一、利用Surfen-Graphene Oxide複合物探針產生螢光回復偵測生物樣品中之硫化醣胺聚醣
硫化醣胺聚醣(sulfated GAGs)不僅是黏多醣症之生物標記物亦參與生物體中各種代謝過程，例如：抗凝血藥成分(Heparin)或生物體內訊號傳遞物質(heparan sulfate)。然而，現今很少文獻開發螢光感測器發展偵測真實樣品中sulfated GAGs。在本實驗中，我們發展一個surfen/few-layer graphene oxide(FLGO)奈米複合材料偵測真實樣品中的sulfated GAGs。Surfen螢光分子藉由靜電作用力自組裝於FLGO表面，surfen/FLGO複合物產生靜態消光(static quenching)與surfen能量轉移至FLGO產生動態消光(dynamic quenching)。當sulfated GAGs出現時，藉由surfen與其具有較強之專一性作用力，從surfen-FLGO複合物變成surfen- sulfated GAGs複合物，並促使螢光產生回復現象。由於FLGO有效降低surfen螢光訊號值加上surfen與sulfated GAGs產生複合物，surfen-FLGO相較於surfen具有較高選擇性與高靈敏性。利用前面提及策略，進行人體血漿中的肝素與人工腦脊液中的sulfated GAGs含量檢測，Heparin、dermatan sulfate與heparin sulfate偵測極限分別為30、30與60 ng/mL。

二、雙磷酸腺苷增強金奈米粒子催化活性結合surfen分子偵測生物樣品中之硫化醣胺聚醣
金奈米粒子作為仿生酵素已廣泛地應用於生物感測，然而，目前金奈米粒子受到低催化活性與偵測靈敏性低的問題，本實驗將開發利用ADP修飾citrate-AuNPs表面有效增強催化Amplex ultrared(AU)。其中，ADP有助於催化原因有兩個：(1)ADP修飾於citrate-AuMPs表面上使其穩定存在催化環境；(2)ADP類似Horseradish peroxidase的distal histidine官能基有效活化H2O2。相較於citrate-AuNPs，ADP-modified AuNPs (ADP-AuNPs)Michaelis constant低4.4倍，最大速率增強2.5倍。帶有正電荷之surfen分子誘導ADP-AuNPs產生聚集，因而抑制AU-H2O2催化活性，接著當加入對surfen具有專一性作用力(靜電作用力)之醣胺聚醣類似物，有效促使ADP-AuNPs回復均勻分散狀態。因此，氧化AU螢光強度隨著Heparin濃度增加而增加，線性範圍1-8 nM，並有效應用於真實樣品進行檢測。進一步，利用ADP有效增強催化應用於FeNPs、PtNPs與BSA-AuNPs材料上，以Michaelis-Menten方程式計算Michaelis constant(Km)隨之下降，Vmax隨之上升。

(a) Surfen-Assembled Graphene Oxide for Fluorescence Turn-On Detection of Sulfated Glycosaminoglycans in Biological Matrix
Sulfated glycosaminoglycans (GAGs) not only serve as biomarker for mucopolysaccharidoses disease but also participate in various biological processes, such as blood clot medication (heparin) and signal transduction (heparan sulfate). However, few fluorescent sensors, such as 1,9-dimethylmethylene blue, have been developed for the detection of sulfated GAGs in the real world. Herein, we fabricated a surfen/few-layer graphene oxide (FLGO) nanocomplex for sensing sulfated GAGs in biological fluids. Surfen molecules are self-assembled onto the surface of FLGO through electrostatic attraction and their fluorescence was then quenched by the creation of the FLGO-surfen complex (static quenching),and partially combined with the energy transfer from surfen to FLGO (dynamic quenching). The presence of sulfated GAGs resulted in the fluorescence recovery through the formation of the surfen-GAGs complex, which exhibits weak binding to FLGO and keeps surfen molecules away from the FLGO surface. Because FLGO efficiently reduced the fluorescence background from surfen and competed with sulfated GAGs for binding to surfen, surfen-assembled FLGO exhibited higher sensitivity andbetter selectivity for sulfated GAGs than surfen. The aforementioned strategy was exemplified by the analysis of heparin in human plasma and sulfated GAGs in artificial cerebrospinal fluid; the limits of detection at a signal-to-noise ratio of 3 for heparin, dermatan sulfate, and heparin sulfate were determined to be 30, 30 and 60 ng/mL, respectively.

(b) Boosted Peroxidase-Like Activity in Gold Nanoparticles by Incorporating Adenosine Diphosphate: Application to Sulfated Glycosaminoglycans Sensing
Gold-based nanomaterials as a mimic peroxidase are of great interest in the development of biosensors. However, they suffer from low catalytic activity, resulting in poor detection sensitivity toward a target of interest. Herein, this study presents that the modification of citrate-capped gold nanoparticles with adenosine diphosphate (ADP) is capable of boosting their catalytic activity for the oxidation reaction of hydrogen peroxide (H2O2) and amplex ultrared (AU). The improved activity resulted from: (1) the attachment of ADP onto the surface of the AuNPs allows them to stabilize in the catalytic condition and (2) ADP mimics as a distal histidine residue of horseradish peroxidase for activating H2O2. Compared to citrate-capped AuNPs, the Michaelis constant of ADP-modified AuNPs (ADP-AuNPs) was lowered to be 4.4-fold and their maximum velocity was enhanced to be 2.5-fold. Cationic surfen molecules were found to be efficient to induce the aggregation of ADP-AuNPs, thereby inhibiting their catalytic activity for the AU-H2O2 reaction. Since heparin specifically binds to surfen through strong electrostatic attraction between them, the presence of heparin disassembled the aggregation of ADP-AuNPs. As a result, the fluorescence of the oxidized AU linearly increased with an increase in the concentration of heparin from 1 to 8 nM. The proposed system was successfully applied for the determination of heparin in plasma.

目錄
論文審定書 i
論文公開授權書 ii
謝誌 iii
摘要 iv
目錄 viii
圖目錄 xi
表目錄 xv
縮寫表 xvi
第一章、利用Surfen-Graphene Oxide複合物探針產生螢光回復偵測生物樣品中之硫化醣胺聚醣 1
一、前言 1
1.1 硫化醣胺聚醣(sulfated Glycosaminoglycans，sulfated GAGs) 1
1.2氧化石墨烯(Graphene Oxide，GO)感測應用 2
二、實驗部分 4
2.1實驗藥品 4
2.2化學結構式 5
2.3儀器裝置 6
2.4樣品配製 8
2.5實驗過程 9
三、結果與討論 12
3.1感測機制建立 12
3.2 證明surfen-assembled FLGO形成 13
3.2.1 表面電位分析(Zeta potential) 13
3.2.2傅立葉轉換紅外線光譜儀( FT-IR) 14
3.2.3 基質輔助雷射脫附游離飛行質譜儀(MALDI-TOF-MS) 14
3.2.4 利用掃描式電子顯微鏡(SEM)、原子力顯微鏡(AFM)、穿透式電子顯微鏡(TEM)鑑定FLGO 14
3.3 Surfen-assembled FLGO探針反應最佳化 19
3.3.1探討不同pH值環境下surfen在FLGO之吸附量 19
3.3.2 pH值與NaCl濃度影響 19
3.3.3不同pH值(4、7、10)環境下之螢光消光效率/螢光生命週期儀 19
3.4探討螢光消光機制（動態、靜態消光） 25
3.5 選擇性探討 31
3.6 Heparin定量分析 38
3.7 人類血漿中真實樣品Heparin定量分析 44
3.8硫化醣胺聚醣(sulfated GAGs)類似物標準溶液定量分析 48
3.9模擬人工腦脊液中之sulfated GAGs含量分辨是否患有MPS 48
四、結論 53
五、參考文獻 54
第二章、雙磷酸腺苷增強金奈米粒子催化活性結合surfen分子偵測生物樣品中之硫化醣胺聚醣 60
一、前言 60
1.1仿生酵素 60
1.2金奈米粒子(AuNPs)作為仿生酵素 60
二、實驗部分 63
2.1 實驗藥品 63
2.2 儀器裝置 63
2.3 樣品配製方法 65
2.4 實驗過程 66
三、結果與討論 70
3.1 雙磷腺苷增強AuNPs催化活性 70
3.2 增強催化活性機制探討 77
3.3 催化動力學探討 82
3.4 ADP增強AuNPs催化活性最佳化探討 84
3.4.1 ADP濃度與反應時間最佳化 84
3.4.2 AuNPs濃度最佳化 84
3.4.3 受質濃度最佳化 84
3.5 利用ADP-AuNPs結合surfen有機分子偵測Sulfated GAGs 88
3.6 Heparin定量 90
3.7 選擇性探討 90
3.8人類血漿中真實樣品Heparin定量分析 94
3.9硫化醣胺聚醣(sulfated GAGs)類似物標準溶液定量分析 97
3.10模擬人工腦脊液中之sulfated GAGs含量分辨是否患有MPS 101
3.11 ADP增強催化效能應用於其他奈米材料 103
四、結論 106
五、參考文獻 107

第一章
1. Sun, X.; Li, L.; Overdier, K. H.; Ammons, L. A.; Douglas, I. S.; Burlew, C. C.; Zhang, F.; Schmidt, E. P.; Chi, L.; Linhardt, R. J., Analysis of Total Human Urinary Glycosaminoglycan Disaccharides by Liquid Chromatography–Tandem Mass Spectrometry. Anal. Chem. 2015, 87 (12), 6220-6227.
2. Tomatsu, S.; Fujii, T.; Fukushi, M.; Oguma, T.; Shimada, T.; Maeda, M.; Kida, K.; Shibata, Y.; Futatsumori, H.; Montaño, A. M.; Mason, R. W.; Yamaguchi, S.; Suzuki, Y.; Orii, T., Newborn screening and diagnosis of mucopolysaccharidoses. Mol. Genet. Metab. 2013, 110 (1–2), 42-53.
3. Trim, P. J.; Hopwood, J. J.; Snel, M. F., Butanolysis Derivatization: Improved Sensitivity in LC-MS/MS Quantitation of Heparan Sulfate in Urine from Mucopolysaccharidosis Patients. Anal. Chem. 2015, 87 (18), 9243-9250.
4. Sridharan, G.; Shankar, A. A., Toluidine blue: A review of its chemistry and clinical utility. J Oral Maxillofac Pathol 2012, 16 (2), 251-255.
5. Säämänen, A.-M.; Tammi, M., Determination of unsaturated glycosaminoglycan disaccharides by spectrophotometry on thin-layer chromatographic plates. Anal. Biochem. 1984, 140 (2), 354-359.
6. Kodama, C.; Ototani, N.; Isemura, M.; Yosizawa, Z., High-Performance Liquid Chromatography of Pyridylamino Derivatives of Unsaturated Disaccharides Produced from Chondroitin Sulfate Isomers by Chondroitinases. J. Biochem. 1984, 96 (4), 1283-1287.
7. Hsieh, C.-C.; Guo, J. Y.; Hung, S.-U.; Chen, R.; Nie, Z.; Chang, H.-C.; Wu, C.-C., Quantitative Analysis of Oligosaccharides Derived from Sulfated Glycosaminoglycans by Nanodiamond-Based Affinity Purification and Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. Anal. Chem. 2013, 85 (9), 4342-4349.
8. Sun, X.; Lin, L.; Liu, X.; Zhang, F.; Chi, L.; Xia, Q.; Linhardt, R. J., Capillary Electrophoresis–Mass Spectrometry for the Analysis of Heparin Oligosaccharides and Low Molecular Weight Heparin. Anal. Chem. 2016, 88 (3), 1937-1943.
9. Novoselov, K. S.; Geim, A. K.; Morozov, S. V.; Jiang, D.; Zhang, Y.; Dubonos, S. V.; Grigorieva, I. V.; Firsov, A. A., Electric Field Effect in Atomically Thin Carbon Films. Science 2004, 306 (5696), 666-669.
10. Allen, M. J.; Tung, V. C.; Kaner, R. B., Honeycomb Carbon: A Review of Graphene. Chem. Rev. 2010, 110 (1), 132-145.
11. (a) Raccichini, R.; Varzi, A.; Passerini, S.; Scrosati, B., The role of graphene for electrochemical energy storage. Nat Mater 2015, 14 (3), 271-279; (b) Liu, Y.; Dong, X.; Chen, P., Biological and chemical sensors based on graphene materials. Chem. Soc. Rev. 2012, 41 (6), 2283-2307; (c) Kim, K. S.; Zhao, Y.; Jang, H.; Lee, S. Y.; Kim, J. M.; Kim, K. S.; Ahn, J.-H.; Kim, P.; Choi, J.-Y.; Hong, B. H., Large-scale pattern growth of graphene films for stretchable transparent electrodes. Nature 2009, 457 (7230), 706-710.
12. (a) Yoo, J. M.; Kang, J. H.; Hong, B. H., Graphene-based nanomaterials for versatile imaging studies. Chem. Soc. Rev. 2015, 44 (14), 4835-4852; (b) Huang, X.; Yin, Z.; Wu, S.; Qi, X.; He, Q.; Zhang, Q.; Yan, Q.; Boey, F.; Zhang, H., Graphene-Based Materials: Synthesis, Characterization, Properties, and Applications. Small 2011, 7 (14), 1876-1902.
13. (a) Hunt, A.; Dikin, D. A.; Kurmaev, E. Z.; Boyko, T. D.; Bazylewski, P.; Chang, G. S.; Moewes, A., Epoxide Speciation and Functional Group Distribution in Graphene Oxide Paper-Like Materials. Adv. Funct. Mater. 2012, 22 (18), 3950-3957; (b) Gao, W.; Alemany, L. B.; Ci, L.; Ajayan, P. M., New insights into the structure and reduction of graphite oxide. Nat Chem 2009, 1 (5), 403-408; (c) Kang, J. H.; Kim, T.; Choi, J.; Park, J.; Kim, Y. S.; Chang, M. S.; Jung, H.; Park, K. T.; Yang, S. J.; Park, C. R., Hidden Second Oxidation Step of Hummers Method. Chem. Mater. 2016, 28 (3), 756-764.
14. Marcano, D. C.; Kosynkin, D. V.; Berlin, J. M.; Sinitskii, A.; Sun, Z.; Slesarev, A.; Alemany, L. B.; Lu, W.; Tour, J. M., Improved Synthesis of Graphene Oxide. ACS Nano 2010, 4 (8), 4806-4814.
15. (a) Liu, Z.; Robinson, J. T.; Sun, X.; Dai, H., PEGylated Nanographene Oxide for Delivery of Water-Insoluble Cancer Drugs. J. Am. Chem. Soc. 2008, 130 (33), 10876-10877; (b) Huang, P.; Xu, C.; Lin, J.; Wang, C.; Wang, X.; Zhang, C.; Zhou, X.; Guo, S.; Cui, D., Folic Acid-conjugated Graphene Oxide loaded with Photosensitizers for Targeting Photodynamic Therapy. Theranostics 2011, 1, 240-250; (c) Kim, Y.-K.; Kim, M.-H.; Min, D.-H., Biocompatible reduced graphene oxide prepared by using dextran as a multifunctional reducing agent. Chem. Commun. 2011, 47 (11), 3195-3197; (d) Georgakilas, V.; Tiwari, J. N.; Kemp, K. C.; Perman, J. A.; Bourlinos, A. B.; Kim, K. S.; Zboril, R., Noncovalent Functionalization of Graphene and Graphene Oxide for Energy Materials, Biosensing, Catalytic, and Biomedical Applications. Chem. Rev. 2016, 116 (9), 5464-5519; (e) Shao, J.-J.; Lv, W.; Yang, Q.-H., Self-Assembly of Graphene Oxide at Interfaces. Adv. Mater. 2014, 26 (32), 5586-5612; (f) Dreyer, D. R.; Park, S.; Bielawski, C. W.; Ruoff, R. S., The chemistry of graphene oxide. Chem. Soc. Rev. 2010, 39 (1), 228-240.
16. Kim, J.; Cote, L. J.; Kim, F.; Yuan, W.; Shull, K. R.; Huang, J., Graphene Oxide Sheets at Interfaces. J. Am. Chem. Soc. 2010, 132 (23), 8180-8186.
17. Shih, C.-J.; Lin, S.; Sharma, R.; Strano, M. S.; Blankschtein, D., Understanding the pH-Dependent Behavior of Graphene Oxide Aqueous Solutions: A Comparative Experimental and Molecular Dynamics Simulation Study. Langmuir 2012, 28 (1), 235-241.
18. Su, Q.; Pang, S.; Alijani, V.; Li, C.; Feng, X.; Müllen, K., Composites of Graphene with Large Aromatic Molecules. Adv. Mater. 2009, 21 (31), 3191-3195.
19. Park, J. S.; Na, H.-K.; Min, D.-H.; Kim, D.-E., Desorption of single-stranded nucleic acids from graphene oxide by disruption of hydrogen bonding. Analyst 2013, 138 (6), 1745-1749.
20. Kim, J.; Cote, L. J.; Kim, F.; Huang, J., Visualizing Graphene Based Sheets by Fluorescence Quenching Microscopy. J. Am. Chem. Soc. 2010, 132 (1), 260-267.
21. Dou, M.; Garcia, J. M.; Zhan, S.; Li, X., Interfacial nano-biosensing in microfluidic droplets for high-sensitivity detection of low-solubility molecules. Chem. Commun. 2016, 52 (17), 3470-3473.
22. Alonso-Cristobal, P.; Vilela, P.; El-Sagheer, A.; Lopez-Cabarcos, E.; Brown, T.; Muskens, O. L.; Rubio-Retama, J.; Kanaras, A. G., Highly Sensitive DNA Sensor Based on Upconversion Nanoparticles and Graphene Oxide. ACS Appl. Mater. Interfaces 2015, 7 (23), 12422-12429.
23. Liu, Z.; Long, T.; Wu, S.; Li, C., Porphyrin-loaded liposomes and graphene oxide used for the membrane pore-forming protein assay and inhibitor screening. Analyst 2015, 140 (16), 5495-5500.
24. Lim, S. K.; Chen, P.; Lee, F. L.; Moochhala, S.; Liedberg, B., Peptide-Assembled Graphene Oxide as a Fluorescent Turn-On Sensor for Lipopolysaccharide (Endotoxin) Detection. Anal. Chem. 2015, 87 (18), 9408-9412.
25. Ryoo, S.-R.; Lee, J.; Yeo, J.; Na, H.-K.; Kim, Y.-K.; Jang, H.; Lee, J. H.; Han, S. W.; Lee, Y.; Kim, V. N.; Min, D.-H., Quantitative and Multiplexed MicroRNA Sensing in Living Cells Based on Peptide Nucleic Acid and Nano Graphene Oxide (PANGO). ACS Nano 2013, 7 (7), 5882-5891.
26. Hong, C.; Baek, A.; Hah, S. S.; Jung, W.; Kim, D.-E., Fluorometric Detection of MicroRNA Using Isothermal Gene Amplification and Graphene Oxide. Anal. Chem. 2016, 88 (6), 2999-3003.
27. Dong, X.; Cheng, J.; Li, J.; Wang, Y., Graphene as a Novel Matrix for the Analysis of Small Molecules by MALDI-TOF MS. Anal. Chem. 2010, 82 (14), 6208-6214.
28. (a) Lu, J.; Wang, M.; Li, Y.; Deng, C., Facile synthesis of TiO2/graphene composites for selective enrichment of phosphopeptides. Nanoscale 2012, 4 (5), 1577-1580; (b) Gulbakan, B.; Yasun, E.; Shukoor, M. I.; Zhu, Z.; You, M.; Tan, X.; Sanchez, H.; Powell, D. H.; Dai, H.; Tan, W., A Dual Platform for Selective Analyte Enrichment and Ionization in Mass Spectrometry Using Aptamer-Conjugated Graphene Oxide. J. Am. Chem. Soc. 2010, 132 (49), 17408-17410.
29. Xie, L.; Ling, X.; Fang, Y.; Zhang, J.; Liu, Z., Graphene as a Substrate To Suppress Fluorescence in Resonance Raman Spectroscopy. J. Am. Chem. Soc. 2009, 131 (29), 9890-9891.
30. (a) Liu, Q.; Wei, L.; Wang, J.; Peng, F.; Luo, D.; Cui, R.; Niu, Y.; Qin, X.; Liu, Y.; Sun, H.; Yang, J.; Li, Y., Cell imaging by graphene oxide based on surface enhanced Raman scattering. Nanoscale 2012, 4 (22), 7084-7089; (b) Fan, Z.; Kanchanapally, R.; Ray, P. C., Hybrid Graphene Oxide Based Ultrasensitive SERS Probe for Label-Free Biosensing. J. Phys. Chem. Lett. 2013, 4 (21), 3813-3818.
31. Ekiz, O. Ö.; Ürel, M.; Güner, H.; Mizrak, A. K.; Dâna, A., Reversible Electrical Reduction and Oxidation of Graphene Oxide. ACS Nano 2011, 5 (4), 2475-2482.
32. Pei, S.; Cheng, H.-M., The reduction of graphene oxide. Carbon 2012, 50 (9), 3210-3228.
33. (a) Zhou, X.; Huang, X.; Qi, X.; Wu, S.; Xue, C.; Boey, F. Y. C.; Yan, Q.; Chen, P.; Zhang, H., In Situ Synthesis of Metal Nanoparticles on Single-Layer Graphene Oxide and Reduced Graphene Oxide Surfaces. J. Phys. Chem. C 2009, 113 (25), 10842-10846; (b) Zhou, M.; Zhai, Y.; Dong, S., Electrochemical Sensing and Biosensing Platform Based on Chemically Reduced Graphene Oxide. Anal. Chem. 2009, 81 (14), 5603-5613.
34. (a) Shan, C.; Yang, H.; Song, J.; Han, D.; Ivaska, A.; Niu, L., Direct Electrochemistry of Glucose Oxidase and Biosensing for Glucose Based on Graphene. Anal. Chem. 2009, 81 (6), 2378-2382; (b) Yang, T.; Li, X.; Li, Q.; Guo, X.; Guan, Q.; Jiao, K., Electrochemically reduced graphene oxide-enhanced electropolymerization of poly-xanthurenic acid for direct, "signal-on" and high sensitive impedimetric sensing of DNA. Polym. Chem. 2013, 4 (4), 1228-1234.
35. (a) Feng, L.; Chen, Y.; Ren, J.; Qu, X., A graphene functionalized electrochemical aptasensor for selective label-free detection of cancer cells. Biomaterials 2011, 32 (11), 2930-2937; (b) Choi, D.; Jeong, H.; Kim, K., Electrochemical thrombin detection based on the direct interaction of target proteins and graphene oxide as an indicator. Analyst 2014, 139 (6), 1331-1333.
36. Bromfield, S. M.; Wilde, E.; Smith, D. K., Heparin sensing and binding - taking supramolecular chemistry towards clinical applications. Chem. Soc. Rev. 2013, 42 (23), 9184-9195.
37. Li, D.; Muller, M. B.; Gilje, S.; Kaner, R. B.; Wallace, G. G., Processable aqueous dispersions of graphene nanosheets. Nat Nano 2008, 3 (2), 101-105.
38. (a) Liu, C.-W.; Chien, M.-W.; Su, C.-Y.; Chen, H.-Y.; Li, L.-J.; Lai, C.-C., Analysis of flavonoids by graphene-based surface-assisted laser desorption/ionization time-of-flight mass spectrometry. Analyst 2012, 137 (24), 5809-5816; (b) Shi, C.; Meng, J.; Deng, C., Enrichment and detection of small molecules using magnetic graphene as an adsorbent and a novel matrix of MALDI-TOF-MS. Chem. Commun. 2012, 48 (18), 2418-2420.
39. Stankovich, S.; Dikin, D. A.; Dommett, G. H. B.; Kohlhaas, K. M.; Zimney, E. J.; Stach, E. A.; Piner, R. D.; Nguyen, S. T.; Ruoff, R. S., Graphene-based composite materials. Nature 2006, 442 (7100), 282-286.
40. Li, S.; Mulloor, J. J.; Wang, L.; Ji, Y.; Mulloor, C. J.; Micic, M.; Orbulescu, J.; Leblanc, R. M., Strong and Selective Adsorption of Lysozyme on Graphene Oxide. ACS Appl. Mater. Interfaces 2014, 6 (8), 5704-5712.
41. (a) Shu, J.; Qiu, Z.; Wei, Q.; Zhuang, J.; Tang, D., Cobalt-Porphyrin-Platinum-Functionalized Reduced Graphene Oxide Hybrid Nanostructures: A Novel Peroxidase Mimetic System For Improved Electrochemical Immunoassay. Sci Rep 2015, 5, 15113; (b) Li, S.; Aphale, A. N.; Macwan, I. G.; Patra, P. K.; Gonzalez, W. G.; Miksovska, J.; Leblanc, R. M., Graphene Oxide as a Quencher for Fluorescent Assay of Amino Acids, Peptides, and Proteins. ACS Appl. Mater. Interfaces 2012, 4 (12), 7069-7075.
42. Radi, A.-E., Electrochemical Aptamer-Based Biosensors: Recent Advances and Perspectives. Int. J. Electrochem. 2011, 2011, 17.
43. Ahmad, A.; Kurkina, T.; Kern, K.; Balasubramanian, K., Applications of the Static Quenching of Rhodamine B by Carbon Nanotubes. Chem. Phys. Chem. 2009, 10 (13), 2251-2255.
44. Morales-Narváez, E.; Merkoçi, A., Graphene Oxide as an Optical Biosensing Platform. Adv. Mater. 2012, 24 (25), 3298-3308.
45. Schuksz, M.; Fuster, M. M.; Brown, J. R.; Crawford, B. E.; Ditto, D. P.; Lawrence, R.; Glass, C. A.; Wang, L.; Tor, Y.; Esko, J. D., Surfen, a small molecule antagonist of heparan sulfate. Proc. Natl. Acad. Sci. U.S.A. 2008, 105 (35), 13075-13080.
46. Lee, C.-Y.; Tseng, W.-L., Molecular Beacon-Based Fluorescent Assay for Specific Detection of Oversulfated Chondroitin Sulfate Contaminants in Heparin without Enzyme Treatment. Anal. Chem. 2015, 87 (10), 5031-5035.
47. Fu, X.; Chen, L.; Li, J.; Lin, M.; You, H.; Wang, W., Label-free colorimetric sensor for ultrasensitive detection of heparin based on color quenching of gold nanorods by graphene oxide. Biosens. Bioelectron. 2012, 34 (1), 227-231.
48. Cao, R.; Li, B., A simple and sensitive method for visual detection of heparin using positively-charged gold nanoparticles as colorimetric probes. Chem. Commun. 2011, 47 (10), 2865-2867.
49. Kuo, C.-Y.; Tseng, W.-L., Adenosine-based molecular beacons as light-up probes for sensing heparin in plasma. Chem. Commun. 2013, 49 (41), 4607-4609.
50. Hung, S.-Y.; Tseng, W.-L., A polyadenosine–coralyne complex as a novel fluorescent probe for the sensitive and selective detection of heparin in plasma. Biosens. Bioelectron. 2014, 57, 186-191.
51. Dai, Q.; Liu, W.; Zhuang, X.; Wu, J.; Zhang, H.; Wang, P., Ratiometric Fluorescence Sensor Based on a Pyrene Derivative and Quantification Detection of Heparin in Aqueous Solution and Serum. Anal. Chem. 2011, 83 (17), 6559-6564.
52. Zhong, Z.; Anslyn, E. V., A Colorimetric Sensing Ensemble for Heparin. J. Am. Chem. Soc. 2002, 124 (31), 9014-9015.
53. (a) Zhan, R.; Fang, Z.; Liu, B., Naked-Eye Detection and Quantification of Heparin in Serum with a Cationic Polythiophene. Anal. Chem. 2010, 82 (4), 1326-1333; (b) Pu, K.-Y.; Liu, B., Conjugated Polyelectrolytes as Light-Up Macromolecular Probes for Heparin Sensing. Adv. Funct. Mater. 2009, 19 (2), 277-284.
54. Sun, W.; Bandmann, H.; Schrader, T., A Fluorescent Polymeric Heparin Sensor. CHEM. EUR. J. 2007, 13 (27), 7701-7707.
55. Yan, H.; Wang, H.-F., Turn-on Room Temperature Phosphorescence Assay of Heparin with Tunable Sensitivity and Detection Window Based on Target-Induced Self-Assembly of Polyethyleneimine Capped Mn-Doped ZnS Quantum Dots. Anal. Chem. 2011, 83 (22), 8589-8595.
56. Zhang, H.; Young, S. P.; Auray-Blais, C.; Orchard, P. J.; Tolar, J.; Millington, D. S., Analysis of Glycosaminoglycans in Cerebrospinal Fluid from Patients with Mucopolysaccharidoses by Isotope-Dilution Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry. Clin. Chem. 2011, 57 (7), 1005-1012.
第二章
1. (a) Wolfenden, R.; Snider, M. J., The Depth of Chemical Time and the Power of Enzymes as Catalysts. Acc. Chem. Res. 2001, 34 (12), 938-945; (b) Garcia-Viloca, M.; Gao, J.; Karplus, M.; Truhlar, D. G., How Enzymes Work: Analysis by Modern Rate Theory and Computer Simulations. Science 2004, 303 (5655), 186-195; (c) Ran, N.; Zhao, L.; Chen, Z.; Tao, J., Recent applications of biocatalysis in developing green chemistry for chemical synthesis at the industrial scale. Green Chemistry 2008, 10 (4), 361-372; (d) Torres, E.; Bustos-Jaimes, I.; Le Borgne, S., Potential use of oxidative enzymes for the detoxification of organic pollutants. Appl. Catal., B 2003, 46 (1), 1-15.
2. Gao, L.; Zhuang, J.; Nie, L.; Zhang, J.; Zhang, Y.; Gu, N.; Wang, T.; Feng, J.; Yang, D.; Perrett, S.; Yan, X., Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. Nat Nano 2007, 2 (9), 577-583.
3. Breslow, R., Biomimetic Chemistry and Artificial Enzymes: Catalysis by Design. Acc. Chem. Res. 1995, 28 (3), 146-153.
4. Lin, Y.; Huang, Y.; Ren, J.; Qu, X., Incorporating ATP into biomimetic catalysts for realizing exceptional enzymatic performance over a broad temperature range. NPG Asia Mater. 2014, 6, e114.
5. Liu, B.; Liu, J., Surface modification of nanozymes. Nano Research 2017, 10 (4), 1125-1148.
6. Yang, Y.-C.; Wang, Y.-T.; Tseng, W.-L., Amplified Peroxidase-Like Activity in Iron Oxide Nanoparticles Using Adenosine Monophosphate: Application to Urinary Protein Sensing. ACS Appl. Mater. Interfaces 2017, 9 (11), 10069-10077.
7. Lin, Y.; Zhao, A.; Tao, Y.; Ren, J.; Qu, X., Ionic Liquid as an Efficient Modulator on Artificial Enzyme System: Toward the Realization of High-Temperature Catalytic Reactions. J. Am. Chem. Soc. 2013, 135 (11), 4207-4210.
8. Zhang, L.-N.; Deng, H.-H.; Lin, F.-L.; Xu, X.-W.; Weng, S.-H.; Liu, A.-L.; Lin, X.-H.; Xia, X.-H.; Chen, W., In Situ Growth of Porous Platinum Nanoparticles on Graphene Oxide for Colorimetric Detection of Cancer Cells. Anal. Chem. 2014, 86 (5), 2711-2718.
9. Singh, S.; Dosani, T.; Karakoti, A. S.; Kumar, A.; Seal, S.; Self, W. T., A phosphate-dependent shift in redox state of cerium oxide nanoparticles and its effects on catalytic properties. Biomaterials 2011, 32 (28), 6745-6753.
10. Masatake, H.; Tetsuhiko, K.; Hiroshi, S.; Nobumasa, Y., Novel Gold Catalysts for the Oxidation of Carbon Monoxide at a Temperature far Below 0 °C. Chem. Lett. 1987, 16 (2), 405-408.
11. Singh, A. V.; Batuwangala, M.; Mundra, R.; Mehta, K.; Patke, S.; Falletta, E.; Patil, R.; Gade, W. N., Biomineralized Anisotropic Gold Microplate–Macrophage Interactions Reveal Frustrated Phagocytosis-like Phenomenon: A Novel Paclitaxel Drug Delivery Vehicle. ACS Appl. Mater. Interfaces 2014, 6 (16), 14679-14689.
12. Daniel, M.-C.; Astruc, D., Gold Nanoparticles:  Assembly, Supramolecular Chemistry, Quantum-Size-Related Properties, and Applications toward Biology, Catalysis, and Nanotechnology. Chem. Rev. 2004, 104 (1), 293-346.
13. Wang, S.; Chen, W.; Liu, A.-L.; Hong, L.; Deng, H.-H.; Lin, X.-H., Comparison of the Peroxidase-Like Activity of Unmodified, Amino-Modified, and Citrate-Capped Gold Nanoparticles. Chem. Phys. Chem. 2012, 13 (5), 1199-1204.
14. Lien, C.-W.; Chen, Y.-C.; Chang, H.-T.; Huang, C.-C., Logical regulation of the enzyme-like activity of gold nanoparticles by using heavy metal ions. Nanoscale 2013, 5 (17), 8227-8234.
15. Shah, J.; Purohit, R.; Singh, R.; Karakoti, A. S.; Singh, S., ATP-enhanced peroxidase-like activity of gold nanoparticles. J. Colloid Interface Sci. 2015, 456, 100-107.
16. Hizir, M. S.; Top, M.; Balcioglu, M.; Rana, M.; Robertson, N. M.; Shen, F.; Sheng, J.; Yigit, M. V., Multiplexed Activity of perAuxidase: DNA-Capped AuNPs Act as Adjustable Peroxidase. Anal. Chem. 2016, 88 (1), 600-605.
17. Liu, B.; Liu, J., Accelerating peroxidase mimicking nanozymes using DNA. Nanoscale 2015, 7 (33), 13831-13835.
18. Deng, H.-H.; Weng, S.-H.; Huang, S.-L.; Zhang, L.-N.; Liu, A.-L.; Lin, X.-H.; Chen, W., Colorimetric detection of sulfide based on target-induced shielding against the peroxidase-like activity of gold nanoparticles. Anal. Chim. Acta 2014, 852, 218-222.
19. Sharma, T. K.; Ramanathan, R.; Weerathunge, P.; Mohammadtaheri, M.; Daima, H. K.; Shukla, R.; Bansal, V., Aptamer-mediated 'turn-off/turn-on' nanozyme activity of gold nanoparticles for kanamycin detection. Chem. Commun. 2014, 50 (100), 15856-15859.
20. Vallabani, N. V. S.; Karakoti, A. S.; Singh, S., ATP-mediated intrinsic peroxidase-like activity of Fe3O4-based nanozyme: One step detection of blood glucose at physiological pH. Colloids Surf., B 2017, 153, 52-60.
21. Liu, Y.-C.; Chang, H.-T.; Chiang, C.-K.; Huang, C.-C., Pulsed-Laser Desorption/Ionization of Clusters from Biofunctional Gold Nanoparticles: Implications for Protein Detections. ACS Appl. Mater. Interfaces 2012, 4 (10), 5241-5248.
22. Tsai, D.-H.; Cho, T. J.; DelRio, F. W.; Gorham, J. M.; Zheng, J.; Tan, J.; Zachariah, M. R.; Hackley, V. A., Controlled Formation and Characterization of Dithiothreitol-Conjugated Gold Nanoparticle Clusters. Langmuir 2014, 30 (12), 3397-3405.
23. Stefan, L.; Denat, F.; Monchaud, D., Insights into how nucleotide supplements enhance the peroxidase-mimicking DNAzyme activity of the G-quadruplex/hemin system. Nucleic Acids Res. 2012, 40 (17), 8759-8772.
24. Liu, Y.; Purich, D. L.; Wu, C.; Wu, Y.; Chen, T.; Cui, C.; Zhang, L.; Cansiz, S.; Hou, W.; Wang, Y.; Yang, S.; Tan, W., Ionic Functionalization of Hydrophobic Colloidal Nanoparticles To Form Ionic Nanoparticles with Enzymelike Properties. J. Am. Chem. Soc. 2015, 137 (47), 14952-14958.
25. (a) Schuksz, M.; Fuster, M. M.; Brown, J. R.; Crawford, B. E.; Ditto, D. P.; Lawrence, R.; Glass, C. A.; Wang, L.; Tor, Y.; Esko, J. D., Surfen, a small molecule antagonist of heparan sulfate. Proc. Natl. Acad. Sci. U. S. A. 2008, 105 (35), 13075-13080; (b) Bromfield, S. M.; Wilde, E.; Smith, D. K., Heparin sensing and binding - taking supramolecular chemistry towards clinical applications. Chem. Soc. Rev. 2013, 42 (23), 9184-9195.
26. Zhang, H.; Young, S. P.; Auray-Blais, C.; Orchard, P. J.; Tolar, J.; Millington, D. S., Analysis of Glycosaminoglycans in Cerebrospinal Fluid from Patients with Mucopolysaccharidoses by Isotope-Dilution Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry. Clin. Chem. 2011, 57 (7), 1005-1012.
27. (a) Xu, C.; Liu, Z.; Wu, L.; Ren, J.; Qu, X., Nucleoside Triphosphates as Promoters to Enhance Nanoceria Enzyme-like Activity and for Single-Nucleotide Polymorphism Typing. Adv. Funct. Mater. 2014, 24 (11), 1624-1630; (b) Yu, C.-J.; Wu, S.-M.; Tseng, W.-L., Magnetite Nanoparticle-Induced Fluorescence Quenching of Adenosine Triphosphate–BODIPY Conjugates: Application to Adenosine Triphosphate and Pyrophosphate Sensing. Anal. Chem. 2013, 85 (18), 8559-8565.
28. Demers, L. M.; Östblom, M.; Zhang, H.; Jang, N.-H.; Liedberg, B.; Mirkin, C. A., Thermal Desorption Behavior and Binding Properties of DNA Bases and Nucleosides on Gold. J. Am. Chem. Soc. 2002, 124 (38), 11248-11249.