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研究生: 蔣明佑
Chiang, Ming-Yu
論文名稱: 探討製備高度達六百微米之高分子微針
Investigation of fabricating polymeric microneedles with 600 micron in height
指導教授: 莊怡哲
Juang, Yi-Je
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年: 2013
畢業學年度: 101
語文別: 中文
論文頁數: 105
中文關鍵詞: 經皮藥物輸送微針陣列感應耦合電漿離子蝕刻等向性濕蝕刻
外文關鍵詞: microneedle, inductively coupled plasma-reactive ion etching(ICP-RIE), wet etching, polyvinylpyrrolidone(PVP)
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  • 經皮藥物輸送為新興起且具有潛力的給藥方式,不需經肝臟初步代謝且能達到無痛給藥,而微針貼片便可用於經皮藥物的輸送。然而由於人體皮膚並非一個平整平面且有大小不一的曲率變化,因此微針須具備一定的機械強度且高度方能刺穿表皮層。目前有關微針陣列之相關文獻用蝕刻矽晶圓的方法製備out of plane的微針(微針垂直於晶圓表面),其高度最高為接近300μm。另外,雖然可利用光阻劑製作高於300 micron的微針,但製作程序相對的繁瑣。
    本研究希望藉由乾濕蝕刻的兩階段方式,製備出高度達600微米的矽基材微針晶片作為母模,以二甲基矽氧烷(polydimethylsiloxane,PDMS)鑄造負向模,應用於鑄模法製備高分子微針。由實驗結果發現,雖然可以成功地製備出第一階段微針,但在第二階段濕蝕刻時,因金屬遮罩覆蓋均勻度不佳,造成蝕刻液滲入遮罩內破壞微針結構。若以CNC雕刻機製備微柱結構或濕蝕刻製備出的燭台結構,則可以PDMS鑄造負向模後,與第一階段微針之負向模貼合,灌入高分子溶液待其乾燥取出,得到高度達600微米的高分子微針陣列。

    Transdermal drug delivery is a new emerging and potential mode of administration. Since the transdermal route bypasses the first-pass effect of the liver and is painless. The microneedles patch is one of the transdermal drug delivery method. Because human skin is not a flat plane with changing curvature, a certain degree of mechanical strength and height for the microneedles to pierce through the epidermis is required. In the literature, it’s rare to find the height of microneedle arrays(out of plane) larger than 300micron. In some cases, they were fabricated by silicon etching or using photoresist which is a relatively cumbersome process.
    In this study, we intended to fabricate silicon microneedle master mold with height larger than 600 micron by using wet etching and dry etching, followed by obtain the PDMS negative mold to produce polymeric microneedles. The results showed that, although the sharp microneedles were produced, they were destroyed during formation of candleholder-like structure by wet etching. This is becomes of the poor coverage of the masking material. The candleholder-like structure was then obtained separately by wet etching process and CNC micromaching. The negative molds of microneedles and candleholder-like structure were produced and bonded together and the 600 micron high polymeric microneedles were then obtained by casting PVP and drying.

    中文摘要...............................................................Ⅰ Abstract...............................................................Ⅱ 致謝...................................................................Ⅲ 目錄...................................................................Ⅳ 表目錄.................................................................Ⅶ 圖目錄.................................................................Ⅷ 第一章 緒論..............................................................1 1.1 前言..............................................................1 1.2 研究動機..........................................................1 第二章 文獻回顧..........................................................3 2.1 經皮藥物輸送....................................................3 2.2 微針陣列製備.....................................................6 2.2.1微針陣列用於經皮藥物輸送...................................6 2.2.2 微針陣列種類與設計.........................................8 2.2.3 實心微針陣列製備...........................................9 2.2.4 空心微針陣列製備..........................................34 第三章 實驗材料與方法...................................................40 3.1矽微針陣列製備..................................................40 3.1.1實驗材料與藥品............................................40 3.1.2實驗儀器與設備............................................41 3.1.3第一階段乾蝕刻............................................49 3.1.4第二階段濕蝕刻製備燭台狀微結構............................53 3.1.5微針結構上金屬遮罩製備....................................55 3.1.6帶有微針陣列進行等向性蝕刻................................57 3.2 底座柱子狀微結構製備............................................59 3.2.1實驗材料..................................................59 3.2.2實驗儀器與設備............................................59 3.2.3 實驗方法與流程............................................60 3.3 鑄模法高分子微針陣列製備........................................61 3.3.1實驗材料..................................................61 3.3.2實驗儀器與設備............................................61 3.3.3 實驗方法與流程............................................63 第四章 微針陣列之製作與探討.............................................66 4.1 乾式蝕刻........................................................66 4.1.1電漿蝕刻製程探討..........................................66 4.1.2一段式乾蝕刻..............................................66 4.1.3二段式乾蝕刻..............................................71 4.2 等向性溼式蝕刻..................................................73 4.2.1 使用200奈米厚之金屬遮罩........................ ..........75 4.2.2使用400奈米厚之金屬遮罩...................................76 4.2.3 調整試片方向對蝕刻深度與均勻度的影響......................78 4.2.4 容器大小對蝕刻深度與均勻度的影............................80 4.2.5試片大小對蝕刻高度均勻性的影響............................82 4.2.6等向性蝕刻之檢驗..........................................83 4.3結合乾式與濕式蝕刻..............................................86 4.3.1在針尖結構上製備蝕刻遮罩..................................87 4.3.2 製備具有針尖結構之燭台....................................88 4.4 使用兩個負向模製備高分子微針....................................90 4.4.1以燭台狀結構為底座........................................91 4.4.2以柱子狀結構為底座........................................92 第五章 結論.............................................................94 第六章 未來工作與建議...................................................96 第七章 參考文獻.........................................................97 附錄一 油珠在微流道內的運動行為........................................101

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