Please use this identifier to cite or link to this item:
DC FieldValueLanguage
dc.contributor.authorChiang, Wei-Yuanen_US
dc.identifier.citation參考文獻 [1] Guiseppi-Elie A, Brahim S, Slaughter G, Ward KR. Design of a subcutaneous implantable biochip for monitoring of glucose and lactate. Sensors Journal, IEEE. 2005;5:345-55. [2] Pereira Rodrigues N, Sakai Y, Fujii T. Cell-based microfluidic biochip for the electrochemical real-time monitoring of glucose and oxygen. Sensors and Actuators B: Chemical. 2008;132:608-13. [3] Patolsky F, Zheng G, Lieber CM. Nanowire-Based Biosensors. Analytical chemistry. 2006;78:4260-9. [4] Cui Y, Wei Q, Park H, Lieber CM. Nanowire Nanosensors for Highly Sensitive and Selective Detection of Biological and Chemical Species. Science (New York, NY). 2001;293:1289-92. [5] Patolsky F, Timko BP, Yu G, Fang Y, Greytak AB, Zheng G, et al. Detection, Stimulation, and Inhibition of Neuronal Signals with High-Density Nanowire Transistor Arrays. Science (New York, NY). 2006;313:1100-4. [6] Uchida T, Fukawa A, Uchida M, Fujita K, Saito K. Application of a Novel Protein Biochip Technology for Detection and Identification of Rheumatoid Arthritis Biomarkers in Synovial Fluid. Journal of Proteome Research. 2002;1:495-9. [7] Culha M, Stokes DL, Griffin GD, Vo-Dinh T. Application of a miniature biochip using the molecular beacon probe in breast cancer gene BRCA1 detection. Biosensors and Bioelectronics. 2004;19:1007-12. [8] Popovtzer R, Neufeld T, Ron Ez, Rishpon J, Shacham-Diamand Y. Electrochemical detection of biological reactions using a novel nano-bio-chip array. Sensors and Actuators B: Chemical. 2006;119:664-72. [9] Ziegler C. Cell-based biosensors. Fresenius J Anal Chem. 2000;366:552-9. [10] Lan S, Veiseh M, Zhang M. Surface modification of silicon and gold-patterned silicon surfaces for improved biocompatibility and cell patterning selectivity. Biosensors & bioelectronics. 2005;20:1697-708. [11] Kharitonov AB, Zayats M, Lichtenstein A, Katz E, Willner I. Enzyme monolayer-functionalized field-effect transistors for biosensor applications. Sensors and Actuators B: Chemical. 2000;70:222-31. [12] Xi Y, Hu C, Zhang X, Zhang Y, Wang ZL. Optical switches based on nanowires synthesized by molten salt solvent method. Solid State Communications. 2009;149:1894-6. [13] Wang CW, Pan CY, Wu HC, Shih PY, Tsai CC, Liao KT, et al. In situ detection of chromogranin a released from living neurons with a single-walled carbon-nanotube field-effect transistor. Small (Weinheim an der Bergstrasse, Germany). 2007;3:1350-5. [14] Cui Y, Zhong Z, Wang D, Wang WU, Lieber CM. High performance silicon nanowire field effect transistors. Nano Letters. 2003;3:149-52. [15] Patolsky F, Lieber CM. Nanowire nanosensors. Materials Today. 2005;8:20-8. [16] Kim A, Ah CS, Yu HY, Yang J-H, Baek I-B, Ahn C-G, et al. Ultrasensitive, label-free, and real-time immunodetection using silicon field-effect transistors. Applied Physics Letters. 2007;91:103901--3. [17] Stern E, Klemic JF, Routenberg DA, Wyrembak PN, Turner-Evans DB, Hamilton AD, et al. Label-free immunodetection with CMOS-compatible semiconducting nanowires. Nature. 2007;445:519-22. [18] Zhang G-J, Zhang G, Chua JH, Chee R-E, Wong EH, Agarwal A, et al. DNA Sensing by Silicon Nanowire: Charge Layer Distance Dependence. Nano Letters. 2008;8:1066-70. [19] Lin MC, Chu CJ, Tsai LC, Lin HY, Wu CS, Wu YP, et al. Control and Detection of Organosilane Polarization on Nanowire Field-Effect Transistors. Nano Letters. 2007;7:3656-61. [20] Pui TS, Agarwal A, Ye F, Tou ZQ, Huang Y, Chen P. Ultra-sensitive detection of adipocytokines with CMOS-compatible silicon nanowire arrays. Nanoscale. 2009;1:159-63. [21] Wanunu M, Meller A. Chemically Modified Solid-State Nanopores. Nano Letters. 2007;7:1580-5. [22] Corey JM, Brunette AL, Chen MS, Weyhenmeyer JA, Brewer GJ, Wheeler BC. Differentiated B104 neuroblastoma cells are a high-resolution assay for micropatterned substrates. Journal of neuroscience methods. 1997;75:91-7. [23] Ren K, Ji J, Shen J. Tunable DNA Release from Cross-Linked Ultrathin DNA/PLL Multilayered Films. Bioconjugate Chemistry. 2005;17:77-83. [24] Sun K, Liu H, Wang S, Jiang L. Cytophilic/Cytophobic Design of Nanomaterials at Biointerfaces. Small (Weinheim an der Bergstrasse, Germany). 2013;9:1444-8. [25] Jing G, Perry SF, Tatic-Lucic S. Precise cell patterning using cytophobic self-assembled monolayer deposited on top of semi-transparent gold. Biomedical microdevices. 2010;12:935-48. [26] Chang JC, Brewer GJ, Wheeler BC. A modified microstamping technique enhances polylysine transfer and neuronal cell patterning. Biomaterials. 2003;24:2863-70. [27] Lin S-P, Chuang T-L, Chen J-JJ, Tzeng S-F. Design of microscopy-based microcontact printing stamp and alignment device for patterned neuronal growth. Journal of Medical and Biological Engineering. 2004;24:45-50. [28] Ulman A. Formation and Structure of Self-Assembled Monolayers. Chemical reviews. 1996;96:1533-54. [29] Flink S, van Veggel FCJM, Reinhoudt DN. Sensor Functionalities in Self-Assembled Monolayers. Advanced Materials. 2000;12:1315-28. [30] Love JC, Estroff LA, Kriebel JK, Nuzzo RG, Whitesides GM. Self-assembled monolayers of thiolates on metals as a form of nanotechnology. Chemical reviews. 2005;105:1103-69. [31] Sugimura H. Self-Assembled Monolayer on Silicon. Nanocrystalline Materials.57-91. [32] Chaki NK, Vijayamohanan K. Self-assembled monolayers as a tunable platform for biosensor applications. Biosensors and Bioelectronics. 2002;17:1-12. [33] Ulman A. Formation and structure of self-assembled monolayers. Chemical reviews. 1996;96:1533. [34] Kessel CR, Granick S. Formation and characterization of a highly ordered and well-anchored alkylsilane monolayer on mica by self-assembly. Langmuir : the ACS journal of surfaces and colloids. 1991;7:532-8. [35] Heister K, Rong HT, Buck M, Zharnikov M, Grunze M, Johansson LSO. Odd−Even Effects at the S-Metal Interface and in the Aromatic Matrix of Biphenyl-Substituted Alkanethiol Self-Assembled Monolayers. The Journal of Physical Chemistry B. 2001;105:6888-94. [36] Tao YT, Huang CY, Chiou DR, Chen LJ. Infrared and Atomic Force Microscopy Imaging Study of the Reorganization of Self-Assembled Monolayers of Carboxylic Acids on Silver Surface. Langmuir : the ACS journal of surfaces and colloids. 2002;18:8400-6. [37] Bernard A, Renault JP, Michel B, Bosshard HR, Delamarche E. Microcontact printing of proteins. Advanced Materials. 2000;12:1067-70. [38] Wilbur JL, Kumar A, Kim E, Whitesides GM. Microfabrication by microcontact printing of self‐assembled monolayers. Advanced Materials. 1994;6:600-4. [39] Mrksich M, Dike LE, Tien J, Ingber DE, Whitesides GM. Using microcontact printing to pattern the attachment of mammalian cells to self-assembled monolayers of alkanethiolates on transparent films of gold and silver. Experimental cell research. 1997;235:305-13. [40] Rozkiewicz DI, Kraan Y, Werten MWT, de Wolf FA, Subramaniam V, Ravoo BJ, et al. Covalent Microcontact Printing of Proteins for Cell Patterning. Chemistry – A European Journal. 2006;12:6290-7. [41] Giaever I, Keese CR. A morphological biosensor for mammalian cells. Nature. 1993;366:591. [42] Ehret R, Baumann W, Brischwein M, Schwinde A, Wolf B. On-line control of cellular adhesion with impedance measurements using interdigitated electrode structures. Medical and Biological Engineering and Computing. 1998;36:365-70. [43] Xiao C, Luong JHT. On-Line Monitoring of Cell Growth and Cytotoxicity Using Electric Cell-Substrate Impedance Sensing (ECIS). Biotechnology Progress. 2003;19:1000-5. [44] Giaever I, Keese CR. Monitoring fibroblast behavior in tissue culture with an applied electric field. Proceedings of the National Academy of Sciences of the United States of America. 1984;81:3761-4. [45] Wang MH, Jang LS. A systematic investigation into the electrical properties of single HeLa cells via impedance measurements and COMSOL simulations. Biosensors & bioelectronics. 2009;24:2830-5. [46] 康毓珊. 以奈米線場效電晶體探討電子元件介面對神經細胞生長的影響. 台中市: 中興大學; 2012. [47] Hou S, Su S, Kasner ML, Shah P, Patel K, Madarang CJ. Formation of highly stable dispersions of silane-functionalized reduced graphene oxide. Chemical Physics Letters. 2010;501:68-74. [48] Chen Q, Han L, Che S. Synthesis of Carboxylic Group Functionalized Monodispersed Mesoporous Silica Spheres (MMSSs) via Costructure Directing Method. Chemistry Letters. 2009;38:774-5. [49] Ting C-C, Vetrivel S. A Simple One-pot Route to Synthesize Mesoporous Silicas SBA-15 Functionalized with Exceptional High Loadings of Pendant Carboxylic Acid Groups Chung-Ta Tsai (蔡忠達), Yu-Chi Pan (潘育麒), Chun-Chiang Ting (丁君強), Shanmugam Vetrivel1, Anthony Shiaw-Tseh Chiang (蔣孝澈) 2, George Ting-Kuo Fey (費定國) 2, and Hsien-Ming Kao (高憲明). [50] 紀天音. 特性化描述與檢測前列腺癌症之矽奈米線場效電晶體. 台中市: 中興大學; 2012. [51] Cui NY, Liu C, Yang W. XPS and AFM characterization of the self‐assembled molecular monolayers of a 3‐aminopropyltrimethoxysilane on silicon surface, and effects of substrate pretreatment by UV‐irradiation. Surface and Interface Analysis. 2011;43:1082-8. [52] Wouters D, Schubert US. Constructive Nanolithography and Nanochemistry:  Local Probe Oxidation and Chemical Modification. Langmuir : the ACS journal of surfaces and colloids. 2003;19:9033-8. [53] Idota N, Tsukahara T, Sato K, Okano T, Kitamori T. The use of electron beam lithographic graft-polymerization on thermoresponsive polymers for regulating the directionality of cell attachment and detachment. Biomaterials. 2009;30:2095-101.en_US
dc.description.abstract一直以來在生物及生理方面的研究都對於細胞生物感測器有很高的興趣,然而在本研究中我們利用矽奈米線場效電晶體(silicon nanowire field effect transistor, SiNW-FET)作為我們生物感測晶片的基材,並透過自組裝薄膜(self-assembled monolayer, SAM) 在基材表面上做特定圖形的修飾,有利於細胞培養在修飾過的表面。藉由3-aminopropyl trimethoxysilane (APTMS)單分子層膜修飾在SiNW達到親細胞(cytophilic)效果,而修飾methoxyl polyethylene glycol silane (mPEG-Si)、N-(trimethoxysilylpropyl) ethylenediamine triacetic acid trisodium salt (EDTAS)、carboxyethylsilanetriol sodium salt (CS) 則是能在SiNW-FET建立出具有斥細胞(cytophobic)的修飾區域。再利用化學分析電子能譜儀(electron spectroscopy for chemical analysis, ESCA)能針對不同的修飾包括APTMS、mPEG-Si、EDTAS及CS做特性上的分析比較,ESCA能分析修飾於矽基材上的化學元素及鍵結;並且比較出這四種不同的修飾都具有獨特的化學結構,藉此證實有成功的修飾在矽基材表面。分析後我們得知EDTAS及CS都具有足以取代價格昂貴的mPEG-Si潛力。透過原子力顯微鏡(atomic force microscopy, AFM)掃描得知表面粗糙度及化學分子的修飾高度,APTMS修飾一小時達到1.5nm、EDTAS修飾兩小時達到2.2nm、CS修飾一小時達到1.39nm有效達到單分子層膜。另外,實驗中利用微接觸式轉印技術(microcontact printing, μCP)物理轉印修飾的化學分子於基材上。控制修飾的斥/親細胞區域,以誘導細胞集中生長在特定親細胞區域。藉由螢光嫁接FITC-PLL的方式證實修飾區域,並植入細胞驗證修飾的結果。此研究最終欲應用在生物感測晶片上,所以透過PC-12細胞種植在實驗設計中的修飾表面,來證實親細胞與斥細胞的表現。利用掃描式電子顯微鏡(scanning electron microscope, SEM) 觀察細胞在生物晶片上的表面型態,瞭解細胞貼附在奈米線上的實際情形。在訊號監測部分,利用HP 4145B semiconductor parameter analyzer量測ISD-VG及Agilent E4980A precision LCR meter做阻抗量測,評估修飾前後及不同修飾方法在植入細胞生長對晶片偵測的影響。當細胞種植在經過區域修飾的SiNW-FET上,細胞就會傾向於貼附在具有親細胞特性APTMS修飾的矽奈米線附近;而APTMS修飾不只增加了細胞貼附性也增加了訊號強度,有種入細胞與未種入細胞的訊號相比訊號差異約20MΩ。結果發現藉由μCP轉印斥細胞分子於基材上,可以讓細胞朝親細胞APTMS分子修飾的奈米線偵測區域生長。有種入細胞與未種入細胞的訊號相比就具有顯著差異,訊號差異度可達176 MΩ;這也強調著區域性的修飾控制對於細胞的貼附,具有重大影響與幫助。zh_TW
dc.description.abstractThere has been a great deal of interest in cell-based biosensors for many biological and physiological applications. In this study, silicon nanowire metal oxide semiconductor field effect transistors (SiNW-FET) were applied to develop cell-based biosensors. In order to make cells reside at sensing nanowires, self-assembled monolayer (SAM) of surface modification technique was used to construct specific cell growth patterns. 3-aminopropyl trimethoxysilane (APTMS) SAM was particularly used to functionalize the SiNW-FET and create cytophilic areas. SAMs of methoxyl polyethylene glycol silane (mPEG-Si), N-(trimethoxysilylpropyl)ethylenediamine triacetic acid trisodium salt (EDTAS) and carboxyethylsilanetriol sodium salt (CS) were independently applied to form cytophobic regions on SiNW-FET. All modified SAM layers, including APTMS, mPEG-Si, EDTAS and CS, were characterized by electron spectroscopy for chemical analysis (ESCA) and atomic force microscopy (AFM). ESCA analyses verified specifically functional groups of each modified SAM layers and showed these 4 varied chemicals were independently and successfully created on the silicon substrates. In particular, we found EDTAS and CS for formation of cytophobic regions were more economic in comparison with expensive mPEG-Si. AFM scanning showed the surface roughness and average thickness of each modified SAM layer; for example, the average thickness of APTMS reached 1.5 nm after 1h modification. The average thicknesses of EDTAS with 2h modification and CS with 1h modification were 2.2 nm and 1.39 nm, respectively. Except SAM technique for creating cytophilic and cytophobic areas, the technique of microcontact printing (μCP) was also used in this study to find the niche in guiding cells growing in specifically cytophilic area. The modification using either SAM or μCP techniques were visualized by fluorescent FITC-PLL and then examined by cell adhesion. Scanning electron microscope displayed PC-12 cells on APTMS modified sensing SiNW. Electrical measurements, including ISD-VG measurement using HP 4145B semiconductor parameter analyzer and impedance change using Agilent E4980A precision LCR meter, were used to show the performance of each SiNW-FET before and after surface modification and cell culture. After cells were cultured on patterned SiNW-FET, cells automatically grew on APTMS-modified cytophilic areas and in proximity to the sensing SiNW. In addition, we found the impedance signals after cell grew on APTMS-modified SiNW-FET increased over time and showed in proportion to the cell attachment. The difference of impedance signals between before and after cell grew on APTMS-SAM-modified SiNW-FET was about 20 MΩ. By contrast, the difference of impedance signals between before and after cell grew on APTMS-μCP-modified SiNW-FET reached 176 MΩ. Our results suggested efficient cytophilic modification on SiNW-FET could significantly enhance the sensing signal and dynamically observe the cell growth.en_US
dc.description.tableofcontents目錄 致謝 I 摘要 II Abstract IV 目錄 VI 圖目錄 VIII 表目錄 X 第一章 緒論 1 1.1. 前言 1 1.2. 場效電晶體(field effect transistor)與矽奈米線場效電晶體(silicon nanowire field effect transistor, SiNW-FET) 2 1.3. 親細胞(cytophilic)與斥細胞(cytophobic)區域 4 1.3.1. 自組裝薄膜(self-assembled monolayer, SAMs) 5 1.3.2. Microcontact printing(μCP) 7 1.4. 感測器量測細胞生理訊號 7 1.5. 研究動機與目的 9 第二章 材料與方法 10 2.1. 實驗材料 10 2.2. 實驗流程 (Processes) 12 2.3. MOSFET元件製程 13 2.4. 微流道製作 14 2.5. 自組裝薄膜表面修飾 16 2.5.1. APTMS 親細胞修飾 16 2.5.2. mPEG-Si 斥細胞修飾 17 2.5.3. EDTAS斥細胞修飾 18 2.5.4. CS斥細胞修飾 19 2.6. Microcontact printing(μCP) and replica molding method 20 2.7. 曝光微影製程修飾法 22 2.7.1 製備方法 22 2.7.2 結合SAMs修飾 23 2.8. 修飾圖形觀察 24 2.9. 細胞培養 24 2.9.1. 細胞株(Cell line) 25 2.9.2. 細胞培養基(Culture medium) 25 2.9.3. 細胞繼代(Subculture) 26 2.10. 電訊量測之架設(electrical measurement system) 27 2.10.1. I-V及impedance量測系統 27 2.11. 實驗儀器分析原理與分析方法 29 2.11.1. 原子力顯微鏡(AFM) 29 2.11.2. 化學分析電子能譜儀(ESCA) 30 2.11.3. 掃描式電子顯微鏡(SEM) 31 第三章 結果與討論 33 3.1 表面修飾分析 33 3.1.1 親細胞區域之化學分析電子能譜儀測量表面化學結構 33 3.1.2 斥細胞區域之化學分析電子能譜儀測量表面化學結構 35 3.1.3 原子力顯微鏡表面型態分析 41 3.2 修飾基材與細胞貼附實驗 45 3.3 區域性修飾控制 46 3.3.1 Microcontact printing(μCP) 46 3.3.2 曝光微影製程修飾 47 3.4 生物感測晶片量測製備 50 3.5 MOS元件特性測量 51 3.6 電訊號測量 53 3.6.1 SMU measurement 53 3.6.2 LCR measurement 57 第四章 結論 64 參考文獻 65zh_TW
dc.subjectsilicon nanowire field effect transistorsen_US
dc.subjectmicrocontact printingen_US
dc.titleStudy of Cytophobic and Cytophilic Modification on Silicon Nanowire Field Effect Transistorsen_US
dc.typeThesis and Dissertationzh_TW
item.openairetypeThesis and Dissertation-
item.fulltextno fulltext-
Appears in Collections:生醫工程研究所
Show simple item record

Google ScholarTM


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.