臺灣博碩士論文加值系統

本論文提出以射頻濺鍍系統(Radio Frequency Sputtering System)、熱蒸鍍系統(Thermal Evaporation System)與網版印刷技術(Screen-Printed Technology)製備氧化銦鎵鋅(Indium Gallium Zinc Oxide, IGZO)感測膜結合葡萄糖氧化酶(Glucose Oxidase, GOx)之酵素式葡萄糖生醫感測器。本論文為了提升酵素式葡萄糖生醫感測器之感測特性加入氧化石墨烯(Graphene Oxide, GO)與磁珠(Magnetic Beads, MBs)修飾感測膜，藉此提高酵素吸附性及感測特性，且透過電化學阻抗分析儀(Electrochemical Impedance Spectroscopy, EIS)進行電子傳遞能力之分析，藉此確認氧化石墨烯與磁珠成功修飾感測膜，根據實驗結果，氧化石墨烯與磁珠修飾之酵素式葡萄糖生醫感測器之平均感測度及線性度分別為10.391 mV/mM 及 0.998。本論文亦探討經氧化石墨烯與磁珠修飾之酵素式葡萄糖感測器的生命週期、穩定性、干擾性、檢測極限特性。最後，亦將酵素式葡萄糖生醫感測器整合於微流體架構以研究動態情況之感測特性，根據實驗結果，於動態情況下，氧化石墨烯與磁珠修飾之酵素式葡萄糖生醫感測器之平均感測度及線性度可提升至12.383 mV/mM 及 0.999。此外，為了發展多功能酵素即時感測系統，本論文亦研究pH感測器及以氧化石墨烯與磁珠修飾之酵素式葡萄糖生醫感測器、乳酸生醫感測器及尿素生醫感測器結合無線感測系統以實現無線感測量測，本論文以XBee 模組、Arduino Mega 2560、讀出電路、生醫感測器及電腦組成無線感測系統，此系統以遵守ZigBee無線網路協定進行量測訊號之傳輸，根據實驗結果，pH感測器及氧化石墨烯與磁珠修飾之酵素式葡萄糖生醫感測器、乳酸生醫感測器及尿素生醫感測器之感測度分別為50.059 mV/pH、10.257 mV/mM、55.747 mV/mM與2.066 mV/(mg/dl)。

In this thesis, it was mentioned the enzymatic glucose biosensor was manufactured by using radio frequency sputtering system, thermal evaporation system and screen-printed technology, whose glucose sensing membrane was composed of indium gallium zinc oxide (IGZO) membrane and glucose oxidase (GOx). For enhancing sensing characteristics of enzymatic glucose biosensor, the sensing membrane was modified by graphene oxide (GO) and magnetic beads (MBs) to improve adsorption of enzyme and sensing characteristics. According to experiential results, the average sensitivity and linearity of enzymatic glucose biosensor modified by GO and MBs were 10.391 mV/mM and 0.998, respectively. To demonstrate that sensing membrane was successfully modified by GO and MBs, the electrochemical impedance spectroscopy (EIS) was used to analyze the capability of electron transfer for sensing membranes. The stability, lifetime, interference and detection limit of the enzymatic glucose biosensor modified by GO and MBs were investigated. Finally, the enzymatic glucose biosensor modified by GO and MBs was integrated with the microfluidic framework and the sensing characteristics under dynamic conditions, i.e., solution under flowing condition, were investigated. According to experiential results, under dynamic conditions, the average sensitivity and linearity of enzymatic glucose biosensor modified by GO and MBs were enhanced to 12.383 mV/mM and 0.999, respectively. Furthermore, in order to develop the real-time sensing system applied in measurement of pH value and multifunctional enzyme, the pH sensor as well as enzymatic glucose, lactate and urea biosensor modified by GO and MBs was combined with wireless sensing system to carry out the wireless sensing measurements, and this system complied with ZigBee wireless networking protocol which consisted of the XBee module, Arduino Mega 2560, readout circuit, biosensor and computer was employed to transmit the measurement signals. According to the experimental results, the average sensitivities of the pH sensor as well as enzymatic glucose, lactate and urea biosensor modified by GO and MBs were 50.059 mV/pH, 10.257 mV/mM, 55.747 mV/mM and 2.066 mV/(mg/dl), respectively.

摘要 ------------------------------------------------------------------------ i
Abstract ------------------------------------------------------------------------ iii
誌謝 ------------------------------------------------------------------------ v
Contents ------------------------------------------------------------------------ vii
List of Tables ------------------------------------------------------------------------ xii
List of Figures ------------------------------------------------------------------------ xiv

Chapter 1 Introduction--------------------------------------------------------- 1
1.1 Background--------------------------------------------------------- 1
1.2 Motivation and Purpose------------------------------------------- 7
1.3 Process and Framework------------------------------------------- 9

Chapter 2 Theoretical Descriptions------------------------------------------ 13
2.1 Classification of the Electrochemical Biosensor-------------- 13
2.1.1 Potentiometric Biosensor ---------------------------------------- 14
2.1.2 Amperometric Biosensor ---------------------------------------- 15
2.1.3 Conductometric Biosensor --------------------------------------- 16
2.2 Sensing Theory of Electrochemical pH Sensor --------------- 17
2.3 Non-Ideal Effect --------------------------------------------------- 20
2.3.1 Drift Effect---------------------------------------------------------- 20
2.3.2 Hysteresis Effect--------------------------------------------------- 21
2.4 Description of Enzyme and Method of Immobilization------ 23
2.4.1 Description of Enzyme-------------------------------------------- 23
2.4.2 Method of Enzyme Immobilization----------------------------- 23
2.5 Catalytic Reaction of the Enzymatic Glucose, Lactate and Urea Biosensor----------------------------------------------------- 26
2.5.1 Catalytic Reaction of the Enzymatic Glucose Biosensor----- 26
2.5.2 Catalytic Reaction of the Enzymatic Lactate Biosensor------ 26
2.5.3 Catalytic Reaction of the Enzymatic Urea Biosensor--------- 28
2.6 Instrumentation Amplifiers--------------------------------------- 29
2.7 Electrochemical Impedance Spectroscopy--------------------- 30
2.8 Microfluidic System----------------------------------------------- 32

Chapter 3 Experimental------------------------------------------------------- 37
3.1 Materials and Instruments --------------------------------------- 37
3.2 Fabrication of the Arrayed Flexible pH Sensor Based on IGZO/Al Sensing Membrane ------------------------------------ 40
3.3 Preparation of the Phosphate Buffered Saline (PBS) Solution------------------------------------------------------------- 42
3.4 Fabrication Processes of the Nafion-GOx/IGZO/Al Glucose Biosensor------------------------------------------------- 43
3.5 Fabrication Processes of the LDH-NAD+/GPTS-Toluene/ IGZO/Al Lactate Biosensor-------------------------------------- 44
3.6 Fabrication Processes of the Urease/Glutaraldehyde/ IGZO/Al Urea Biosensor----------------------------------------- 45
3.7 Preparation of the MBs-EDC Mixture-------------------------- 46
3.8 Fabrication of the Nafion-MBs-GOx/GO/IGZO/Al Glucose Biosensor------------------------------------------------------------ 47
3.9 Fabrication of the MBs-LDH-NAD+/GPTS-Toluene/GO/ IGZO/Al Lactate Biosensor-------------------------------------- 48
3.10 Fabrication of the MBs-Urease/Glutaraldehyde/GO/ IGZO/Al Urea Biosensor----------------------------------------- 49
3.11 Fabrication of the Microfluidic Device------------------------- 51
3.12 Voltage-Time Measurement System and Microfluidic Framework---------------------------------------------------------- 52
3.13 Analysis of the Electrochemical Impedance Spectroscopy (EIS)----------------------------------------------------------------- 54
3.14 Analysis of the Surface Roughness of Sensing Membranes- 55
3.15 Analysis of the Crystal Structures of Sensing Membranes--- 56
3.16 Real-Time Wireless Sensing System--------------------------- 57

Chapter 4 Results and Discussion-------------------------------------------- 77
4.1 Analysis of the Arrayed Flexible IGZO/Al pH Sensor------- 77
4.1.1 Comparisons of the Average Sensitivity and Linearity for pH Sensor Based on IGZO and IGZO/Al Sensing Membranes under the Static Conditions-----------------------77
4.1.2 Characteristic Analysis of the IGZO/Al pH Sensor under the Dynamic Conditions------------------------------------------ 79
4.1.3 Measurement of the Lifetime for the IGZO/Al pH Sensor under the Dynamic Conditions----------------------------------- 81
4.1.4 Non-Ideal Effect of the IGZO/Al pH Sensor------------------- 82
4.1.5 Effect of Temperature on the Average Sensitivity of the IGZO/Al pH Sensor----------------------------------------------- 84
4.1.6 Response Time of the IGZO/Al pH Sensor under the Static Conditions---------------------------------------------------------- 86
4.2 Analysis of the Electrochemical Impedance Spectroscopy-- 87
4.2.1 Electrochemical Impedance Characteristics for the IGZO/Al and IGZO Sensing Membranes ---------------------- 87
4.2.2 Electrochemical Impedance Characteristics for the Nafion-GOx/IGZO/Al Sensing Membranes Modified by Different Contents of GO ----------89
4.2.3 Electrochemical Impedance Characteristics for the Nafion-GOx/IGZO/Al Sensing Membranes Modified by GO and MBs -------------------90
4.3 Analysis of the Surface Roughness of the IGZO/Al Thin Film Modified by GO and MBs --------------------- 91
4.4 Analysis of the Crystal Structures of the IGZO/Al Thin Film Modified by GO and MBs -------------------------92
4.5 Analysis of the Nafion-GOx/IGZO/Al Glucose Biosensor ----------------------------------------------94
4.5.1 Characteristic Analysis of the Nafion-GOx/IGZO/Al Glucose Biosensor under the Static and Dynamic Conditions --------------------------95
4.5.2 Measurement of the Lifetime for the Nafion-GOx/IGZO/Al Glucose Biosensor under the Static and Dynamic Conditions -------------------------97
4.5.3 Effect of Temperature on the Average Sensitivity of the Nafion-GOx/IGZO/Al Glucose Biosensor------------------100
4.5.4 Characteristic Analysis of the Nafion-MBs-GOx/GO/ IGZO/Al Glucose Biosensor under the Static and Dynamic Conditions----------------101
4.5.5 Analysis of the Reliability of the Nafion-MBs-GOx/GO/IGZO/Al Glucose Biosensor under the Static and Dynamic Conditions-----------107
4.5.6 Interference Study of the Nafion-MBs-GOx/GO/IGZO/Al Glucose Biosensor under the Static Conditions----------109
4.5.7 Analysis of Measurement Range and Minimal Measurement Limit of the Nafion-MBs-GOx/GO/IGZO/Al Glucose Biosensor under the Static Conditions --------------111
4.5.8 Measurement of the Lifetime for the Nafion-MBs-GOx/GO/IGZO/Al Glucose Biosensor under the Static and Dynamic Conditions----------113
4.5.9 Response Time of the Nafion-MBs-GOx/GO/IGZO/Al Glucose Biosensor under the Static Conditions--------------- 115
4.6 Characteristic Analysis of the MBs-LDH-NAD+/ GPTS-Toluene/GO/IGZO/Al Lactate Biosensor under the Static and Dynamic Conditions--116
4.6.1 Analysis of Measurement Range and Minimal Measurement Limit of the MBs-LDH-NAD+/ GPTS-Toluene/GO/IGZO/Al Lactate Biosensor under the Static Conditions----------------------- 118
4.7 Characteristic Analysis of the MBs-Urease/Glutaraldehyde/GO/IGZO/Al Urea Biosensor under the Static and Dynamic Conditions----------120
4.7.1 Analysis of Measurement Range and Minimal Measurement Limit of the MBs-Urease/Glutaraldehyde/GO/IGZO/Al Urea Biosensor under the Static Conditions-----------------122
4.8 Real-Time Wireless Sensing Measurement of the pH Sensor and Enzymatic Biosensor Based on XBee Module ---------------124

Chapter 5 Conclusions--------------------------------------------- 184

Chapter 6 Future Prospects---------------------------------------- 186

References-------------------------------------------------------- 187

Appendix I ------------------------------------------------------- 204

[1]S. H. Kim, A. Umar, S. W. Hwang, 2015, “Rose-like CuO nanostructures for highly sensitive glucose chemical sensor application,” Ceramics International, vol. 41, pp. 9468-9475.
[2]S. A. Zaidi, J. H. Shin, 2016, “Recent developments in nanostructure based electrochemical glucose sensors,” Talanta, vol. 149, pp. 30-42.
[3]J. Zhang, J. Ma, S. Zhang, W. Wang, Z. Chen, 2015, “A highly sensitive nonenzymatic glucose sensor based on CuO nanoparticles decorated carbon spheres,” Sensors and Actuators B: Chemical, vol. 211, pp. 385-391.
[4]D. M. Kim, S. J. Cho, C. H. Cho, K. B. Kim, M. Y. Kim, Y. B. Shim, 2016, “Disposable all-solid-state pH and glucose sensors based on conductive polymer covered hierarchical AuZn oxide,” Biosensors and Bioelectronics, vol. 79, pp. 165-172.
[5]A. L. Rinaldi, R. Carballo, 2016, “Impedimetric non-enzymatic glucose sensor based on nickelhydroxide thin film onto gold electrode,” Sensors and Actuators B: Chemical, vol. 228, pp. 43-52.
[6]X. Wang, X. Zhang, 2013, “Electrochemical co-reduction synthesis of graphene/nano-goldcomposites and its application to electrochemical glucose biosensor,” Electrochimica Acta, vol. 112, pp. 774-782.
[7]Z. Liu, Y. Guo, C. Dong, 2015, “A high performance nonenzymatic electrochemical glucose sensor based on polyvinylpyrrolidone–graphene nanosheets–nickel nanoparticles–chitosan nanocomposite,” Talanta, vol. 137, pp. 87-93.
[8]D. P. Hickey, R. C. Reid, R. D. Milton, S. D. Minteer, 2016, “A self-powered amperometric lactate biosensor based on lactate oxidase immobilized in dimethylferrocene-modified LPEI,” Biosensors and Bioelectronics, vol. 77, pp.26-31.
[9]Q. Yan, T. C. Major, R. H. Bartlett, M. E. Meyerhoff, 2011, “Intravascular glucose/lactate sensors prepared with nitric oxide releasing poly(lactide-co-glycolide)-based coatings for enhanced biocompatibility,” Biosensors and Bioelectronics, vol. 26, pp. 4276-4282.
[10]K. Rathee, V. Dhull, R. Dhull, S. Singh, 2016, “Biosensors based on electrochemical lactate detection: A comprehensive review,” Biochemistry and Biophysics Reports, vol. 5, pp. 35-54.
[11]L. V. Shkotova, N. Y. Piechniakova, O. L. Kukla, S. V. Dzyadevych, 2016, “Thin-film amperometric multibiosensor for simultaneous determination of lactate and glucose in wine,” Food Chemistry, vol. 197, pp. 972–978.
[12]A. Uzunoglu, L. A. Stanciu, 2016, “Novel CeO2–CuO-decorated enzymatic lactate biosensors operating in low oxygen environments,” Analytica Chimica Acta, vol. 909, pp. 121-128.
[13]Z. P. Yang, X. Liu, C. J. Zhang, B. Z. Liu, 2015, “A high-performance nonenzymatic piezoelectric sensor based on molecularly imprinted transparent TiO2 film for detection of urea,” Biosensors and Bioelectronics, vol. 74, pp. 85-90.
[14]R. Ahmad, N. Tripathy, Y. B. Hahn, 2014, “Highly stable urea sensor based on ZnO nanorods directly grown on Ag/glass electrodes,” Sensors and Actuators B: Chemical, vol. 194, pp. 290-295.
[15]A. Hamilton, C. B. Breslin, 2014, “The development of a novel urea sensor using polypyrrole,” Electrochimica Acta, vol. 145, pp. 19-26.
[16]M. Zhybak, V. Beni, M.Y. Vagin, E. Dempsey, A.P.F. Turner, Y. Korpan, 2016, “Creatinine and urea biosensors based on a novel ammonium ion-selective copper-polyaniline nano-composite,” Biosensors and Bioelectronics, vol. 77, pp. 505-511.
[17]A. Elagli, K. Belhacene, C. Vivien, P. Dhulster, R. Froidevaux, P. Supiot, 2014, “Facile immobilization of enzyme by entrapment using aplasma-deposited organosilicon thin film,” Journal of Molecular Catalysis B: Enzymatic, vol. 110, pp. 77-86.
[18]L. Reverté, B. Prieto-Simón, M. Campàs, 2016, “New advances in electrochemical biosensors for the detection of toxins: Nanomaterials, magnetic beads and microfluidics systems. A review,” Analytica Chimica Acta, vol. 908, pp. 8-21.
[19]X. Zhang, Q. Liao, M. Chu, S. Liu, Y. Zhang, 2014, “Structure effect on graphene-modified enzyme electrode glucose sensors,” Biosensors and Bioelectronics, vol. 52, pp. 281-287.
[20]S. Z. Bas, 2015, “Gold nanoparticle functionalized graphene oxide modified platinum electrode for hydrogen peroxide and glucose sensing,” Materials Letters, vol. 150, pp. 20-23.
[21]J. Biscay, M. B. G. García, A. C. García, 2014, “Electrochemical biotin determination based on a screen printed carbon electrode array and magnetic beads,” Sensors and Actuators B: Chemical, vol. 205, pp. 426-428.
[22]A. Erdem, G. Congur, 2014, “Voltammetric aptasensor combined with magnetic beads assay developed for detection of human activated protein C,” Talanta, vol. 128, pp. 428-433.
[23]J. C. Chou, R. T. Chen, Y. H. Liao, J. W. Lin, C. Y. Lin, C. Y. Jhang, H. T. Chou, 2015, “Fabrication of potentiometric enzymatic glucose biosensor based on graphene and magnetic beads,” IEEE Sensors Journal, vol. 15, pp. 5278-5284.
[24]X. Lin, X. Sun, S. Luo, B. Liu, C. Yang, 2016, “Development of DNA-based signal amplification and microfluidic technology for protein assay: A review,” TrAC Trends in Analytical Chemistry, vol. 80, pp. 132–148.
[25]D. Zhao, Z. He, G. Wang, H. Wang, Q. Zhang, Y. Li, 2016, “A novel efficient ZnO/Zn(OH)F nanofiber arrays-based versatile microfluidic system for the applications of photocatalysis and histidine-rich protein separation,” Sensors and Actuators B: Chemical, vol. 229, pp. 281-287.
[26]K. Nomura, H. Ohta, A. Takagi, T. Kamiya, M. Hirano, H. Hosono, 2004, “Room-temperature fabrication of transparent flexible thin-film transistors using amorphous oxide semiconductors,” Nature, vol.432, pp. 488-492.
[27]H. Yabuta, M. Sano, K. Abe, T. Aiba, T. Den, and H. Kumoni, 2006, “High-mobility thin film transistor with amorphous InGaZnO4 channel fabricated by room temperature rf-magnetron sputtering,” Applied Physics Letters, vol. 89, pp. 112123-1-3.
[28]D. Sun, H Matsui, C.N. Wu, H Tabata, 2015, “Surface treatment on amorphous InGaZnO4 thin film for single-stranded DNA biosensing,” Applied Surface Science, vol. 324, pp. 310-318.
[29]D. J. Yang, G. C. Whitfield, N. G. Cho, P.S. Cho, Il-Doo Kim, H. M. Saltsburg, H. L. Tuller, 2012, “Amorphous InGaZnO4 films: gas sensor response and stability,” Sensors and Actuators B: Chemical, vol. 171-172, pp.1166-1171.
[30]C. M. Yang, J. C. Wang, T. W. Chiang, Y.T Lin, T. W. Juan, T. C. Chen, M. Y. Shih, C. E. Lue, C. S. Lai, 2014, “Hydrogen ion sensing characteristics of IGZO/Si electrode in EGFET,” International Journal of Nanotechnology, vol. 11, pp. 15-26.
[31]W. T. Sung, J. H. Chen, K. Y. Chang, 2014, “Trust function for multi-physiological signals fusion,” Measurement, Vol. 47, pp. 827–840.
[32]A. A. Rezaee, M. H. Yaghmaee, A. M. Rahmani, A. H. Mohajerzadeh, 2014, “HOCA: Healthcare Aware Optimized Congestion Avoidance and control protocol for wireless sensor networks,” Journal of Network and Computer Applications, Vol. 37, pp. 216-228.
[33]C. M. Yang, I. S. Wang, Y. T. Lin, C. H. Huang, T. F. Lu, C. E. Lue, 2013, “Low cost and flexible electrodes with NH3 plasma treatments in extended gate field effect transistors for urea detection,” Sensors and Actuators B: Chemical, vol.187, pp. 274-279.
[34]J. Leroy, C. Dalmay, A. Landoulsi, F. Hjeij, C. Mélin, B. Bessette, C. B. M. D. Puch, S. Giraud, C. Lautrette, S. Battu, F. Lalloué, M.O. Jauberteau, A. Bessaudou, P. Blondy, A. Pothier, 2015, “Microfluidic biosensors for microwave dielectric spectroscopy,” Sensors and Actuators A: Physical, vol. 229, pp.172-181.
[35]Y. Qin, P. Yeh, X. Hao, X. Cao, 2015, “Developing an ultra non-fouling SU-8 and PDMS hybrid microfluidic device by poly(amidoamine) engraftment,” Colloids and Surfaces B: Biointerfaces, vol. 127, pp. 247-255.
[36]M. Javadi, S. Sheikhaei, A. S. Kashi, H. Pourmodheji, 2013, “Design of a direct conversion ultra low power ZigBee receiver RF front-end for wireless sensor networks,” Microelectronics Journal, vol. 44, pp. 347-353.
[37]https://zh.wikipedia.org/wiki/ZigBee
[38]L.K. Wadhwa, R. S. Deshpande, V. Priye, 2016, “Extended shortcut tree routing for ZigBee based wireless sensor network,” Ad Hoc Networks, vol. 37, pp. 295-300.
[39]D. Quesada-González, A. Merkoçi, 2015, “Nanoparticle-based lateral flow biosensors,” Biosensors and Bioelectronics, vol. 73, pp. 47–63.
[40]E. B. Bahadır, M. K. Sezgintürk, 2015, “Electrochemical biosensors for hormone analyses,” Biosensors and Bioelectronics, vol. 68, pp.62-71.
[41]A. Tereshchenko, M. Bechelany, R. Viter, V. Khranovskyy, V. Smyntyna, N.Starodub, R. Yakimova, 2016, “Optical biosensors based on ZnO nanostructures: advantages and perspectives. A review,” Sensors and Actuators B: Chemical, vol. 229, pp. 664-677.
[42]A. Ahmadalinezhad, A. Chen, 2011, “High-performance electrochemical biosensor for the detection of total cholesterol,” Biosensors and Bioelectronics, vol. 26, pp. 4508-4513.
[43]A. Meena, L. Rajendran, 2010, “Mathematical modeling of amperometric and potentiometric biosensors and system of non-linear equations – Homotopy perturbation approach,” Journal of Electroanalytical Chemistry, vol. 644, pp. 50-59.
[44]Y. Kanno, K. Ino, C. Sakamoto, K. Y. Inoue, M. Matsudaira, A. Suda, R. Kunikata, T. Ishikawa, H. Abe, H. Shiku, T. Matsue, 2016, “Potentiometric bioimaging with a large-scale integration (LSI)-based electrochemical device for detection of enzyme activity,” Biosensors and Bioelectronics, vol. 77, pp. 709-714.
[45]C.A. Cordeiro, M.G. de Vries, T. I. F. H. Cremers, B. H. C. Westerink, 2016, “The role of surface availability in membrane-induced selectivity for amperometric enzyme-based biosensors,” Sensors and Actuators B: Chemical, vol. 223, pp. 679-688.
[46]M. Verrastro, N. Cicco, F. Crispo, A. Morone, M. Dinescu, M. Dumitru, F. Favati, D. Centonze, 2016, “Amperometric biosensor based on laccase immobilized onto a screen-printed electrode by matrix assisted pulsed laser evaporation,” Talanta, vol. 154, pp. 438-445.
[47]I. S. Kucherenko, D. Y. Kucherenko, O. O. Soldatkin, F. Lagarde, S. V. Dzyadevych, A. P. Soldatkin, 2016, “A novel conductometric biosensor based on hexokinase for determination of adenosine triphosphate,” Talanta, vol. 150, pp. 469-475.
[48]C.C. Adley, M.P. Ryan, 2015, “Conductometric biosensors for high throughput screening of pathogens in food,” High Throughput Screening for Food Safety Assessment, pp. 315-326.
[49]L. Manjakkal, K. Cvejin, J. Kulawik, K. Zaraska, D. Szwagierczak, G. Stojanovic, 2015, “Sensing mechanism of RuO2–SnO2 thick film pH sensors studied by potentiometric method and electrochemical impedance spectroscopy,” Journal of Electroanalytical Chemistry, vol. 759, pp. 82-90.
[50]L. Manjakkal, E. Djurdjic, K. Cvejin, J. Kulawik, K. Zaraska, D. Szwagierczak, 2015, “Electrochemical impedance spectroscopic analysis of RuO2 based thick film pH sensors,” Electrochimica Acta, vol. 168, pp. 246–255.
[51]Y. S. Chiu, C. Y. Tseng, C. T. Lee, 2012, “Nanostructured EGFET pH sensors with surface-passivated ZnO thin-film and nanorod array,” IEEE Sensors Journal, vol. 12, pp. 930-934.
[52]A. Sardarinejad, D.K. Maurya, K. Alameh, 2014, “The effects of sensing electrode thickness on ruthenium oxide thin-film pH sensor,” Sensors and Actuators A: Physical, vol. 214, pp. 15-19.
[53]D.K. Maurya, A. Sardarinejad, K. Alameh, 2013, “High-sensitivity pH sensor employing a sub-micron ruthenium oxide thin-film in conjunction with a thick reference electrode,” Sensors and Actuators A: Physical, vol. 203, pp. 300-303.
[54]J. C. Chou, K. Y. Huang, J. S. Lin, 2000, “Simulation of time-dependent effects of pH-ISFETs,” Sensors and Actuators B: Chemical, vol. 62, pp. 88-91.
[55]J. C. Chou, C. N. Hsiao, 2000, “Drift behavior of ISFETs with a-Si : H-SiO2 gate insulator,” Materials Chemistry and Physics, vol. 63, pp. 270-273.
[56]K. M. Chang, C. T. Chang, K. Y. Chao, C. H. Lin, 2010, “A Novel pH-dependent drift improvement method for zirconium dioxide gated pH-ion sensitive field effect transistors,” Sensors, vol. 10, pp. 4643-4654.
[57]J. C. Chou, H. M. Tsai, C. N. Shiao, J. S. Lin, 2000, “Study and simulation of the drift behaviour of hydrogenated amorphous silicon gate pH-ISFET,” Sensors and Actuators B: Chemical, vol. 62, pp. 97-101.
[58]J. C. Chou, C. N. Hsiao, 2000, “The hysteresis and drift effect of hydrogenated amorphous silicon for ISFET,” Sensors and Actuators B: Chemical, vol. 66, pp. 181-183.
[59]J. Yang, F. Yang, Y. Yang, G. Xing, C. Deng, Y. Shen, L. Luo, B. Lia, H. Yuan, 2016, “A proposal of “core enzyme” bioindicator in long-term Pb-Zn ore pollution areas based on topsoil property analysis,” Environmental Pollution, vol. 213, pp. 760-769.
[60]B. Zhang, P. Li, H. Zhang, H. Wang, X. Li, L. Tian, N. Ali, Z. Ali, Q. Zhang, 2016, “Preparation of lipase/Zn3(PO4)2 hybrid nanoflower and its catalytic performance as an immobilized enzyme,” Chemical Engineering Journal, vol. 291, pp. 287-297.
[61]L. Shen, K. C. K. Cheng, M. Schroeder, P. Yang, E. N. G. Marsha, J. Lahann, Z.Chena, 2016, “Immobilization of enzyme on a polymer surface,” Surface Science, vol. 648, pp. 53-59.
[62]J. H. Kim, S. A. Jun, Y. Kwon, S. Ha, B. I. Sange, J. Kim, 2015, “Enhanced electrochemical sensitivity of enzyme precipitate coating (EPC)-based glucose oxidase biosensors with increased free CNT loadings,” Bioelectrochemistry, vol. 101, pp. 114-119.
[63]L. Wu, S. Wu, Z. Xu, Y. Qiu, S. Li, H. Xu, 2016, “Modified nanoporous titanium dioxide as a novel carrier for enzyme immobilization,” Biosensors and Bioelectronics, vol. 80, pp. 59-66.
[64]F. Gashtasbi, G. Ahmadian, K. A. Noghabi, 2014, “New insights into the effectiveness of alpha-amylase enzyme presentation on the Bacillus subtilis spore surface by adsorption and covalent immobilization,” Enzyme and Microbial Technology, vol. 64-65, pp. 17-23.
[65]X. Huang, Y. Zhu, X. Zhang, Z. Bao, D. Y. Lei, W. Yu, J. Dai, Y. Wang, 2016, “Clam-inspired nanoparticle immobilization method using adhesive tape as microchip substrate,” Sensors and Actuators B: Chemical, vol. 222, pp. 106-111.
[66]L. T. I. Živković, L. S. Živković, B. M. Babić, M. J. Kokunešoski, B. M. Jokić, I. M. Karadžić, 2015, “Immobilization of Candida rugosa lipase by adsorption onto biosafe meso/macroporous silica and zirconia,” Biochemical Engineering Journal, vol. 93, pp. 73-83.
[67]M. L. E. Gutarra, L. S. M. Miranda, R. O. M. A. de Souza, 2016, “Chapter 4 – Enzyme Immobilization for Organic Synthesis, Organic Synthesis Using Biocatalysis,” pp. 99-126.
[68]M. Matto, Q. Husain, 2009, “Calcium alginate–starch hybrid support for both surface immobilization and entrapment of bitter gourd (Momordica charantia) peroxidase,” Journal of Molecular Catalysis B: Enzymatic, vol. 57, pp.164-170.
[69]A. Elagli, K. Belhacene, C. Vivien, P. Dhulster, R. Froidevaux, P. Supiot, 2014, “Facile immobilization of enzyme by entrapment using a plasma-deposited organosilicon thin film,” Journal of Molecular Catalysis B: Enzymatic, vol. 110, pp. 77-86.
[70]G. W. Zheng, H. L. Yu, C. X. Li, J. Pan, J. H. Xu, 2011, “Immobilization of Bacillus subtilis esterase by simple cross-linking for enzymatic resolution of DL-menthyl acetate,” Journal of Molecular Catalysis B: Enzymatic, vol.70, pp. 138-143.
[71]M. Ghiaci , M. Tghizadeh , A. A. Ensafi, N. Zandi-Atashbar , B. Rezaei, 2016, “Silver nanoparticles decorated anchored type ligands as new electrochemical sensors for glucose detection,” Journal of the Taiwan Institute of Chemical Engineers, In press.
[72]S. M. U. Ali, O. Nur, M. Willander, B. Danielsson, 2010, “A fast and sensitive potentiometric glucose microsensor based on glucose oxidase coated ZnO nanowires grown on a thin silver wire,” Sensors and Actuators B: Chemical, vol. 145, pp. 869-874, 2010.
[73]I.S. Kucherenko, O.O. Soldatkin, F. Lagarde, N. Jaffrezic-Renault, S. V. Dzyadevych, A.P. Soldatkin, 2015, “Determination of total creatine kinase activity in blood serum using an amperometric biosensor based on glucose oxidase and hexokinase, ” Talanta, vol. 144, pp. 604-611.
[74]J. C. Chou, T. Y. Cheng, G. C. Ye, Y. H. Liao, S. Y. Yang, H. T. Chou, 2013, “Fabrication and investigation of arrayed glucose biosensor based on microfluidic framework,” IEEE Sensors Journal, vol. 13, pp. 4180-4187.
[75]J. C. Chou, D. G. Wu, S. C. Tseng, C. C. Chen, G. C. Ye, 2013, “Application of microfluidic device for Lactic biosensor,” IEEE Sensors Journal, vol. 13, pp. 1363-1370.
[76]Y. Ram, T. Yoetz-Kopelman, Y. Dror, A. Freeman, Y. Shacham-Diamand, 2016, “Impact of molecular surface charge on biosensing by electrochemical impedance spectroscopy,” Electrochimica Acta, vol. 200, pp.161-167.
[77]K. Nikolaev, S. Ermakov, Y. Ermolenko, E. Averyaskina, A. Offenhäusser, Y. Mourzina, 2015, “A novel bioelectrochemical interface based on in situ synthesis of gold nanostructures on electrode surfaces and surface activation by Meerwein's salt. A bioelectrochemical sensor for glucose determination,” Bioelectrochemistry, vol. 105, pp. 34-43.
[78]D.V. Ribeiro, J.C.C. Abrantes, 2016, “Application of electrochemical impedance spectroscopy (EIS) to monitor the corrosion of reinforced concrete: A new approach,” Construction and Building Materials, vol. 111, pp. 98-104.
[79]http://w.pic.com.tw/newsdetail.php?id=1169.
[80]J. C. Chou, Y. L. Tsai, T. Y. Cheng, Y. H. Liao, G.C. Ye, S. Y. Yang, 2014, “Fabrication of arrayed flexible screen-printed glucose biosensor based on mircofluidic framework,” IEEE Sensors Journal, vol. 14, pp. 178-183.
[81]R. Vedalakshmi, V. Saraswathy, H. W. Song, N. Palaniswamy, 2009, “Determination of diffusion coefficient of chloride in concrete using Warburg diffusion coefficient, ” Corrosion Science, vol. 51, pp. 1299-1307.
[82]J. C. Chou, C. M. Chu, Y. H. Liao, C. H. Huang, Y. J. Lin, H. Wu, Y. H. Nien, 2015, “Fabrication and photovoltaic properties of dye-sensitized solar cells modified by graphene oxide and magnetic bead,” IEEE Electron Device Letters, vol. 36, pp. 711-713.
[83]J. C. Chou, C. Y. Jhang, Y. H. Liao, J. W. Lin, R. T. Chen, H. T. Chou, 2014 “Research of stability and interference with the potentiometric flexible arrayed glucose sensor based on microfluidic framework,” IEEE Transactions on Semiconductor Manufacturing, vol. 27, pp. 523-529.
[84]R. T. Chen, 2015, “Integrating the fabrication of the differential reference electrode and graphene modified in arrayed flexible glucose biosensor system based on magnetic beads and microfluidic framework as well as the measurement and impedance analysis of the system”, National Yunlin University of Science and Technology, Master Thesis.
[85]J. C. Chou, T. Y. Cheng, G. C. Ye, Y. H. Liao, S. Y. Yang, H. T. Chou, 2013, “Fabrication and Investigation of Arrayed Glucose Biosensor Based on Microfluidic Framework,” IEEE Sensors Journal, vol. 13, pp. 4180-4187.
[86]S. C. Tseng, T. Y. Wu, J. C. Chou, Y. H. Liao, C. H. Lai, J. S. Chen, M. S. Huang, 2016, “Research of non-idea effect and dynamic measurement of the flexible arrayed chlorine ion sensor,” IEEE Sensors Journal, vol. 16, pp. 4683-4690.
[87]https://en.wikipedia.org/wiki/Atomic-force_microscopy
[88]https://en.wikipedia.org/wiki/X-ray_crystallography
[89]Y. S. Chiu, C. T. Lee, L. R. Lou, S. C. Ho, C. T. Chuang, 2013, “Wide linear sensing sensors using ZnO:Ta extended-gate field-effect-transistors,” Sensors and Actuators B: Chemical, vol. 188, pp. 944-948.
[90]H. H. Li, C. E. Yang, C. C. Kei, C. Y. Su, W. S. Dai, J. K. Tseng, P. Y. Yang, J. C. Chou, H. C. Cheng, 2013, “Coaxial-structured ZnO/silicon nanowires extended-gate field-effect transistor as pH sensor,” Thin Solid Films, vol. 529, pp. 173-176.
[91]Z. Yule, Z. Shouan, L. Tao, 1994 “Drift characteristics of pH-ISFET output,” Chinese Journal of Semiconductors, vol. 12, pp. 838-843.
[92]S. Jamasb, S. Collins, R. L. Smith, 1998, “A physical model for drift in pH ISFETs,” Sensors and Actuators B: Chemical, vol. 49, pp.146-155.
[93]C. N. Tsai, J. C. Chou, T. P. Sun, S. K. Hsiung, 2005, “Study on the sensing characteristics and hysteresis effect of the tin oxide pH electrode,” Sensors and Actuators B: Chemical, vol. 108, pp. 877-882.
[94]M. S. Huang, 2016, “Fabrication of arrayed flexible IGZO pH sensor and glucose biosensor modified by magnetic beads and graphene based on microfluidic framework as well as equivalent circuit analysis,” Department of Electronic Engineering, National Yunlin University of Science and Technology, Research Project.
[95]A. Sardarinejad, D.K. Maurya, M. Khaled, K. Alameh, 2015, “Temperature effects on the performance of RuO2 thin-film pH sensor,” Sensors and Actuators A: Physical, vol. 233, pp. 414-421.
[96]C. E. Lue, I. S. Wang, C. H. Huang, Y. T. Shiao, H. C. Wang, C. M. Yang, S. H. Hsu, C. Y. Chang, W. Wang, C. S. Lai, 2012, “pH sensing reliability of flexible ITO/PET electrodes on EGFETs prepared by a roll-to-roll process,” Microelectronics Reliability, vol. 52, pp. 1651.1654.
[97]J. L. Chiang, Y. C. Chen, J. C. Chou, C. C. Cheng, 2012, “Temperature effect on AlN/SiO2 gate pH-Ion-sensitive field-Effect transistor devices,” Japanese Journal of Applied Physics, Vol 41, pp. 541-545.
[98]Y. Lu, Z. Guo, J. J. Song, Q. A. Huang, S. W. Zhu, X. J. Huang, Y. Wei, 2016, “Tunable nanogap devices for ultra-sensitive electrochemical impedance biosensing,” Analytica Chimica Acta, vol. 905, pp. 58-65.
[99]J. C. Chou, J. L. Chen, Y. H. Liao, J. T. Chen, C. Y. Lin, J. W. Lin, C. Y. Jhang, R. T. Chen, 2015, “Fabrication and characteristic analysis of a remote real-time monitoring applied to glucose sensor system based on microfluidic framework,” IEEE Sensors Journal, vol. 15, pp. 3234-3240.
[100]S. Ameen, M. S. Akhtar, H. S. Shin, 2016, “Nanocages-augmented aligned polyaniline nanowires as unique platform for electrochemical non-enzymatic glucose biosensor,” Applied Catalysis A: General, vol. 517, pp. 21-29.
[101]J. C. Chou, R. T. Chen, Y. H. Liao, J. S. Chen, M. S. Huang, H. T. Chou, 2015, “Dynamic and wireless sensing measurements of potentiometric glucose biosensor based on graphene and magnetic beads,” IEEE sensors journal, vol. 15, pp. 5718-5725.
[102]A. Samphao, P. Butmee, J. Jitcharoen, Ľ. Švorc, G. Raber, K. Kalcher, 2015, “Flow-injection amperometric determination of glucose using a biosensor based on immobilization of glucose oxidase onto Au seeds decorated on core Fe3O4 nanoparticles,” Talanta, vol.142, pp. 35-42.
[103]J. C. Chou, H. Y. Yang, and C. W. Chen, 2010, “Glucose biosensor of ruthenium-doped TiO2 sensing electrode by co-sputtering system” Microelectronics Reliability, vol. 50, pp. 753-756.
[104]C. W. Liao, J. C. Chou, T. P. Sun, S. K. Hsiung, J. H. Hsieh, 2007 “Preliminary investigations on a glucose biosensor based on the potentiometric principle,” Sensors and Actuators B: Chemical, vol. 123, pp. 720-726.
[105]http://www.wcjs.tc.edu.tw/bio/cairoom/8707/content/enzyme-01.htm
[106]K. Khun, Z. H. Ibupoto, J. Lu, M. S. AlSalhi, M. Atif, A. A. Ansari, M. Willander, 2012, “Potentiometric glucose sensor based on the glucose oxidase immobilized iron ferrite magnetic particle/chitosan composite modified gold coated glass electrode,” Sensors and Actuators B: Chemical. vol. 173, pp. 698-703.
[107]J. W. Lin, 2014, “Integration and fabrication of the flexible arrayed glucose biosensor based on magnetic beads and microfluidic framework,” Department of Electronic Engineering, National Yunlin University of Science and Technology, Master Thesis.
[108]J. C. Chou, J. S. Chen, Y. H. Liao, C. H. Lai, M. S. Huang, T. Y. Wu, B. Y. Zhuang, S. J. Yan, H. T. Chou, C. C. Hsu, 2016, “Effect of different contents of magnetic beads on enzymatic IGZO glucose biosensor,” Materials Letters, vol. 175, pp. 241-243.
[109]A. Fulati, S. M. U. Ali, M. H. Asif, N. U. H. Alvi, M. Willander, C. Brännmark, P. Strålfors, S. I. Börjesson, F. Elinder, B. Danielsson, 2010, “An intracellular glucose biosensor based on nanoflake ZnO,” Sensors and Actuators B:Chemical,vol. 150, pp. 673-680.
[110]T. M. Pana, M. D. Huanga, C. W. Lina, M. H. Wu, 2010, “Development of high-κ HoTiO3 sensing membrane for pH detection and glucose biosensing,” Sensors and Actuators B: Chemical, vol. 144, pp. 139-145.
[111]H. Hu, M. Feng, H. Zhan, 2015, “A glucose biosensor based on partially unzipped carbon nanotubes,” Talanta, vol. 141, pp. 66-72.
[112]J.R. Anusha, C. J. Raj, B. B. Cho, A. T. Fleming, K. H. Yu, B. C. Kim, 2015, “Amperometric glucose biosensor based on glucose oxidase immobilized over chitosan nanoparticles from gladius of Uroteuthis duvauceli,” Sensors and Actuators B: Chemical, vol. 215, pp. 536-543.
[113]R. Devasenathipathy, V. Mani, S. M. Chen, S. T. Huang, T. T. Huang, C. M. Lin, K. Y. Hwa, T. Y. Chen, B. J. Chen, 2015, “Glucose biosensor based on glucose oxidase immobilized at gold nanoparticles decorated graphene-carbon nanotubes,” Enzyme and Microbial Technology, vol. 78, pp. 40-45.
[114]W. Ngeontae,W. Janrungroatsakul, P. Maneewattanapinyo, Sanong Ekgasit, W. Aeungmaitrepirom, T. Tuntulani, 2009, “Novel potentiometric approach in glucose biosensor using silver nanoparticles as redox marker,” Sensors and Actuators B: Chemical, vol. 137, pp. 320-326.
[115]L. Fang, B. Liang, G. Yang, Y. Hu, Q. Zhu, X. Ye, 2014, “Study of glucose biosensor lifetime improvement in 37 ℃ serum based on PANI enzyme immobilization and PLGA biodegradable membrane,” Biosensors and Bioelectronics, vol. 56, pp. 91-96.
[116]N. C. Sekar, S. A. M. Shaegh, S. H. Ng, L. Ge, S. N. Tan, 2014, “A paper-based amperometric glucose biosensor developed withPrussian Blue-modified screen-printed electrodes,” Sensors and Actuators B: Chemical, vol. 204, pp. 414-420.
[117]C. G. d. Jesus, D. Lima, V. d. Santos, K. Wohnrath, C. A. Pessôa, 2013, “Glucose biosensor based on the highly efficient immobilization of glucose oxidase on layer-by-layer films of silsesquioxane polyelectrolyte,” Sensors and
Actuators B: Chemical, vol. 186, pp.44-51.