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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/123456789/64894
完整後設資料紀錄
DC 欄位值語言
dc.contributor.advisor黃念祖(Nien-Tsu Huang)
dc.contributor.authorJhih-Siang Chenen
dc.contributor.author陳志翔zh_TW
dc.date.accessioned2021-06-16T23:06:13Z-
dc.date.available2021-03-03
dc.date.copyright2020-03-03
dc.date.issued2020
dc.date.submitted2020-02-24
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28. Alex, P., et al., Distinct Cytokine Patterns Identified from Multiplex Profiles of Murine DSS and TNBS-Induced Colitis. Inflammatory Bowel Diseases, 2008. 15(3): p. 341-352.
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32. Zhu, J., et al., An integrated adipose-tissue-on-chip nanoplasmonic biosensing platform for investigating obesity-associated inflammation. Lab on a Chip, 2018. 18(23): p. 3550-3560.
33. Cai, Y., et al., Magnet Patterned Superparamagnetic Fe3O4/Au Core–Shell Nanoplasmonic Sensing Array for Label-Free High Throughput Cytokine Immunoassay. Advanced Healthcare Materials, 2019. 8(4): p. 1801478.
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35. Oh, B.-R., et al., Multiplexed Nanoplasmonic Temporal Profiling of T-Cell Response under Immunomodulatory Agent Exposure. ACS Sensors, 2016. 1(7): p. 941-948.
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dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64894-
dc.description.abstract細胞激素作為免疫系統中重要的溝通橋樑,能調節免疫反應,且其與發炎與感染反應有高度相關,故細胞激素的種類及濃度變化可用於觀察人體即時的免疫系統狀態。然而,現今標準的細胞激素檢測技術因其需要使用螢光標定檢測,往往需要大量的樣本體積量、繁複的的標定程序及冗長的反應時間,使其只能量測最後反應的濃度值,無法即時觀察隨著療程而變化的狀態。為了突破上述限制,免標定檢測技術在近幾十年來時常被使用作為細胞激素檢測的平台,而相較於其他類型的免標定檢測技術,光學式的感測器,例如奈米電漿子感測器,則因為其無須複雜系統架設及高靈敏度特性受到相當高的關注,此外將奈米電漿子整合在微流道之裝置還有微量化樣品量、簡化繁複的樣品準備過程、避免樣本損耗甚至能縮短檢測時間的優勢。
在本篇論文中,我們提出兩種製程方式包含快速熱退火及雷射雙光干涉微影結合奈米壓印技術以製作大面積奈米電漿子生物感測器(約平方公分),另外,我們也將自動化微流道裝置、客製化光學平台與奈米電漿子生物感測器整合,用以進行免標定、多重與多工細胞激素檢測同時避免潛在操作錯誤及勞力密集之標定步驟。我們相信此系統能應用於多種生物分子檢測並且充分顯示具有研究細胞表型及疾病診斷之潛力。
zh_TW
dc.description.abstractCytokines are important bridges in the immune system and regulate the immune response, which are highly related to inflammation and infection. Hence, cytokine detection is a perfect index for observing the immune system. However, the current golden standard techniques for cytokine detection not only require large sample volume and labor-intensive labeling processes but also time-consuming and even readout end-point results. To eliminate these limitations, label-free sensors have been applied for cytokine detection over the decades. Compared to other label-free biosensors, optical sensors such as nanoplasmonic sensors receive lots of attention due to its simple system setup and high sensitivity nature. Moreover, nanoplasmonic-integrated microfluidics takes advantage of combining many features in one chip for minimizing the sample volume, simplifying the complicated sample preparation, preventing the sample loss and even shortening the detection time.
In this thesis, we propose two methods to fabricate large-scale nanoplasmonic biosensor (about cm2), rapid thermal annealing (RTA) and laser interference lithography (LIL) combing nanoimprint lithography (NIL). Furthermore, an automated microfluidics control system and a customized optical platform are integrated with the nanoplasmonic biosensor for label-free, multi-parallel and multiplex cytokine detection to avoid any potential operational error and labor-intensive labeling process. We believe this system can be applied for multiple biomarkers detection, which shows the great potential in studying cellular phenotyping and disease diagnosis.
en
dc.description.provenanceMade available in DSpace on 2021-06-16T23:06:13Z (GMT). No. of bitstreams: 1
ntu-109-R06945004-1.pdf: 4789252 bytes, checksum: 9dc4d299a5427129f1f8a9ad6f2c7583 (MD5)
Previous issue date: 2020
en
dc.description.tableofcontents口試委員會審定書 #
誌謝 i
中文摘要 ii
ABSTRACT iii
CONTENTS iv
LIST OF FIGURES vii
LIST OF TABLES xiii
LIST OF ABBREVIATIONS xiv
Chapter 1 Introduction 1
1.1 Research background and motivation 1
1.1.1 Cytokine detection 1
1.1.2 Label-free and real-time biosensing 2
1.1.3 System integration and automation 3
1.2 Literature review 4
1.2.1 Cytokine detection with label-free sensors 4
1.2.2 LSPR technique for multiplex cytokine measurement 5
1.2.3 Automated microfluidics integration 9
1.2.4 Nanoplasmonic and microfluidics system for cellular phenotyping 11
1.3 Thesis structure 13
Chapter 2 Plasmonic theory 14
2.1 Fundamentals of surface plasmons 14
2.2 Theory of localized surface plasmons 16
Chapter 3 Materials and methods 18
3.1 Nanoplasmonic sensor fabrication 18
3.1.1 RTA sensor 18
3.1.2 NHA sensor 19
3.2 Nanoplasmonic sensing system 23
3.2.1 Multiplex microchannel device 23
3.2.2 Automatic microfluidic control system (LabSmith) 25
3.2.3 Optical platform 28
3.3 Immunoassay protocol 30
3.4 Cell trapping device 31
3.5 Cell trapping protocol 32
3.6 Cell culture method 32
3.7 Sample preparation 33
Chapter 4 Simulation 35
4.1 Simulation model 35
4.2 Simulation results and discussion 36
4.2.1 Spectrum and electric field characteristic 36
4.2.2 The influences of geometry 38
Chapter 5 Results and discussion 40
5.1 Nanoplasmonic sensing analysis 40
5.1.1 Nanostructure morphology 40
5.1.2 Spectrum measurement 43
5.2 Dual-mode LabSmith operation validation 46
5.3 Bio-molecule detection 47
5.3.1 Multi-parallel and multiplex immunoglobulin G detection 47
5.3.2 Multi-parallel and multiplex tumor necrosis factor alpha measurement 52
5.3.3 Multi-parallel and multiplex c-reactive protein measurement 55
5.3.4 Multiplex tumor necrosis factor alpha/iummoglobulin G measurement 58
5.4 THP-1 cell trapping in microfluidics 60
5.4.1 THP-1 trapping performance at different loading volumes 62
5.4.2 THP-1 trapping performance at different flow rates 64
Chapter 6 Conclusion and future work 67
Reference 69
dc.language.isoen
dc.subject微流道zh_TW
dc.subject奈米電漿子zh_TW
dc.subject細胞激素zh_TW
dc.subject多重檢測zh_TW
dc.subject多工檢測zh_TW
dc.subjectCytokinesen
dc.subjectNanoplasmonicen
dc.subjectMicrofluidicsen
dc.subjectMultiplex detectionen
dc.subjectMulti-parallel detectionen
dc.title奈米電漿子整合自動化微流道控制系統進行免標定即時多重多工細胞激素檢測zh_TW
dc.titleA Nanoplasmonic-integrated Automatic Microfluidics Control System for Label-free, Real-time, Multi-parallel and Multiplex Cytokine Detectionen
dc.typeThesis
dc.date.schoolyear108-1
dc.description.degree碩士
dc.contributor.oralexamcommittee王倫(Lon A. Wang),林致廷(Chih-Ting Lin),陳奕帆(Yih-Fan Chen)
dc.subject.keyword微流道,奈米電漿子,細胞激素,多重檢測,多工檢測,zh_TW
dc.subject.keywordMicrofluidics,Nanoplasmonic,Cytokines,Multi-parallel detection,Multiplex detection,en
dc.relation.page74
dc.identifier.doi10.6342/NTU202000515
dc.rights.note有償授權
dc.date.accepted2020-02-25
dc.contributor.author-college電機資訊學院zh_TW
dc.contributor.author-dept生醫電子與資訊學研究所zh_TW
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