Solution 52
3.4 Measurement System of the pH Sensor and the Glucose Biosensor 54
3.4.1 Design of the Voltage-Time (V-T) Measurement System 54
3.4.2 Design of the Miniaturized Measurement System 57
3.4.3 Design of the Readout Circuit Chip 59
3.4.3.1 Design of the Operational Amplifier 59
3.4.3.2 Design of the Instrumentation Amplifier 66
3.4.4 Layout of the Readout Circuit Chip 68
3.4.4.1 Layout of the Two-Stage OPA and INA 68
3.4.4.2 Layout of the Folded-Cascode OPA and INA 72
Chapter 4 Results and Discussion 76
4.1 Material Analysis of the MgO Sensing Layer 76
4.1.1 FE-SEM Analysis of the MgO Sensing Layer 76
4.1.2 XPS Analysis of the MgO Sensing Layer 80
4.1.3 AFM Analysis of the MgO Sensing Layer 83
4.2 Sensing Characteristics of the pH Sensor 87
4.2.1 Average Sensitivity and Linearity of the pH Sensor 87
4.2.2 Drift Effect of the pH Sensor 91
4.2.3 Hysteresis Effects of the pH Sensor 93
4.2.4 Reproducibility of the pH Sensor 95
4.2.5 Repeatability of the pH Sensor 97
4.2.6 Response Time of the pH Sensor 99
4.2.7 Interference Effect of the pH Sensor 101
4.2.8 Sensing Characteristics Comparisons of the pH Sensor Based on Difference Sensing Electrode Structures 103
4.3 Sensing Characteristics of the Glucose Biosensor 105
4.3.1 Average Sensitivity, Linearity, and LOD of the Glucose Biosensor 105
4.3.2 Interference Effect of the Glucose Biosensor 108
4.3.3 Response Time of the Glucose Biosensor 110
4.3.4 Drift Effect of the Glucose Biosensor 112
4.3.5 Reproducibility of the Glucose Biosensor 114
4.3.6 Repeatability of the Glucose Biosensor 116
4.3.7 Response Time of the Glucose Biosensor 118
4.3.8 Sensing Characteristics Comparisons of the Glucose Biosensor Based on Difference Sensing Electrode Structure 120
4.4 Sensing Characteristics of the Multi-Sensor 123
4.4.1 Electrochemical Impedance Spectroscopy Analysis of the MgO Multi-Sensor Characteristic 123
4.4.2 Sensing Performance of the MgO Multi-Sensor 125
4.4.3 Repeatability of the MgO Multi-Sensor 127
4.4.4 Interference Effect of the MgO Multi-Sensor 129
4.5 Design Results and Specifications of the Readout Circuit Chip 130
4.5.1 Simulation Results of the Two-Stage OPA Driven by the Constant gm Bias Circuit 130
4.5.2 Simulation Results of the Folded-Cascode OPA Driven by the Constant gm Bias Circuit 144
4.5.3 Simulation Results of the INA Based on the Two-Stage OPA 154
4.5.4 Measurement Results of the Readout Circuit Chip 162
Chapter 5 Conclusions 173
Chapter 6 Future Works 175
References 177
附錄 187

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