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標題: | 整合晶片內全血處理及多種原位生物標記物檢測之自動化微流道系統 The Automated Microfluidic Systems for On-chip Whole Blood Processing and In-situ Multiple Biomarkers Detection |
作者: | 官大涵 Da-Han Kuan |
指導教授: | 黃念祖 Nien-Tsu Huang |
關鍵字: | 微流道,血液處理,系統整合, Microfluidics,Blood Processing,System Integration, |
出版年 : | 2023 |
學位: | 博士 |
摘要: | 血液當中富含血球、蛋白質及外泌體等多種多種物質可供檢測,但傳統的血液分析技術往往耗時耗力且需要大量的血液樣本進行處理,為了解決傳統所遇到的問題,科學家開發了許多血液處理或是感測的微流道系統。然而,在這些系統當中僅有少數將血液處理及感測整合於一個晶片當中,而且感測也往往只針對單一生物標記物。更糟糕的是,大多數的系統還是依賴繁雜的操作,而導致更大的人力需求。有鑑於此,我們目標開發四個整合晶片內全血處理及多種原位生物標記物檢測的自動化微流道系統以針對血液當中的不同成分進行處理和檢測。首先,MBCS可以在單一晶片上針對全血同時進行血漿、紅血球及白血球的分離。而且因為取出來的檢體仍保留著原本的特性,以此可以繼續進行後續檢測。再來,MIPD展示了整合晶片內全血處理及即時血紅素及糖化血色素感測的自動化微流道系統,並實現了”樣本進-結果出”的概念。第三個系統 – MPPS則是可以從僅僅100微升的全血當中抽取血漿,且不造成任何稀釋及血球破裂等狀況。此外,MPPS亦使用自動化控制以進行血漿抽取及感測器清潔等流程。最後,MEVF則是證明了可以利用奈米粒子的尺寸及電性的特性進行二維分離,並展示可以進行外泌體分選的潛力。基於上述結果,我們相信這四個系統具有應用在定點照護進行多生物標記物檢測的潛力。 Blood contains multiple components, including cells, proteins, and extracellular vesicles. Conventional blood analysis techniques are labor-intensive, time-consuming, and large sample volume-required. Many microfluidic systems have been developed to address these problems. However, only a few integrate blood processing and detection into a single chip. The detection is often feasible only for sensing a single biomarker. Even worse, most systems rely on trivial manipulation leading to a higher labor intensiveness. Therefore, we aim to build microfluidic systems integrating on-chip blood processing and in-situ multiple biomarkers detection with automated fluidic control and data acquisition. The first system MBCS enables the simultaneous extraction of plasma, red blood cell, and white blood cell trapping in a single chip. The extracted samples remain at their original properties for further detection. The second system MIPD demonstrates the automated microfluidic system for on-chip whole blood processing and real-time detection of hemoglobin and glycated hemoglobin. The system fulfills the sample-in-result-out concept. The third system MPPS realizes dilution-free and hemolysis-free plasma extraction with only 100 μL blood using sedimentation and filtration. Moreover, the system makes the plasma extraction and sensor washing fully automated. The last system MEVF shows the size and charge-based 2D fractionation for nanoparticles, indicating the potential to separate extracellular vesicles. Based on the result, we believe the four systems can potentially achieve multiple biomarkers measurements in a point-of-care setting. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/87827 |
DOI: | 10.6342/NTU202300658 |
全文授權: | 同意授權(限校園內公開) |
顯示於系所單位: | 生醫電子與資訊學研究所 |
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