本論文研究方向有二:第一部份發展以CdS量子點作為基質應用在質譜分析上，硫化鎘奈米晶體 (CdS nanocrystal) 在室溫下其塊材能隙為2.42 eV，其臨界波長的光 (約為496 nm)，因此照射小於此波長的光，可讓價帶上的電子遷躍到傳導帶。因此使用337 nm的雷射光去激發游離它，加上奈米晶體本身的熱膨脹係數 (thermal expansion coefficient) 比一般晶體幾乎大一倍，主要原因來自於晶界組成的貢獻，所以吸熱性質也比較好。因此本論文主要是用硫化鎘奈米晶體 (CdS nanocrystal) 與生化分子之間的鍵結作用結合質譜，探討是否有助於分析物的游離以及改善訊號。此外也針對蛋白質酵素消化反應藉由切完的胜肽片段和奈米晶體之間電荷作用關係，提升其訊號效率。在低能量激發下可以得到一個平均分子量(MH+)的訊號，但往更大的分子量產生的機率更低 (20–30％)。由於使用雷射能量很高時，通常會造成分析物的碎片，所以需要加入傳統基質，藉由吸收雷射光可以提供足夠的游離能傳遞給分析物而游離出來，此方法為就是所謂軟性游離法(soft ionization)所示，但往往只能得到一個大概值，無法明確地去確認。而在本實驗系統中也做了高能量的雷射光去激發它，意外地發現到可以得到單一分子量的訊號，但此機率並不高約5–10％成功機率。但比較之前文獻研究所報導的質量上限更往上延伸且得到的解析度更佳。
第二部分則以二氧化鈦奈米晶體的衍生物作為輔助基質，由於此無機材料在波長紫外光337 nm波長有良好的吸收度，而結構上可分為 Anatase 晶型 與 Rutile 晶型，此兩種晶型在紫外光照射後，電子將由價帶躍遷到傳導帶，產生電子電洞對，電子在從傳導帶回到價帶時其電子電洞對進行結合。Anatase 晶型的能隙為 3.2 eV， Rutile晶型的能隙為 3.0 eV，能隙小的晶型容易進行電子電洞對結合，其光催化效果較差。所以本實驗將以TiO2氧化物放置在 500℃來進行煅燒，以利於Anatase晶型之形成作為前驅物。在開發表面不同的修飾官能基的無機材料 (TiO2@Dopamine及TiO2-CdS)改善其游離效果以拓展SALDI (Surface assisted laser desorption ionization)可以測得到的大分子質量上限。此外在磷酸根蛋白質對此類似金屬氧化物有良好的親和力所以也嘗試做為親和探針，由於磷酸化胜肽本身含量不多，在質譜分析中往往會受到非磷酸根的離子峰干擾，所以利用此親和力關係去對複雜樣品中微量的磷酸化胜肽進行選擇性分析。

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中文摘要 ….……………………………………………………………… I
謝誌 ….……………………………………………………………............III
目錄 ………………………………………………………………………. V
圖表目錄 ….……………………………………………………………....XI

第一章 緒論 ………………………………………………………….. 1
1-1 前言 ……………………………………………………………. 1
1-2 基質輔助雷射脫附游離法之簡介 …………………………… 1
1-3離子形成的MALDI脫附游離機制 ……………………......... 3
1-3-1 一次離子的形成機制 .………………………………… 4
1-3-2 二次離子的形成機制 .………………………………… 6
1-4 MALDI基質的功能及特性 .…………………………………... 9
1-5 MALDI質譜法 .………………………………………………... 10
1-6 MALDI-MS發展歷史 ………………………………………..... 10
1-7 無機材料為MALDI基質的發展 …………………………….. 11
1-7-1 碳材做為基質輔助雷射脫附游離質譜法 ..…………..... 11
1-7-2 鑽石奈米粒子 ..………………………………………..... 12
1-7-3 金奈米粒子 ..…………………………………………..... 13
1-7-4 矽及其衍生物 ..………………………………………..... 14
1-8 無機奈米晶體 ………………………………………………..... 16
1-9 量子侷限效應 ………………………………………………..... 17
1-10胰蛋白酶酵素消化反應介紹 ………………………………… 18
1-10-1 蛋白質磷酸化作用 …………………………………..... 19
1-10-2 分析磷酸化蛋白質的方法 …………………………..... 21
1-10-3 質譜分析的確認 ……………………………………..... 22
1-11 發展親和質譜法 ……………………………………………... 23
1-12 論文目標 ……………………………………………………... 25
第二章 CdS 量子點輔助雷射脫附游離法………………………..... 27
2-1 背景介紹 ……………………………………………………..... 27
2-1-1 半導體奈米粒子於生醫的應用 ………………………... 27
2-1-2 量子點和生物分子的五種常見的結合方式 …………... 30
2-2 實驗部分 ……………………………………………………..... 31
2-2-1 藥品及材料 ……………………………………………... 31
2-2-2 實驗儀器 ………………………………………………... 33
2-2-3 實驗步驟與流程 ………………………………………... 35
2-2-3-1-1 硫化鎘量子點(CdS Quantum Dots)之合成 ……….. 35
2-2-3-1-2 CdS Quantum Dots探針抓取蛋白質之流程圖 ……. 37
2-2-3-1-3 紫外-可見光吸收光譜儀 …………………………... 37
2-2-3-1-4 螢光光譜儀 ………………………………………… 37
2-2-3-1-5 傅立葉轉換紅外線光譜儀 ……………………….... 38
2-2-3-1-6 場發射型掃描式電子顯微鏡＆能量分散光譜儀 .... 38
2-2-3-1-7 解析型穿透式電子顯微鏡 ……………………….... 39
2-2-3-1-8 偵測CdS量子點吸附Ribonuclease A之效果 …… 39
2-2-3-2 標準蛋白質樣品進行酵素消化反應 ………………... 40
2-2-3-2-1 CdS量子點萃取吸附蛋白質，進行酵素消化反應... 41
2-2-3-3基質溶液的配製 …………………………………….... 41
2-3 結果與討論 …………………………………………………… 42
2-3-1 硫化鎘量子點奈米材料性質之鑑定 ………………….. 42
2-3-1-1 TEM與EDS觀察量子點之型態與元素組成分析....... 42
2-3-1-2 SEM與EDS觀察量子點之型態與元素分析 ………. 46
2-3-1-3 紫外-可見光吸收光譜分析 ………………………….. 48
2-3-1-4 FT-IR光譜分析 ……………………………………….. 49
2-3-1-5 估算整個溶液中量子點所修飾的3-MPA分子總數 .. 51
2-3-1-6紫外-可見光吸收光譜來測試CdS@MPA探針對Ribonuclease A蛋白質的吸附效果 ..……………………….. 51
2-3-2 蛋白質酵素消化的萃取 …………………………........ 52
2-3-2-1 Cytochrome c之胰蛋白酶消化產物為分析樣品….......53
2-3-2-2 Myoglobin之胰蛋白酶消化產物為分析樣品 ………. 55
2-3-2-3 Lysozyme之胰蛋白酶消化產物為分析樣品 ……….. 58
2-3-3 硫化鎘奈米晶體輔助雷射脫附游離質譜法 ………….. 61
2-3-3-1 生化小分子-胜肽之分析 …………………………….. 61
2-3-3-2 生化大分子-蛋白質之分析 ………………………….. 71
2-3-3-3 產生離子機制的推導 ………………………………... 82
2-4 結論 …………………………………………………………… 84
第三章 TiO2奈米晶體衍生物輔助雷射脫附游離法………………. 85
3-1 前言 …………………………………………………………… 85
3-1-1 二氧化鈦之簡介 ……………………………………….. 86
3-1-2 溶膠-凝膠法 ……………………………………………. 87
3-2 二氧化鈦奈米晶體修飾不同官能基的延伸探討 ……………. 88
3-2-1 二氧化鈦奈米晶體修飾多巴胺形成錯合物 ………….. 88
3-2-2 二氧化鈦奈米晶體結合硫化鎘奈米晶體的複合材料........... 89
3-3 實驗部分……………………………………………………….. 90
3-3-1 藥品及材料 …………………………………………...... 90
3-3-2 實驗儀器 ……………………………………………….. 91
3-3-3 實驗步驟與流程 ……………………………………….. 92
3-3-3-1 修飾不同官能基金屬氧化物奈米粒子之合成步驟 ... 93
3-3-3-1-1 二氧化鈦(TiO2)奈米晶體-Anatase晶型的合成 ….. 93
3-3-3-1-2 TiO2-CdS複合材料奈米粒子之合成 ……………… 94
3-3-3-1-3 TiO2@Dopamine奈米粒子之合成 ……………….... 94
3-3-3-2 酵素消化反應 ………………………………………... 94
3-3-3-2-1 酪蛋白樣品的前處理 …………………………….... 94
3-3-3-2-2 牛奶和雞蛋為樣品的前處理 …………………….... 96
3-3-3-3 奈米粒子萃取樣品＆磷酸胜肽之萃取流程..………... 96
3-3-3-4 紫外-可見光吸收光譜儀之測量 …………………….. 98
3-3-3-5 傅立葉轉換紅外線光譜儀 …………………………... 98
3-3-3-6 X光粉末繞射儀 (XRD) ……………………………. 99
3-4 結果與討論 …………………………………………………… 99
3-4-1 UV/Vis 吸收光譜之分析結果 …………………………. 99
3-4-2 掃描式電子顯微鏡及穿透式電子顯微鏡 …………….. 100
3-4-2-1 TiO2-CdS奈米粒子的分析 ………………………… 100
3-4-2-2 TiO2@Dopamine奈米粒子的分析 …………………... 102
3-4-2-3 TiO2奈米粒子的分析 ……………………………….... 104
3-4-3 XRD光譜分析 ………………………………………….. 106
3-4-4 FT-IR光譜分析 …………………………………………. 107
3-4-5 磷酸化蛋白質的酵素消化分析 ………………………... 109
3-4-5-1 α-酪蛋白經胰蛋白酶酵素消化產物為分析樣品.…….. 109
3-4-5-2 β-酪蛋白經胰蛋白酶酵素消化產物為分析樣品 ……. 114
3-4-5-3 牛奶經胰蛋白酶酵素消化產物為分析樣品 ………... 119
3-4-5-4 雞蛋蛋白液經胰蛋白酶酵素消化產物為分析樣品 ... 124
3-4-6 胜肽的分析 ……………………………………………... 128
3-4-7 蛋白質的分析 …………………………………………... 134
3-4-8 多巴胺之濃縮萃取分析 ………………………………... 139
3-5 結論 ……………………………………………………………. 141
第四章 總結 ……………………………………………………….... 142
參考文獻 …………………………………………………………… 143
附錄 ………………………………………………………………… 160

1. Sunner, J. ; Dratz, E. ; Chen. Y.C., Graphite Surface-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry of Peptides and Proteins from Liquid Solution. Anal. Chem. 1995, 67, 4335.
2. Nordhoff, E. ; Ingendoh A. ; Cramer, R.; Overberg, A. ; Stahl, B.; Karas, M. ; Hillenkamp, F. ; Crain, P.,F., ; Chait, B. Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry of Nucleic Acids with Wavelengths in the Ultraviolet and Infrared. Rapid Commun. Mass Spectrom. 1992, 6, 771.
3. www.magnet.fsu.edu/.../ionization_maldi.html
4. Karas, M.; Bahr, U. Matrix Assisted Laser Desorption Ionization Mass Spectrometry. Mass Spectrom Rev. 1991, 10, 335.
5. Ehring, H.; Karas, M.; Hillenkamp, F. Role of Photoionization and Photochemistry in Ionization Processes of Organic Molecules and Relevance for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. Org. Mass Spectrom. 1992, 27, 427.
6. Ehring, H.; Sundqvist, B.U.R. Studies of the MALDI process by Luminescence Spectroscopy. J. Mass Spectrom. 1995, 30, 1303.
7. Ehring, H.; Sundquivst, B.U.R. Excited state relaxation processes of MALDI-matrices studied by luminescence spectroscopy. Appl. Surf. Sci. 1996, 96-8, 577.
8. Cramer, R. Haglund, R.F.; Hillenkamp, F. 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. 1997, 169, 51.
9. Knochenmuss, R.; Dubois, F.; Dale, M.J.; Zenobi, R. The Matrix suppression effect and ionization mechanisms in matrix-assisted laser desorption/ionization. Rapid Commun. Mass Spectrom. 1996, 10, 871.
10. Zenobi, R.; Knochenmuss, R. Ion Formation in MALDI Mass Spectrometry. Mass Spectrom. Rev. 1998, 17, 337.
11. 陳月枝，現代生化質譜術-基質輔助雷射脫附游離質譜法. 化學 民國九十一年, 第六十卷, (第二期), 頁 229.
12. Karas, M.; Ehring, H.; Nordhoff, E.; Stahl, B.; Strupat, K.; Hillenkamp, F.; Grethl, M.; Krebs, B. Matrix-Assisted Laser-Desorption Ionization Mass-Spectrometry with Additives to 2,5-Dihydroxybenzoic Acid. Org. Mass Spectrom. 1993, 28, 1476.
13. Sunner J.; Ikpnomou, M.G.; Kebarle, P. Kinetic Modeling of Fast Atom Bombardment Spectra of Glycerol-DiethanolamineMixtures. Anal. Chem. 1988, 60, 98.
14. Sunner, J. Ionization in Liquid Secondary-Ion Mass-Spectrometry (LSIMS). Org. Mass Spectrom. 1993, 28, 805.
15. Preston-Schaffter, L.M.; Kinsel, G.R.;Russell, D.H. Effects of Heavy Atom Substituents on Matrices used for Matrix-Assisted Laser Desorption Ionization Mass Spectrometry. J. Am. Soc. Mass. Spectrom. 1994, 5, 800.
16. Zhu, Y.F.; Lee, K.L.; Tang, K.; Allman, S.L.; Taranencko, N.I.; Chen, C.H. Revisit of MALDI for Small Proteins. Rapid Commun. Mass Spectrom. 1995, 9, 1315.

17. Karas, M.; Bachmann, D.; Bahr, U.; Hillenkamp, F. Int. J. Mass Spectrom. Ion processes 1987, 78, 53.
18. Harrison, A.G. The gas-phase basicities and proton affinities of amino acids and peptides. Mass Spectrom. Rev. 1997, 16, 201.
19. Karas, M.; Kruger, R. Ion formation in MALDI: The Cluster ionization mechanism. Chem. Rev. 2003, 103, 427.
20. higilei, L.V.; Kodali, P.B.S.; Garrison, B.J. On the threshold behavior in laser ablation of organic solids. Chem. Phys. Lett. 1997, 276, 269.
21. Zhigilei, L.V. ; Kodali, P.B.S.; Garrison, B.J. Molecular dynamics model for laser ablation and desorption of organic solids. J. Phys. Chem. B 1997, 101, 2028.
22. Zhigilei, L.V.; Garrison, B.J. Microscopic mechanisms of laser ablation of organic solids in the thermal and stress confinement irridation regimes. J. of Appl. Phys. 2000, 88, 1281.
23. Zhigilei, L.V.;Garrison, B.J. Velocity distributions of analyte molecules in matrix-assisted laser desorption from computer simulations. Rapid Commun. Mass Spectrom. 1998, 12, 1273.
24. Verentchikov, A.; Smirnov, I.; Vestal, M.L. Proceeding of the 47th ASMS Conference on Mass Spectrometry and Allied Topics 1999, Dallas, TX, June 13-17.
25. Bahr, U. ; Karas, M. and Hillenkamp, F. Analysis of biopolymers by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. Fresen J. Anal. Chem. 1994, 66, 783.
26. Hong, R.E. ; Woolston, F. R. Laser-Induced of Electrons, Ions, and Neutral Atoms from solid surface. Apply. Phys. Lett. 1963, 2, 138.

27. Vastola, F. J. ; Mumma, R.O. ; pirone, A.J. Analysis of Organic Salts by Laser Ionization. ORG. MASS SPECTRUM. 1969, 3, 101.
28. Jagtap, R.N. ; Ambre, A.H. Overview Literature on Matrix Assisted Laser Desorption Ionization Mass Spectrometry (MALDI-MS): Basic And Its Application in Characterizing Polymeric Materials. Bull. Material. Sci. 2005, 28, 515.
29. Posthumus, M. A .; Kistemker, P.G.; C.,M.H.L.; Brauw, M.C.,Laser Desorption-Mass Spectrometry of polar NonvolatileBio-Organic Molecules. Anal. Chem. 1978, 50, 985.
30. Tabet, J.C. ; Cotter, R.J., Laser Desorption Time-of-Flight Mass Spectrometry of High Mass Molecules. Anal. Chem. 1984, 56, 1662.
31. Tanaka, K. ; Ido, Y.; Akita, S. Detection of High Mass Molecules by Laser Desorption Time-of-Flight Mass Spectrometry. Proceedings of the Second Japan-China Joint Symposium on Mass Spectrometry. 1987, 185.
32. Nelson, R.W. ; Dogruel, D .; Williams, P. Mass Determination of Human Immunoglobulin IgM Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Rapid Commun. Mass Spectrom. 1994, 8, 627.
33. Karas, M. ; Bachmann, D.; Hillenkamp, F. Influence of the Wavelength in High-Irradiane Ultraviolet Laser Desorption Mass Spectrometry of Organic Molecules. Anal. Chem. 1985, 57, 2935.
34. Karas, M.; Hillenkamp, F., Laser Desorption Ionization of Proteins with Molecular Masses Excending 10000 Daltons. Anal. Chem. 1998, 60, 2299.

35. Kim, J.; Kang, W. Use of Graphite Plate for Homogeneous Sample Preparation in Matrix/Surface-Assisted Laser Desorption and Ionization of Polypropyleneglycol and Polystrene. Bull. Korean Chem. Soc. 2000, 21, 401.
36. Kim, H.-J.; Lee, J.-K.; Park, S.-J.; Ro, H.W.; Yoo, D.Y.; Yoon,D.Y. Observation of Low Molecular Weight Poly(methylsilsequioxane)s by Graphite Plate Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Anal. Chem. 2000, 72, 5673.
37. Huang, J.-P.; Yuan, C.-H.; Shiea, J.; Chen, Y.-C. Rapid Screening for Diuretic Doping Agents in Urine by C-60-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry. J. Anal. Toxicol. 1999, 23, 337.
38. Shiea, J.; Huang, J.-P.; Teng, C.-F.; Jeng, J.; Wang, L.Y.; Chiang, L.Y. Use of a Water-Soluble Fullerence Derivative as Precreipitating Reagent and Matrix-Assisted Laser Desorption/Ionization Matrix To Selectively Detect Charged Species in Aqueous Solutions. Anal. Chem. 2003, 75, 3587.
39. Xu, S.; Li, Y.; Zou, H.; Qiz, J.;Guo, Z.; Guo, B. Carbon Nanotubes as Assisted Matrix for Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. Anal. Chem. 2003, 75, 6191.
40. Kong, X.L.; Huang, L.C.L.; Hsu, C.-M.; Chen, W.-H.; Han, C.-C.; Chang, H.-C. High-affinity capture of proteins by diamond nanopatricles for mass spectrometric analysis. Anal. Chem. 2005, 77, 259.


41. Kong, X.L.; Huang, L.C.L.; Liau, S.-C.V.; Han, C.-C.; Chang, H.-C. Polylysine-coated diamond nanocrystals for MALDI-TOF mass analysis of DNA oligonucleotides. Anal. Chem. 2005, 77, 4273.
42. Najam-ul-Haq, M.; Rainer, M.; Huck, C.W.; Stecher, G.; Feuerstein, I.; Steinmuller, D.; Bonn, G. K. Chemically Modified Nano Crystalline Diamond Layer as Material Enhanced Laser Desorption Ionisation (MELDI) Surface in Protein Profiling. Curr Nanosci. 2006, 2, 1-7.
43. Han, M.S.; Lytton-Jean, AKR; Oh, B.K .; Heo, J.; Mirkin, C.A. Colorimetric screening of DNA-binding molecules with gold nanoparticle probes. Angew. Chem. Int. Ed. 2006, 45, 1807.
44. Stoeva, S.I.; Lee, J.S.; Thaxton, C.S.; Mirkin, C.A. Multiplexed DNA detection with biobarcoded nanoparticle probes. Angew. Chem. Int. Ed. 2006, 45, 3303.
45. Li, H.; Wang, C.; Ma, Z.; Su, Z. Colorimetric detection of immunoglobulin G by use of functionalized gold nanoparticles on polyethylenimine film. Anal. Bioanal. Chem. 2006, 384, 1518.
46. de la Fuente, J.M.; Berry, C.C.; Riehle, M.O.;Curtis, A.S.G. Nanoparticle Targeting at Cells. Langmuir. 2006, 22, 3286.
47. Chen, S.J.; Chang, H.T. Nile red-adsorbed gold nanoparticles for selective determination of thiols based on energy transfer and aggregation. Anal. Chem. 2004, 76, 3727.
48. Mirkin, C.A. Programming the Assembly of Two- and Three-
Dimensional Architectures with DNA and Nanoscale Inorganic Building Blocks. Inorg. Chem. 2002, 39, 2258.

49. Huang, Y.F.; Chang, H.T. Nile Red-Adsorbed Gold Nanioparticle Matrixes for Determining Aminothiols through Surface-Assisted Laser Desorption/Ionization Mass Spectrometry. Anal. Chem. 2006, 78, 1485.
50. Daniel, M.C.; Astruc, D. Gold nanoparticles: assembly, supramolecular chemistry, quantum-sized-related properties, and applications toward biology, catalysis, and nanotechnology. Chem. Rev. 2004, 104, 293.
51. Love, J.C.; Estroff, L.A.; Kriebel, J.K., et al. Self-assembled monolayers of thiolates on metals as a form of nanotechnology. Chem. Rev. 2005, 105, 1103.
52. McLean, J.A.; Stumpo, K.A.; Russell, D.H. Size-Selected (2-10 nm) Gold nanoparticles for Matrix Assisted Laser Desorption Ionization of Peptides. J. Am. Chem. Soc. 2005, 127, 5304.
53. Wei, J.; Buriak, J. M.; Siuzdak, G. Desorption–ionizationmass Spectrometry on porous silicon. Nature 1999, 399, 243-246.
54. http://www.ceps.com.tw/ec/ecjnlarticleView.aspx?jnlcattype=1&jnlptype=3&jnltype=18&jnliid=956&issueiid=11081&atliid=153238
55. (a) Bruchez, M.J.; Moronne, M.; Gin, P. ; Weiss, S. ; Alivisatos, A.P. Semiconductor nanocrystals as fluorescent biologiclal labels. Science 1998, 281, 2013. (b) Dubertret, B. ; Skourides, P. ; Norris, D.J. ; Noireaux, V. ; Brivanlou, A.H. ; Libchaber, A. In Vivo Imaging of Quantum Dots Encapsulated in Phospholipid Micelles. Science 2002, 298, 1759.
56. Klimov, V.I. ; Mikhailovsky, A.A. ; Xu, S. ; Malko, A. ; Hollingsworth, J.A. ; Leatherdale, C.A. ; Eisler, H. ; Bawendi, M.G. Optical gain and stimulated emission in nanocrystal quantum dots. Science 2000, 290, 314.
57. (a) Huynh, W.U. ; Dittmer, J.J. ; Alivisatos, A.P. Hybrid Nanorod-Polymer Solar Cells. Science 2002, 295, 2425. (b) Leatherdale, C.A. ; Kagan, C.R. ; Morgan, N.Y. ; Empedocles, S.A. ; Kastner, M.A. ; Bawendi, M.G. Photoconductivity in CdSe quantum dot solids. Phys. Rev. B 2000, 62, 2669.
58. Coe, S. ; Woo, W.-K. ; Bawendi, M.G. ; Bulovic, V. Electroluminescence from single monolayers of nanocrystals in molecular organic devices. Nature 2002, 420, 800.
59. Lee, J. ; Sundar, V.C. ; Heine, J.R.; Bawendi, M.G.; Jensen, K.F. Full color emission from II-VI Semiconductor quantum dot-polymer composites. Adv. Mater. 2000, 12, 1102.
60. Schlamp, M.C.; Peng, X.G.; Alivisators, A.P. Improved Efficiencies in Light Emitting Diodes Made with CdSe(CdS) Core/Shell Type Nanocrystals and a Semiconducting Polymer. J. Appl. Phys. 1997, 82, 5837.
61. Gao, M.Y.; Richter, B.; Kirstein, S. White-light electroluminescent from self-. assembled Q-CdS/PPV multilayer structures. Adv. Mater. 1997, 9, 802.
62. Coe, S.; Woo, W.-K.; Steckel, J.S.; Bawendi, M.G.; Bulovic, V. Tuning the performance of hybrid organic/inorganic quantum dot light-emitting devices. Organic. Electronics 2003, 4, 123.
63. Chaudhary, S.; Ozkan, M.; Warren, C.W. Chan. Strain-tunable silicon photonic band gap microcavities in optical waveguides. J. Appl. Phys. 2004, 84, 2925.
64. Alivisatos, A.P. Semiconductor Clusters, Nanocrystals, and Quantum Dots. Science 1996, 271, 933.
65. (a) Takagahara, T.; Takeda, K. Theory of the quantum confinement effect on excitions in quantum dots of indirect-gap materials. Phys. Rev. B 1992, 46, 398. (b) Veprek, S. Electronic and Mechanical Properties of nanocrystalline composites when approaching molecular size. Thin Solid Films. 1997, 297, 145.
66. 楊衷核; 以無機量子點及溶膠-凝膠製程製備高效能奈米有機發光元件, 國立交通大學應用化學所博士論文 民國九十六年三月
67. 林振平;光聚合高分子在微流體管道上的設計與製作, 國立成功大學化學所碩士論文 民國九十三年七月
68. Gibson, B.W.; Biemann, K. Strategy for the mass spectrometric verification and correction of primary structures of proteins deduced from their DNA sequences. Proc. Natal. Acad. Sci. 1984, 81, 1956
69. Henzel, W.J.; Billeci, T.M.; Stults, J.T.; Wong, S.C.; Grimley, C.; Watanabe, C. Identifying proteins from two-dimensional gels by molecular mass searching of peptide fragments in protein sequence database. Proc. Natal. Acad. Sci. 1993, 90, 5011.
70. Hunter, T. The Croonian Lecture 1997. The Phosphorylation of Proteins on Tyrosine : Its Role in Cell Growth and Disease. Phil. Trans. R. Soc. Lond. B 1998, 353, 583.
71. Krebs, E.G. Historical Perspectives on Protein Phosphorylation and a Classification Systems for Protein Kinases. Phil. Trans. R. Soc. Lond. B 1983, 302, 3.
72. Yan, J.X.; Packer, N.H.; Gooley, A.A.; Williams, K.L. Protein Phosphorylation: Technologies for the Identification of Phosphoamino Acids. J. Chromatogr. A. 1998, 808, 23.
73. http://www.scq.ubc.ca/?p=372
74. Mann, M.; Ong, S.E.; Grønborg, M.; Steen, H.; Jensen, O.N.; Pandey, A. Analysis of protein Phosphorylation Using Mass Spectrometry: Deciphering yje Phosphoproteome. Trends Biotechnol. 2002, 20, 261.
75. Ficarro, S.B.; McCleland, M.L.; Stukenberg, P.T.; Burke, D.J.; Ross, M.M.; Shabanowitz, J.; Hunt, D.F.; White, F.M. Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat Biotechnol. 2002, 20 ,301.
76. Oda, Y. ; Nagasu, T. ; Chait, B.T. Enrichment analysis of phosphorylated proteins as a tool for probing the phosphoproteome. Nat Biotechnol. 2001, 19, 379.
77. Pandey, A.; Podtelejnikov, A.V.; Blagoev, B.; Bustelo, X.R.; Mann, M.; Lodish, H.F. Analysis of receptor signaling pathways by mass spectrometry: identification of vav-2 as a substrate of the epidermal and platelet-derived growth factor receptors. Proc Natl Acad Sci USA. 2000, 97, 179.
78. Barria, A.; Muller, D.; Derkach, V.; Griffith, L.C.; Soderling, T.R. Regulatory phosphorylation of AMPA-type glutamate receptors by CaM-KII during long-term potentiation. Science. 1997, 276, 2042.
79. Pinkse, M.W.; Uitto, P.M.; Hilhorst, M.J.; Ooms, B.; Heck, A.J. Selective isolation at the femtomole level of phosphopeptides from proteolytic digests using 2D-NanoLC-ESI-MS/MS and titanium oxide precolumns. Anal Chem. 2004, 76, 3935.
80. Wolschin, F.; Wienkoop, S.; Weckwerth, F. Enrichment of Phosphorylated Proteins and Peptides from Complex Mixtures Using Metal Oxide/Hydroxide Affinity Chromatography (MOAC) Proteomics, 2005, 5, 4389.
81. Kweon, H.K.; Håkansson, K. Selective Zirconium Dioxide-Based Enrichment of Phosphorylated Peptides for Mass Spectrometric Analysis. Anal. Chem. 2006, 78, 1743.
82. Larsen, M.R.; Graham, M.E.; Robinson, P.J.; Roepstorff, P. Improved detection of hydrophilic phosphopeptides using graphite powder microcolumns and mass spectrometry: evidence for in vivo doubly phosphorylated dynaminⅠand dynaminⅢ. Mol Cell Proteomics, 2004, 3, 56.
83. Beausoleil, S.A.; Jedrychowski, M.; Schwartz, D.; Elias, J.E.; Villen, J.; Li, J.; Cohn, M.A.; Cantley, L.C.; Gygi, S.P. Large-scale characterization of HeLa cell nuclear phosphoproteins. Proc Natl Acad Sci USA. 2004, 101, 12130.
84. Chen, C.T.; Chen, Y.C. Fe3O4/TiO2 Core/Shell Nanoparticles as Affinity Probes for the Analysis of Phosphopeptides Using TiO2 Surface-Assisted Laser Desorption/Ionization Mass Spectrometry. Anal. Chem. 2005, 77, 5912.
85. Chen, C.T.; Chen, W.Y.; Tsai, P.J.; Chen, K.Y.; Yu, J.S.; Chen, Y.C. Rapid Enrichment of Phosphopeptides and phosphoproteins from Complex Samples Using Magnetic Particles Coated With Alumina as the Concentrating Probes for MALDI MS Analysis. J. Proteome Res. 2007, 6, 316.
86. Annan, R.S; Carr, S.A. Phosphopeptide Analysis by Matrix-Assisted Laser Desorption Time-of-Flight Mass Spectrometry. Anal. Chem. 1996, 68, 3413.
87. Stensballe, A.; Andersen, S.; Jensen, O.N. Characterization of Phosphoproteins from Electrophoretic Gels by Nanoscale Fe (III) Affinity Chromatography with Off-Line Mass Spectrometry Analysis. Proteomics 2001, 1, 207.
88. Brockman, A.H.; Shah, N.N.; Orlando, R. Optimization of a Hydrophobic Solid-phase Extraction Interface for Matrix-Assisted Laser Desorption/Ionization. J. Mass Spectrum. 1998, 33, 1141.
89. Xu, Y.; Watson, J.T.; Bruening, M.L. Patterned Monolayers/Polymer Films for Analysis of Dilute or Salt-Contaminated Protein Samples by MALDI-MS. Anal. Chem. 2003, 75, 185.
90. Sudhir, P.; Wu, H.F.; Zhou, Z.C. Identification of peptides using gold nanoparticles-assisted single drop microextraction coupled with AP-MALDI mass spectrometry. Anal. Chem. 2005, 77, 7380.
91. Agrawal, Kavita.; Wu, H.F. Bare silica nanoparticles as concentrating and affinity probes for rapid analysis of aminothiols, lysozyme and peptide mixtures using AP-MALDI/ion trap and MALDI/TOF mass spectrometry. Rapid Commun. Mass Spectrom. 2008, 22, 283.
92. Shrivas, Kamlesh.; Wu, H.F. Modified Silver Nanoparticle as Hydrophobic Affinity Probes for Rapid Analysis of Peptide and Proteins in Biological Samples by coupling liquid-liquid microextraction (LLME) with AP-MALDI/ion trap and MALDI Time-of-Flight Mass Spectrometry. Anal. Chem. 2008, 80, 2583.
93. Hsieh, Shuchen.; Ku, H.Y.; Ke, Y.T.; Wu, H.F. Self-Assembled Monolayer Modified Silicon Substrate to enhance the sensitivity of peptide detection for AP-MALDI Mass Spectrometry. J. Mass Spectrom. 2007, 42, 1628.
94. Zhang, Yahong.; Wang, Xianoyan.; Shan, Wei.; Wu, Biyun.; Fan, Huizhi.; Yu, Xijuan.; Tang, Yi.; Yang, Pengyuan. Enrichment of Low-Abundance Peptides and Proteins on Zeolitte Nanocrystals for Direct MALDI-TOF MS Analysis. Angew. Chem. Int. Ed. 2005, 44, 615.
95. Jia, Weitao.; Chen, Xuehua.; Lu, Haojie.; Yang, Pengyuan. CaCO3-Poly(methyl methacrylate) Nanoparticles for Fast Enrichment of Low-Abundance Peptides Followed by CaCO3-Core Removal for MALDI-TOF MS Analysis. Angew. Chem. Int. Ed. 2006, 45, 615.
96. Xiong, H.M.; Guan, X.Y., Jin, L.H., Shen, W.W.; Lu, H.J.; Xia, Y.Y. Surfactant-Free Synthesis of SnO2@PMMA and TiO2@PMMA Core Shell Nanobeads Designed for Peptide/Protein Enrichment and MALDI-TOF MS Analysis. Angew. Chem. Int. Ed. 2008, 47, 4204.
97. Chang, C.K.; Wu, C.C.; Wang, Y.S.; Chang, H.C. Selective Extraction and Enrichment of Multiphosphorylated Peptides Using Polyarginine-Coated Diamond Nanoparticles. Anal. Chem. 2008, 80, 3791.
98. Chen, Yongfen.; Rosenzweig, Zeev. Luminescent CdS Quantum Dots as Selective Ion Probes. Anal. Chem. 2002, 74, 5132.
99. Lizmarzan, L.M. ; Giersig, M. ; Mulvaney, P. Synthesis of Nanosized Gold-Silica Core-Shell Particles. Langmuir 1996, 12, 4329.
100. Correa-Duartea, M.A.; Giersigb, M.; Liz-Marzána, L.M. Stabilization of CdS semiconductor nanoparticles against photodegradation by a silica coating procedure. Chem. Phys. Lett. 1998, 286, 497.
101. Warren, C.W. Chan.; Shuming, N. Quantum Dot Bioconjugates for Ultrasensitive Nonisotopic Detection. Science 1998, 281, 2016.
102. Xiaohu, G.; Warren, C.W. Chan.; Shuming, N. Quantum-dot
nanocrystal for ultrasensitive biological labeling and multicolor
optical encoding. Journal of Biomedical Optics. 2002, 7, 532.
103. 楊智惠, 黃耿祥, 王英基, 林裕城. 量子點-奈米彩虹標籤, 科學發展, 2008, 422期, 46.
104. Li, H.; Shih, W.Y.; Shih, W.H. Synthesis and characterization of Aqueous Carboxyl-Capped CdS Quantum Dots for Bioapplications. Ind. Eng. Chem. Res. 2007, 46, 2013.
105. Caruso, F. Colloids and Colloid Assemblies Synthesis, Modification, Organization, and Utilization of Colloid Particles. John Wiely & Sons, Inc, 2004.
106. 林佳玫; 利用表面修飾半胱胺酸金奈米微粒辨識特定銅離子濃度範圍之研究, 國立清華大學化學研究所碩士論文 民國九十二年 六月
107. Macha, S.F.; McCarley, T.D.; Limbach, P.A. Influence of Ionization Energy On Charge-Transfer Ionization In Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. Analytica Chimica Acta. 1999, 397, 235.
108. Karbach, V.; Knochenmuss, R. Do Single Matrix Molecules Generate Primary Ions in Ultraviolet Matrix-Assisted Laser Desorption/Ionization. Rapid Commun. Mass Spectrom. 1998, 12, 968.
109. Teng, C.H.; Ho, K.C.; Lin, Y.S.; Chen, Y.C. Gold Nanoparticles as Selective and Concentrating Probes for Samples in MALDI MS Analysis. Anal. Chem. 2004, 76, 4337.
110. Castellana, E.T.; Russell, D.H. Tailoring Nanoparticle Surface Chemistry to Enhance Laser Desorption Ionization of Peptides and Proteins. Nano Lett. 2007, 7, 3023.
111. Wei, Y.; Wu, R.; Zhang, Y. Preparation of Monodispersed Spherical TiO2 Powder by Forced Hydrolysis of Ti(SO4)2 Solution. Mater. Lett. 1999, 41, 101.
112. Kinumi, T.; Saisu, T.; Takayama, M.; Niwal, H. Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry Using an Inorganic Particles Matrix for Small Molecule Analysis. J. Mass Spectrom. 2000, 35, 417.
113. Chen, C.T.; Chen, Y.C. Desorption/Ionization Mass Spectrometry on Nanocrystalline Titania Sol-Gel-Deposited Films. Rapid Commun. Mass Spectrom. 2004, 18, 1956.
114. Chen, C.T.; Chen, Y.C. Molecularly Imprinted TiO2-Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry for Selectively Detecting α-Cyclodextrin. Anal. Chem. 2004, 76, 1453.
115. Yuan, M.; Shan, Z.; Tian, B.; Tu, B.; Yang, P.; Zhao, D. Preparation of Highly Ordered Mesoporous WO3-TiO2 as Matrix in Matrix-Assisted Laser Desorption/Inization Mass Spectrometry. Microporous Mesoporous Mater. 2005, 78, 37.
116. Ko, E.I. “ Sol-gel Process”, Handbook of Heterogeneous Catalysis ed. By Ertl, G.; Knozinger, H.; Weitkamp, J. VCH 1997, 1, 86.
117. Rajh, T.; Chen, L.X.; Lukas, K.; Liu, T.; Thurnauer, M.C.; Tiede, D.M. Surface Restructuring of Nanoparticles: An Efficient Route for Ligand-Metal Oxide Crosstalk. J. Phys. Chem. B 2002, 106, 10543.
118. Arroyo, M.V.; LeBreton, P.R.; Rajh, T.; Zapol, P.; Curtiss, L.A. Density Functional Study of the TiO2-Dopamine Complex. Chem. Phys. lett. 2005, 406, 306.
119. Gopidas, K.R.; Bohorquez, M.; Kamat, P.V. Photophysical and Photochemical Aspects of Coupled Semiconductors Charge-Transfer Processes In Colloidal CdS-TiO2 and CdS-AgI Systems. J. Phys. Chem. 1990, 94, 6435.
120. Sun, W.T.; Yu, Y.; Pan, H.Y.; Gao, X.F.; Chen, Q.; Peng, L.M. CdS Quantums Dots Sensitized TiO2 Nanotube-Array Photoelectrodes. J. Am. Chem. Soc. 2008, 130, 1124.
121.Yan, Z.; Caldwell, G.W.; Jones, W.J.; Masucci, J.A. A Simple Method to Improve Spectral Quality in Matrix-Assisted Laser Desorption/
Ionization Time-Of-Flight Mass Spectrometric Analysis by Using Micro Mate Labeling Tape as a Sample Support. Anal. Biochem. 2000, 277, 267.
122.Wattenberg, A.; Sobott, F.; Barth, H.D.; Brutschy, B. Studying noncovalent protein complexes in aqueous solution with laser desorption mass spectrometry. Interna. Journal of Mass Spectrometry. 2000, 203, 49.
123. Ehring, H.;Stömberg, S.;Tjernberg, A.; Norĕn, B. Matrix-assisted Laser Desorption/Ionization Mass Spectrometry of Proteins Extracted Direcly From Sodium Dodecyl Sulphate-Polyacrylamide Gels. Rapid Commun. Mass Spectrom. 1997, 11, 1867.
124.Zhang, S.K.; Lu, F.; Jiang, Z.M.; Wang, X. Coulomb charging in Ge quantum dots studied by deep level transient spectroscopy. Thin solid films. 2000, 369, 65.
125.Colvin, V.L.; Alivisatos, A.P. Valence-Band Photoemission from a Quantum-Dot System. Phys. Chem. Review. 1991, 66, 21.