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研究生:葉楚彤
研究生(外文):YEH, CHU-TUNG
論文名稱:具自我補償之高穩定度波導模態共振生物感測系統及在C反應蛋白之快速檢測
論文名稱(外文):Highly-Stable Self-Compensated Guided-Mode-Resonance Biosensing System for Rapid CRP Detection
指導教授:張國恩張國恩引用關係
指導教授(外文):CHANG, GUO-EN
口試委員:謝文馨周禮君陳國平
口試委員(外文):HSIEH, WEN-HSINCHAU, LAI-KWANKUO-PING CHEN
口試日期:2020-03-25
學位類別:碩士
校院名稱:國立中正大學
系所名稱:機械工程系研究所
學門:工程學門
學類:機械工程學類
論文種類:學術論文
論文出版年:2020
畢業學年度:108
語文別:中文
論文頁數:55
中文關鍵詞:波導模態共振LED自我補償CRP
外文關鍵詞:Guided-mode resonanceLEDself-compensatedCRP
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本研究發展新型具自我補償機制之高穩定性是以波導模態共振生物感測系統為基礎進行改善,以光強度變化取代光譜儀共振波長飄移變化作為其檢測機制,大幅降低檢測系統架設成本;以系統自我補償方式處理外在環境因素對長時間檢測所造成的系統穩定度問題,並利用波導模態共振式生物晶片結構簡單、高靈敏度與即時檢測等優點,節省量測時間與晶片製作成本。
本研究中為改善傳統系統光源雷射的不穩定性,將量測系統光源更換為二階發光的白光LED搭配濾波片,避免外在環境因素如電壓不穩等情況造成的劇烈強度變化,並為進一步優化量測系統的性能,在量測系統中新增偏振分光鏡,分別離出白光LED中TM mode與TE mode的光強度訊號,其中TE mode用以作為背景訊號,TM mode用以進行實驗量測,並經由設計的補償公式進行運算後得到一新光強度訊號以實現系統自我補償功能,降低系統雜訊以改善系統性能。
而完成自我補償且高穩定的波導模態共振量測系統後,本研究進行折射率實驗與生化實驗驗證系統性能;折射率實驗中我們藉由新系統補償量測到的訊號,將系統之折射率解析度由 RIU降至 RIU;生化實驗中我們測量了兩種生物標記,分別為IgG與CRP,偵測極限(LoD)則分別為 與 ,證明此量測系統對於生化反應檢測的可行性。
藉由架設的新系統可以優秀的量測到敗血症(Sepsis)臨床定義以下的CRP濃度 ,並改善外在環境對量測系統造成的影響,有助於我們繼續將CRP檢測極限降低,以應用在除了敗血症(Sepsis)以外的病症檢測。

This study develops a new type of highly-stable self-compensated guided-mode-resonance (GMR) biosensing system with improved sensing performance. The resonance wavelength shift arose from the change in Refractive Index utilized to change the light intensity to reduce the cost and detection time of the GMR bio-sensing system. An intensity self-compensation method was proposed and developed to reduce the instability caused by external environmental factors for long time detection. The developed GMR biosensing system has the advantages of simple structure, high sensitivity, and rapid detection for cost-effective, rapid, and stable biosensing.
In this study, to improve the laser instability of the traditional system light source, the measurement system light source was replaced with a white LED with a band-pass filter to reduce intensity variation caused by external environmental factors such as voltage instability and temperature. For further optimizing the performance of the measurement system, a polarized beam-splitter was adopted to separate the TM-polarized light and the TE-polarized light from the white LED, in which the TE-polarized light was used as the background signal, and TM-polarized light was used as the light source for the GMR biosensors. After compensating the background noises, our system exhibit significantly reduced noise and improved system performance.
After completing the highly-stable self-compensated guided-mode-resonance measurement system, this study conducted refractive index experiments and biochemical experiments to verify the system performance. In the refractive index experiment, we compensated the measured signal with the new system and reduced the refractive index resolution of the system from 8.62 10-5 RIU to 3.07 10-5 RIU. In biochemical experiments, we measured two biomarkers, namely IgG and CRP, and detection limits (LoD) were 5.5 10-6 g/ml and 1.95 10-8 g/ml respectively, proving the feasibility of this measurement system for biochemical reaction detection.
With the new system installed, the detectable CRP concentration can be lower than the clinical definition of sepsis 5 10-6 g/ml, and the impact of the external environment on the measurement system can be improved. The low LoD of CRP can also enable another diagnosis for clinic applications.

目錄
致謝 i
摘要 ii
Abstract iii
圖目錄 viii
表目錄 xi
第一章 緒論 1
1-1 前言 1
1-2 生物晶片發展近況 2
1-3 光學式生物晶片介紹與選擇 3
1-4 C反應蛋白於敗血症(Sepsis)的檢測標準與檢測近況 3
1-5 文獻回顧 4
1-6 研究動機 14
1-7 論文架構及研究流程 15
第二章 波導模態共振原理 16
2-1 波導理論 16
2-2 繞射光柵原理 18
2-3 漸逝波基本原理 19
2-4 波導模態共振理論 20
2-5 波導模態共振條件 21
2-6 波導模態共振生物感測系統檢測原理 23
2-6-1 光譜共振波長飄移變化 23
2-6-2 光強度變化 24
第三章 波導模態共振感測系統性能提升 25
3-1 運算放大器 26
3-2 LED光源更換 30
3-3 新補償方式建立 30
第四章 訊號補償公式設計及具自我補償之物感測系統驗證 32
4-1 偏振分光鏡式光學量測系統架構 33
4-2 訊號補償公式設計及實驗驗證 35
4-2-1 實驗步驟 35
4-2-2 TM及TE模態訊號強度差值直接補償 37
4-2-3 TM及TE模態雜訊訊號強度倍率補償 39
4-2-4 TM及TE模態雜訊訊號強度標準差倍率補償 42
第五章 具自我補償之高穩定波導模態生物感測系統 46
5-1 免疫球蛋白G(Immunoglobulin G,IgG)生化檢測 46
5-1-1 實驗步驟 47
5-1-2 偵測極限之計算 47
5-1-3 IgG生化檢測實驗結果 49
5-2 C反應蛋白(C-Reactive Protein,CRP)生化檢測 50
5-2-1 實驗步驟 51
5-2-2 偵測極限之計算 52
5-2-3 CRP生化檢測實驗結果 52
第六章 結論及未來研究方向 54
6-1 結論 54
6-2 未來研究方向 54
6-2-1 成功在偏振分光鏡式光學量測系統檢測其他生物發炎因子 54
6-2-2 反射式偏振分光鏡式光學量測系統建立 54
參考文獻 56


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