Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/3962
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dc.contributor林淑萍zh_TW
dc.contributor.author江維元zh_TW
dc.contributor.authorChiang, Wei-Yuanen_US
dc.contributor.other生醫工程研究所zh_TW
dc.date2013en_US
dc.date.accessioned2014-06-06T06:25:09Z-
dc.date.available2014-06-06T06:25:09Z-
dc.identifierU0005-1608201320220000en_US
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dc.identifier.urihttp://hdl.handle.net/11455/3962-
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.language.isozh_TWen_US
dc.publisher生醫工程研究所zh_TW
dc.relation.urihttp://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1608201320220000en_US
dc.subject矽奈米線場效電晶體zh_TW
dc.subjectsilicon nanowire field effect transistorsen_US
dc.subject親細胞zh_TW
dc.subject斥細胞zh_TW
dc.subject微接觸式轉印技術zh_TW
dc.subjectcytophilicen_US
dc.subjectcytophobicen_US
dc.subjectmicrocontact printingen_US
dc.title於奈米場效電晶體上親細胞與斥細胞修飾的研究zh_TW
dc.titleStudy of Cytophobic and Cytophilic Modification on Silicon Nanowire Field Effect Transistorsen_US
dc.typeThesis and Dissertationzh_TW
item.languageiso639-1zh_TW-
item.openairetypeThesis and Dissertation-
item.cerifentitytypePublications-
item.grantfulltextnone-
item.fulltextno fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
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