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  1. NTU Theses and Dissertations Repository
  2. 工學院
  3. 應用力學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64667
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor黃榮山
dc.contributor.authorKai-Fung Changen
dc.contributor.author張凱峯zh_TW
dc.date.accessioned2021-06-16T22:57:07Z-
dc.date.available2012-08-15
dc.date.copyright2012-08-15
dc.date.issued2012
dc.date.submitted2012-08-09
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64667-
dc.description.abstract隨著近年來社會走向高齡化的趨勢下,對於生醫檢測晶片的需求也日漸增大,對此,本研究建立於微奈米機電系統技術平台下發展生醫感測晶片,並以一個跨領域的整合式系統,具有可攜式、微型化、低成本、高靈敏度、少量檢體、免螢光標記、快速檢測的優勢,以改善傳統大型且高成本的量測設備,研究探討電場操控蛋白質佈植之壓阻微懸臂梁感測系統,對於抗癲癇藥物丙戊酸(Valproic acid)的藥物監測,由於此為常用的藥物,且藥物在血液內濃度過高會導致不良反應(ADR),因此可見藥物監測之重要性。
以壓阻式微懸臂梁發展免螢光標定之生物感測器,生物訊號以力學基礎轉換成電阻訊號做為量測生物濃度的辨識,測量前與自組裝分子(SAM)鍵結後,再與辨識元蛋白(Probing protein)接合固定後,便可量測藥物的反應量。而生物感測器由於在固定辨識元蛋白不良時,造成測量藥物的反應量較小而不易辨認。本研究利用控制不同酸鹼值的溶液環境使辨識元蛋白帶正電性,以電場操控之技術提升辨識元蛋白於壓阻式微懸臂梁感測表面的固定效率,藉此提升藥物測量的反應量。並在上流道設計增加銦錫氧化物(ITO)導電薄膜,結合微懸臂梁內的壓阻作為一對電極成為具有電場操控之微懸臂梁生物感測器。運用電場操控辨識元蛋白質高效率佈植,討論不同電壓下對辨識元蛋白固定後量測丙戊酸(Valproic acid)之影響,實驗成功在電壓60 V下提升辨識元蛋白固定效率後提高測量丙戊酸(Valproic acid)反應3倍之多,而在藥物濃度監測中,在電壓30 V與60 V下成功的定性與定量分析出丙戊酸(Valproic acid)濃度50 ~ 500 μg/mL。
本研究利用電場操控辨識元蛋白之技術,增加辨識元蛋白之固定效率,在此情況下可提升測量的反應量,換個角度看,在同樣的反應量下可減少辨識元蛋白檢體的濃度,以降低生物樣品浪費,對於壓阻式微懸臂梁生物感測器上發展策略性之規劃。
zh_TW
dc.description.abstractTherapeutic drug monitoring is a growing issue to measure specific drugs at timed intervals in order to maintain a relatively constant concentration of the medication in the bloodstream. Recognition and quantification of bio-molecules are irreplaceable in biomedical tests and disease diagnosis. This study focus on the piezoresistive microcantilever biosensor embedded with electrodes for manipulation and enhancement of probing protein immobilization onto sensing surfaces. The electrically protein-manipulated, nanomechanics-based biosensor is featured with significant reduction of usage in probing biomaterials, low production cost and high sensistivity; in addition, real-time detection provide immediate and efficient cares for patients at home or bedside point of care.
Connecting ITO conductive film and piezoresisitive film in microcantilever, to fabricate a biosensor that is capable of manipulating electric field. Based on changes in electrical charges of the protein in different solution environments, the approach in this study enhanced the immobilization efficiency of probing protein onto the surfaces of microcantilever by applying electric field.
As expected, most charged proteins distributed in solution are effectively attracted onto the sensing gold within electric field in high voltage. Under the influence of electric field, the experiment successfully increased the effectiveness of probing protein immobilization by 3 times in which the microcantilever was used in real-time measurement of Valproic acid drug, and its deflection indicates a proportional concentration amount of antigen-antibody interaction. The Valproic acid drug concentration of 50~500 μg/mL has been demonstrated by using this microcantilever biosensor with manipulating electric field.
en
dc.description.provenanceMade available in DSpace on 2021-06-16T22:57:07Z (GMT). No. of bitstreams: 1
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Previous issue date: 2012
en
dc.description.tableofcontents誌謝 i
中文摘要 ii
ABSTRACT iii
圖目錄 vii
表目錄 xiii
符號對照表 xiv
第一章 緒論 1
1.1前言 1
1.2研究動機及目的 2
1.3文獻回顧 3
1.3.1蛋白質特性與其吸附應用之研究 3
1.3.2微懸臂梁生物感測器用於生化檢測 5
1.3.3癲癇症與抗癲癇藥物 12
1.4論文大綱 18
第二章 生物感測器 20
2.1 生物的免疫反應 20
2.1.1抗體 21
2.1.2抗體-抗原辨識 23
2.1.3分子間作用力 24
2.1.4 分子間的親和力與結合常數 25
2.2生物感測器之基本原理 27
2.3.辨識分子層之固定技術 29
2.4螢光免疫分析法 31
2.5 微懸臂梁生物感測器 33
2.6 微懸臂梁的應力變化定義 37
第三章 電場操控壓阻式微懸臂梁之理論分析 40
3.1壓阻材料特性分析 40
3.1.1壓阻因子 41
3.1.2壓阻效應與應力分析 42
3.1.3 多晶矽材料特性與製程分析 49
3.2 微懸臂梁尺寸分析 54
3.3雜訊分析 56
3.4蛋白質操控 58
3.4.1 蛋白質之表面電性 58
3.4.2 電場操控蛋白質之電泳應用 58
3.4.2 電場操控蛋白質之生物感測應用 59
第四章 電場操控型壓阻式微懸臂梁感測器 61
4.1壓阻與中性軸位置之討論 61
4.2壓阻與導線之形狀與尺寸設計 62
4.3陣列壓阻式微懸臂梁感測器之製作 63
4.3.1微懸臂梁薄膜成長與離子佈值 64
4.3.2定義壓阻位置 65
4.3.3定義導線位置與沉積上保護層 66
4.3.4電極區開孔與微懸臂梁厚度校正 67
4.3.5定義微懸臂梁形狀、背蝕刻與感測層金的位置 68
4.3.6 KOH背蝕刻 69
4.3.7 晶圓切割 71
4.4 電場型微流道系統之設計與製作 73
4.4.1 微流道基板製作 73
4.4.2 具電極的流道上蓋製作 74
4.5電路板之設計與製作 79
4.6電場操控壓阻式微懸臂梁感測晶片之封裝 79
4.7壓阻因子之量測 81
4.7.1中性軸計算 81
4.7.2壓阻因子實驗與計算 82
第五章 實驗架構與結果討論 85
5.1溫度補償架構與方法 85
5.2未加電場於丙戊酸之反應量測 87
5.2.1實驗架構與方法 87
5.2.2實驗結果 91
5.3電場操控辨識元蛋白質之研究與實驗結果 94
5.3.1電場操控辨識元蛋白質之操作與實驗設置 94
5.3.2電場操控辨識元蛋白質之元素分析量測 97
5.3.3電場操控辨識元蛋白質之定性照片分析 99
5.3.4 電場操控對於相異濃度丙戊酸之量測反應比較 100
第六章 結論與未來展望 105
6.1結論 105
6.2未來展望 106
參考文獻 107
dc.language.isozh-TW
dc.subject微懸臂梁zh_TW
dc.subject電場操控zh_TW
dc.subject壓阻zh_TW
dc.subject辨識元蛋白zh_TW
dc.subject丙戊酸zh_TW
dc.subjectproteinen
dc.subjectmicrocantileveren
dc.subjectvalproic aciden
dc.subjectpiezoresistiveen
dc.subjectelectric fielden
dc.title利用電場操控蛋白質佈植於壓阻式生物感測器之藥物治療監測應用zh_TW
dc.titleDetection of Anti-epileptic Drug Valproic Acid by Piezoresistive Microcantilever Biosensor with Electric Field Enhanced Probing Protein Immobilizationen
dc.typeThesis
dc.date.schoolyear100-2
dc.description.degree碩士
dc.contributor.oralexamcommittee沈弘俊,王安邦
dc.subject.keyword壓阻,微懸臂梁,丙戊酸,辨識元蛋白,電場操控,zh_TW
dc.subject.keywordpiezoresistive,microcantilever,protein,electric field,valproic acid,en
dc.relation.page112
dc.rights.note有償授權
dc.date.accepted2012-08-10
dc.contributor.author-college工學院zh_TW
dc.contributor.author-dept應用力學研究所zh_TW
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