臺灣博碩士論文加值系統

本論文提出一結合氧化鎳薄膜於可撓式陣列型結構之pH感測器，可藉由改變濺鍍氣體中之氧含量以提升其感測度，並找出最佳化之氧化鎳薄膜以應用於乳酸生醫感測器和葡萄糖生醫感測器。接著，將乳酸脫氫酶和葡萄糖氧化酶固化於上述結構之氧化鎳薄膜上，可分別製備一可撓式陣列型結構之乳酸生醫感測器和一可撓式陣列型結構之葡萄糖生醫感測器。本論文利用氧化石墨烯和磁珠修飾氧化鎳感測膜，以提升酵素吸附及生醫感測器之感測能力；並透過電化學阻抗分析儀進行電化學阻抗分析，以確認氧化石墨烯與磁珠成功修飾感測膜；爾後，分別探討經氧化石墨烯與磁珠修飾之乳酸生醫感測器和葡萄糖感測器的響應時間、衰退率、抗干擾性和檢測極限等特性。此外，藉由微流體測量系統，探討待測溶液於不同流速影響經氧化石墨烯與磁珠修飾之乳酸生醫感測器和葡萄糖感測器的感測特性。最後，再將經氧化石墨烯與磁珠修飾之乳酸生醫感測器和葡萄糖感測器，結合XBee模組之無線測量系統，以實現無線遠端偵測。

In this thesis, nickel oxide (NiO) was applied to a flexible arrayed pH sensor, and its sensitivity could be enhanced by changing oxygen content of sputtering gas. The optimal NiO film was applied to a flexible arrayed lactate biosensor and a flexible arrayed glucose biosensor. After that, lactate dehydrogenase (LDH) and glucose oxidase (GOD) were immobilized on the NiO film of above structure to fabricate the flexible arrayed lactate biosensor and flexible arrayed glucose biosensor, respectively. We used graphene oxide (GO) and magnetic beads (MBs) to modify the sensing film, which could enhance the ability of enzyme adsorption and the characteristics of the biosensors. Moreover, the electrochemical impedance spectroscopy was used to analyze the electrochemical impedance and confirm whether GO and MB did successfully modify the sensing film. Subsequently, it was investigated the response time, decay rate, interference effect and detection limit of the lactate and glucose biosensors based on NiO film modified by GO and MBs, respectively. In addition, the lactate and glucose biosensors based on NiO film modified by GO and MBs were integrated in the microfluidic framework, which sensing characteristics were respectively researched under different flow rates. Finally, the lactate and glucose biosensors based on NiO film modified by GO and MBs were combined in the wireless real-time sensing system based on XBee module to realize remote monitoring.

摘要 i
ABSTRACT ii
誌謝 iii
Contents iv
List of Tables vii
List of Figures viii
Chapter 1 Background 1
1.1 Evolution 1
1.2 Motivation and Purpose 3
1.3 Thesis Outline 6
Chapter 2 Introduction 8
2.1 Sensing Materials and Nanomaterials 8
2.1.1 Nickel Oxide 9
2.1.2 Graphene Oxide 11
2.1.3 Magenetic Beads 12
2.2 Electrochemical Sensor 12
2.2.1 Sensing Theory of Electrochemical Sensor 13
2.2.2 Sesning Characteristics of Electrochemical Sensor 15
2.3 Enzymatic Biosensor 20
2.3.1 Enzyme and Immobilization Thereof 20
2.3.2 Reaction Mechanism of Enzymatic Lactate Biosensor 23
2.3.3 Reaction Mechanism of Enzymatic Glucose Biosensor 24
2.4 Measurement System 25
2.4.1 Potentiometric Measurement System 25
2.4.2 Microfluidic Measurement System 27
2.4.3 Wireless Real-Time Sensing System 28
2.4.4 Electrochemical Impedance Spectroscopy 29
Chapter 3 Experimental 41
3.1 Materials, Reagents and Instruments 41
3.2 Fabrication of Flexible Arrayed pH Sensors Based on NiO Films 44
3.3 Fabrication of Flexible Arrayed Lactate Biosensors 46
3.3.1 Lactate Biosensors Based on LDH-NAD+/GPTS/NiO Film 46
3.3.2 Lactate Biosensors Based on LDH-NAD+/GPTS/GO/NiO Film 47
3.3.3 Lactate Biosensors Based on LDH-NAD+-MBs/GPTS/GO/NiO Film 48
3.4 Fabrication of Flexible Arrayed Glucose Biosensors 49
3.4.1 Glucose Biosensors Based on Nafion-GOD/NiO Film 49
3.4.2 Glucose Biosensors Based on Nafion-GOD/GO/NiO Film 50
3.4.3 Glucose Biosensors Based on Nafion-GOD-MBs/GO/NiO Film 51
3.5 Monitoring under Static and Dynamic Test Solutions 52
3.6 Analysis of Electrochemical Impedance Spectroscopy 53
3.7 Remote Monitoring using Wireless Real-Time Sensing System 53
Chapter 4 Results and Discussion 65
4.1 Analysis of Flexible Arrayed pH Sensor 65
4.1.1 Comparison of Average Sensitivity and Linearity for pH Sensors Based on Different NiO Films under Static pH Solutions 65
4.1.2 Drift Effect of pH Sensor Based on NiO Film 68
4.1.3 Hysteresis Effect of pH Sensor Based on NiO Film 70
4.1.4 Electrochemical Impedances between NiO Film and pH Solutions 71
4.2 Analysis of Flexible Arrayed Lactate Biosensor 72
4.2.1 Characterization of Lactate Biosensors Based on LDH-NAD+/GPTS/NiO Film under Static Lactate Solutions 72
4.2.2 Characterization of Lactate Biosensors Based on LDH-NAD+/GPTS/NiO Film Modified by GO under Static Lactate Solutions 73
4.2.3 Characterization of Lactate Biosensors Based on LDH-NAD+/GPTS/GO/NiO Film Modified by MBs under Static and Dynamic Lactate Solutions 74
4.2.3.1 Average Sensitivity and Linearity of Lactate Biosensors under Static Lactate Solutions 74
4.2.3.2 Average Sensitivity and Linearity of Lactate Biosensor under Dynamic Lactate Solutions 76
4.2.3.3 Drift Effect of Lactate Biosensor under Static Lactate Solutions 77
4.2.3.4 Hysteresis Effect of Lactate Biosensor under Static Lactate Solutions 78
4.2.3.5 Response Time of Lactate Biosensor under Static Lactate Solutions 78
4.2.3.6 Decay Rate of Lactate Biosensor under Static Lactate Solutions 79
4.2.3.7 Detection Limit of Lactate Biosensor under Static Lactate Solutions 80
4.2.3.8 Interference Effect of Lactate Biosensor under Static Lactate Solutions 81
4.2.3.9 Temperature Effect of Lactate Biosensor under Static Lactate Solutions 82
4.2.3.10 Comparisons of Sensing Characteristics for Lactate Biosensor 83
4.3 Analysis of Flexible Arrayed Glucose Biosensor 86
4.3.1 Characterization of Glucose Biosensor Based on Nafion-GOD/NiO Film under Static Glucose Solutions 86
4.3.2 Characterization of Glucose Biosensors Based on Nafion-GOD/NiO Film Modified by GO under Static Glucose Solutions 87
4.3.3 Characterization of Glucose Biosensors Based on Nafion-GOD/GO/NiO Film Modified by MBs under Static and Dynamic Glucose Solutions 88
4.3.3.1 Average Sensitivity and Linearity of Glucose Biosensors under Static Glucose Solutions 88
4.3.3.2 Average Sensitivity and Linearity of Glucose Biosensor under Dynamic Glucose Solutions 89
4.3.3.3 Drift Effect of Glucose Biosensor under Static Glucose Solutions 90
4.3.3.4 Response Time of Glucose Biosensor under Static Glucose Solutions 91
4.3.3.5 Decay Rate of Glucose Biosensor under Static Glucose Solutions 91
4.3.3.6 Detection Limit of Glucose Biosensor under Static Glucose Solutions 92
4.3.3.7 Interference Effect of Glucose Biosensor under Static Glucose Solutions 93
4.3.3.8 Temperature Effect of Glucose Biosensor under Static Glucose Solutions 94
4.3.3.9 Comparisons of Sensing Characteristics for Glucose Biosensor 95
4.4 Electrochemical Impedances for Enzyme-MBs/GO/NiO Films 97
4.5 Surface Areas of NiO Film and GO Film 99
4.6 Analysis of Remote Monitoring for Lactate and Glucose 100
Chapter 5 Conclusions 148
Chapter 6 Future Work 153
References 154
Appendix I 173

List of Tables
Table 2-1 The comparisons of characteristics with different techniques in WPAN [68, 76]. 40
Table 3-1 The concentrations of interfering substance solutions. 64
Table 4-1 The comparisons of average sensitivity and linearity for flexible arrayed pH sensors based on NiO films with different oxygen contents under static pH solutions from pH 1 to pH 13. 134
Table 4-2 The comparisons of drift rates with different sensing materials. 135
Table 4-3 The comparisons of hysteresis effects with different sensing materials measured in different conditions. 136
Table 4-4 The comparisons of average sensitivity and linearity for flexible arrayed lactate biosensors based on LDH-NAD+/GPTS/NiO film immobilized by using different GPTS contents under static lactate solutions from 0.2 mM to 3 mM. 137
Table 4-5 The comparisons of average sensitivity and linearity for flexible arrayed lactate biosensors based on LDH-NAD+/GPTS/GO/NiO film with different GO contents under static lactate solutions from 0.2 mM to 3 mM. 138
Table 4-6 The comparisons of average sensitivity and linearity for flexible arrayed lactate biosensors based on LDH-NAD+-MBs/GPTS/GO/NiO film with different MB contents under static lactate solutions from 0.2 mM to 3 mM. 139
Table 4-7 The comparisons of average sensitivity and linearity for flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GPTS/GO/NiO film immersed in lactate solutions from 0.2 mM to 3 mM at different flow rates from 0 μl/min to 30 μl/ml. 140
Table 4-8 The comparisons of sensitivity and linearity for lactate biosensors with various films. 141
Table 4-9 The average sensitivity and linearity of flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GPTS/GO/NiO film for 21 days. 142
Table 4-10 The average sensitivity and linearity of flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GPTS/GO/NiO film at different temperatures. 143
Table 4-11 The comparisons of average sensitivity and linearity for flexible arrayed glucose biosensor based on Nafion-GOD-MBs/GO/NiO film immersed in glucose solutions from 3 mM to 7 mM at different flow rates from 0 μl/min to 30 μl/ml. 144
Table 4-12 The comparisons of sensitivity and linearity for glucose biosensors with various films. 145
Table 4-13 The average sensitivity and linearity of flexible arrayed glucose biosensor based on Nafion-GOD-MBs/GO/NiO film for 21 days. 146
Table 4-14 The average sensitivity and linearity of flexible arrayed glucose biosensor based on Nafion-GOD-MBs/GO/NiO film at different temperatures. 147

List of Figures
Fig. 2-1 The schematic diagrams of two-dimensional (a) stoichiometric NiO (b) non-stoichiometric NiO [42]. 31
Fig. 2-2 The schematic diagram of the hole migration in non-stoichiometric NiO [43]. 32
Fig. 2-3 The schematic diagrams of (a) site-binding, (b) electrical double layer at the metal oxide-solution interface and (c) hydrated ions [51, 53]. 33
Fig. 2-4 The schematic diagram of potentiometric measurement system. 34
Fig. 2-5 The schematic diagram of microfluidic measurement system. 35
Fig. 2-6 (a) The 3D schematic diagram and (b) size diagram of microfluidic device [75]. 36
Fig. 2-7 The schematic diagram of wireless real-time sensing system. 37
Fig. 2-8 The schematic diagram of electrochemical instrument for EIS. 38
Fig. 2-9 The schematic diagrams of (a) interfacial electrochemical reaction with diffusion and double layer components, (b) equivalent circuit and (c) Nyquist diagram [77]. 39
Fig. 3-1 The flow chart in this thesis. 54
Fig. 3-2 The photo of radio frequency sputtering system. 55
Fig. 3-3 The photo of semi-automatic screen printer. 56
Fig. 3-4 The schematic diagram of flexible arrayed pH sensor based on NiO film. 57
Fig. 3-5 The schematic diagram of flexible arrayed lactate biosensor based on NiO film. 58
Fig. 3-6 The schematic diagram of flexible arrayed lactate biosensor based on NiO film modified by GO. 59
Fig. 3-7 The schematic diagram of flexible arrayed lactate biosensor based on NiO film modified by GO and MBs. 60
Fig. 3-8 The schematic diagram of flexible arrayed glucose biosensor based on NiO film. 61
Fig. 3-9 The schematic diagram of flexible arrayed glucose biosensor based on NiO film modified by GO. 62
Fig. 3-10 The schematic diagram of flexible arrayed glucose biosensor based on NiO film modified by GO and MBs. 63
Fig. 4-1 The average sensitivity and linearity for flexible arrayed pH sensor based on NiO film with varying oxygen content of sputtering gas. 102
Fig. 4-2 The responses of flexible arrayed pH sensor based on NiO film under static pH solutions from pH 1 to pH 13. 103
Fig. 4-3 The FE-SEM (a) top view and (b) cross sectional view of NiO film. 104
Fig. 4-4 The drift effects of flexible arrayed pH sensor based on NiO film immersed in pH 1, pH 7 and pH 13 solutions for 12 hr, respectively. 105
Fig. 4-5 The hysteresis effects of flexible arrayed pH sensor based on NiO film in loops of (a) pH 7-3-7-11-7, (b) pH 7-11-7-3-7, (c) pH 3-7-11-7-3 and (d) pH 11-7-3-7-11. 106
Fig. 4-6 The Nyquist diagram of flexible arrayed pH sensor based on NiO film in different pH solutions. 107
Fig. 4-7 The responses of flexible arrayed lactate biosensor based on LDH-NAD+/GPTS/NiO film with 1:2 volume ratio of GPTS-toluene mixture under static lactate solutions from 0.2 mM to 3 mM. 108
Fig. 4-8 The responses of flexible arrayed lactate biosensor based on LDH-NAD+/GPTS/GO/NiO film with 0.3 wt% GO under static lactate solutions from 0.2 mM to 3 mM. 109
Fig. 4-9 The responses of flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GPTS/GO/NiO film with 0.75 ml MBs under static lactate solutions from 0.2 mM to 3 mM. 110
Fig. 4-10 The responses of flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GPTS/GO/NiO film immersed in lactate solutions from 0.2 mM to 3 mM at different flow rates from 0 μl/min to 30 μl/ml. 111
Fig. 4-11 The drift effect of flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GPTS/GO/NiO film immersed in 1.3 mM lactate solution. 112
Fig. 4-12 The hysteresis effect of flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GPTS/GO/NiO film in a loop of 1.3-0.2-1.3-3-1.3 mM. 113
Fig. 4-13 The response time of flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GPTS/GO/NiO film immersed in 1.3 mM lactate solution. 114
Fig. 4-14 The decay rate of flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GPTS/GO/NiO film within 21 days. 115
Fig. 4-15 The detection range of flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GPTS/GO/NiO film. 116
Fig. 4-16 The anti-intereference effects of flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GPTS/GO/NiO film against various substances. 117
Fig. 4-17 The average sensitivity and linearity of flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GPTS/GO/NiO film at different temperatures. 118
Fig. 4-18 The responses of flexible arrayed glucose biosensor based on Nafion-GOD/NiO film under static glucose solutions from 3 mM to 7 mM. 119
Fig. 4-19 The responses of flexible arrayed glucose biosensor based on Nafion-GOD/GO/NiO film under static glucose solutions from 3 mM to 7 mM. 120
Fig. 4-20 The responses of flexible arrayed glucose biosensor based on Nafion-GOD-MBs/GO/NiO film under static glucose solutions from 3 mM to 7 mM. 121
Fig. 4-21 The responses of flexible arrayed glucose biosensor based on Nafion-GOD-MBs/GO/NiO film immersed in glucose solutions from 3 mM to 7 mM at different flow rates from 0 μl/min to 30 μl/ml. 122
Fig. 4-22 The drift effect of flexible arrayed glucose biosensor based on Nafion-GOD-MBs/GO/NiO film immersed in 5 mM glucose solution. 123
Fig. 4-23 The response time of flexible arrayed glucose biosensor based on Nafion-GOD-MBs/GO/NiO film immersed in 5 mM glucose solution. 124
Fig. 4-24 The decay rate of flexible arrayed glucose biosensor based on Nafion-GOD-MBs/GO/NiO film within 21 days. 125
Fig. 4-25 The detection range of flexible arrayed glucose biosensor based on Nafion-GOD-MBs/GO/NiO film. 126
Fig. 4-26 The anti-intereference effects of flexible arrayed glucose biosensor based on Nafion-GOD-MBs/GO/NiO film against various substances. 127
Fig. 4-27 The average sensitivity and linearity of flexible arrayed glucose biosensor based on Nafion-GOD-MBs/GO/NiO film at different temperatures. 128
Fig. 4-28 The Nyquist diagram of (1) LDH-NAD+/GPTS/NiO film, (2) LDH-NAD+/GPTS/GO/NiO film and (3) LDH-NAD+-MBs/GPTS/GO/NiO film immersed in 0.5 mM potassium hexacyanoferrate solution. 129
Fig. 4-29 The Nyquist diagram of (1) Nafion-GOD/NiO film, (2) Nafion-GOD/GO/NiO film and (3) Nafion-GOD-MBs/GO/NiO film immersed in 0.5 mM potassium hexacyanoferrate solution. 130
Fig. 4-30 The FE-SEM top view of GO film. 131
Fig. 4-31 The responses of flexible arrayed lactate biosensor based on LDH-NAD+-MBs/GO/NiO film integrated in wireless real-time sensing system. 132
Fig. 4-32 The responses of flexible arrayed glucose biosensor based on Nafion-GOD-MBs/GO/NiO film integrated in wireless real-time sensing system. 133

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