原子力顯微鏡 (Atomic Force Microscope) 是探索奈米尺度下力學性質的有利工具之ㄧ，除了可以產生高解析度的影像與表面力學特性外，也可以利用其探針在物體表面進行蝕刻。
本研究先利用原子力顯微鏡對胰島素類澱粉纖維 (Insulin Amyloid Fibrils) 進行黏著力圖 (Adhesion Map) 測量，再利用探針對表面進行機械性蝕刻 (Mechanical Lithography)，分別討論探針對表面施加不同力與不同速度對胰島素類澱粉纖維所產生的影響。根據奈米壓痕理論以及赫茲模型 (Hertzian Model)，可由力與壓痕 (Force-Indentation) 關係得出胰島素類澱粉纖維的楊氏模數 (Young’s Modulus)，之後利用探針對胰島素類澱粉纖維進行切割，結果顯示了當原子力顯微鏡施加力 3.23 nN 時，胰島素類澱粉纖維開始產生斷裂，而施加到 7.07 nN 時，胰島素類澱粉纖維則輕易的被切斷，因此可藉由原子力顯微鏡將胰島素類澱粉纖維截斷成不同的長度與部份，以及排列成想要的圖案。

Atomic force microscopy is one of the powerful instruments used to explore the mechanical properties of nanoscale materials. It not only can produce high-resolution images and surface mechanical properties, but also can make use of its probe for surface etching.
In this study, we first use atomic force microscopy to measure the Adhesion Map of insulin amyloid fibers, then conduct mechanical lithography on the surface with the probe. In the end, we discuss the effect on insulin amyloid fibrils due to exert different forces and different speeds with the probe.
According to Nanoindentation theory and Hertzian model, we can derive the Young's modulus of insulin amyloid fibrils from force-indentation relations. Then we cut the Insulin amyloid fibers with probe. The results showed that when we applied 3.23 nN force by the probe, the insulin amyloid fibers began to break. When we applied 7.07 nN force, insulin amyloid fibers are cut off easily. Therefore, we can bite off insulin amyloid fibers of different lengths and sections, and arrange in the desired pattern by atomic force microscope.

中文摘要………………………………………………………………………… i
英文摘要………………………………………………………………………… ii
目錄………………………………………………………………………… iii
圖目錄…………………………………………………………………………v
表目錄…………………………………………………………………………viii

第壹章 緒論…………………………………………………………………1
1-1 前言…………………………………………………………………1
1-2 原子力顯微鏡的應用………………………………………………4
1-3 研究動機……………………………………………………………6
第貳章 儀器與實驗………………………………………………………7
2-1 原子力顯微鏡………………………………………………………7
2-1.1 原子力顯微鏡簡介…………………………………………7
2-1.2 原子力顯微鏡工作模式……………………………………8
2-2 力距離曲線…………………………………………………………10
2-3 黏著力圖……………………………………………………………12
2-4 原子力顯微鏡蝕刻…………………………………………………13
2-5 實驗材料……………………………………………………………19
2-6 樣品製備……………………………………………………………20
2-6.1 胰島素類澱粉纖維的形成…………………………………20
2-6.2 胰島素類澱粉纖維在矽晶圓基板的吸附…………………20
2-6.3 使用原子力顯微鏡對胰島素類澱粉纖維進行測量………20
第參章 奈米壓痕理論……………………………………………………21
3-1 奈米壓痕理論………………………………………………………21
3-2 彈性碰撞理論………………………………………………………22
3-3 接觸面理論…………………………………………………………26
3-4 赫茲理論……………………………………………………………26
第肆章 實驗結果與討論…………………………………………………29
4-1 使用原子力顯微鏡觀察胰島素類澱粉纖維的生長情形…………29
4-2黏著力圖測量………………………………………………………31
4-3利用原子力顯微鏡對胰島素類澱粉進行機械性蝕刻……………37
4-3.1 固定探針施加的力，改變探針的移動速度………………38
4-3.1 固定探針的移動速度，改變探針所施加的力……………41
4-4利用原子力顯微鏡對胰島素類澱粉纖維進行操控………………47
第伍章 結論………………………………………………………………54
第陸章 未來展望…………………………………………………………55
References…………………………………………………………………57

1. Harper, J. D.; Lieber, C. M.; Lansbury, P. T. Chem. Biol. 1997, 4, 951-959.
2. Sipe, J. D.; Cohen, A. S. J. Struct. Biol. 2000, 130, 88-98.
3. Stefani, M.; Dobson, C. M. J. Mol. Med. 2003, 81, 678-699.
4. Dobson, C. M. Nature 2003, 426, 884-890.
5. Fandrich, M. Cell. Mol. Life Sci. 2007, 64, 2066-2078.
6. Dobson, C. M. Nature 2005, 435, 747-749.
7. Jansen, R.; Dzwolak, W.; Winter, R. Biophys. J. 2005, 88, 1344-1353.
8. Bekard, I. B.; Dunstan, D. E. J. Phys. Chem. B 2009, 113, 8453-8457.
9. Eanes, E. D.; Glenner, G. G. J. Histochem. Cytochem. 1968, 16, 673-&.
10. Jimenez, J. L.; Nettleton, E. J.; Bouchard, M.; Robinson, C. V.; Dobson, C. M.; Saibil, H. R. Proc. Natl. Acad. Sci. U. S. A. 2002, 99, 9196-9201.
11. Nelson, R.; Sawaya, M. R.; Balbirnie, M.; Madsen, A. O.; Riekel, C.; Grothe, R.; Eisenberg, D. Nature 2005, 435, 773-778.
12. Keten, S.; Xu, Z. P.; Ihle, B.; Buehler, M. J. Nat. Mater. 2010, 9, 359-367.
13. Greenwood, N. N.; Earnshaw, A. Chemistry of the Elements, 2nd Ed.; Oxford: Butterworth-Heinemann., 1997.
14. Blanksby, S. J.; Ellison, G. B. Acc. Chem. Res. 2003, 36, 255-263.
15. Wenger, M. P. E.; Bozec, L.; Horton, M. A.; Mesquida, P. Biophys. J. 2007, 93, 1255-1263.
16. Grant, C. A.; Brockwell, D. J.; Radford, S. E.; Thomson, N. H. Appl. Phys. Lett. 2008, 92, 233902.
17. Guo, S. L.; Akhremitchev, B. B. Biomacromolecules 2006, 7, 1630-1636.
18. Dupres, V.; Verbelen, C.; Dufrene, Y. F. Biomaterials 2007, 28, 2393-2402.
19. GarciaParajo, M.; Longo, C.; Servat, J.; Gorostiza, P.; Sanz, F. Langmuir 1997, 13, 2333-2339.
20. Akhremitchev, B. B.; Walker, G. C. Langmuir 1999, 15, 5630-5634.
21. Dimitriadis, E. K.; Horkay, F.; Maresca, J.; Kachar, B.; Chadwick, R. S. Biophys. J. 2002, 82, 2798-2810.
22. Johnson, K. L. Contact mechanics; Cambridge University Press: Cambridge: U.K., 1985.
23. Liu, G. Y.; Xu, S.; Qian, Y. L. Acc. Chem. Res. 2000, 33, 457-466.
24. Nyffenegger, R. M.; Penner, R. M. Chem. Rev. 1997, 97, 1195-1230.
25. Kim, B.; Pyrgiotakis, G.; Sauers, J.; Sigmund, W. M. Colloids Surf., A 2005, 253, 23-26.
26. Tseng, A. A.; Shirakashi, J.; Jou, S.; Huang, J. C.; Chen, T. P. J. Vac. Sci. Technol., B 2010, 28, 202-210.
27. Sugimura, H.; Nakagiri, N. J. Am. Chem. Soc. 1997, 119, 9226-9229.
28. Binnig, G.; Quate, C. F.; Gerber, C. Phys. Rev. Lett. 1986, 56, 930-933.
29. Piner, R. D.; Zhu, J.; Xu, F.; Hong, S. H.; Mirkin, C. A. Science 1999, 283, 661-663.
30. Meyer, E.; Heinzelmann, H.; Grutter, P.; Jung, T.; Weisskopf, T.; Hidber, H. R.; Lapka, R.; Rudin, H.; Guntherodt, H. J. J. Microsc. 1988, 152, 269-280.
31. Mate, C. M.; Lorenz, M. R.; Novotny, V. J. J. Chem. Phys. 1989, 90, 7550-7555.
32. Moiseev, Y. N.; Mostepanenko, V. M.; Panov, V. I.; Sokolov, I. Y. Sov. Phys. Tech. Phys. 1990, 35, 84-88.
33. Tabata, O.; Kawahata, K.; Sugiyama, S.; Igarashi, I. Sens. Actuators 1989, 20, 135-141.
34. Virwani, K. R.; Malshe, A. P.; Schmidt, W. F.; Sood, D. K. Smart Mater. Struct. 2003, 12, 1028-1032.
35. Tseng, A. A.; Shirakashi, J. I.; Nishimura, S.; Miyashita, K.; Notargiacomo, A. J. Appl. Phys. 2009, 106, 044314.
36. Fischer-Cripps, A. C. Introduction to Contact Mechanics Springer: Boston, MA, 2007.
37. Oliver, W. C.; Pharr, G. M. J. Mater. Res. 2004, 19, 3-20.
38. Jones, R.; Pollock, H. M.; Cleaver, J. A. S.; Hodges, C. S. Langmuir 2002, 18, 8045-8055.
39. Schafer, A.; Vehoff, T.; Glisovic, A.; Salditt, T. Eur. Biophys. J. 2008, 37, 197-204.
40. Max, E.; Hafner, W.; Bartels, F. W.; Sugiharto, A.; Wood, C.; Fery, A. Ultramicroscopy 2010, 110, 320-324.
41. Geisler, M.; Pirzer, T.; Ackerschott, C.; Lud, S.; Garrido, J.; Scheibel, T.; Hugel, T. Langmuir 2008, 24, 1350-1355.
42. Smith, J. F.; Knowles, T. P. J.; Dobson, C. M.; MacPhee, C. E.; Welland, M. E. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 15806-15811.
43. Griffith, A. A. Philos. Trans. R. Soc. London, Ser. A 1921, 221, 163-198.
44. Klotzsch, E.; Smith, M. L.; Kubow, K. E.; Muntwyler, S.; Little, W. C.; Beyeler, F.; Gourdon, D.; Nelson, B. J.; Vogel, V. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 18267-18272.
45. Kreuzer, H. J. Chin. J. Phys. 2005, 43, 249-272.