(3.238.96.184) 您好!臺灣時間:2021/05/18 14:57
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:丁仁奎
研究生(外文):Jen-Kuei Ting
論文名稱:硫醇基丙基三甲氧基矽烷應用於封裝植入式電子功能器之玻璃與白金電極孔隙之探討
論文名稱(外文):Using (3-Mercaptopropyl)trimethoxysilanes as an Adhesion Material for Binding Glass and Platinum in Implantable Bio-electronic Device Application
指導教授:婁世亮
學位類別:碩士
校院名稱:中原大學
系所名稱:醫學工程研究所
學門:工程學門
學類:綜合工程學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:92
中文關鍵詞:生物相容性白金玻璃植入式功能器硫醇基丙基三甲氧基矽烷
外文關鍵詞:3-mercaptopropyltrimethoxysilaneImplantable deviceBoron silicaBiocompatibilityPlatinum
相關次數:
  • 被引用被引用:0
  • 點閱點閱:266
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
植入式電子功能器主要由微印刷電路板和電極所組成,為求微印刷電路板不受體內濕氣所破壞,對其密封有其必要。當硼矽玻璃選用為封裝材料,且貴族金屬選用為電極時,熱熔玻璃封裝法經常是首選。然而,二者之熱膨脹係數不同,密封的要求更顯困難。硫醇基丙基三甲氧基矽烷(3-mercaptopropyltrimethoxysilane, MPTMS) 經水解-縮合反應後形成網狀結構,藉此材料具有silane以及thiol兩種官能基,將其塗附於封裝的接口,有助於接合密封玻璃與白金。本課題探討MPTMS對水氣之阻隔能力;探討MPTMS的物理及化學特性外;並以體外細胞實驗與動物實驗來驗證此材料之生物相容性。研究結果顯示,MPTMS對氦氣之滲透率低達 0.3×10-10 cm3.atm/s,將其浸泡於磷酸鹽緩衝溶液中30天後,該材料對於氦氣亦有雷同之阻隔能力。MPTMS體外細胞實驗結果顯示,它不會使巨噬細胞產生發炎反應。MPTMS植入於老鼠的實驗結果顯示,該材料也不會對生物組織有不良反應。本研究證實MPTMS是生物相容性材料,且對氦氣具阻隔性,具有應用於封裝白金電極與玻璃之可行性。
An implantable electronic device mainly consists of miniaturized electronic print circuit boards (μ-PCB) and metal electrodes. To avoid the μ-PCB from damage by moisture within human body, there is a need to encapsulate it hermetically. The electrodes on the other hand must be touched with body tissues. For a device with such component configuration, the contact between packaging materials used and metal electrodes is inevitable. When boron silica is used as the encapsulating material, often the sintering technology is applied. However, due to the different material’s dissimilar thermal expansion coefficients, tiny gaps around the interface are issues to be overcome. MPTMS (3-mercaptopropyltrimethoxysilane) is proposed to close the gaps. The rationale is that MPTMS contains silane and thiol functional groups that can be bonded to boron silica and platinum, respectively. The physical and chemical properties, the moisture penetrability, and the biocompatibility of MPTMS were investigated. The proof of the bonding between MPMPS and platinum was confirmed by the FTIR, SEM and XPS studies. According to the results of the moisture penetration study, MPTMS was able to minimize the helium leak rate to a level of 0.3×10-10 cm3.atm/s. Furthermore, the biocompatibility study results showed that there was no inflammation response in macrophage cultivations with MPTMS. Finally, when MPTMS was implanted into muscles of rats, no adverse reaction evoked was identified. In conclusion, MPTMS has a great potential to serve as a material for the applications of implantable device that require closing the interface gaps between boron silica and platinum electrodes.
目錄
摘要 I
Abstract II
謝誌 III
目錄 IV
圖索引 VIII
表索引 XII
第一章 緒論 1
1-1前言 1
1-2 文獻回顧 1
1-2-1 MPTMS於電極之應用 2
1-2-2 MPTMS於二氧化矽之應用 3
1-2-3 材料封裝測試相關文獻 3
1-3動機與目的 4
1-4論文架構 5
第二章 理論基礎 6
2-1 溶膠-凝膠法 6
2-2 真空測試與測漏 7
2-2-1真空測漏基本概念 8
2-2-2 系統漏氣之研判 8
2-3 巨噬細胞與發炎反應 9
2-3-1 巨噬細胞(Macrophages) 9
2-3-2內毒素脂多糖 (Lipopolysaccharide, LPS): 9
2-3-3 一氧化氮 (Nitric oxide, NO) 10
2-4 傷口癒合過程 10
第三章 研究方法與設計 12
3-1 研究架構 12
3-2 實驗材料與製備 13
3-2-1 硫醇基丙基三甲氧基矽烷(MPTMS) 14
3-2-2 基底材料 14
3-2-3 玻璃的改質 15
3-2-4 MPTMS 溶膠-凝膠法配製 15
3-3 實驗設計與方法 16
3-3-1材料特性評估 16
3-3-2 封裝孔隙測試 19
3-3-3生物相容性測試 26
第四章 結果與討論 38
4-1 MPTMS複合材料材料特性評估 38
4-1-1 傅立葉轉換紅外線光譜儀 38
4-1-2 X射線光電子光譜 42
4-1-3 掃描式電子顯微鏡/ 能量分散光譜 44
4-2 MPTMS複合材料封裝特性測試 46
4-2-1 電化學離子通透度測試 47
4-2-2 二氧化碳氣體通透度測試 50
4-2-3 氦氣測漏儀封裝測試 51
4-2-4 MPTMS複合材料之穩定性測試 53
4-2-5 MPTMS複合材料封裝於玻璃及白金電極孔隙之抗剪應力探討 54
4-2-6材料拉伸側試 55
4-3 細胞生物相容評估 57
4-3-1 NO 分析 (Nitric Oxide Assay) 57
4-3-2 不同濃度脂多醣對於巨噬細胞的存活率 57
4-3-3 MPTMS複合材料對於巨噬細胞產生Nitrite之影響 59
4-3-4 MPTMS複合材料對於巨噬細胞產生細胞激素 (IL-6) 之影響 64
4-3-5 組織特性評估 65
第五章 結論與未來展望 68
5-1結論 68
5-2未來展望 69
參考文獻 70
附錄A實驗試劑 74
附錄B實驗儀器表 76
附錄C 細胞解凍及繼代培養 77
C-1 RAW 264.7解凍 77
C-2 RAE 264.7繼代培養 77
C-3 RAW 264.7冷凍保存 78
附錄D hematoxylin-eosin (H.E.)染色過程 79





























圖索引
圖2-1待測物抽真空後連接測漏儀器,輔以噴氦氣探針之漏氣位置測定裝置示意圖,稱為真空法 8
圖2-2待測物通以式漏氣體後,以連接吸器探針之測漏儀器測定漏器位製裝置示意圖,稱為充氣法 9
圖3-1研究架構 13
圖3-2 MPTMS結構式 14
圖3-3 MPTMS三維網狀結構 14
圖3-4基材實照圖 (A) 玻璃;(B) 不鏽鋼 和(C) 白金片 15
圖3-5實驗設計項目規劃 16
圖3-6循環伏安法電流-電位關係圖 [26] 21
圖3-7 二氧化碳氣體測漏測試模型 22
圖3-8 (A) 氣體流量裝制 (B) 玻璃管實照圖 23
圖3-9 (A)氦氣測漏儀實照圖(B)測試模組 24
圖3-10 MPTMS複合物長效性探討實驗示意圖 25
圖3-11 MPTMS複合物之抗剪力試驗示意圖 25
圖3-12白金片與玻璃黏合實照圖 (A) 白金片(B) 改質玻璃 26
圖3-13白蛋白檢量曲線 33
圖3-14細胞激素IL-6之檢量曲線 35
圖3-15材料植入實照圖 (A)背部除毛;(B)背部開約1公分之傷口;(C)植入針將 材料植入老鼠背部肌肉和(D)傷口縫合 37
圖3-16 組織包埋機製作組織蠟塊 (A) 組織包埋機;(B) 冰凍蠟塊和(C) 製作完成之石蠟塊 37
圖4-1 (A) MPTMS複合物塗附於改質玻璃之鍵結示意圖(B) MPTMS複合物塗附於不鏽鋼濺鍍白金之鍵結示意圖 39
圖4-2 MPTMS複合物塗附於不鏽鋼濺鍍白金之傅立葉轉換紅外線光譜圖 40
圖4-3 MPTMS複合物塗附於改質玻璃之傅立葉轉換紅外線光譜圖 41
圖4-4 MPTMS複合物塗附於改質玻璃之傅立葉轉換紅外線光譜之硫醇官能基於2500 ~ 2700 cm-1之細掃圖 41
圖4-5 MPTMS複合物塗附於白金底材之高解析電子顯微鏡全能譜圖 42
圖4-6 MPTMS複合物塗附於改質玻璃底材之高解析電子顯微鏡全能譜圖 43
圖4-7 MPTMS複合物塗附於白金底材之高解析電子顯微鏡S2p細掃圖 43
圖4-8 MPTMS複合物塗附於白金底材之SEM圖 44
圖4-9 MPTMS複合物塗附於改質玻璃底材之SEM圖 45
圖4-10 MPTMS複合物塗附於不鏽鋼濺鍍白金之EDX表面元素分析 46
圖4-11 MPTMS複合物塗附於改質玻璃之EDX表面元素分析 46
圖4-12電化學循環伏安法 (A) 拋光白金電極 (B) 塗附2 μL MPTMS複合物於白金電極,掃描溶液:5 mM K3[Fe(CN)6],掃描速率:50 ms 47
圖4-13電化學安培法-白金電極塗附MPTMS複合物,電極保存於PBS溶液中,測試溶液:0.2 mM H2O2 於PBS溶液 48
圖4-14電化學安培法-白金電極塗附MPTMS複合物,於室溫乾燥時間關係圖測試溶液:0.2 mM H2O2 於PBS溶液 49
圖4-15二氧化碳氣體通透-MPTMS複合物塗附於玻璃及白金接合處,以二氧化碳做測試,測試時間24小時 50
圖4-16剪應力與塗附量關係圖 – 分別以3、4及5 μL 之MPTMS複合物黏著改質玻璃與白金片,黏著面積0.88 cm2 56
圖4-17單位面積剪應力與塗附量關係圖 – 分別以3、4及5 μL 之MPTMS複合物黏著改質玻璃與白金片,黏著面積0.88 cm2 56
圖4-18 比較1、10、100及1000 ng/mL 四種不同濃度脂多醣 (LPS) 對於巨噬細胞存活率影響,共培養24小時 58
圖4-19 比較1、10、100及1000 ng/mL 四種不同濃度脂多醣 (LPS) 對於巨噬細胞存活率影響,共培養48小時 59
圖4-20 MPTMS複合物塗附改質玻璃與不鏽鋼濺鍍白金與巨噬細胞共培養24小時(A) 巨噬細胞與材料共培養24小時後,釋放NO之吸光值,(B) 巨噬細胞與材料共培養24小時後之蛋白質含量(BCA) 61
圖4-21 MPTMS複合材料與巨噬細胞共培養48小時後,巨噬細胞產生亞硝酸鹽之定量分析 61
圖4-22 MPTMS複合物塗附改質玻璃與不鏽鋼濺鍍白金與巨噬細胞共培養48小時(A) 巨噬細胞與材料共培養48小時後,釋放NO之吸光值,(B) 巨噬細胞與材料共培養48小時後之蛋白質含量(BCA) 63
圖4-23 MPTMS複合材料與巨噬細胞共培養48小時後,巨噬細胞產生亞硝酸鹽之定量分析 64
圖4-24 MPTMS複合材料與巨噬細胞共培養24小時後,巨噬細胞所釋放出細胞激素(IL-6)之分泌量 65
圖4-25老鼠之體溫量測 66
圖4-26組織切片圖 (A) Normal 40倍;(B) Normal 100倍;(C) 材料與組織切口40倍 和(D) 材料與組織切口100倍 67













表索引
表3-1 RAW 264.7細胞株相關資料 27
表4-1 MPTMS複合物之官能基FTIR圖譜分布範圍 39
表4-2 氦氣測漏儀-MPTMS複合物塗附於玻璃及白金電極封裝孔隙,分別塗附5、10及20μL之MPTMS複合物 52
表4-3 氦氣測漏儀-MPTMS塗附於玻璃及白金電極封裝孔隙之乾燥時間探討 53
表4-4 氣體通透度測試- MPTMS塗附於玻璃及白金電極接合孔隙之長效性探討,將樣品浸入磷酸鹽緩衝溶液1-30天 54
表4-5 MPRMS複合物塗附於玻璃及白金電極封裝孔隙之牢固性 55
[1] J. Gillberg, “Detection of cardiac tachyarrhythmias in implantable devices”, Journal of Electrocardiology, Vol. 40, pp.123~128, 2007.
[2] K. Fritzsche, F. Forster, A. Schweickhardt, et al. “Depressive coping is a predictor for emotional distress and poor quality of life in a German-Austrian sample of cardioverter-defibrillator implant recipients at 3 months and 1 year after implantation”, General Hospital Psychiatry, Vol. 29, pp. 526~236, 2007.
[3] B. Richter, S. EiBele, R. Laszig, E. Lohle, “Receptive and expressive language skill of 106 children with a minimum of 2 years’ experience in hearing with a cochlear implant”, International Journal of Pediatric, Vol. 64, pp. 111~125, 2002.
[4] T. Cameron, “Micromodular Implants to Provide Electrical Stimulation of Paralyzed Muscles and Limbs”, IEEE Transaction on Biomedical Engineering, Vol. 44, No. 9, 1997.
[5] G.E. Loeb, R.A. Peck, W.H. Moore, K. Hood, “BION system for distributed neural prosthetic interfaces”, Medical Engineering & Physics, Vol. 23, pp. 9~18, 2001.
[6] H.J. Park, H.J. Shin, H.S. Jung, “Iodine-catalyzed chemical vapor deposition of Cu on MPTMS monolayer surface in a low deposition temperature regime”, Surface & Coatings Technology, Vol. 201, pp. 9432~9436, 2007.
[7] R. Brito, V.A. Rodriguez, J. Figueroa, C.R. Cabrera, “Adsorption of 3-mercaptopropyltrimethoxysilane and 3-aminopropyltrimethoxysilane at platinum electrodes”, Journal of Electroanalytical Chemistry, Vol. 520, pp. 47~52, 2002.
[8] Y. Shen, T. Wu, Y. Zhang, J. Li, “Comparison of two-type (3-mercaptopropyl)trimethethoxysilane-based networks on Au substrates”, Talanta, Vol. 65, pp. 481~488, 2005.
[9] J. Niedziolka, B. Palys, Robert, Nowakowski, Marcin Opallo,”Characterisation of gold electrodes modified with methyltrimethoxusilane and (3-mercaptopropyl)trimethoxysiloane sol-gel processed films”, Journal of Electroanalytical Chemistry, Vol. 578, pp.239~245, 2005.
[10] Jin-Li Zhang, Wei Li, YI Zhai, et al. ”Growth of SnO2 thin films on self-assembled layers of the short-chain alkoxysilane”, Applied Surface Science, Vol. 245, pp. 94~101, 2005.
[11] H. Shin, M. Agarwal, M. R. DE Guire , A. H. Heuer, “Deposition mechanism of oxide thin films on self-assembled organic momolayers”, Department of Materials Science and Engineering, pp. 801~815, 1997.
[12] Yi Ma, Minghai Li, Hatim Mohamed El-Khair, et al. “Room temperature self-assembly of CdSe nanocrystals on SiO2-coated Si wafer”, Physica E 15, pp. 48~52, 2002.
[13] M. Ben Ali, F. Bessueille, J.M. Chovelon, et al. “Use of ultra-thin organic silane films for the improvement of gold adhesion to the silcon dioxide wafers for biosensor applications”, Materials Science and Engineering C 28, pp. 628~632, 2008.
[14] Xin Liu, Qi Wang, Liu-Ping Chen, “In situ functionalized self-assembled monolayer surfaces for selective chemical vapor deposition of copper”, Applied Surface Science, Vol. 255, pp. 3789~3794, 2009.
[15] Minghui Hu, Suguru Noda, Tatsuya Okubo, et al. “Structure and morphology of self-assambled 3-mercaptopropyltrimethoxysilane layers on silicon oxide”, Applied Surface Science, Vol.181, pp. 307~316, 2001.
[16] 鄭文玲, “共軛亞麻油酸再脂多醣誘發RAW264.7巨噬細胞發炎反應相關事件之影響”, 中山醫學大學營養科學研究所碩士論文, 2003.
[17] D. Heumann, T. Roger, “Initial responses to endotoxins and Gram-nagative bacteria”, Clinica Chimica Acta, pp. 59~72, 2002.
[18] Jen-Yung Tseng, Ming-Hsiang Lin, Lai-Kwan Chau, “Preparation of colloidal gold multilayers with 3-(mercaptopropyl)-trimethocysilane as a linker molecule”, Colloids and Surfaces, Vol. 182, pp. 239~245, 2001.
[19] X. chen and G.S. Wilson, “Electrochemical and Spectroscopic Characterization of Surface Sol-gel Processes”, Langmuir, pp. 8762~8767, 2004.
[20] Ying-Sing Li, Yu Wang, Tuan Tran, Anshion Perkins, “Vibrational spectroscopic studies of (3-mercaptopropyl)trimethoxylsilane sol-gel and its coating”, Spectrochimica Acta, Part A 61, pp. 3032~3037, 2005.
[21] G.E. Loeb, R.A. Peck, J. Singh, et al. “Mechanical Loading of Rigid intramuscular implants”, Biomed Microdevices, pp. 901~910, 20007.
[22] Alexander Kros, Martijn Gerritisen, Vera S.I. Sprakel, Nico A.J.M. Sommerdijk, John A.Jansen, Roeland J.M. Nolte, “Silica-based Hybrid Materials as biocompatible coatings for glucose sensors”, Sensors and Activators B Vol. 81, pp. 68~75, 2001.
[23] Biologicla evaluation of medical devices-part 6:Tests for local effects after implantation, ISO 10993-6, 2007.
[24] P. Pallavicini, G. Dacarro, M. Patrini, “Spectroscopic evaluation of surface functionalization efficiency in the preparation of mercaptopropyltrimethoxysilane self-assembled monolayers on glass”, Journals of Colloid and Interface Science, 2009.
[25] J. Zhao, M. Chem, F. Yan, “Preparation and micro-mechanicla studies of polysiloxane-containing dual-layer film on Au surface”, Colloids and Surface A: Physicochem. Eng. Aspects, 2009.
[26] 吳溪煌, “電化學-理論與應用”, 高立圖書有限公司, 2006.
[27] 呂登復, “實用真空技術”, 黎明出版社, 2000.
[28] 丁南宏, 方宏聲, 方振洲, “真空技術與應用”, 行政院國家科學委員會精密儀器發展中心 2001.
[29] 魏正男, “殘留氣體分析儀在真空設備之應用”, 中原大學碩士論文, 2005.
[30] 劉振軒, 何逸遷, 張文發, “組織病理染色技術與圖譜”, 台灣養豬科學研究所, 1996.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top