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  1. NTU Theses and Dissertations Repository
  2. 電機資訊學院
  3. 生醫電子與資訊學研究所
請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/93071
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dc.contributor.advisor黃念祖zh_TW
dc.contributor.advisorNien-Tsu Huangen
dc.contributor.author葉冠均zh_TW
dc.contributor.authorKuan-Chun Yehen
dc.date.accessioned2024-07-17T16:15:55Z-
dc.date.available2024-07-18-
dc.date.copyright2024-07-17-
dc.date.issued2024-
dc.date.submitted2024-07-10-
dc.identifier.citationREFERENCE
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/93071-
dc.description.abstract在生物感測應用中,侷限型表面電漿共振感測技術因其無標記、動態和易操作的特性而受到廣泛關注。然而,降低製造成本並提高靈敏度仍然是一個挑戰。在本研究中,我們提出了兩種LSPR感測器製造方法,具有 (1) 易於生產;(2) 平方公分等級的感測面積和(3)高靈敏度的特性。第一種製程 (AAO-LSPR感測器) 涉及在多孔、緊密堆積和周期排列的陽極氧化鋁上蒸鍍不同厚度的金奈米陣列。第二種方法(eRTA-LSPR感測器)涉及優化蝕刻時間以在金薄膜上形成粗糙的表面,然後進行快速退火過程以生成隨機排列的奈米金粒子。兩者相比之下, AAO-LSPR感測器具有更高的靈敏度 (193.3 nm/RIU) 和低了一個數量級的最低檢測濃度,而eRTA-LSPR感測器則具備大量生產的商業潛力和更高的均勻性。我們還開發了一種光譜掃描演算法,以減少由於感測器表面微小差異引起的消光光譜標準偏差。在程式的幫助下,我們能夠實時觀察生物分子的反應情況以優化各種檢測參數並取得最佳結果。最終,成功使用AAO-LSPR感測器測量了濃度範圍為0.1至3 μg/mL的C反應蛋白 (CRP)和濃度範圍為1至10000 ng/mL的降鈣素原 (PCT);eRTA-LSPR感測器則涵蓋了濃度範圍為1至10 μg/mL的CRP和濃度範圍為10至10000 ng/mL的PCT。本研究提出兩種LSPR感測器並以label-free的方式成功量測接近臨床參考值的生物分子,在臨床定點照護儀器上具有重要發展潛力。zh_TW
dc.description.abstractLocalized surface plasmon resonance (LSPR) has gained significant attention in biosensing due to its label-free, dynamic, and easy-to-operate nature. However, challenges remain in reducing fabrication costs and increasing sensitivity. This study proposes two LSPR sensor fabrication methods aimed at (1) ease of production, (2) cm² scale sensing area, and (3) high sensitivity. AAO-LSPR sensor involves creating nano-gold arrays with varying thicknesses on porous, closely-packed, and periodically arranged AAO. eRTA-LSPR sensor uses different etching times to form irregular surface undulations on gold, followed by RTA to generate randomly arranged nano-gold particles. Comparatively, the AAO-LSPR sensor shows higher sensitivity (193.3 nm/RIU) and a detection limit improved by an order of magnitude. In contrast, the eRTA-LSPR sensor has significant commercial potential due to its mass production capability and higher uniformity. Additionally, a spectrum mapping algorithm was developed to reduce the standard deviation of the extinction spectra caused by subtle surface differences. This program allowed real-time observation (approximately every 2 seconds) of biomolecule binding, optimizing various detection parameters. Ultimately, successful measurements were achieved using the AAO-LSPR sensor for CRP concentrations ranging from 0.1 to 3 µg/mL and PCT concentrations from 1 to 10,000 ng/mL. The eRTA-LSPR sensor covered CRP concentrations from 1 to 10 µg/mL and PCT concentrations from 10 to 50,000 ng/mL. This study proposes two LSPR sensor fabrication methods that successfully measure biomolecules near clinical reference values in a label-free manner, demonstrating significant potential for development in point-of-care clinical instruments.en
dc.description.provenanceSubmitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-07-17T16:15:55Z
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dc.description.provenanceMade available in DSpace on 2024-07-17T16:15:55Z (GMT). No. of bitstreams: 0en
dc.description.tableofcontents口試委員會審定書 i
誌謝 ii
中文摘要 iii
ABSTRACT iv
CONTENTS v
LIST OF FIGURES vii
LIST OF TABLES xi
Chapter 1 Introduction 1
1.1 Plasmonic sensing systems 1
1.2 Literature review 3
1.2.1 Plasmonic sensing techniques for biomolecular detection 3
1.2.2 Fabrication methods of nanostructures 9
1.2.3 Applications of anodic aluminum oxide (AAO) 12
1.2.4 Applications of RTA processing 17
1.2.5 Research motivation 19
Chapter 2 LSPR theory 20
Chapter 3 Materials and methods 22
3.1 AAO-LSPR sensor without lift-off process 22
3.1.1 Anodization of aluminum 22
3.1.2 AAO fabrication process improvement 25
3.1.3 Current fabrication problems 27
3.2 Fabrication of AAO-LSPR sensor 27
3.2.1 Surface pre-cleaning of glass substrate 27
3.2.2 MPTMS modification on glass substrate 27
3.2.3 Formation of gold nanodisk structures on the glass substrate 28
3.2.4 Microfluidic channel attachment 29
3.3 Fabrication of eRTA-LSPR sensor 30
3.4 Comparison of three LSPR sensor fabrication methods. 33
3.5 The spectrum mapping algorithm and data filtering 35
3.6 Preparation and antibody modification of the sensor 37
3.6.1 Storage of chemicals and biomolecules for surface modification 37
3.6.2 Surface modification procedure 37
3.7 Optical setup and automated microfluidic control system 40
Chapter 4 Results and discussion 43
4.1 Particle size and period analysis 43
4.2 Optimization of AAO-LSPR sensor fabrication method 44
4.3 Optimization of eRTA-LSPR sensor fabrication method 46
4.4 Extinction spectra post processing 48
4.5 Optimization of antibody modification density 49
4.5.1 Without BSA blocking 49
4.5.2 With 1% BSA blocking 51
4.6 Biomarker detection 54
4.6.1 CRP detection 54
4.6.2 PCT detection 57
Chapter 5 Conclusion 59
Chapter 6 Future work 60
REFERENCE 62
-
dc.language.isoen-
dc.subject快速熱退火zh_TW
dc.subjectC反應蛋白zh_TW
dc.subject降鈣素原zh_TW
dc.subject生物感測器zh_TW
dc.subject光譜掃描演算法zh_TW
dc.subject侷限型表面電漿共振zh_TW
dc.subject陽極氧化鋁zh_TW
dc.subjectSpectrum mapping algorithmen
dc.subjectPCTen
dc.subjectCRPen
dc.subjectBiosensorsen
dc.subjectRTAen
dc.subjectAAOen
dc.subjectLSPRen
dc.title陽極氧化鋁基板與蝕刻式快速熱退火製造侷限型表面電漿共振感測器進行生物分子之檢測zh_TW
dc.titleThe Anodic Aluminum Oxide (AAO) Templates and Etching-based Rapid Thermal Annealing (eRTA) Fabricated Localized Surface Plasmon Resonance Sensors for Biomolecular Detectionen
dc.typeThesis-
dc.date.schoolyear112-2-
dc.description.degree碩士-
dc.contributor.oralexamcommittee林鼎晸;林致廷;王倫zh_TW
dc.contributor.oralexamcommitteeDing-Zheng Lin;Chih-Ting Lin;Lon Wangen
dc.subject.keyword侷限型表面電漿共振,陽極氧化鋁,快速熱退火,生物感測器,C反應蛋白,降鈣素原,光譜掃描演算法,zh_TW
dc.subject.keywordLSPR,AAO,RTA,Biosensors,CRP,PCT,Spectrum mapping algorithm,en
dc.relation.page66-
dc.identifier.doi10.6342/NTU202401662-
dc.rights.note同意授權(限校園內公開)-
dc.date.accepted2024-07-11-
dc.contributor.author-college電機資訊學院-
dc.contributor.author-dept生醫電子與資訊學研究所-
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