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研究生:陳國平
研究生(外文):Kuo-Ping Chen
論文名稱:多層膜SPR生醫感測元件之光學導納軌跡設計法與晶片製作
論文名稱(外文):Optical Admittance Loci Design and Chip Fabrication of Multilayer SPR Bio-sensor Device
指導教授:林啟萬林啟萬引用關係
指導教授(外文):Chii-Wann Lin
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:醫學工程學研究所
學門:工程學門
學類:綜合工程學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:英文
論文頁數:80
中文關鍵詞:表面電漿共振生物感測器光學導納軌跡圖
外文關鍵詞:SPRbio-sensoroptical admittance diagram
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表面電漿共振感測器 ( Surface Plasmon Resonance Sensor) 是一種光學式的生物/化學感測器。它具有高靈敏度、免螢光標的物、即時監控、和大量平行篩檢等優點。本實驗室整合SPR感測器為生物晶片中感測元件的部份,可用來檢測介面上的折射率或薄膜厚度的微小變化。利用分析生物分子間的交互作用,將有助於新藥物的開發、疾病的快速檢測、與奈米生物學的發展。
本論文利用薄膜光學的概念來設計製作新式的SPR薄膜元件,引入導納軌跡圖 (Admittance loci) 的設計方法,來調變SPR共振角發生的位置,並改善訊號的解析度。利用高低折射率相間隔的介電質膜與金膜所製作而成的SPR多層膜元件,與傳統單層金膜元件之比較可將原本在74度的SPR共振角調變為63度,訊號的半高寬也減小了三倍以上。此改善將有助於光學量測系統的架設,提高訊號的靈敏度、與增大動態量測的範圍。
在本論文實驗中,我們已成左漣Q用橢偏儀校正了奈米等級 (20~50nm) 的薄膜厚度與其光學常數。在量測系統上,利用反射強度變化可準確的量測到溶液折射率變化量為Δn=9.6*10-6,並及時監控生物分子附著的情形。利用晶片表面固定抗體檢測流道中的禽類白血病病毒,靈敏度可達30 ng/ml。乾燥狀態下表面物理性吸附DNA分子的附著情形,檢測靈敏度可達93.5 ng/ml。並利用微陣列式SPR影像量測,推算不同濃度DNA溶液所形成的表面生物薄膜厚度。
Surface plasmon resonance (SPR) sensor is a kind of optical bio/chemical sensors. It has advantages of high sensitivity, non-labeling, real-time and possible parallel detection. It thus becomes an essential part of integrated biochip system and can be used to detect the tiny changes of the refractive index and film thickness at the interface. By analyzing the interactions of bio-molecules, it is useful for drug screening, high throughput analysis, diseases diagnosis, and the research of nano-biotechnology.
We have applied “admittance loci” method to design our new SPR thin-film device for smaller resonant angle and peak width. By using alternative high/low refractive index dielectric materials of SiO2/TiO2 and gold film, this new multilayer device has the SPR angle of 63 degree (traditional device is 74 degree) and 3 times decreasing of the peak width in the water with BK7 coupling prism and 632nm light source. This improvement is helpful for the optical system alignment, enhancement of sensitivity and extension of the measurement range.
In the experiments of this thesis, we have successfully calibrated the thin-film thickness and the optical parameters by ellipsometry. With this device, we have achieved the resolution of refractive index change of the solution to Δn= 9.6*10-6 by intensity measurement. Avian Leucosis Virus can be detected by the immobilized antibody and the sensitivity can reach 30 ng/ml. The adsorption of DNA molecules can also be measured and the sensitivity can reach 93.5 ng/ml. The microarray SPR image is used to estimate the DNA thinfilm thickness in dry condition.
致謝 I
中文摘要 II
Abstract III
Contents IV
Graph Index VI
Table Index X
Chapter 1 Introduction 1
1.1. Background of the SPR device as a sensor 2
1.2. Motivation 4
1.3. Paper review 6
1.4. Contribution 8
1.5. Structure of this thesis 9
Chapter 2 Surface plasmon resonance 11
2.1. Physics of Surface Plasmon Resonance 11
2.1.1. Plasma 11
2.1.2. Plasmon 13
2.1.3. Surface plasmon (SP) 14
2.2. Excitation of Surface Plasmon Resonance 18
2.2.1. Prism coupling and Total internal reflection 19
2.2.2. Otto and Kretschmann’s configurations for surface plasmon excitation. 20
2.3. Optical thin film simulation 23
2.3.1. Reflectance at the interface 23
2.3.2. Characteristic matrix and equivalent layer 25
2.3.3. Simulation of surface plasmon resonance 26
Chapter 3 Admittance loci applied to SPR thin film design 29
3.1. Admittance Loci 29
3.2 Admittance Loci about surface plasmon resonance 32
3.2.1. Admittance loci of metallic film 32
3.2.2. Admittance loci about oblique incident and TIR 34
3.2.3. Admittance about surface plasmon phenomenon 36
3.3 Simulation program for thin film design 37
3.3.1 Matlab GUI programming 37
3.3.2 Modulating the SPR angle by thin film design 40
Chapter 4 Fabrication and system setup 43
4.1 Thin-film deposit processes 43
4.2 Material calibration test for thin film deposition 47
4.3 SPR measurement system 49
4.3.1 Structure of the prism coupling 49
4.3.2 Optical system setup 51
4.3.3 Self-Assembly monolayer formation 53
Chapter 5 Experimental results and discussion 55
5.1 Material test result 55
5.2 Properties of the multi-layer SPR device 60
5.3 Transmittance and Reflectance measurement 61
5.4 Application experiment 63
5.4.1 Glucose solutions 63
5.4.2. Biomolecule interactions of Antibody–Antigen reaction 67
5.4.3. DNA immobilization 71
Chapter 6 Conclusions and Future works 75
6.1 Conclusions 75
6.2. Future works 77
Bibliography 78
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