摻鍺二氧化矽光波導表面電漿共振生物感測晶片之研發

Design and Development of Surface Plasmon Resonance Biosensor Chip Based On Ge-doped SiO2 Optical Waveguide

李政隆(Cheng-Lung Lee)

指導教授 ： 林啟萬

國立臺灣大學/工學院/醫學工程學研究所/碩士(2004年)

https://doi.org/10.6342/NTU.2004.10362

摘要

在本研究中，主要目的為設計一新型之表面電漿共振( Surface Plasmon Resonance, SPR )光波導生物感測器之設計研發，目標為簡便、便宜且精密的疾病偵測，其優點在於微小化的設計，可以使得樣本需求量減少、更便宜、更方便。
有鑑於傳統表面電漿共振感測元件之量測不易、待測樣本需求量高、量測系統複雜等缺點，故於本研究中，為了改良以上所述之缺點，乃將SPR原理以半導體光微機電技術加以實現，其主要結構為利用半導體製程中的電漿輔助氣相沈積法( Plasmon Enhanced Chemical Vapor Deposition, PECVD )製造摻鍺二氧化矽( )材料，做為光波導材料，研製SPR生物感測晶片，特色為使量測系統微小化、簡單化，並達到少量樣品多參數之高通量檢測。
本研究為求感測元件設計之完整性，設計材料折射率量測、製程參數及軟體模擬等相關實驗，用來得到波導材料的完整物理特性以及製程參數之影響，目的在於使往後的研究能夠以此為基礎，可以根據不同的分析物採用特定之光波導，達到最佳化的感測效率。在材料實驗上，採用摻入不同濃度的鍺，量測其折射率、蝕刻率、沉積率等重要參數，其與濃度和退火溫度之間的關係。
本研究中設計並實現了折射率為1.491之光波導SPR感測晶片，在水溶液的條件下，由數學模擬得知其共振波長大約在600nm~800nm之間。在晶片的設計上，實現了感測區長度分別為200um、250um、500um之單通道感測器，以及感測區長度500um之雙通道感測器，還有感測區長度500um之彎曲雙通道感測器。
實驗的架構上，採用直接以物鏡將光波耦合進波導，再由物鏡加以放大，以觀察光場強度之平面分布，最後再上橫磁波的偏振片，以濾除橫電波，再由光譜儀接收，得到SPR的頻譜。
在波導導光的實驗中，直波導的場型可以被明顯的量測出來，為一多模態之波導，證明所製造的波導是可行的。在彎曲波導的實驗中，並無法得到訊號，可由光阻之照片得知其原因，由於波導的邊壁太過於粗糙造成光訊號損失過大，故無法量測得到光場強度訊號。
在SPR實驗中，採用甘油與水的混合溶液做為量測之物質，因為甘油的折射率較高，而水的折射率低，二者取比例混合後，調配20%、30%、40%、50%、60%之溶液，採用標準的溶液折射率計量測其折射率分別為1.361、1.376、1.391、1.405、1.418，以此做為感測器特性量測的待測物以及模擬的參數。實驗結果顯示，此感測器在20%、30%、40%、50%、60%之甘油溶液中，分別在波長624.5nm、645.7nm、692.5nm、708.5nm、754.3nm產生SPR的現象，與模擬的結果比較，顯示其趨勢相同，可證明此感測器確實可用。
在偏振片放置不同位置之實驗中，當偏振片放置於光源位置時，會有較強的能量，但是是整個頻譜的提升，對於SPR現象並無影響。
在單通道的不同感測長度的實驗中，當感測長度越長時，其SPR共振之波長不變，但強度變化與感測長度成正比，也就是感測面積大時，其變化明顯，這與所預期有相同的結果。
在雙通道的實驗中，分別在兩個通道上滴上20%及60%的溶液，經由可以得到兩個不同共振波長629.1nm及751.2nm的峰值，證明雙通道的概念是可行的，並且可以延伸至多通道。
在生物實驗中，使用鳥類白血病的病毒為感測對象，先固定抗體於晶片上，再滴入病毒，量測其共振波長的變化為2.01nm左右，證實此感測器可做為生物感測之用途。

關鍵字

表面電漿子 ； 生物晶片 ； 生物感測器 ； 光波導 ； 摻鍺二氧化矽 ； 多通道 ； 彎曲光波導 ； 二氧化矽 ； 電漿輔助化學氣相沈積

並列摘要

In the development of miniature surface plasmon resonance (SPR) devices for possible handheld system, integrated optics offer unique capabilities for novel implementations. In this thesis, a Ge-doped silica waveguide, which is fabricated by Plasmon Enhanced Chemical Vapor Deposition (PECVD) and MicroElectroMechanical System (MEMS) technologies, has been completed to demonstrate its feasibility as an SPR biosensor along with a low cost portable system. Compared to the traditional SPR biosensors, our waveguide SPR sensor (WGSPRS) does offer features of miniature in size and sensitivity control through opening window dimensions.
The waveguide materials used in this thesis are silica whose refractive index is 1.469 and Ge-doped silica whose refractive index is 1.492. Both are produced by standard PECVD and wet etching processes, which is highly compatible with existing semi-conductor technology. Optimal process parameters have been acquired during pre-fabrication studies to understand the relationship between the resultant refractive index and its controlling variables, such as doped concentration, spatial variation and annealing temperature.
Three types of ridge waveguides are designed and fabricated in this paper with different claimed features. The first one is a short straight waveguide whose footprint for length and width are 1 cm with a single opening windows and a reference channel. The second one is a long straight waveguide whose length is 3 cm and width is 1 cm with two opening windows for possible cross referencing between samples. The third one is a bending waveguide whose width is 3cm and length is 1 cm with input and output on the same edge of the Si chip for easier alignment with hand held device.
The SPR sensing areas are formed by depositing thickness of 1nm Cr and 50nm Au on opening areas of fabricated waveguides. The effect of various window sizing is tested on the first type of WGSPRS, which include 200um, 250um and 500um length of sensing area. The rest of the two types are having two sensing areas, each with 500um length, on a waveguide for two-channel applications.
The performance of these fabricated WGSPRSs is tested by using different refractive index solutions, which are prepared by mixing different glycerol and water ratio. The concentration ranges from 20%, 30%, 40%, 50% to 60% and whose measured refractive index are 1.361、1.376、1.391、1.405 and 1.418, respectively.
The experimental results on one channel WGSPRSs clearly demonstrated their successes as an SPR sensor. The resonant wavelength, where SPR occurs, in different solutions can be easily observed with a spectrophotometer. Its position changes with the refractive index of the solutions. The different lengths of sensing areas will have effects on the resonant loss of reflective intensity at the SPR occurred wavelengths, which results in better sensitivity and accuracy due to increasing of surface interaction area.
The successful demonstration of two-channel WGSPRSs provides the necessary background for high throughput applications. Two resonant peaks at different wavelengths, 629.1nm and 751.2nm, can be observed on a spectrum when two different kinds of solution are dropped on the two sensing areas of WGSPRS.
In applications of biomolecular interactions, the sensing areas of the WGSPRSs are pre-immobilized with antibody, then the antigen was added to the sensing areas. It results in a 2.01nm shift of resonant peak position.

並列關鍵字

optical waveguide ； Ge-SiO ； biosensor ； biochip ； SPR

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