本篇論文中，描述如何改良一般商業用原子力顯微鏡(Atomic Force Microscopy, AFM)探針，形成特殊的多頭結構，並用於高速與高解析之奈米級動態檢測，其針尖曲率半徑可達2.5奈米，且在偵測壓電致動器(Piezoelectric Actuator, PZT)上顆粒位移時，其時間解析可達10毫秒，多頭探針亦可偵測生物分子的奈米級位移。
為了要更進一步提高在偵測分子時的時間解析能力，本研究提出一種更簡單的方式來直接偵測奈米級動態，主要是將AFM探針改成多頭結構，可有效的把時間解析提升到毫秒等級(與傳統方式相比改善了近10倍)，且空間解析與AFM機台仍維持一致，而這種多頭探針是被設計用來偵測F1型三磷酸腺苷合成酶(F1 Adenosine Triphosphate Synthase, F1-ATPase)之動態。
實驗結果顯示，多頭探針已成功的透過奈米金球(Gold Nanaparticles, GNPs)沉積與反應式離子蝕刻(Reactive Ion Etching, RIE)製造出，並用來偵測奈米級位移，接著我們展現了單頭與多頭探針偵測PZT和F1-ATPase之結果。

In this paper, we nano-engineered commercial atomic force microscope (AFM) probes with multi nano tip structures for high speed/resolution dynamic nanodetection. The tip radius could be shrunk down to 2.5 nm, and the time resolution could be approaching 10 ms for measuring particle movement on piezoelectric actuator (PZT). The multi tip AFM can be applicable for detecting the dynamic movement of bio-molecules.
To further enhance the time resolution for resolving molecule movement, this research proposes a simpler method to detect dynamic nanomovement by modifying the AFM tip from single tip into multi tips, which can greatly enhance the time resolution into ms level (10 times improvement), while spatial resolution is kept at standard value and the AFM control system is kept unchanged. The multi head tips are designed to measure nano displacement of F1 adenosine triphosphate synthase (F1-ATPase).
From the experimental results, multi tips probe has successfully manufactured by deposition of gold nanaparticles (GNPs) and reactive ion etching (RIE) for dynamic nanodetection. Then we demonstrate that single tip and multi tips probe can detecting nanomovement of PZT and F1-ATPase.

摘要 i
Abstract ii
誌謝 iii
總目錄 iv
表目錄 vi
圖目錄 vii
第一章 緒論 1
1.1 前言 1
1.2 研究目的 1
第二章 文獻回顧 3
2.1 懸臂樑陣列 3
2.2 高速AFM架構與生物性應用 6
2.3 F1-ATPase之動態偵測 10
2.4 全內角反射式螢光顯微鏡 13
2.5 初代多頭探針 13
2.6 奈米金球沉積 15
第三章 實驗原理與方法 17
3.1 原子力顯微鏡發展與原理 17
3.1.1 接觸式 19
3.1.2 非接觸式 20
3.1.3 半接觸式 20
3.2 實驗流程設計 20
3.2.1 奈米金球接合 21
3.2.2 乾式蝕刻 22
3.2.3 多頭探針製備 22
3.2.4 動態檢測 23
3.3 實驗耗材與儀器 25
3.3.1 實驗耗材 25
3.3.2 實驗儀器 26
第四章 實驗步驟 30
4.1 多頭試片 30
4.1.1 試片清潔 30
4.1.2 試片表面胺基修飾 30
4.1.3 奈米金球接合 31
4.1.4 反應式離子蝕刻 31
4.1.5 奈米金球移除 31
4.2 多頭探針 32
4.2.1 針尖研磨 32
4.2.2 多頭探針 32
4.3動態樣本製備 32
第五章 結果與討論 34
5.1 試片製備 34
5.1.1 奈米金球接合前測試 34
5.1.2 奈米金球沉積 35
5.1.3 使用SF6進行蝕刻 41
5.1.4 改用CF4進行蝕刻 45
5.2探針製備 58
5.2.1 針尖研磨 58
5.2.2 奈米金球沉積與蝕刻 62
5.2.3 九頭探針 78
5.2.4 五頭探針 80
5.2.5 三頭探針 82
5.3 動態檢測 83
5.3.1 壓電致動器 83
5.3.2 F1-ATPase 88
第六章 結論 93
6.1 多頭探針製作 93
6.2 動態檢測 93
第七章 未來工作 94
第八章 文獻回顧 95

[1] G. Binnig, C. F. Quate, Ch. Gerber. (1986). "Atomic Force Microscope." Physical Review Letters : volume 56, number 9.
[2] M. Despont, J. Brugger, U. Drechsler,et al. (1999)."VLSI-NEMS chip for parallel AFM data storage." IEEE Sensors and Actuators A – Physical : volume 80, issue 2, 100 – 107.
[3] Sarov Y, Frank A, Ivanov T, Zollner JP, Ivanova K, Volland B, Rangelow IW, Brogan A, Wilson R, Zawierucha P, Zielony M, Gotszalk T, Nikolov N, Zier M, Schmidt B, Kostic I. (2009). "Parallel proximal probe arrays with vertical interconnections." Journal of Vacuum Science & Technology B : volume 27, number 6.
[4] Toshio Ando, Takayuki Uchihashi, Noriyuki Kodera, Daisuke Yamamoto, Atsushi Miyagi, Masaaki Taniguchi, Hayato Yamashita. (2008). ''High-speed AFM and nano-visualization of biomolecular processes.'' Pflügers Archiv - European Journal of Physiology : volume 456, issue 1, 211 - 225.
[5] Viani MB, Schäffer TE, Paloczi GT, Pietrasanta LI, Smith BL, Thompson JB, Richter M, Rief M, Gaub HE, Plaxco KW, Cleland AN, Hansma HG, Hansma PK. (1999). ''Fast imaging and fast force spectroscopy of single biopolymers with a new atomic force microscope designed for small cantilevers.'' Review of Scientific Instruments : volume 70, 4300 – 4303.
[6] Schäffer TE, Cleveland JP, Ohnesorge F, Walters DA, Hansma PK (1996). ''Studies of vibrating atomic force microscope cantilevers in liquid. '' Journal of Applied Physics : volume 80, issue 7, 3622 – 3627.
[7] Ando T, Kodera N, Takai E, Maruyama D, Saito K, Toda A (2001). ''A high-speed Atomic force microscope for studying biological macromolecules. '' Proceedings of the National Academy of Sciences of the United States of America : volume 98, number 22, 12468 – 12472.
[8] Kodera N, Sakashita M, Ando T (2006). ''Dynamic proportional-integral-differential controller for high-speed atomic force microscopy''. Review of Scientific Instruments : volume 77, issue 8, 083704.
[9] Ando T, Kodera N, Naito Y, Kinoshita T, Furuta K, Toyoshima YY (2003). ''A high-speed atomic force microscope for studying biological macromolecules in action. '' Chem Phys Chem : volume 4, issue 11, 1196 – 1202.
[10] Ando T, Uchihashi T, Kodera N, Miyagi A, Nakakita R, Yamashita H, Matada K (2005). ''High-speed atomic force microscopy for capturing dynamic behavior of protein molecules at work.'' Japanese Journal of Applied Physics : volume 45, number 3B.
[11] Ando T, Uchihashi T, Kodera N, Miyagi A, Nakakita R, Yamashita H, Sakashita M (2006). ''High-speed atomic force microscopy for studying the dynamic behavior of protein molecules at work. '' Japanese Journal of Applied Physics : volume 45, 1897 – 1903.
[12] Yamashita H, Kodera N, Miyagi A, Uchihashi T, Yamamoto D, Ando T (2007). ''Tip-sample distance control using photo-thermal actuation of a small cantilever for high-speed atomic force microscopy. '' Review of Scientific Instruments : volume 78, 083702.
[13] Kitazawa M, Shiotani K, Toda A (2003). ''Batch fabrication of sharpened silicon nitride tips. '' Japanese Journal of Applied Physics : volume 42, 4844 – 4847.
[14] Schiener J, Witt S, Stark M, Guckenberger R (2004). ''Stabilized atomic force microscopy imaging in liquids using second harmonic of cantilever motion for setpoint control. '' Review of Scientific Instruments : volume 75, 2564 – 2568.
[15] Uchihashi T, Ando T, Yamashita H (2006). ''Fast phase imaging in liquids using a rapid scan atomic force microscope. '' Applied Physics Letters : volume 89, issue 21, 213112.
[16] Stark M, Guckenberger R (1999). ''Fast low-cost phase detection setup for tapping-mode atomic force microscopy. '' Review of Scientific Instruments : volume 70,3614 – 3619.
[17] Fantner GE, Hegarty P, Kindt JH, Schitter G, Cidade GAG, Hansma PK (2005). ''Data acquisition system for high speed atomic force microscopy. '' Review of Scientific Instruments : volume 76, 026118.
[18] Fantner GE, Schitter G, Kindt JH, Ivanov T, Ivanova K, Patel R, Holten-Andersen N, Adams J, Thuner PJ, Rangelow IW, Hansma PK (2006). ''Components for high-speed atomic fore microscopy. '' Ultramicroscopy : volume 106, 881 – 887.
[19] Nidhi Nath, Ashutosh Chilkoti. (2002). "A Colorimetric Gold Nanoparticle Sensor To Interrogate Biomolecular Interactions in Real Time on a Surface." Analytical Chemistry : volume 74, number 3.
[20] Matthieu Lagouge. (2006). "Discovering MEMS and Microtechnology - Material Etching. Website : http://matthieu.lagouge.free.fr".
[21] University of leicester. " Total Internal Reflection Fluorescence Microscopy (TIRFM) and Single Molecule Detection. Website : http://www2.le.ac.uk/departments/biochemistry/staff/bagshaw/research/tirf".
[22] Joe-Ming Chang. Fabrication of the multi head tip by focused ion beam (FIB).
[23] Timothy Elston, Hongyun Wang & George Oster. (1998). '' Energy transduction in ATP synthase. '' Letters to nature : volume 391, number 29.
[24] Uchihashi, Takayuki; Iino, Ryota; Ando, Toshio; Noji, Hiroyuki. (2011). ''High-speed atomic force microscopy reveals rotary catalysis of rotor-less F1-ATPase. '' Science : volume 333, number 6043, 755 – 758.