生醫樣品準備微流道元件開發

近幾年來，個人照護系統的開發是學界與業界極力發展的目標之一。其中，生物樣品前處理的功能是生醫系統開發所需要的。一般來說，生物樣品準備是將待測樣品經由多重步驟的處理，以提高後段生物分子感測器的精確度及可靠度。然而，現今臨床上主要的樣品準備儀器十分昂貴，並且體積龐大，此特性不利於發展個人照護系統。因此，微流道元件提供了十分有潛力的方法以完成個人照護系統中的樣品準備功能。在此論文中，其目標即是開發適用於個人健康照護系統的樣品準備微流道元件。首先本論文所開發的樣品準備元件為微型流式細胞儀，是藉由單層流道結構及單鞘流注入的微流道元件達成三維空間的粒子聚焦，此單鞘流注入結構可減少外接注入管的數量，減少元件前置校正作業以及元件操作時的誤差。接著，我們期望能夠將樣品準備微流道元件與現今行動裝置完成概念性的整合，以應用於未來行動醫療照護之中。因此，我們進一步開發低功率且電致動的粒子過濾樣品準備元件。其原理是利用行進波電滲泳與粒子表面電滲泳的耦合下，以達成粒子過濾功能。在實驗中，我們成功地過濾HL-60細胞與人體血球。另外，我們利用此元件設計，更進一步利用互補式金氧半(CMOS)的標準製程，實現了流體幫浦整合晶片。最後，為了能夠提高前述的粒子過濾樣品準備元件功能，我們則是進一步開發出小體積、低功率且不需要外加流體幫浦的粒子分離元件，此元件能進一步的將待測樣品中的目標粒子分離出來，其設計原理是利用行進波電滲泳與介電泳兩項電動力學機制，我們成功地達成了1微米與15微米的粒子分離，以及進一步地利用頻率調變達成6微米與10微米的粒子分離。綜合以上所述的三項樣品準備微流道元件，能夠提供一個元件設計概念，使得樣品準備的功能簡易地與其它照護系統的元件相互整合，以達成完整的個人照護系統與行動健康照護系統。

關鍵字

微流道元件；樣品準備；電致動；電滲泳；介電泳；個人照護檢測；行動健康照護

並列摘要

Because of the needs of personalized healthcare, the development of microfluidic devices for miniaturized healthcare systems has been investigated intensively. Sample preparation is one of the important processes in the clinical diagnosis. It is crucial to ensure proper pre-treatment for chemical analysis in various biomedical applications. However, the current sample process is tedious, time consuming, and requires professional operation. Moreover, the clinical instrument is expensive and hard to integrate with the personalized health care system. Therefore, in this thesis, our goal is to develop sample preparation microfluidic devices which are utilized to personal health care system. First, flow cytometry is a well-developed instrument which is usually used in the current sample preparation and clinical diagnosis. However, the traditional flow cytometry is unable to achieve the requirements of the personal health care systems. Therefore, we developed a microfluidic flow cytometry which is characterized of the portability and low cost. Furthermore, the microfluidic flow cytometry is composed of single channel layer and single sheath-flow inlet which is able to eliminate the tedious flow interconnections and complicated operation. Besides the micro flow cytometry, we further develop a particle filtration microfluidic device which is able to be driven through the electricity and low power consumption. Based on this design, it is possible to integrate the sample preparation microfluidic device into the current mobile device. This developed particle filtration microfluidic device is realized through the combining effect of the travelling-wave electroosmosis and electroosmosis on the surface of particle. In the experiments, we successfully filtered out the HL-60 cells and human blood cells. Furthermore, we demonstrated a fluid pump chip integrated with driving circuit using the standard CMOS fabrication. Finally, to expand the sample preparation function based on the electrokinetic mechanisms, we further developed a particle separation microfluidic device with the characteristics of small volume, low-power consumption, and in-situ pump. This particle separation microfluidic device is able to separate the target particles from the test sample. We used the travelling-wave electroosmosis and the dielectrophoresis to achieve the particle separation of the particles in diameter of 1mm and 15um. In addition, we could reduce the size difference of particle separation through tuning applied frequency. In conclusion, this thesis successfully proved three designed concepts for sample preparation microfluidic devices. We expect that these designs provide new methods to develop the sample preparation function utilized in the point-of-care testing, and the mobile healthcare systems.

並列關鍵字

microfluidic device ； sample preparation ； electrokinetic ； electroosmosis ； dielectrophoresis ； point-of-care testing ； mobile healthcare

參考文獻

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生醫樣品準備微流道元件開發

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