為了監測活體動物腦中能量代謝物質的動態變化趨勢，本研究結合酵素固定與三維列印技術，開發酵素功能化三維列印反應器裝置，並實際應用於分析大鼠腦細胞間液內因生理刺激所造成葡萄糖和乳酸濃度的動態變化趨勢。本研究發現透過將酵素固定於三維列印反應器內，可提高樣品與酵素的接觸面積來縮短分析時間。此外，本研究進一步利用鉑金奈米粒子取代天然酵素辣根過氧化物酶，並固定於三維列印多孔盤反應裝置中進行反應，研究中發現可大幅降低連續添加辣根過氧化物酶的試劑成本。
在完成上述分析方法最佳化探討與分析效能驗證之後，本研究針對大鼠腦組織細胞間液內葡萄糖和乳酸分子，進行線上連續偵測的分析工作，結果顯示在經過高濃度鉀離子灌流刺激後，確時引發腦組織細胞間液內葡萄糖濃度下降而乳酸濃度上升的動態變化情形，說明本研究所建立之分析方法，確實具有監測大鼠腦組織細胞間液內，葡萄糖和乳酸濃度動態變化趨勢的能力，預期本研究所發展之酵素功能化三維列印反應裝置，應可為日後三維列印技術的發展與奈米物質仿生酵素的研究提供一個嶄新的跨領域思維方向。

To investigate the dynamic changes in the concentrations of living rat brain extracellular glucose and lactate following an acute depolarization simulation, for the first time the enzyme immobilized strategies and the three-dimensional printing (3DP) technologies are combined, and two novel enzyme-functionalized 3D-printed devices were constructed by means of (i) glutaraldehyde-facilitated crosslinking of glucose oxidase and lactate oxidase on the surfaces of 3D-printed bioreactors, and (ii) coating of peroxidase-mimicking platinum nanoparticles on the 3D-printed multi-well plates.
After method’s optimization and validation, the dynamic variations of glucose and lactate concentrations in living rat brain extracellular fluids in response to the stimulus of perusing a high-K+ medium through the implanted microdialysis probe were revealed. Our analytical results and demonstrations confirm that post-printing functionalization of analytical devices manufactured using 3DP technologies can be a powerful strategy for extending the diversity and adaptability of currently existing analytical configurations.

中文摘要 i
英文摘要 ii
謝誌 iii
目錄 iv
圖目錄 viii
表目錄 xi
第1章 前言 1
1.1 腦部能量代謝物質對人體的重要性 1
1.1.1 人體及腦部中的能量代謝 1
1.1.2 葡萄糖及乳酸對於腦部疾病的影響 3
1.2 酵素衍生化輔助分析葡萄糖與乳酸 7
1.3 酵素衍生化輔助分析葡萄糖和乳酸的困難 9
1.4 酵素輔助分析技術的延伸應用 13
1.4.1 酵素衍生化反應裝置與三維列印技術 13
1.4.2 仿生過氧化物酶的研究進展 15
1.5 研究目的及方法 16
第2章 實驗儀器、裝置及原理 18
2.1 微透析取樣裝置 18
2.2 螢光分析原理 19
2.3 螢光分光光譜儀 21
2.4 三維列印技術 25
第3章 實驗材料與方法 28
3.1 儀器裝置、實驗藥品及實驗動物 28
3.1.1 儀器裝置與配件 28
3.1.2 實驗藥品及試劑 29
3.1.3 實驗用水 31
3.1.4 實驗動物 31
3.2 分析系統的清洗與保存 32
3.2.1 微透析探針於實驗前後的清洗與保存 32
3.2.2 自動化閥相輔助線上分析系統於實驗前後的清洗及保存 32
3.3 微透析取樣串聯三維列印裝置與螢光分析儀連線即時監測活體動物腦細胞間液內葡萄糖和乳酸 32
3.3.1 三維列印反應器的設計及酵素固定方法 32
3.3.1.1 三維列印反應器的設計與列印 33
3.3.1.2 固定酵素於三維列印反應器 34
3.3.1.3 固定化酵素最佳化實驗條件 35
3.3.2 連線系統之建立與最佳化條件探討 36
3.3.2.1 連線系統之建立 36
3.3.2.1 連線系統之最佳化條件探討 38
3.3.2.2 連線系統之分析效能的評估 39
3.3.2.3 監測大鼠腦細胞間液內葡萄糖及乳酸濃度的動態變化趨勢 40
3.4 固定具有過氧化酶催化活性之鉑金奈米粒子於三維列印多孔盤反應裝置並應用於分析生物樣品中葡萄糖與乳酸濃度 41
3.4.1 鉑金奈米粒子作為仿生過氧化酶 41
3.4.1.1 合成鉑金奈米粒子於三維列印裝置之最佳化探討 41
3.4.1.2 分析過氧化氫之最佳化條件探討 42
3.4.1.3 固定在三維列印多孔盤反應裝置內鉑金奈米粒子催化動力學探討 42
3.4.2 鉑金奈米粒子三維列印多孔盤反應裝置應用於分析葡萄糖與乳酸 43
3.4.2.1 鉑金奈米粒子多孔盤反應裝置之分析效能的評估 43
3.4.2.2 真實樣品分析及方法間比對 44
3.4.2.2.1 真實樣品中測定葡萄糖與乳酸 44
3.4.2.2.2 以市售葡萄糖和乳酸測樣品中的葡萄糖與乳酸 45
第4章 結果與討論 49
4.1 微透析取樣串聯三維列印裝置與螢光分析儀連線即時監測活體動物腦細胞間液內葡萄糖和乳酸 49
4.1.1 三維列印反應器的設計與酵素固定化方法 49
4.1.1.1 三維列印反應器的設計 49
4.1.1.2 固定化酵素之最佳化實驗條件 51
4.1.2 微透析取樣串聯三維列印裝置與螢光分析儀連線系統之建立與最佳化條件探討 58
4.1.2.1 連線分析系統之最佳化條件探討 58
4.1.2.2 連線系統之分析效能的評估 63
4.1.2.3 監測活體動物腦細胞間液內葡萄糖與乳酸的動態變化 65
4.2 固定具過氧化物酶催化活性之鉑金奈米粒子於三維列印多孔盤反應裝置應用於分析生物樣品中葡萄糖與乳酸 67
4.2.1 鉑金奈米粒子作為仿生過氧化物酶 67
4.2.1.1 固定鉑金奈米粒子於三維列印裝置最佳化探討 69
4.2.1.2 分析過氧化氫之最佳化條件談討 74
4.2.1.3 固定之鉑金奈米粒子催化動力學探討 75
4.2.2 鉑金奈米粒子仿生過氧化酶三維列印多孔盤裝置應用於分析葡萄糖與乳酸 78
4.2.2.1 分析效能的評估 78
4.2.2.2 真實樣品分析及方法間比較 81
第5章 結論 85
第6章 參考文獻 87

1. Nelson, D. L; Cox, M. M. Principles of Biochemistry. Rerrman and Company, New York, YSA. 2008.
2. Castro, M. A.; Beltran, F. A.; Brauchi, S.; Concha, I. I. A Metabolic Switch in Brain: Glucose and Lactate Metabolism Modulation by Ascorbic Acid. J. Neurochem. 2009, 110, 423−440.
3. Dienel, G. Lactate Shuttling and lactate use as fuel after Traumatic Brain Injury: Metabolic Considerations. J. Cereb. Blood Flow Metab. 2014, 34, 1736−1748.
4. Oliveira-Ferreira, A. I; Winkler, M. L.; Reiffurth, C.; Milakara, D.; Woitzik, J.; Dreier, J.P. Spreading Depolarization, a Pathophysiological Mechanism of Stroke and Migraine Aura. Future Neurol. 2012, 7, 45−64.
5. Hu, Y.; Wilson, G. S.; A Temporary Local Energy Pool Coupled to Neuronal Activity: Fluctuations of extracellular lactate levels in rat brain monitored with Rapid-Response Enzyme-Based Sensor. J. Neurochem. 1997, 69, 1484−1490.
6. Giza, C. C.; Hovda, D. A. The Neurometabolic Cascade of Concussion. J. Athl. Train. 2001, 36, 228–235.
7. Newman, M. F.; Grocott, H. P.; Mathew, J. P.; White, W. D.;Landolfo, K.; Reves, J. G.; Laskowitz, D. T.; Mark, D. B.; Blumenthal, J. A. Report of the Substudy Assessing the Impact of Neurocognitive Function on Quality of Life 5 Years After Cardiac Surgery. Stroke 2001, 32, 2874−2881.
8. Arai, K.; Nishiyama, N.; Matsukim, N.; Ikegaya, Y. Neuroprotective Effects of Lipoxygenase Inhibitors Against Ischemic Injury in Rat Hippocampal Slice Cultures. Brain Res. 2001, 904, 167−172.
9. Matute, C.; Domercq, M.; Pérez-Samartín, A.; Ransom, B.R. Protecting White Matter from Stroke Injury. Stroke 2013, 44, 1204−1211.
10. Parkin, M.; Hopwood, S.; Jones, D. A.; Hashemi, P.; Landolt, H.; Fabricius, M.; Lauritzen, M.; Boutelle, M. G.; Strong, A. J. Dynamic Changes in Brain Glucose and Lactate in Pericontusional Areas of The Human Cerebral Cortex, monitored with Rapid Sampling On-Line Microdialysis: Relationship with Depolarisation-Like Events. J. Cereb. Blood Flow Metab. 2005, 25, 402−413.
11. Roger, M. L.; Reuerstin, D.; Leong, C. L.; Takagaki, M.; Niu, X.; Graf, R.; Boutelle, M. G. Continuous Online Microdialysis Using Microfluidic Sensor: Dynamic Neurometabolic Changes during Spreading Depolarization. ACS Chem. Neurosci. 2013, 4, 799–807.
12. Clark, L. C.; Lyons, C. Electrode Systems for Continuous Monitoring in Cardiovascular Surgery. Ann. N. Y. Acad. Sc. 1962, 102, 29−45.
13. Wang, J. Glucose Biosensors: 40 Years of Advances and Challenges. Electroanalysis 2002, 12, 983−988.
14. Foulds, N. C.; Lowe, C. R. Enzyme entrapment in Electrically Conducting Polymers. Immobilisation of Glucose Oxidase in polypyrrole and its application in Amperometric Glucose Sensors. J. Chem. Soc. Faraday Trans. 1986, 82, 1259−1264.
15. Zang, W.; Li, G. Third-Generation Biosensors Based on the Direct Electron Transfer of Proteins. Anal. Sci. 2004, 20, 603−609.
16. Rocchitta, G.; Secchi, O.; Alvau, M.D.; Farina, D.; Bazzu, G.; Calia, G.; Migheli, R.; Desole, M.S.; O’Neill, R. D.; Serra, P. A. Simultaneous Telemetric Monitoring of Brain Glucose and Lactate and Motion in Freely Moving Rats. Anal. Chem. 2013, 85, 10282−10288.
17. Mohamad, N. R.; Marzuki, N. G. C.; Buang, N. A.; Huyop, F.; Wahab, R. A. An Overview of Technologies for Immobilization of Enzymes and Surface Analysis Techniques for Immobilized Enzymes. Biotehnol. Biotechnol. Equip. 2015, 29, 205-220.
18. Watson, C. J.; Venton, B. J.; Kennedy, R. T. In Vivo Measurements of Neurotransmitters by Microdialysis Sampling. Anal. Chem. 2006, 78, 1391–1399.
19. Torto, N.; Laurell, T.; Gorton, L.; Marko-Varga, G. Recent Trends in the Application of Microdialysis in Bioprocesses. Anal. Chim. Acta 1998, 374, 111–135.
20. Wang, M.; Roman, G. T.; Schultz, K.; Jennings, C.; Kennedy, R. T. Improved Temporal Resolution for in Vivo Microdialysis by Using Segmented Flow. Anal. Chem. 2008, 80, 5607−5615.
21. Ghica, M.E.; Brett, C. M. A. Development of A Carbon Film Electrode Ferrocene-Mediated Glucose Biosensor. Anal. Lett. 2005, 38, 907–920.
22. Sharma, S. K.; Sehgal, N.; Kumar, A. Biomolecules for Development of Biosensors and Their Applications. Curr. Appl. Phys. 2003, 3, 307–316.
23. Costantini, F.; Tiggelaar, R.; Sennato, S.; Mura, F.; Schlautmann, S.; Bordi, F.; Garde, H.; Manetti, C. Glucose Level Determination with A Multi-Enzymatic Cascade Reaction in A Functionalized Glass Chip. Analyst 2013, 138, 5019–5024.
24. Palazzo, G.; Colafemmina, G. C.; Iudice, C. G.; Mallaidi, A. Three Immobilized Enzymes Acting in Series in Layer by Layer Assemblies: Exploiting the Trehalase-Glucose Oxidase-Horseradish Peroxidase Cascade Reactions for The Optical Determination of Trehalose. Sens. actuators. B Chem. 2014, 202, 217–223.
25. Forera, S.; Kuhn, P.; Lombardi, D.; Schluter, A. D.; Dittrich, P. S.; Walde, P. Sequential Immobilization of Enzymes in Microfluidic Channels for Cascade Reactions. Chem. Plus. Chem. 2012, 77, 98–101.
26. Sackmann, E. K.; Fulton, A. L.; Beebe, D. J. The Present and Future Role of Microfluidics in Biomedical Research. Nature 2014, 507,181–189.
27. Choi, C. J.; Cunningham, B. T. A 96-Well Microplate Incorporating a Replica Molded Microfluidic Network Integrated with Photonic Crystal Biosensors for High Throughput Kinetic Biomolecular Interaction Analysis. Lab Chip 2007, 7, 550–556.
28. Chen, C.; Mehl, B. T.; Munshi, A. S.; Spence, A.D.; Martin, R.S. 3D-Printed Microfluidic Devices: Fabrication, Advantages and Limitations—A Mini Review. Anal. Methods 2016, 8, 6005–6012.
29. Bhattacharjee, N.; Urrios, A.; Kang, S.; Folch, A. The Upcoming 3D-Printing Revolution in Microfluidics. Lab Chip 2016, 16, 1720–1742.
30. Chang, T. C.; Mikheev, A. M.; Huynh, W.; Monnat, R. J.; Rostomily, R. C.; Folch, A. Parallel Microfluidic Chemosensitivity Testing on Individual Slice Cultures. Lab Chip 2014, 14, 4540–4551.
31. Ho, C. M.; Ng, S. H.; Li, K. H.; Yoon, Y. J. 3D Printed Microfluidics for Biological Application. Lab Chip 2015, 15, 3627–3637.
32. Munshi, A. S.; Martin, R. S. Microchip-Based Electrochemical Detection Using A 3-D Printed Wall-Jet Electrode Device. Analyst 2016, 141, 862–869.
33. Lee, K. G. ;Park, K. J. ; Seok, S. ; Shin, S.; Kim, D. H.;Park, J. Y.;Heo, Y. S. ; Lee, S. J.;Lee, T. J. 3D Printed Modules For Integrated Microfluidic Devices. RSC Adv. 2014, 4, 32876–32880.
34. Au, A. K.; Bhattacharjee, N.; Horowitz, L. F; Chang, T. C. ; Folch, A. 3D-printed Microfluidic Automation. Lab Chip 2015, 15, 1934–1941.
35. Choban, E. R.; Markoski, L. J. ; Wieckowski, A.; Kenis, P. J. A. Microfluidic Fuel Cell Based on Laminar Flow. J. Power Sources 2004, 128, 54–60.
36. Tsai, J. H.; Lin, L. W. Active Microfluidic Mixer and Gas Bubble Filter Driven by Thermal Bubble Micropump. Sens. Actuators A 2002, 97, 665–671.
37. Hong, C. C.; Choi, J. W.; Ahn, C. H. A Novel in-Plane Passive Microfluidic Mixer with Modified Tesla Structures. Lab Chip 2004, 4, 109–113.
38. Kitson, P. J.; Symes, M. D.; Dragone, V.; Cronin, L. Combining 3D Printing and Liquid Handling to Produce User-Friendly Reactionware for Chemical Synthesis and Purification. Chem. Sci. 2013, 4, 3099–3103.
39. Kazenwadel, F.; Biegert, E.; Wohlgenuth, J.; Wagner, H.; Franzreb, M. A 3D-printed Modular Reactor Setup Including Temperature and pH Control for The Compartmentalized Implementation of Enzyme Cascades. Eng. Life Sci. 2016, 16, 560−567.
40. Xie, J. X.; Zhang, X. D.; Wang, H.; Zheng, H. Z.; Huanf, Y. M.; Xie, J. X. Analytical and Environmental Applications of Nanoparticles as Enzyme Mimetics. Anal. Chem. 2012, 39, 114−129.
41. Gao, L. Z.; Zhuang, J.; Nie, L.; Zhang, J. B.; Zhang, Y.; Gu, N.; Wang, T. H.; Fang, J.; Yang, D. L.; Perrett, S.; Yan, X. Y. Intrinsic Peroxidase-Like Activity of Ferromagnetic Nanoparticles. Nat. Nanotechnol. 2007, 2, 577–583.
42. Mu, J.; Wang, Y.; Zhao, M.; Zhanga, L. Intrinsic Peroxidase-Like Activity and Catalase-Like Activity of Co3O4 Nanoparticles. Chem. Commun. 2012, 48, 2540–2542.
43. Liu, Y.; Wu, H.; Li, M.; Yin, J. J.; Zie, Z. pH Dependent Catalytic Activities of Platinum Nanoparticles with Respect to The Decomposition of Hydrogen Peroxide and Scavenging of Superoxide and Singlet Oxygen. Nanoscale 2014, 6, 11904–11910.
44. Zhou, Y. T.; He, W. W.; Wanner, W. G.; Hu, X. O.; Wu, Z. C.; Lo, Y. M.; Yin, J. J. Enzyme-Mimetic Effects of Gold@Platinum Nanorods on the Antioxidant Activity of Ascorbic Acid. Nanoscale 2013, 5, 1583–1591.
45. Li, X.; Qi, Z.; Liang, K.; Bai, X.; Xu, J.; Liu, J.; Shen, J. An Artificial Supramolecular Nanozyme Based on β-Cyclodextrin-Modified Gold Nanoparticles. Catal. Lett. 2008, 124, 413–417.
46. Li, Y.; Ma, Q.; Liu, Z.; Wang, X.; Su, X. A Novel Enzyme-Mimic Nanosensor Based on Quantum Dot-Au Nanoparticle@Silica Mesoporous Microsphere for the Detection of Glucose. Anal. Chim. Acta. 2014, 840, 68–74.
47. Slocik, J. M.; Govorov, A. O.; Naik, R. R. Photoactivated Biotemplated Nanoparticles as an Enzyme Mimic. Angew. Chem. Int. Ed. 2008, 47, 5335–5339.
48. Peng, F. F.; Zhang, Y.; Gu, N. Size-Dependent Peroxidase-Like Catalytic Activity of Fe3O4 Nanoparticles. Chin. Chem. Lett. 2008, 19, 730–733.
49. Kotov, N. A. Chemistry. Inorganic Nanoparticles as Protein Mimics. Science 2010, 330, 188–189.
50. Wei, H.; Wang, E. Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes. Chem. Soc. Rev. 2013, 42, 6060–6093.
51. Dond, Y.L.;Zhang, H. G.; Rahman, Z. U.; Chen, X. J.; Hu, J.; Chen, X. G. Graphene oxide–Fe3O4 magnetic nanocomposites with Peroxidase-Like Activity for Colorimetric Detection of Glucose. Nanoscale 2012, 4, 3969–3976.
52. Gao, Z.; Xu, M.; Hou, L.; Chen, G.; Tang, D. Irregular-Shaped Platinum Nanoparticles as Peroxidase Mimics for Highly Efficient Colorimetric Immunoassay. Anal. Chim. Acta 2013, 776, 79–86.
53. Li, Y.; Gao, Y.; Yang, C. A facile and Efficient Synthesis of Polystyrene/Gold–Platinum Composite Particles and Their Application for Aerobic Oxidation of Alcohols in Water. Chem. Commun. 2015, 51, 7721–7724.
54. Li, H.; He, J.; Zhao, Y.; Wu, D.; Cai, Y.; Wei, Q.; Yang, M. Immobilization of Glucose Oxidase and Platinum on Mesoporous Silica Nanoparticles for The Fabrication of Glucose Biosensor. Electrochim. Acta. 2011, 56, 2960–2965.
55. Chen, J.; Ge, J.; Zhang, L.; Li, Z.; Qu, L. Poly(styrene sulfonate) and Pt Bifunctionalized Graphene Nanosheetsas an Artificial Enzyme to Construct A Colorimetric Chemosensor for Highly Sensitive Glucose Detection. Sens. Actuator B-Chem. 2016, 233, 438–444.
56. Kim, M. I.; Kim, M. S.; Woo, M.; Ye, Y.; Kang, K. S.; Lee, J.; Park, H. G. Highly Efficient Colorimetric Detection of Target Cancer Cells Utilizing Superior Catalytic Activity of Graphene Oxide–Magnetic-Platinum Nanohybrids. Nanoscale 2014, 6, 1529–1536.
57. Wang, Y.; Zhang, X.; Luo, Z.; Huang, X.; Tan, C.; Li, H.; Zheng, B.; Li, B.; Huang, Y.; Yang, J.; Zong, Y.; Ying, Y.; Zhang, H. Liquid-Phase Growth of Platinum Nanoparticles on Molybdenum Trioxide Nanosheets: An Enhanced Catalyst with Intrinsic Peroxidase-Like Catalytic Activity. Nanoscale 2014, 6, 12340–12344.
58. Lin, X. Q.; Deng, H. H.; Peng, H. P.; Liu, A. L.; Lin, X. H.; Chen, W. Platinum Nanoparticles/Graphene-Oxide Hybrid with Excellent Peroxidase-Like Activity and Its Application for Cysteine Detection. Analyst 2015, 140, 5251–5256.
59. Ungerstedt, U.; Hallstrom, A. In Vivo Microdialysis–A New Approach to the Analysis of Neurotransmitters in The Brain. Life sciences 1987, 41, 861–864.
60. Chaurasia, C. S.; Müller, M.; Bashaw, E. D.; Benfeldt, E.; Bolinder, J.; Bullock, R.; Bungay, P. M.; DeLange, E. C.; Derendorf, H.; Elmquist, W. F.; Udenaes, M. H.; Joukhadar, C.; KelloggJr, D. L.; Lunte, C. E.; Nordstrom, C. H.; Rollema, H.; Sawchuk, R. J.; Belinda, W. Y.; Shah, V. P.; Ungerstedt, U.; Welty, D. F.; Yeo, H. AAPS-FDA Workshop White Paper: Microdialysis Principles, Application and Regulatory Perspectives. Pharm. Res. 2007, 24, 1014–1025.
61. Torto, N.; Mwastseteze, J.; Sawula, G. A Study of Microdialysis Sampling of Metal ions. Anal. Chim. Acta 2002, 456, 253–261.
62. Heine, J.; Mȕller-Buschbaum, K. Engineering Metal-Based Luminescence in Coordination Polymers and Metal–Organic Frameworks. Chem. Soc. Rev. 2013, 42, 9232–9242.
63. Lackowicz, J. Principle of Fluorescence Spectroscopy. Chapter 4, 2006, 1, 10.
64. Palmer, C.; Loewen, E. G.; Thermo, R. Diffraction Grating Handbook. Newport Corporation Springfield, Ohio, USA. 2005.
65. Skoog, D. A.; Holler, F. J.; Crouch, S. R. Principles of Instrumental Analysis. Thomson brooks/cole, 2007, 6th, 195.
66. Lei, S.; Nihtianov, S.; Comparative Study of Silicon-Based Ultraviolet Photodetectors. IEEE sens. J. 2012, 12, 2453-2459.
67. Ziemian, C. W.；Crawn III, P. M.； Computer Aided Decision Support for Fused Deposition Modeling. Rapid Prototyping J. 2001, 7, 138–147.
68. Zein, I.; Hutmacher, D.W.; Tan, K. C.; Teoh, S. H. Fused Deposition Modeling of Novel Scaffold Architectures for Tissue Engineering Applications. Biomaterials 2002, 23, 1169–1185.
69. Au, A. K.; Huynh, W.; Horowitz, L. F.; Folch, A. 3D-Printed Microfluidics. Angew. Chem. Int. Ed. 2016, 55, 3862–3881.
70. Walt, D.R.; Agayn, V. I. The Chemistry of Enzyme and Protein Immobilization with Glutaraldehyde. Trac-trend. Anal. Chem. 1994, 13, 425–430.
71. Jansen, E.; Olson, A. C. Properties and Enzymatic Activites of Papain Insolubilied with Glutaraldehyde. Arch. Biochem. Biophys. 1969, 129, 221–227.
72. Migneault, I.; Dartiguenave, C.; Bertrand, M. J.; Waldron, K. C. Glutaraldehyde: Behavior in Aqueous Solution, Reaction with Proteins, and Application to Enzyme Crosslinking. BioTechniques 2004, 37, 790–802
73. Carter, R. E.; Aiba, I.; Dietz, R. M.; Sheline, C. T.; Shuttleworth, C. W. Spreading Depression and Related Events are Signification Sources of Neuronal Zn2+ Release and Accumulation. J. Cereb. Blood Flow Metab. 2011, 31, 1073–1084.
74. McNay, E. C.; Fries, T. M.; Gold, P. E. Decreases in Rat Extracellular Hippocampal Glucose Concentration Associated with Cognitive Demand during A Spatial Task. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 2881–2885.
75. Rogers, M. L.; Feuerstein, D.; Leong, C. L.; Takagaki, M.; Niu, X.; Graf, R.; Boutelle, M. G. Continuous Online Microdialysis Continuous Online Microdialysis Using Microfluidic Sensors: Dynamic Neurometabolic Changes during Spreading Depolarization. Neurometabolic Changes during Spreading Depolarization. ACS Chem. Neurosci. 2013, 4, 799 –807.
76. Hopwood, S. E.; Parkin, M. C.; Bezzina, E. L.; Boutelle, M. G.; Strong, A. J. The Cortical Ischaemic Penumbra Associated with Occlusion of the Middle Cerebral Artery in the Cat: 1. Topography of Changes in Blood Flow, Potassium Ion Activity, and EEG. J. Cereb. Blood Flow Metab. 2005, 25, 391–401.
77. Darbin, O.; Carre, E.; Naritoku, D.; Risso, J. J.; Lonjon, M.; Patrylo, P.R. Glucose Metabolites in The Striatum of Freely Behaving Rats Following Infusion of Elevated Potassium. Brain Res. 2006, 1116, 127–131.
78. Kimelberg, H. K.; Bowman, C.; Biddlecome, S.; Bourke, R.S. Cation Transport and Membrane Potential Properties of Primary Astroglial Cultures from Neonatal Rat Brains. Brain Res. 1979, 177, 533–550.
79. Wang, M.; Slaney, T.; Mabrouk, O.; Kennedy, R.T. Collection of Nanoliter Microdialysate Fractions in Plugs for Off-Line in Vivo Chemical Monitoring with up to 2 S Temporal Resolution. J Neurosci. Methods 2010, 190, 39–48.
80. Sü en, F.; Go1kagˇacü, G. Different Sized Platinum Nanoparticles Supported on Carbon: An XPS Study on These Methanol Oxidation Catalysts. J. Phys. Chem. C 2007, 111, 5715–5720.
81. Kaidanovych, Z.; Kalishyn, Y.; Strizhak, P. Deposition of Monodisperse Platinum Nanoparticles of Controlled Size on Different Supports. Advances in Nanoparticles, 2013, 2, 32–38
82. Teranishi, T.; Hosoe, M.; Tanaka, T.; Miyake, M. Size Control of Monodispersed Pt Nanoparticles and Their 2D Organization by Electrophoretic Deposition. J. Phys. Chem. B, 1999, 103, 3818–3827.
83. Yan. Y.; Qi, P.; Zhang, D.; Wu, J.; Wang, Y. Manganese Oxide Nanowire-Mediated Enzyme-Linked Immunosorbent Assay. Biosens. Bioelectron. 2012, 33, 69-72.
84. Miyake, M.; Miyabayashi, K. Shape and Size Controlled Pt Nanocrystals as Novel Model Catalysts. Catal. Surv. Asia 2012, 16, 1–13.
85. Alpeeva, I.S.; Soukharev, V.S.; Alexandrove, L.; Shilova, N.V.; Bovin, N.V.; Ryabov, A.D.; Sakharov, I.Y. Cyclomethalated Ruthenium (III) Complexes as Efficient Redox Mediators in Peroxidase Catalysis. J. Biol. Inorg. Chem. 2003, 8, 683–688.
86. Malomo, S. O.; Adeoye, R. I.; Babatunde, L.; Saheed, I. A.; Iniaghe, M. O.; Olorunniji, F. J. Suicide Inactivation of Horseradish Peroxidase by Excess Hydrogen Peroxide: The Effects of Reaction pH, Buffer Ion Concentration, and Redox Mediation. Biokemistri, 2011, 23, 124–128.
87. Fan, J.; Yin, J. J.; Wu, X.; Hu, Y.; Ferrari, M.; Aderson, G. J.; Wei, J.; Nie, G. Direct evidence for catalase and peroxidase activities of ferritin-platinum nanoparticles. Biomaterials 2011, 32, 1611–1618.
88. Chen, L.; Wang, N.; Wang, X.; Ai, S. Protein-Directed in Situ synthesis of Platinum Nanoparticles with Superior Peroxidase-like Activity, and Their Use for Photometric Determination of Hydrogen Peroxide. Microchim. Acta 2013, 180, 1517–1522.
89. Cai, K.; Lv, Z.; Chen, K.; Huang, L.; Wang, J.; Shao, F.; Wang, Y.; Han, H. Aqueous Synthesis of Porous Platinum Nanotubes at Room Temperature and Their Intrinsic Peroxidase-like Activity. Chem. Commun. 2013, 49, 6024–6026.
90. Fu, Y.; Zhao, X.; Zhang, J.; Li, W. DNA-Based Platinum Nanozymes for Peroxidase Mimetics. J. Phys. Chem. C 2014, 118, 18116–18125.
91. Wang, Y.; Zhang, X.; Luo, Z.; Huang, X.; Tan, C.; Li, H.; Zheng, B.; Lim B.; Huang, Y.; Yang, J.; Zong, Y.; Ting, Y.; Zhang, H. Nanoscale 2014, 6, 12340–12344.
92. Ju, Y.; Kim, J. Dendrimer-Encapsulated Pt Nanoparticles with Peroxidase-Mimetic Activity as Biocatalytic Labels for Sensitive Colorimetric Analyses. Chem. Commun. 2015, 51, 13752–13755.
93. Jin, L.; Meng, Z.; Zhang, Y.; Cai, S.; Zhang, Z.; Li, C.; Shang, L.; Shen, Y. Ultrasmall Pt Nanoclusters as Robust Peroxidase Mimics for Colorimetric Detection of Glucose in Human Serum. ACS Appl. Mater. Interfaces 2017, 9, 10027–10033.
94. Gao, L.; Wu, J.; Gao, D. Enzyme-Controlled Self-Assembly and Transformation of Nanostructures in a Tetramethylbenzidine/Horseradish Peroxidase/H2O2 System. ACS Nano 2011, 5, 6736-6742.
95. Kulshreshtha, A. K.; Singh, B. P.; Sharma, Y. N. Viscometric Determination of Compatibility in PVC/ABS Polyblends. Part III. Choice of a Common Solvent and Its Effect on Results. Eur. Polym. J. 1988, 24, 191-194.