臺灣博碩士論文加值系統

本研究主要在於利用焦耳熱效應選擇性移除自組裝單分子層聚乙二醇矽烷(MPEG-sil)以及十八烷基三氯矽烷(OTS)，選擇性修飾目的為降低非偵測區外非專一性吸附來提高低濃度生醫檢測靈敏度。本研究利用離子佈值技術在矽奈米元件通道中間創造出一低離子濃度參雜的元件結構作為進行焦耳熱的加熱區，結合低濃度參雜區域電阻較高以及矽奈米元件中低濃度參雜區域對表面電位變化較為靈敏的特性，成功地將焦耳熱技術與生醫感測結合，並將streptavidin以及DNA修飾於元件感測區，同時利用自組裝單分子層做保護層有別於傳統利用鐵氟龍或PMMA，可有效地降低施加焦耳熱效應的功率並維持元件的次臨界擺幅以利後續的生醫感測應用。由原子力顯微鏡的量測證明可以將加熱區表面的單分子層燒除，進而修飾可以捕捉待測物的生物分子，並與帶有螢光的待測物進行結合，螢光出現的位置也與原子力顯微鏡對應，證明選擇性修飾的完整性。對於電性量測而言，因為選擇性修飾可有效地將待測檢體集中於矽奈米元件高靈敏度感測區而提升了偵測速度以及偵測極限，實驗結果證明，有選擇性修飾的元件偵測streptavidin極限可以推至15 pM，而沒有的只能至150 pM。由本研究的結果我們可以預期此技術將可成功的在早期生醫檢測領域做出重大的貢獻。

In this study, selective ablation of self-assembly monolayer methoxy-poly (ethylene glycol) silane (MPEG-sil) and Octadecyltrichlorosilane (OTS) on silicon nanoelectronic devices by localize joule heating was demonstrated for biosensing application. Lightly doped region in a silicon nanoelectronic device is usually functioned as the active channel which is sensitive to the change of surface potential. And, the resistance of this region is higher compared to other regions in a device so that the electric power consumed. SAMs on lightly doped region were ablated during Joule heating leaving the rest area passivated. The subthreshold swing of nanoelectronic device almost kept unchanged after Joule heating. AFM was adopted to characterize the device surface before and after Joule heating and selective biomolecule modifications. Analysis of fluorescent results showed consistency with AFM results that selectivity in surface modofications was achieved. We found that SAM-ablated device possess potential in the increase of sensing response and in the increase of sensitivity for low concentration detection. In streptavidin detection, the device with selective modification exhibited a detection limits of 15 pM, while the device without selective modification showed an order of magnitude higer in its limit of detection.

Abstract II
誌謝 III
目錄 IV
第一章 緒論 1
1-1前言 1
1-2 矽奈米線生物感測器 2
1-3 自組裝單分子層簡介以及應用 4
1-4 利用修飾MPEG-sil減少非專一性蛋白鍵結提高檢測靈敏度 6
1-5 利用修飾MPEG-sil保護可提高biosensor偵測速度 7
1-6 利用有機矽烷作阻擋層對生物固定化之影響 8
1-7 利用焦耳熱做選擇性修飾 11
1-8 利用焦耳熱做選擇性修飾應用於生醫感測 12
1-9利用模擬驗證焦耳熱相關研究 14
1-10利用選擇性修飾可提高矽奈米線場效電晶體偵測速度 16
1-11 實驗動機和研究目標 17
1-11-1 研究動機 17
1-11-2 研究目標 18
1-11-3 研究架構 18
第二章 材料與製程 19
2-1電阻式nanobelt矽奈米元件製作 19
2-1-1電阻式nanobelt矽奈米元件製作流程 19
2-2 單晶矽nanobelt矽奈米元件製作 20
2-2-1單晶矽nanobelt矽奈米元件製作流程 20
2-3 自組裝單分子層分析與鑑定 22
2-3-1表面修飾methoxy-poly(ethylene glycol) silane (MPEG-sil) 22
2-3-2表面修飾octadecyltrichlorosilane(OTS) 23
2-3-3原子力顯微鏡探測表面形貌 23
2-3-4 接觸角測量儀初步判斷表面修飾狀況 23
2-4表面修飾 24
2-4-1表面修飾APTES 24
2-4-2表面修飾biotin- streptavidin 24
2-4-3表面修飾deoxyribonucleic acid (DNA) 25
2-5焦耳熱實驗 27
2-5-1利用自組裝單分子層可降低施加焦耳熱功率 27
2-5-2 焦耳熱效應模擬之參數設定 27
2-5-3利用焦耳熱選擇性修飾biotin-streptavidin 31
2-5-4利用焦耳熱選擇性修飾deoxyribonucleic acid (DNA) 32
2-6矽奈米元件生醫感測 32
2-6-1奈米元件場效電晶體電性量測 32
2-6-2 即時量測不同酸鹼度緩衝溶液 34
2-6-3 即時量不同濃度streptavidin 34
第三章 實驗結果與討論 35
3-1自組裝單分子層薄膜形成與鑑定 35
3-2選擇性表面修飾biotin- streptavidin 43
3-3選擇性表面修飾deoxyribonucleic acid (DNA) 46
3-4焦耳熱原理以及模擬驗證 50
3-5利用焦耳熱選擇性修飾biotin- streptavidin 55
3-6利用焦耳熱選擇性修飾deoxyribonucleic acid (DNA) 65
3-7 真空中作焦耳熱產生的影響 68
3-8利用自組裝單分子層可降低施加焦耳熱功率 73
3-9不同自組裝單分子層在微流道系統行為 75
3-10選擇性修飾可提高感測速度及降低量測所需時間 76
3-11 nanobelt矽奈米元件即時量測緩衝溶液酸鹼值 79
3-12利用單晶矽nanobelt矽奈米元件即時量測生物分子 82
第四章 結論與未來展望 85
4-1結論 86
4-2未來展望 87
參考文獻 88

[1] Y. Cui, Q. Wei, H. Park, and C. M. Lieber, "Nanowire nanosensors for highly sensitive and selective detection of biological and chemical species," Science, vol. 293, pp. 1289-92, Aug 17 2001.
[2] M. Mrksich and G. M. Whitesides, "Using Self-Assembled Monolayers to Understand the Interactions of Man-made Surfaces with Proteins and Cells," Annual Review of Biophysics and Biomolecular Structure, vol. 25, pp. 55-78, June 1 1996.
[3] J. Sagiv, "Organized monolayers by adsorption. 1. Formation and structure of oleophobic mixed monolayers on solid surfaces," Journal of the American Chemical Society, vol. 102, pp. 92-98, Jan 1980.
[4] I. Choi, S. K. Kang, J. Lee, Y. Kim, and J. Yi, "In situ observation of biomolecules patterned on a PEG-modified Si surface by scanning probe lithography," Biomaterials, vol. 27, pp. 4655-60, Sep 2006.
[5] S. Lan, M. Veiseh, and M. Zhang, "Surface modification of silicon and gold-patterned silicon surfaces for improved biocompatibility and cell patterning selectivity," Biosens Bioelectron, vol. 20, pp. 1697-708, Mar 15 2005.
[6] S. S. Shah, M. C. Howland, L. J. Chen, J. Silangcruz, S. V. Verkhoturov, E. A. Schweikert, A. N. Parikh, and A. Revzin, "Micropatterning of proteins and mammalian cells on indium tin oxide," ACS Appl Mater Interfaces, vol. 1, pp. 2592-601, Nov 2009.
[7] Y. Kanari, Y. Shoji, H. Ode, T. Miyake, T. Tanii, T. Hoshino, and I. Ohdomari, "Protein Adsorption on Self-Assembled Monolayers Induced by Surface Water Molecule," Japanese Journal of Applied Physics, vol. 46, pp. 6303-6308, 2007.
[8] M. R. Leyden, R. J. Messinger, C. Schuman, T. Sharf, V. T. Remcho, T. M. Squires, and E. D. Minot, "Increasing the detection speed of an all-electronic real-time biosensor," Lab Chip, vol. 12, pp. 954-9, Mar 7 2012.
[9] T. Tanii, T. Hosaka, T. Miyake, G.-J. Zhang, T. Zako, T. Funatsu, and I. Ohdomari, "Preferential immobilization of biomolecules on silicon microstructure array by means of electron beam lithography on organosilane self-assembled monolayer resist," Applied Surface Science, vol. 234, pp. 102-106, 2004.
[10] I. Park, Z. Li, A. P. Pisano, and R. S. Williams, "Selective Surface Functionalization of Silicon Nanowires via Nanoscale Joule Heating," Nano Lett, vol. 7, pp. 3106-3111, Oct 1 2007.
[11] G. Begtrup, K. Ray, B. Kessler, T. Yuzvinsky, H. Garcia, and A. Zettl, "Probing Nanoscale Solids at Thermal Extremes," Physical Review Letters, vol. 99, 2007.
[12] L. Maiolo, M. Cuscunà, L. Mariucci, A. Minotti, A. Pecora, D. Simeone, A. Valletta, and G. Fortunato, "Analysis of self-heating related instability in n-channel polysilicon thin film transistors fabricated on polyimide," Thin Solid Films, vol. 517, pp. 6371-6374, 2009.
[13] H. Wang, M. Wang, and Z. Yang, "Finite element analysis of temperature distribution of polycrystalline silicon thin film transistors under self-heating stress," Frontiers of Electrical and Electronic Engineering in China, vol. 4, pp. 227-233, 2009.
[14] C. C. Chen, Y. S. Lin, C. H. Sang, and J. T. Sheu, "Localized joule heating as a mask-free technique for the local synthesis of ZnO nanowires on silicon nanodevices," Nano Lett, vol. 11, pp. 4736-41, Nov 9 2011.
[15] H. Zhang, C. L. Wong, Y. Hao, R. Wang, X. Liu, F. Stellacci, and J. T. Thong, "Self-aligned nanolithography by selective polymer dissolution," Nanoscale, vol. 2, pp. 2302-6, Oct 2010.
[16] O. H. Elibol, B. Reddy, and R. Bashir, "Localized heating and thermal characterization of high electrical resistivity silicon-on-insulator sensors using nematic liquid crystals," Applied Physics Letters, vol. 93, p. 131908, 2008.
[17] M. H. Bae, Z. Y. Ong, D. Estrada, and E. Pop, "Imaging, Simulation, and Electrostatic Control of Power Dissipation in Graphene Devices," Nano Lett, Jun 3 2010.
[18] K. Nagato, Y. Kojima, K. Kasuya, H. Moritani, T. Hamaguchi, and M. Nakao, "Local Synthesis of Tungsten Oxide Nanowires by Current Heating of Designed Micropatterned Wires," Applied Physics Express, vol. 1, p. 014005, 2008.
[19] A. Evgrafov, K. Maute, R. G. Yang, and M. L. Dunn, "Topology optimization for nano-scale heat transfer," International Journal for Numerical Methods in Engineering, vol. 77, pp. 285-300, 2009.
[20] G. Zhang, Q.-X. Zhang, D. Kavitha, and G.-Q. Lo, "Time dependent thermoelectric performance of a bundle of silicon nanowires for on-chip cooler applications," Applied Physics Letters, vol. 95, p. 243104, 2009.
[21] G. Zhang, Q. Zhang, C.-T. Bui, G.-Q. Lo, and B. Li, "Thermoelectric performance of silicon nanowires," Applied Physics Letters, vol. 94, p. 213108, 2009.
[22] H. Fangohr, D. S. Chernyshenko, M. Franchin, T. Fischbacher, and G. Meier, "Joule heating in nanowires," Physical Review B, vol. 84, p. 054437, 2011.
[23] D. R. Kim and X. Zheng, "Numerical Characterization and Optimization of the Microfluidics for Nanowire Biosensors," Nano Lett, vol. 8, pp. 3233-3237, Oct 8 2008.
[24] E. Stern, J. F. Klemic, D. A. Routenberg, P. N. Wyrembak, D. B. Turner-Evans, A. D. Hamilton, D. A. LaVan, T. M. Fahmy, and M. A. Reed, "Label-free immunodetection with CMOS-compatible semiconducting nanowires," Nature, vol. 445, pp. 519-22, Feb 1 2007.
[25] F. Patolsky, G. Zheng, and C. M. Lieber, "Fabrication of silicon nanowire devices for ultrasensitive, label-free, real-time detection of biological and chemical species," Nat Protoc, vol. 1, pp. 1711-24, 2006.
[26] Z. Yang, J. A. Galloway, and H. Yu, "Protein Interactions with Poly(ethylene glycol) Self-Assembled Monolayers on Glass Substrates:  Diffusion and Adsorption," Langmuir, vol. 15, pp. 8405-8411, 1999/11/01 1999.
[27] S. Pillai and R. K. Pai, "Controlled growth and formation of SAMs investigated by atomic force microscopy," Ultramicroscopy, vol. 109, pp. 161-6, Jan 2009.
[28] Y. Wang and M. Lieberman, "Growth of Ultrasmooth Octadecyltrichlorosilane Self-Assembled Monolayers on SiO2," Langmuir, vol. 19, pp. 1159-1167, Feb 1 2003.
[29] P. Gao and Y. Cai, "A method for fabricating protein patterns on the octadecyltrichlorosialne(OTS) surface through paper swabbing," Ultramicroscopy, vol. 109, pp. 1023-8, Jul 2009.