臺灣博碩士論文加值系統

基質輔助雷射脫附游離質譜法（matrix-assisted laser desorption ionization mass spectrometry，MALDI MS）因擁有快速、操作容易、高靈敏度、高偵測質量範圍等特性，已被廣泛地使用於生物巨分子的分析，然而在進行MALDI-TOF MS分析時，分析物訊號會受到來自於樣品溶液中過量鹽類或是界面活性劑的抑制效應，如果能將目標分子與複雜基質溶液預先分離，則可以避免此抑制效應。因此，實驗中使用氧化鐵奈米粒子從樣品溶液中捕捉帶電荷的分析物，將氧化鐵奈米粒子的表面以油酸鈉鹽修飾成帶負電之探針，然後經由靜電作用力來吸附樣品溶液中胜肽和蛋白質的樣品。由於胜肽或蛋白質具有不同等電點的特性，可在不同pH值的環境下使其帶有不同的正負電性，可藉著pH值之改變而利用油酸鈉鹽修飾的氧化鐵奈米粒子（iron oxide nanoparticle modified with oleic acid, IONP@oleate）篩選濃縮特定的目標生化分子，然後利用磁鐵將這些IONP@oleate粒子很容易的從樣品溶液中分離出來，而達到快速分離的目的，再將這些奈米粒子經由簡單清洗後，藉由MALDI-TOF MS做為確認分析的方法。在此研究中可以證明帶負電荷表面的IONP@oleate粒子，可以適當地從水溶液中有選擇性的去捕捉帶正電荷的蛋白質。另外，也能成功地使用以IONP@oleate粒子作為探針，去捕捉細胞色素C酵素消化產物的胜肽片段。

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is used widely in various fields because it has the characteristics of speed, ease of use, high sensitivity, and wide detectable mass range. However the MALDI technique suffered from suppression effect for samples containing excessive amounts of salts or surfactants. The suppression effects can be avoided if target species are isolated from complicated matrix solutions in advance. Hence, we describe a strategy that uses iron oxide nanoparticles to capture charged species from a sample solution. Sodium oleate treated IONPs were employed as affinity probes to selectively concentrate trace amount of peptides and proteins from sample solutions through electrostatic interactions. Because peptides and proteins have unique isoelectric points (pI), by varying the values of pH of the sample solution, specific target proteins or peptides can be concentrated selectively on the surface of the sodium oleate treated IONPs. The IONP@oleate particle then could be easily isolated from the sample solution by employing a magnetic field. After isolation, the target species attached on the surfaces of the IONP@oleate particles were characterized by MALDI-TOF MS after a simple washing. We demonstrate that IONP@oleate particles having negatively charged surfaces are suitable probes for selectively trapping positively charged proteins from aqueous solutions. In addition, we have employed IONP@oleate probe to capture the peptide residues from the enzymatic digest products of cytochrome C.

中文摘要 I
英文摘要 II
誌謝 III
目錄 V
圖目錄 VIII
表目錄 X
壹、緒論 1
一、前言 1
二、基質輔助雷射脫附游離飛行時間質譜法（Matrix- Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry, MALDI-TOF MS）的簡介 4
2-1 MALDI的發展 4
2-2 MALDI樣品配製 7
2-3 基質的特性 8
2-4 MALDI離子形成的機制 13
2-5 飛行時間質量分析儀的原理 23
2-6 MALDI-TOF MS的特點 28
2-7 影響分析物在MALDI-TOF MS中訊號強弱的因素 29
2-8 MALDI-TOF MS的應用 31
三、磁性奈米粒子的簡介 39
3-1 磁性奈米粒子的性質 41
3-2 磁性奈米粒子的製備 41
3-3 磁性奈米粒子的應用 43
四、研究動機與目的 46
貳、實驗 48
一、藥品 48
二、實驗設備 51
三、實驗方法 53
3-1 藥品配製 53
3-2 氧化鐵磁性奈米粒子的製備與表面修飾 54
3-3 IONP@oleate粒子為探針之實驗 57
參、結果與討論 62
一、氧化鐵奈米粒子(IONP)鑑定與特性分析 62
二、蛋白質及胜肽最佳吸附條件之研究 66
三、以MALDI-TOF MS進行蛋白質和胜肽的分析 74
四、以IONP@oleate為探針吸附溶液中微量分析物之探討 80
五、蛋白質和胜肽含干擾物之研究 88
六、以IONP@oleate應用於蛋白質消化產物的萃取 97
肆、結論 105
參考文獻 106

1.M. S. B. Munson, and F. H. Field, “Chemical Ionization Mass Spectrometry,” J. Am. Chem. Soc., Vol. 88, pp. 2621-2630 (1966).
2.R. J. Cotter, “Plasma Desorption Mass Spectrometry,” Anal. Chem., Vol. 60, pp. 781A-782A (1998).
3.S. J. Pachuta, and R. G. Cooks, “Mechanisms in Molecular SIMS,” Anal. Rev., Vol. 87, pp. 647-669 (1987).
4.M. Barbar, R. S. Bordoli, G. J. Elliott, “Fast Atom Bombardment Mass Spectrometry,” Anal. Chem., Vol. 54, pp. 645A-646A (1982).
5.M. A. Posthumus, P. G. Kistemker, H. L. C. Meuzelaar, “Laser Desorption Mass Spectrometry of Polar Nonvolatile Bio-Organic Molecules,” Anal. Chem., Vol. 50, pp. 985-991 (1978).
6.J. C. Tabet, R. J. Cotter, “Laser Desorption Time-of-Flight Mass Specrometry of High Mass Molecules,” Anal. Chem., Vol. 56, pp. 1662-1667 (1984).
7.R. E. Hoing, J. R. Woolston, “Laser-Induced Emission of Electrons, Ions, And Neutral atoms from Solid Surfaces,” Appl. Phys. Lett., Vol. 2, pp. 138-139 (1963).
8.F. J. Vastola, A. J. Pirone, “Ionization of Organic Solid by Laser Irradiation,” Adv. Mass Spectrom., Vol. 4, pp. 107-111 (1968).
9.F. J. Vastola, R. O. Mumma, A. J. Pirone, “Analysis of Organic Salts by Laser Ionization,” J. Org. Mass Spectrom., Vol. 3, pp. 101-104 (1970).
10.M. Karas, D. Bachmann, F. Hillenkamp, “Influence of the Wavelength in High-Irradiance Ultraviolet Laser Desorption Mass Spectrometry of Organic Molecules,” Anal. Chem., Vol. 57, pp. 2935-2939 (1985).
11.M. Karas, D. Bachmann, U. Bahr, F. Hillenkamp, “Matrix Assisted Ultraviolet Laser Desorption of Non-Volatile Compounds,” Int. J. Mass Spectrom. Ion Processes, Vol. 78, pp. 53-68 (1987).
12.K. Tanaka, Y. Ido, S. Akita, Y. Yoshida and T. Yoshida, “Detection of High Mass Molecules by Laser Desorption Time-of-Flight Mass Spectrometry,” Second Japan-China Joint Symposium on Mass Spectrometry, pp. 185-188 (1987).
13.K. Tanaka, H. Waki, Y. Ido, S. Akita, Y. Yoshida, T. Yoshida, “Protein and Polymer Analyses up to m/z 100000 by Laser Ionization Time-of-Flight Mass Spectrometry,” Rapid Commum. Mass Spectrom., Vol. 2, pp. 151-153 (1988).
14.M. Karas, F. Hillenkamp, “Laser Desorption Ionization of Proteins with Molecular Masses Exceeding 10000 Daltons,” Anal. Chem., Vol. 60, pp. 2299-2301 (1988).
15.B. Linder, U. Seydel, “Laser desorption Mass Spectrometry of Nonvolatiles under Shock Wave Conditions,” Anal. Chem., Vol. 57, pp. 895-899 (1985).
16.A. Overberg, A. Hassenburger, F. Hillenkamp, Mass Spectrometry in the Biological Sciences: A Tutorial, M. L. Gross Ed., Kluwer Academic Publisher press, Netherlands., pp. 181-197 (1992).
17.K. K. Murray, K. L. Caldwell, “Mid-Infrared Matrix Assisted Laser Desorption Ionization with a Water/Glycerol Matrix,” Applied Surface Science, Vol. 127-129, pp. 242-247 (1998).
18.L. F. Marvin, M. A. Roberts, L. B. Fay, “Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry in Clinical Chemistry,” Clinica Chimica Acta., Vol. 337, pp. 11-21 (2003).
19.M. Kussmann, E. Nordhoff, H. Rahbek-Nielsen, S. Haebel, M. Rossel-Larsen, L. Jakobsen, J. Gobom, E. Mirgorodskaya, A. Kroll-Kristensen, L. Palm, P. Roepstorff, “Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Sample Preparation Techniques Designed for Various Peptide and protein Analytes,” J. Mass Spectrom., Vol. 32, pp. 593-601 (1997).
20.R. Zenobi, R. Knochenmuss, “Ion Formation in MALDI Mass Spectrometry,” Mass Spectrom. Rev., Vol. 17, pp. 337-366 (1998).
21.R. J. Levis, “Laser-Desorption and Ejection of Biomolecules from the Condensed-Phase into the Gas-Phase,” Annu. Rev. Phys. Chem., Vol. 45, pp.483-518 (1994)
22.A. Overberg, M. Karas, U. Bahr, R. Kaufmann, F. Hillenkamp, “Matrix-Assisted Infrared-Laser (2.94 mm) Desorption/Ionization Mass Spectrometry of Large Biomolecules,” Rapid Commun. Mass Spectrom., Vol. 4, pp. 293-296 (1990).
23.U. Bahr, M. Karas, F. Hillenkamp, “Analysis of Biopolymers by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry,” Fresenius J. Anal. Chem., Vol. 348, pp. 783-791 (1994).
24.M. C. Fitzgerald, G. R. Parr, L. M. Smith, “Basic Matrixes for the Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry of Proteins and Oligonucleotides,” Anal. Chem., Vol. 65, pp. 3204-3211 (1993).
25.M. Karas, U. Bahr, “Matrix Assisted Laser Desorption Ionization Mass Spectrometry,” Mass Spectrom. Rev., Vol. 10, pp. 335-357 (1991).
26.H. Ehring, M. Karas, F. Hillenkamp, “Role of Photoionization and Photochemistry in Ionization Processes of Organic Molecules and Relevance for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry,” Org. Mass Spectrom., Vol. 27, pp. 472-480 (1992).
27.H. Ehring, B. U. R. Sundqvist, “Studies of the MALDI process by Luminescence Spectroscopy,” J. Mass Spectrom., Vol. 30, pp. 1303-1310 (1995).
28.H. Ehring, B. U. R. Sundqvist, “Excited State Relaxation Processes of MALDI-Matrices Studied by Luminescence Spectroscopy,” Appl. Surf. Sci., Vol. 96-98, pp. 577-580 (1996).
29.R. Cramer, R. F. Haglund Jr, F. Hillenkamp, “Matrix-Assisted laser desorption and ionization in the O-H and C=O absorption bands of aliphatic and aromatic matrices: dependence on laser wavelength and temporal beam profile,” Int. J. Mass Spectrom. Ion Processes, Vol. 169-170, pp. 51-67 (1997).
30.R. Knochenmuss, F. Dubois, M. J. Dale, R. Zenobi, “The Matrix Suppression Effect and Ionization Mechanisms in Matrix-Assisted Laser Desorption/Ionization,” Rapid Commun. Mass Spectrom., Vol. 10, pp. 871-877 (1996).
31.J. Sunner, M. G. Ikpnomou, P. Kebarle, “Kinetic Modeling of Fast Atom Bombardment Spectra of Glycerol-Diethanolamine Mixtures,” Anal. Chem., Vol. 60, pp. 98-104 (1988).
32.J. Sunner, “Ionization in Liquid Secondary Ion Mass Spectrometry (LSIMS),” Org. Mass Spectrom., Vol. 28, pp. 805-823 (1993).
33.P.-C. Liao, J. Allison, “Ionization Processes in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry: Matrix-Dependent Formation of [M+H]+ vs [M+Na]+ Ions of Small Peptides and Some Mechanistic Comments,” J. Mass Spectrom., Vol. 30, pp. 408-423 (1995).
34.J. Krause, M. Stoeckli, U. P. Schluneggar, “Studies on the Selection of New Matrices for Ultraviolet Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry,” Rapid Commun. Mass Spectrom., Vol. 10, pp. 1927-1933 (1996).
35.M. Karas, H. Ehring, E. Nordhoff, B. Stahl, K. Strupat, F. Hillenkamp, M. Grehl, B. Krebs, “Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry with additives to 2,5-Dihydroxybenzoic Acid,” Org. Mass Spectrom., Vol. 28, pp. 1476-1481 (1993).
36.V. Karbach and R. Knochenmuss, “Do Single Matrix Molecules Generate Primary Ions in Ultraviolet Matrix-Assisted Laser Desorption/Ionization,” Rapid Commun. Mass Spectrom., Vol. 12, pp. 968-974 (1998).
37.M. Karas, U. Bahr, J. R. Stah-Zeng, In: Large Ions: Their Vaporization, Detection and Structural Analysis, T. Bear, C.Y. Ng, I. Powis Eds., Wiely: London, pp. 27 (1996).
38.Y. F. Zhu, K. L. Lee, K. Tang, S. L. Allman, N. I. Taranencko, C. H. Chen, “Revisit of MALDI for Small Proteins,” Rapid Commun. Mass Spectrom., Vol. 9, pp. 1315-1320 (1995).
39.J. Sunner, E. Dratz, Y.-C. Chen, “Graphite Surface-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry of Peptides and Proteins from Liquid Solutions,” Anal. Chem., Vol. 67, pp. 4335-4442 (1995).
40.A. G. Harrison, “The Gas-Phase Basicities and Proton Affinities of Amino Acids and Peptides,” Mass Spectrom. Rev., Vol. 16, pp. 201-217 (1997).
41.C. F. Llenes, R. M. O’Malley, R. J. Cotter, “Cation Attachment in the Analysis of Polystyrene and Polyethylene Glycol by Laser-Desorption Time-of-Flight Mass Spectrometry,” Rapid Commun. Mass Spectrom., Vol. 6, pp. 564-570 (1992).
42.A. M. Belu, J. M. DeSimone, R. W. Linton, G. W. Lange, R. M. Friedman, “Evaluation of Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry for Polymer Characterization,” J. Am. Soc. Mass Spectrom., Vol. 7, pp. 11-24 (1996).
43.M. J. Deery, K. R. Jennings, C. B. Jasieczek, D. M. Haddleton, A. T. Jackson, H. T. Yates and J. H. Scrivens, “A Study of Cation Attachment to Polystyrene by Means of Matrix-Assisted Laser Desorption/Ionization and Electrospray Ionization-Mass Spectrometry,” Rapid Commun. Mass Spectrom., Vol. 11, pp. 57-62 (1997).
44.I. A. Mowat, R. J. Donovan, and R. R. J. Maier, “Enhanced Cationization of Polymers Using Delayed Ion Extraction with Matrix-Assisted Laser Desorption/Ionization,” Rapid Commun. Mass Spectrom., Vol. 11, pp. 89-98 (1997).
45.A. K. Chaudhary, G. Critchley, A. Diaf, E. J. Beckman, and A. J. Russell, “Characterization of Synthetic Polymers Using Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry,” Macromol., Vol. 29, pp. 2213-2221 (1996).
46.吳慧芬、呂麗琪，「2002年的諾貝爾化學獎–質譜儀分析技術的突破開展生化科技新領域」，科學發展，第362卷，第48-51頁（2003）。
47.C. K. G. Piyadasa, P. Håkansson, and T. R. Ariyaratne, “A High Resolving Power Multiple Reflection Matrix-Assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometer,” Rapid Commun. Mass Spectrom., Vol. 13, pp. 620-624 (1999).
48.R. J. Cotter, In: Time-of-Flight Mass Spectrometry, American Chemical Society, Washington, DC. pp. 19-45 (1997).
49.W. C. Wiley, and I. H. McLaren, “Time-of-Flight Mass Spectrometer with Improved Resolution,” Rev. Sci. Instr., Vol. 26, pp. 1150-1157 (1955).
50.B. A. Mamyrin, V. I. Karataev, D. V. Shmikk, V. A. Zagulin, “The Mass Reflectron: A New Non-Magnetic Time-of-Flight Mass Spectrometer with High Resolution,” Sov. Phys. JETP, Vol. 37, pp. 45-48 (1973).
51.R. P. Schmid, C. Weickhardt, “Designing Reflectron Time-of-Flight Mass Spectrometers With and Without Grids: A Direct Comparison,” Int. J. Mass Spectrom., Vol. 206, pp. 181-190 (2001).
52.B. Spengler, D. Kirsch, R. Kaufmann, “Peptide Sequencing by Matrix-Assisted Laser-Desorption Mass Spectrometry,” Rapid Commun. Mass Spectrom., Vol. 6, pp. 105-108 (1992).
53.R. J. Cotter, In: Time-of-Flight Mass Spectrometry, American Chemical Society, Washington, DC. pp. 169-201 (1997).
54.D. C. Schriemer, L. Li, “Detection of High Molecular Weight Narrow Polydisperse Polymers up to 1.5 Million Daltons by MALDI Mass Spectrometry,” Anal. Chem., Vol. 68, pp. 2721-2725 (1996).
55.K. C. Hung, H. Ding, and B. Guo, “Use of Poly(tetrafluoroethylene)s as a Sample Support for the MALDI-TOF Analysis of DNA and Proteins,” Anal. Chem., Vol. 71, pp. 518-521 (1999).
56.Y. Xu, J. T. Wastson, and M. L. Bruening, “Patterned Monlayer/Polymer Films for Analysis of Dilute or Salt-Contaminated Protein Samples by MALDI-MS,” Anal. Chem., Vol. 75, pp. 185-190 (2003).
57.J. M. Asara and J. Allison, “Enhanced Detection of Oligonucleotides in UV MALDI MS Using the Tetraamine Spermine as a Matrix Additive,” Anal. Chem., Vol. 71, pp. 2866-2870 (1999).
58.H. Therisod, V. Labas, and M. Caroff, “Direct Microextraction and Analysis of Rough-Type Lipopolysaccharides by Combined Thin-Layer Chromatography and MALDI Mass Spectrometry,” Anal. Chem., Vol. 73, pp. 3804-3807 (2001).
59.V. Horneffer, K. Dreisewerd, H.-C. Lüdemann, F. Hillenkamp, M. Läge, K. Strupat, “Is the Incorporation of Analytes into Matrix Crystals a Prerequisite for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry? A study of Five Positional Isomers of Dihydroxybenzoic Acid,” Int. J. Mass Spectrom., Vol. 185/186/187, pp. 859-870 (1999).
60.K. K. Mock, C. W. Sutton, J. S. Cottrell, “Sample Immobilization Protocols for Matrix-Assisted Laser Desorption Mass Spectrometry,” Rapid Commun. Mass Spectrom., Vol. 6, pp. 233-238 (1992).
61.J. C. Ford, J. A. Smith, “Synthetic Peptide Purification by Application of Linear Solvent Strength Gradient Theory,” J. Chromatogr., Vol. 483, pp. 131-143 (1989).
62.J. Wei, J. M. Buriak, G. Siuzdak, “Desorption-Ionization Mass Spectrometry on Porous Silicon,” Nature, Vol. 399, pp. 243-246 (1999).
63.S. A. Hefta, D. C. Stahl, A. M. Mahrenholz, P. A. Martino,S. M. Rutherford, T. D. Le, “Analysis of Highly Glycosylated or Hydrophobic Menbrane Protein by Laser Desorption Time-of-Flight Mass Spectrometry,” Proceedings of the 39th Conference on Mass Spectrometry and Applied Topics, pp. 1416 (1991).
64.T. W. Hutchens, T. T. Yip, “New Desorption Strategies for the Mass Spectrometric Analysis of Macromolecules,” Rapid Commun. Mass Spectrom., Vol. 7, pp. 576-580 (1993).
65.T. A. Worrall, R. J. Cotter, and A. S. Woods, “Purification of Contaminated Peptides and Proteins on Synthetic Membrane Surfaces for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry,” Anal. Chem., Vol. 70, pp. 750-756 (1998).
66.I. P. Smirnov, L. R. Hall, P. L. Ross, and L. A. Haff, “Application of DNA-Binding Polymers for Preparation of DNA for Analysis by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry,” Rapid Commun. Mass Spectrom., Vol. 15, pp. 1427-1432 (2001).
67.Y. Xu, M. L. Bruening, and J. T. Watson, “Non-Specific, On-Probe Cleanup Methods for MALDI-MS Samples,” Mass Spectrom. Rev., Vol. 22, pp. 429-440 (2003).
68.M. Schuerenberg, C. Luebbert, H. Eickhoff, M. Kalkum, H. Lehrach, and E. Nordhoff, “Prestructured MALDI-MS Sample Supports,” Anal. Chem., Vol. 72, pp. 3436-3442 (2000).
69.M. E. Warren, A. H. Brockman, and R. Orlando, “On-Probe Solid-Phase Extraction/MALDI-MS Using Ion-Pairing Interactions for the Cleanup of Peptides and Proteins,” Anal. Chem., Vol. 70, pp. 3757-3761 (1998).
70.L. Zhang and R. Orlando, “Solid-Phase Extraction/MALDI-MS: Extended Ion-Pairing Surfaces for the On-Target Cleanup of Protein Samples,” Anal. Chem., Vol. 71, pp. 4753-4757 (1999).
71.T. Rabilloud, Proteome Research: Two Dimensional Gel Electrophoresis and Identification Methods, Spriner, Germany (2000).
72.U. Pieles, W. Zurcher, M. Schar, H. E. Ser, “Matrix-Assisted Laser-Desorption Ionization Time-of-Flight Mass-Spectrometry–A Powerful Tool for the Mass and Sequence-Analysis of Natural and Modified Oligonucleotides,” Nucl. Acids Res., Vol. 21, pp. 3191-3196 (1993).
73.C. Fenselau and P. A. Demirev, ‘Characterization of Intact Microorganisms by MALDI Mass Spectrometry,” Mass Spectrom. Rev., Vol. 20, pp. 157-171 (2001).
74.P. A. Demirev, Y.-P. Ho, V. Ryzhov, and C. Fenselau, “Microorganism Identification by Mass Spectrometry and Protein Database Searches,” Anal. Chem., Vol. 71, pp. 2732-2738 (1999).
75.F. J. Pineda, J. S. Lin, C. Fenselau, and P. A. Demirev, “Testing the Significance of Microorganism Identification by Mass Spectrometry and Proteome Database Search,” Anal. Chem., Vol. 72, pp. 3739-3744 (2000).
76.P. A. Demirev, J. S. Lin, F. J. Pineda, and C. Fenselau, “Bioinformatics and Mass Spectrometry for Microorganism Identification: Proteome-Wide Post-Translational Modifications and Database Search Algorithms for Characterization of Intact H. pylori,” Anal. Chem., Vol. 73, pp. 4566-4573 (2001).
77.H. Ji, N. Sato, Y. Nakamura, Y. Wan, A. Howell, Q. A. Thomas, R. F. Storey, W. K. Nonidez, and J. W. Mays, “Characterization of Polyisobutylene by Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry,” Macromol., Vol. 35, pp. 1196-1199 (2002).
78.H. Nonami, F. Wu, R. P. Thummel, Y. Fukuyama, H. Yamaoka, R. Erra-Balsells, ‘Evaluation of Pyridoindoles, Pyridylindoles, and Pyridylpyridoindoles as Matrices for Ultraviolet Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry,” Rapid Commun. Mass Spectrom., Vol. 15, pp. 2354-2373.
79.牟中原、陳家俊，「奈米材料研究發展」，科學發展，第28卷，第281-288頁（2000）。
80.E. Gaffer, M. Tachikart, O. E. Kedim, and R. Rahouadj, “Nanostructural Materials Formation by Mechanical Alloyine: Morphologic Analysis Based on Transmission and Scanning Electron Microscopic Observations,” Mater. Charact., Vol. 36, pp. 185-190 (1996).
81.B. I. Haukanes, C. Kvam, “Application of Magnetic Beads in Bioassays,” Bio/Technology, Vol. 11, pp. 60-63 (1993).
82.J.-L. Guesdon and S. Avrameas, “Magnetic Solid Phase Enzyme-Immunoassay,” Immunochemistry, Vol. 14, pp. 443-447 (1977).
83.P. Tartaj, M. P. Morales, S. V. Verdaguer, T. G. Carreño, C. J. Serna, “The Preparation of Magnetic Nanoparticles for Applications in Biomedicine,” J. Phys. D: Appl. Phys., Vol. 36, pp. R182-R197 (2003).
84.D. K. Kim, M. Mikhaylova, Y. Zhang, M. Muhammed, “Protective Coating of Superparamagnetic Iron Oxide Nanoparticles,” Chem. Mater., Vol. 15, pp. 1617-1627 (2003).
85.Y. S. Kang, S. Risbud, J. F. Rabolt, P. Stroeve, “Synthesis and Characterization of Nanometer-Size Fe3O4 and g-Fe2O3 Particles,” Chem. Mater., Vol. 8, pp. 2209-2211 (1996).
86.K. M. Partington, E. J. Jenkinson, G. Anderson, “A Novel Method of Cell Separation Based on Dual Parameter immunomagnetic Cell Selection,” J. Immunol. Methods, Vol. 223, pp. 195-205 (1999).
87.Q. A. Pankhurst, J. Connolly, S. K. Jones, J. Dobson, “Applications of Magnetic Nanoparticles in Biomedicine,” J. Phys. D: Appl. Phys., Vol. 36, pp. R167-R184 (2003).
88.Y. S. Kang, D. K. Lee, C. S. Lee, P. Stroeve, “In Situ Observation of domain Structure in Monolayers of Arachidic Acid/g-Fe2O3 Nanoparticle Complexes at the Air/Water Interface,” J. Phys. Chem. B, Vol. 106, pp. 9341-9346 (2002).
89.D. K. Kim, Y. Zhang, W. Voit, K. V. Rao, M. Muhammed, “Synthesis and Characterization of Surfactant-Coated Superparamagnetic Monodispersed Iron Oxide Nanoparticles,” J. Magn. Magn. Mater., Vol. 225, pp. 30-36 (2001).
90.J.-Y. Yoon, H.-Y. Park, J.-H. Kim, W.-S. Kim, “Adsorption of BSA on Highly Carboxylated Microspheres-Quantitative Effects of Surface Functional Groups and Interaction Forces,” J. colloid interface sci., Vol. 177, pp. 613-620 (1996).
91.F. Hillenamp and M. Karas, “Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry of Biopolymers,” Anal. Chem., Vol. 63, pp. 1193A-1202A (1991).
92.C.-T. Chen and Y.-C. Chen, “Molecularly Imprinted TiO2-Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry for Selectively Detecting a-Cyclodextrin,” Anal. Chem., Vol. 76, pp. 1453-1457 (2004).
93.C.-T. Chen and Y.-C. Chen, “Fe3O4/TiO2 Core/Shell Nanoparticles as affinity Probes for the Analysis of Phosphopeptides using TiO2 Surface-Assisted Laser Desorption/Ionization Mass Spectrometry,” Anal. Chem., Vol. 77, pp. 5912-5919 (2005).
94.C. A. Mirkin, “Programming the Assembly of Two- and Three-Dimensional Architectures with DNA and Nanoscale Inorganic Building Blocks,” Inorg. Chem., Vol. 39, pp. 2258-2272 (2000).
95.C.-H. Teng, K.-C. Ho, Y.-S. Lin, Y.-C. Chen, “Gold Nanoparticles as Selective and Concentrating Probes for Samples in MALDI MS Analysis,” Anal. Chem., Vol. 76, pp. 4337-4342 (2004).
96.Y.-F. Huang and H.-T. Chang, “Nile Red-Adsorbed Gold Nanoparticle Matrixes for Determining Aminothiols through Surface-Assisted Laser Desorption/Ionization Mass Spectrometry,” Anal. Chem., Vol. 78, pp. 1485-1493 (2006).
97.J. S. Kirk and P. W. Bohn, “Surface Adsorption and Transfer of Organomercaptans to Colloidal Gold and Direct Identification by Matrix Assisted Laser Desorption/Ionization Mass Spectrometry,” J. Am. Chem. Soc., Vol. 126, pp. 5920-5926 (2004).
98.J. A. McLean, K. A. Stumpo, D. H. Russell, “Size-Selected (2-10 nm) Gold Nanoparticles for Matrix Assisted Laser Desorption Ionization of Peptides,” J. Am. Chem. Soc., Vol. 127, pp. 5304-5305 (2005).
99.Y.-S. Lin, P.-J. Tsai, M.-F. Weng, Y.-C. Chen, “Affinity Capture Using Vancomycin-Bound Magnetic Nanoparticles for the MALDI-MS Analysis of Bacteria,” Anal. Chem., Vol. 77, pp. 1753-1760 (2005).
100.P.-H. Chou, S.-H. Chen, H.-K. Liao, P.-C. Lin, G.-R. Her, A. C.-Y. Lai, J.-H. Chen, C.-C. Lin, Y.-J. Chen, “Nanoprobe-Based Affinity Mass Spectrometry for Selected Protein Profiling in Human Plasma,” Anal. Chem., Vol. 77, pp. 5990-5997 (2005).
101.M. B. Pepys and G. M. Hirschfield, “C-Reactive Protein: A Critical Update,” J. Clin. Invest., Vol. 111, pp. 1805-1812 (2003).
102.M. V. Ugarov, T. Egan, D. V. Khabashesku, J. A. Schultz, H. Peng, V. N. Khabashesku, H. Furutani, K. S. Prather, H-W. J. Wang, S. N. Jackson, A. S. Woods, “MALDI Matrices for Biomolecular Analysis Based on Functionalized Carbon Nanomaterials,” Anal. Chem., Vol. 76, pp. 6734-6742 (2004).
103.S. Xu. Y. Li, H. Zou, J. Qiu, Z. Guo, B. Guo, “Carbon nanotubes as Assisted Matrix for Laser Desorption/Ionization Time-of-Flight Mass Spectrometry,” Anal. Chem., Vol. 75, pp. 6191-6195 (2003).
104.X. L. Kong, L. C. Huang, C.-M. Hsu, W.-H. Chen, C.-C. Han, H.-C. Chang, “High-Affinity Capture of Proteins by Diamond Nanoparticles for Mass Spectrometric Analsis,” Anal. Chem., Vol. 77, pp. 259-265 (2005).
105.X. Kong, L. C. L. Huang, S.-C. V. Lian, C.-C. Han, H. C. Chang, “Polylysine-Coated Diamond Nanocrystals for MALDI-TOF Mass Analysis of DNA Oligonucleotides,” Anal. Chem., Vol. 77, pp. 4273-4277 (2005).
106.K. Turney, T. J. Drake, J. E. Smith, W. Tan, W. W. Harrison, “Functionalized Nanoparticles for Liquid Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization Peptide Analysis,” Rapid Commun. Mass Spectrom., Vol. 18, pp. 2367-2374 (2004).