近年來基於奈米滴管(nanopipette)的掃描探針技術(scanning probe microscopy)：掃描離子電導顯微鏡(scanning ion conductance microscopy, SICM)以及掃描電化學顯微鏡(scanning electrochemical microscopy, SECM)常搭配有限元素法(finite element method)模擬進行研究，但現有的SICM有限元素法模擬為使模型複雜度較低易於計算，多是採用二維軸對稱的模型，直接將樣品基質設定成遠大於探針大小且將探針中心放置在樣品中心垂直線上，難以體現SICM高解析度和掃描的特點；另一方面對SECM的實驗研究則有部分超微電極測到的法拉第電流不成穩態，與理論不符的現象。本研究對SICM中探針處於各種異質帶電基質不同位置的情況進行有限元素法模擬研究，並與實際SICM掃描的圖形做對照討論。另外，對超微電極非穩態電流訊號的猜測成因進行有限元素法模擬研究，驗證造成不穩定訊號的原因。結果顯示出SICM訊號受探針-樣品距離、樣品尺寸、樣品帶電量等參數改變的影響、得出SICM對樣品表面電荷的空間解析度。此外，SECM部份模擬結果與實驗測到超微電極不成穩態的循環伏安電流有良好吻合，驗證非穩態電流源自於隔板破洞的猜想。

In recent years, researchs about scanning probe microscopy based on nanopipette: scanning ion conductance microscopy (SICM) and scanning electrochemical microscopy (SECM) are often used with finite element methods (FEMs) simulation. Most of the existing SICM simulation use a two-dimensional axisymmetric model to make the model less complicated and easy to calculate. It is difficult to show the high resolution and scanning characteristics of SICM. In previous studies, it was found that the unsteady redox current in SECM. In this study, the FEMs will be used for the situation that the probe is put in different positions of the charged substrate of various sizes in the SICM. The finite element method simulation studys on the double-channel nanopipette of the diaphragm hole which is guessed as the reason for unsteady current. The results show how the SICM signal is affected by the probe-sample distance, sample size, sample charge and other parameters. The spatial resolution of SICM on the surface charge of the sample is approximately 8 times the probe radius. In addition, the simulation of the double-channel nanopipette with a partition hole model is also consistent with the experimental current. It is verified that partition hole cause the unsteady current.

1. Karoutsos, V., Scanning Probe Microscopy: Instrumentation and Applications on Thin Films and Magnetic Multilayers. J. Nanosci. Nanotechnol. 2009, 9, 6783-6798.
2. Poggi, M. A.; Gadsby, E. D.; Bottomley, L. A.; King, W. P.; Oroudjev, E.; Hansma, H., Scanning Probe Microscopy. Anal. Chem. 2004, 76, 3429-3444.
3. Bottomley, L. A.; Coury, J. E.; First, P. N., Scanning Probe Microscopy. Anal. Chem. 1996, 68, 185-230.
4. Hansma, P.; Drake, B.; Marti, O.; Gould, S.; Prater, C., The Scanning Ion-Conductance Microscope. Science 1989, 243, 641-643.
5. Rheinlaender, J.; Geisse, N. A.; Proksch, R.; Schäffer, T. E., Comparison of Scanning Ion Conductance Microscopy with Atomic Force Microscopy for Cell Imaging. Langmuir 2011, 27, 697-704.
6. Seifert, J.; Rheinlaender, J.; Novak, P.; Korchev, Y. E.; Schäffer, T. E., Comparison of Atomic Force Microscopy and Scanning Ion Conductance Microscopy for Live Cell Imaging. Langmuir 2015, 31, 6807-13.
7. Gorelik, J.; Shevchuk, A. I.; Frolenkov, G. I.; Diakonov, I. A.; Lab, M. J.; Kros, C. J.; Richardson, G. P.; Vodyanoy, I.; Edwards, C. R. W.; Klenerman, D.; Korchev, Y. E., Dynamic Assembly of Surface Structures in Living Cells. Proc. Natl. Acad. Sci. 2003, 100, 5819.
8. Shin, W.; Gillis, K. D., Measurement of Changes in Membrane Surface Morphology Associated with Exocytosis Using Scanning Ion Conductance Microscopy. Biophys. J. 2006, 91, L63-L65.
9. Nakajima, M.; Mizutani, Y.; Iwata, F.; Ushiki, T., Scanning Ion Conductance Microscopy for Visualizing the Three-Dimensional Surface Topography of Cells and Tissues. Semin. Cell Dev. Biol. 2018, 73, 125-131.
10. Bard, A. J.; Fan, F. R. F.; Kwak, J.; Lev, O., Scanning Electrochemical Microscopy. Introduction and Principles. Anal. Chem. 1989, 61, 132-138.
11. Izquierdo, J.; Nagy, L.; Varga, Á.; Bitter, I.; Nagy, G.; Souto, R. M., Scanning Electrochemical Microscopy for the Investigation of Corrosion Processes: Measurement of Zn2+ Spatial Distribution with Ion Selective Microelectrodes. Electrochim. Acta 2012, 59, 398-403.
12. Varga, Á.; Nagy, L.; Izquierdo, J.; Bitter, I.; Souto, R. M.; Nagy, G., Development of Solid Contact Micropipette Zn-Ion Selective Electrode for Corrosion Studies. Anal. Lett. 2011, 44, 2876-2886.
13. Hwang, H. J.; Byun, K. R.; Kang, J. W., Carbon Nanotubes as Nanopipette: Modelling and Simulations. Phys. E 2004, 23, 208-216.
14. Rheinlaender, J.; Schäffer, T. E., Image Formation, Resolution, and Height Measurement in Scanning Ion Conductance Microscopy. J. Appl. Phys. 2009, 105, 094905.
15. Perry, D.; Al Botros, R.; Momotenko, D.; Kinnear, S. L.; Unwin, P. R., Simultaneous Nanoscale Surface Charge and Topographical Mapping. ACS Nano 2015, 9, 7266-7276.
16. Momotenko, D.; McKelvey, K.; Kang, M.; Meloni, G. N.; Unwin, P. R., Simultaneous Interfacial Reactivity and Topography Mapping with Scanning Ion Conductance Microscopy. Anal. Chem. 2016, 88, 2838-2846.
17. Rees, H. R.; Anderson, S. E.; Privman, E.; Bau, H. H.; Venton, B. J., Carbon Nanopipette Electrodes for Dopamine Detection in Drosophila. Anal. Chem. 2015, 87, 3849-3855.
18. 朱常瑞. 利用COMSOL Multiphysics模擬奈米滴管探針的電化學行為. 國立成功大學, 碩士論文, 台南市, 2019.
19. 蔡竣宇. （1）製備由特定尺寸分佈之氧化石墨烯組成之朗謬耳-布洛傑特薄膜（2）奈米碳電極的製備與電化學性質鑑定. 國立成功大學, 碩士論文, 台南市, 2019.
20. Bruckbauer, A.; James, P.; Zhou, D.; Yoon, J. W.; Excell, D.; Korchev, Y.; Jones, R.; Klenerman, D., Nanopipette Delivery of Individual Molecules to Cellular Compartments for Single-Molecule Fluorescence Tracking. Biophys. J. 2007, 93, 3120-3131.
21. Laforge, F. O.; Carpino, J.; Rotenberg, S. A.; Mirkin, M. V., Electrochemical Attosyringe. Proc. Natl. Acad. Sci. 2007, 104, 11895.
22. Rodolfa, K. T.; Bruckbauer, A.; Zhou, D.; Korchev, Y. E.; Klenerman, D., Two-Component Graded Deposition of Biomolecules with a Double-Barreled Nanopipette. Angew. Chem., Int. Ed. 2005, 44, 6854-6859.
23. Suryavanshi, A. P.; Yu, M.-F., Electrochemical Fountain Pen Nanofabrication of Vertically Grown Platinum Nanowires. Nanotechnol. 2007, 18, 105305.
24. Iwata, F.; Nagami, S.; Sumiya, Y.; Sasaki, A., Nanometre-Scale Deposition of Colloidal Au Particles Using Electrophoresis in a Nanopipette Probe. Nanotechnol. 2007, 18, 105301.
25. Bard, A. J.; Fan, F.-R. F.; Pierce, D. T.; Unwin, P. R.; Wipf, D. O.; Zhou, F., Chemical Imaging of Surfaces with the Scanning Electrochemical Microscope. Science 1991, 254, 68.
26. Kranz, C., Recent advancements in nanoelectrodes and nanopipettes used in combined scanning electrochemical microscopy techniques. Analyst 2014, 139, 336-352.
27. Takahashi, Y.; Kumatani, A.; Shiku, H.; Matsue, T., Scanning Probe Microscopy for Nanoscale Electrochemical Imaging. Anal. Chem. 2017, 89, 342-357.
28. Proksch, R.; Lal, R.; Hansma, P. K.; Morse, D.; Stucky, G., Imaging the Internal and External Pore Structure of Membranes in Fluid: TappingMode Scanning Ion Conductance Microscopy. Biophys. J. 1996, 71, 2155-2157.
29. Parsons, R., Electrical Double Layer: Recent Experimental and Theoretical Developments. Chem. Rev. 1990, 90, 813-826.
30. Stern, O., Zur Theorie der Elektrolytischen Doppelschicht. Z. Elektrochem. Angew. Phys. Chem. 1924, 30, 508-516.
31. Wu, J.; Risalvato, F. G.; Ke, F.-S.; Pellechia, P. J.; Zhou, X.-D., Electrochemical Reduction of Carbon Dioxide I. Effects of the Electrolyte on the Selectivity and Activity with Sn Electrode. J. Electrochem. Soc. 2012, 159, F353-F359.
32. Momotenko, D.; Cortés-Salazar, F.; Josserand, J.; Liu, S.; Shao, Y.; Girault, H. H., Ion Current Rectification and Rectification Inversion in Conical Nanopores: a Perm-Selective View. Phys. Chem. Chem. Phys. 2011, 13, 5430-5440.
33. Wei, C.; Bard, A. J.; Feldberg, S. W., Current Rectification at Quartz Nanopipet Electrodes. Anal. Chem. 1997, 69, 4627-4633.
34. Yin, X.; Zhang, S.; Dong, Y.; Liu, S.; Gu, J.; Chen, Y.; Zhang, X.; Zhang, X.; Shao, Y., Ionic Current Rectification in Organic Solutions with Quartz Nanopipettes. Anal. Chem. 2015, 87, 9070-9077.
35. Kosińska, I. D.; Fuliński, A., Asymmetric Nanodiffusion. Phys. Rev. E 2005, 72, 011201.
36. Siwy, Z.; Kosińska, I. D.; Fuliński, A.; Martin, C. R., Asymmetric Diffusion through Synthetic Nanopores. Phys. Rev. Lett. 2005, 94, 048102.
37. Sa, N.; Lan, W.-J.; Shi, W.; Baker, L. A., Rectification of Ion Current in Nanopipettes by External Substrates. ACS Nano 2013, 7, 11272-11282.
38. Perry, D.; Paulose Nadappuram, B.; Momotenko, D.; Voyias, P. D.; Page, A.; Tripathi, G.; Frenguelli, B. G.; Unwin, P. R., Surface Charge Visualization at Viable Living Cells. J. Am. Chem. Soc. 2015, 138, 3152-3160.
39. Li, C.; Johnson, N.; Ostanin, V.; Shevchuk, A.; Ying, L.; Korchev, Y.; Klenerman, D., High Resolution Imaging Using Scanning Ion Conductance Microscopy with Improved Distance Feedback Control. Prog. Nat. Sci. 2008, 18, 671-677.
40. Shevchuk, A. I.; Gorelik, J.; Harding, S. E.; Lab, M. J.; Klenerman, D.; Korchev, Y. E., Simultaneous Measurement of Ca2+ and Cellular Dynamics: Combined Scanning Ion Conductance and Optical Microscopy to Study Contracting Cardiac Myocytes. Biophys. J. 2001, 81, 1759-64.
41. Polcari, D.; Dauphin-Ducharme, P.; Mauzeroll, J., Scanning Electrochemical Microscopy: A Comprehensive Review of Experimental Parameters from 1989 to 2015. Chem. Rev. 2016, 116, 13234-13278.
42. Zoski, C. G., Ultramicroelectrodes: Design, Fabrication, and Characterization. Electroanalysis 2002, 14, 1041-1051.
43. Bard, A. J.; Faulkner, L. R., Electrochemical Methods and Applications. Wiley-Interscience: New York; London, 2000.
44. Franklin, R. In vivo Electrochemical Sensors. University of Michigan, Doctor of Philosophy, Michigan, 2010.
45. Walsh, D. A.; Lovelock, K. R. J.; Licence, P., Ultramicroelectrode Voltammetry and Scanning Electrochemical Microscopy in Room-Temperature Ionic Liquid Electrolytes. Chem. Soc. Rev. 2010, 39, 4185-4194.
46. Arca, M.; Bard, A. J.; Horrocks, B. R.; Richards, T. C.; Treichel, D. A., Advances in Scanning Electrochemical Microscopy. Plenary lecture. Analyst 1994, 119, 719-726.
47. O’Connell, M. A.; Wain, A. J., Mapping Electroactivity at Individual Catalytic Nanostructures Using High-Resolution Scanning Electrochemical–Scanning Ion Conductance Microcopy. Anal. Chem. 2014, 86, 12100-12107.
48. Takahashi, Y.; Shevchuk, A. I.; Novak, P.; Zhang, Y.; Ebejer, N.; Macpherson, J. V.; Unwin, P. R.; Pollard, A. J.; Roy, D.; Clifford, C. A.; Shiku, H.; Matsue, T.; Klenerman, D.; Korchev, Y. E., Multifunctional Nanoprobes for Nanoscale Chemical Imaging and Localized Chemical Delivery at Surfaces and Interfaces. Angew. Chem., Int. Ed. 2011, 50, 9638-9642.
49. Nadappuram, B. P.; McKelvey, K.; Al Botros, R.; Colburn, A. W.; Unwin, P. R., Fabrication and Characterization of Dual Function Nanoscale pH-Scanning Ion Conductance Microscopy (SICM) Probes for High Resolution pH Mapping. Anal. Chem. 2013, 85, 8070-8074.
50. Page, A.; Kang, M.; Armitstead, A.; Perry, D.; Unwin, P. R., Quantitative Visualization of Molecular Delivery and Uptake at Living Cells with Self-Referencing Scanning Ion Conductance Microscopy-Scanning Electrochemical Microscopy. Anal. Chem. 2017, 89, 3021-3028.
51. Morris, C. A.; Chen, C.-C.; Baker, L. A., Transport of Redox Probes through Single Pores Measured by Scanning Electrochemical-Scanning Ion Conductance Microscopy (SECM-SICM). Analyst 2012, 137, 2933-2938.
52. Wert, S.; Baluchová, S.; Schwarzová-Pecková, K.; Sedláková, S.; Taylor, A.; Matysik, F.-M., A Cost-Efficient approach for Simultaneous Scanning Electrochemical Microscopy and Scanning Ion Conductance Microscopy. Monatsh. Chem. 2020, 151, 1249-1255.
53. Takahashi, Y.; Shevchuk, A. I.; Novak, P.; Murakami, Y.; Shiku, H.; Korchev, Y. E.; Matsue, T., Simultaneous Noncontact Topography and Electrochemical Imaging by SECM/SICM Featuring Ion Current Feedback Regulation. J. Am. Chem. Soc. 2010, 132, 10118-10126.
54. Tognoni, E.; Baschieri, P.; Ascoli, C.; Pellegrini, M.; Pellegrino, M., Characterization of Tip Size and Geometry of the Pipettes Used in Scanning Ion Conductance Microscopy. Micron 2016, 83, 11-18.
55. 吳文馨. 功能性奈米滴管探針之製備於電化學分析之應用. 國立成功大學, 碩士論文, 台南市, 2019.
56. Rheinlaender, J.; Schäffer, T. E., Lateral Resolution and Image Formation in Scanning Ion Conductance Microscopy. Anal. Chem. 2015, 87, 7117-7124.
57. Miao, W.; Ding, Z.; Bard, A. J., Solution Viscosity Effects on the Heterogeneous Electron Transfer Kinetics of Ferrocenemethanol in Dimethyl Sulfoxide−Water Mixtures. J. Phys. Chem. B 2002, 106, 1392-1398.