| 研究生: |
熊思愷 Hsiung, Suz-Kai |
|---|---|
| 論文名稱: |
整合微鏡片之微流體系統及其相關應用 Microfluidic Systems Integrated with Microlens and Their Applications |
| 指導教授: |
李國賓
Lee, Gwo-Bin |
| 學位類別: |
博士 Doctor |
| 系所名稱: |
工學院 - 工程科學系 Department of Engineering Science |
| 論文出版年: | 2006 |
| 畢業學年度: | 94 |
| 語文別: | 英文 |
| 論文頁數: | 105 |
| 中文關鍵詞: | 去氧核糖核酸及蛋白質分析 、毛細管電泳 、微流體聚焦 、多波長光學偵測 、微型鏡組 、微機電系統 、移動壁 、微型混合器 、微流體 、預濃縮 、交流電滲透流 |
| 外文關鍵詞: | Pre-concentration, Microfluidics, MEMS, Moving wall, Micro-mixers, Multi-wavelength detection, Flow focusing, DNA/Protein analysis, Capillary Electrophoresis, AC electroosmosis, Micro-lens |
| 相關次數: | 點閱:180 下載:2 |
| 分享至: |
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近年來,微機電系統製程技術已被廣泛應用於各種微型流體晶片及元件之研究與製作,並有效應用於各種生物醫學之相關領域及應用。應用微機電製程技術所製作之微型流體元件具有降低樣本及試劑使用量、高解析度、快速檢測及降低消耗功率等之優點。而將多種微型流體元件設置於一晶片平台,即可有效達成實驗室晶片(LOC)之概念,並可使多種關鍵之微流體樣本之操控及偵測功能於單一實驗流程中完成。在本論文中,應用一簡單而可靠之微機電製程方法於製作以玻璃及高分子材料為基材之微流體晶片。利用以上技術,本論文成功發展出微光學鏡組及微型樣本預濃縮元件。此外,亦發展出另一簡單而有效之氣動式側向腔體結構。利用將上述腔體設置於微流體管道側之設計,一間隔於兩者之間隙可用於製作一可控制式移動壁結構。此可控制式移動壁裝置可有效應用於控制管道容積,而其變形後之表面輪廓可做為一微型透鏡之應用,更可利用其可控制管道容積之特性,製作一主動控制式微混合器裝置。
本論文藉由整合上述微流體元件,發展出一具備多波長螢光偵測功能之微型生物分子分析偵測系統。藉由設置一組以上之多模態光纖於微型分離管道下游,可使本晶片具有同時偵測多種波長之螢光訊號之功能。為增強測得之螢光訊號強度,一組以上之微透鏡裝置整合於晶片系統中並設置於激發光傳導光纖及偵測光纖前端,藉以有效將激發光源及螢光訊號予以聚焦。此外,於本論文中亦探討一可控制式微鏡組系統。藉由在光纖管道及微分離管道間設置一氣動式側向腔體結構,當介質匹配流體進入腔體結構,流體壓力將使側向腔體結構與微分離管道間之間隙產生形變,而此間隙即為可控制式微透鏡結構。而可控制式微透鏡結構受壓力所產生之變形可用於將激發光源及螢光訊號予以聚焦。由實驗結果可知,上述之微流體晶片可於單一操作過程中有效偵測不同螢光標定之流體樣本。
藉由上述之可控制式微透鏡結構之設計概念,本論文亦發展出一可有效應用於改變微流道容積之可控制式移動壁結構,並將此結構應用於設計一主動式微型混合器裝置。藉由一簡單可靠之母模製作及翻模製程,可快速製作出以彈性高分子材料為基礎之微流體晶片。在主動式微型混合器應用中,可控制式移動壁結構所產生之變形主要應用於微管道內流體樣本之擾動並使兩樣本產生一均勻混合之狀態。藉由改變側向腔體結構之驅動氣壓頻率及氣體壓力,可得到不同之混合效率。此外,藉由側向腔體間不同之操作順序,亦可得到不同之混合效果。於本論文中亦探討一微型毛細管電泳晶片整合交流電滲透流機制之微型樣本預濃縮晶片。為有效提高低濃度樣本之偵測極限,樣本預濃縮裝置的使用則顯得相當重要。在本論文中之濃縮區藉由設置一電極於玻璃基底之微流體管道上,當通入交流電於電極可有效產生交流電滲透流並濃縮流體樣本。流體樣本在進入微分離管道前,可經由預濃縮裝置濃縮流體樣本濃度,並可有效提高螢光訊號強度及偵測極限。
In the last decade, MEMS (Micro-Electro-Mechanical-system) has been widely employed for the microfluidic chip device fabrication, and seems to be a promising technology for the biological analysis application. There are several advantages can be found for the minimization of the microfluidic chip device utilizing MEMS technology including lower sample consumption, high resolution, high throughput analysis, and lower energy consumption. The idea of LOC (Lab-on-a-chip) can be achieved after the integration of several microfluidic components onto one single chip device, and then several curial detection and manipulation procedure of the samples can be completed within one single test. In this study, simple and reliable fabrication processes for polymer material and glass-base microfluidic chip device were developed. Within these approaches, optical detection and microfluidic components including micro-lens structure and sample pre-concentration device were demonstrated and investigated. Furthermore, a simple design of a pneumatic side-chamber was also developed. By placing the pneumatic side-chamer next to the micro sample flow channel, the interval between the side-chamber and microchannel can be used to construct a controllable moving wall structure, so that the proposed moving wall structure can be used for several applications such as active-micromixer.
This study presents a new microfluidic device for high-throughput capillary electrophoresis (CE) analysis utilizing multi-wavelength detection. Pairs of multi-mode optic fibers are embedded at the downstream of the separation channel of the micro-CE chips for multiple-wavelength fluorescence detection. To enhance the fluorescence signals for detection, pairs of micro-focusing lens structures are integrated at the outlets of excitation fibers and inlets of detection fibers, respectively. Moreover, a controllable micro-lens structure was developed by placing pair of pneumatic side-chamber between the micro CE channel and optic fiber channel, after the pressurized index-matching fluid injection, the deformation of the interval between the side-chamber and microchannel can be used to focus the light source and enhance the fluorescent emission. The proposed device can detect multiple samples labeled with different kinds of fluorescent dyes in the same channel in a single run.
According to the design of the controllable micro-lens structure, a novel and simple design of a controllable moving wall structure has been demonstrated for mixing applications. Rapid and reliable fabrication techniques involving standard SU-8 lithography and PDMS replication were employed for the formation of the proposed chip device. The moving wall structures were activated pneumatically to deform the channel walls and generate disturbance effect to the sample stream. By using the electromagnetic valves, the compressed air can be used to control the deflection of the moving wall structures. The effect of the operation frequency has also been investigated. Once the input operation frequency was higher than the response limitation, the mixing efficiency drops sharply because of the moving wall can not be completely deflected to generate enough disturbance effect to the sample stream. The experimental results indicated that the proposed chip device can mix two different samples successfully.
The study also reports a new micro capillary electrophoresis (CE) chip integrated with a sample pre-concentration device utilizing alternating current (AC) electro-osmosis effect. To increase the detectable limits, pre-concentration micro-devices prior to sample separation/detection are of crucial needs. In this study, we utilize a pair of electrodes to generate AC electroosmosis forces such that DNA samples can be focused in a concentration zone, and thus increasing the fluorescence signals. Sample plugs in the microchannel are thus concentrated in the pre-concentration zone. Concentrated samples are then injection into the subsequent separation channels. The developed micro CE devices with the pre-concentration devices can have significant potential for the analysis of the dilute and low concentration DNA samples.
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