發展微流體離心平台上血漿分離及樣本前處理技術

Development of Microfluidic Centrifugal Platform for Plasma Separation and Sample Preparation

陳宣甫(Xuan-fu Chen)

指導教授 ： 郭如男

國立虎尾科技大學/工程學院/自動化工程研究所/碩士(2014年)

https://doi.org/10.6827/NFU.2014.00248

摘要

本研究目的是在微流體離心平台上發展快速血漿分離、平均分流與傾注及混合技術，設計兩組微流體系統包括血漿分離模組、平均分流與傾注模組、微閥門及血漿混合模組並加以整合。第一組晶片設計先將血液注入到血漿分離模組的血液注入槽，當光碟旋轉至第一段轉速時進行血漿分離，分離完的血漿用第二段轉速使得血漿流至平均分流模組達到血漿平均分流，再提高轉速讓血漿定量傾注至檢測槽。第二組晶片設計以第一段轉速將血液離心沉澱分離，再提高轉速將血漿傾注至傾注槽，最後再以混合模組加以混合以血漿與去離子水或凝血酶原試劑進行血漿混合檢測凝血酶原時間。本研究先使用有限元素分析軟體COMSOL來模擬血漿分離、血漿平均分流與傾注及血漿混合的流場分析，模擬出來的結果再經由實驗驗證其正確性。晶片製作是採用微機電製程，先製造出SU-8母模，再利用高分子材料PDMS使用澆注的方式進行翻模，之後將晶片利用氧電漿的方式接合在光碟片上即完成微流體光碟片。實驗顯示血漿分離模組可在光碟1800 rpm，血球容積比6%情況在5~ 6秒達到96%分離效率；所設計的血漿平均分流模組，改變寬度與角度可使分流的差異量在0.5 nL以內達到平均分流，而傾注的部分是依轉速的改變將定量的血漿傾注至檢測槽，混合模組設計有三種Type微流道實驗結果以Type 3的混合效率最高，在轉速3400 rpm時5秒可達到97%的混合效率。

關鍵字

微流體 ； 離心平台 ； 血漿分離 ； 混合 ； COMSOL ； PDMS

並列摘要

In performing blood tests for clinical diagnosis purposes, it is first necessary to separate the plasma from the whole human blood. However, traditional methods for separating and preparing plasma are labor intensive and time consuming. Accordingly, the present study proposes a simple lab-on-CD device in which the plasma is first separated from the whole human blood, then divided into two samples of equal volume, and finally decanted into a detection chamber for analysis purposes. The optimal geometry parameters of the Y-shaped microchannel used to divide the plasma sample are determined by means of computational fluid dynamics (CFD) simulations. The performance of the proposed device is then evaluated using blood samples with hematrocrit concentrations ranging from 6~48%. The results show that given a CD rotation speed of 1800 rpm for a blood sample with a hematocrit concentration of 6%, a separation efficiency of 96% can be achieved within 5~6 s. Moreover, the two plasma samples collected from the left and right branches of the optimized Y-shaped splitter network differ in volume by no more than 0.5 nL. Finally, it is shown that the volume of plasma decanted into the detection chamber can be precisely controlled through an appropriate manipulation of the disk rotation speed. The second objective of this work is to design a microfluidic platform for the separation of plasma from whole human blood and the subsequent mixing of the plasma with a prothrombin time reagent. The results show that mixing efficiency of more than 97% can be obtained within 5 s given a CD rotation speed of 3400 rpm.

並列關鍵字

Centrifugal platform ； Microchannel ； Mixing ； Plasma separation ； COMSOL ； PDMS

參考文獻

[49] 邱繼鋒，“血液在表面張力驅動微流道內之分析”，國立台灣大學工學院應用力學研究所，碩士論文，2007。

[2] A. Manz, N. Graber, and H. M. Widmer, “Miniaturized Total Analysis Systems: A Novel Concept for Chemical Sensing,” Sensors and Actuators B: Chemical, vol. 1, pp. 244-248, 1990.

[3] N. Vandelli, D. Wroblewski, M. Velonis, and T. Bifano, “Development of a MEMS microvalve array for fluid flow control,” Journal of Microelectromechanical Systems, vol. 7, no. 4, pp. 395-403, 1998.

[4] K. S. Yun, I. J. Cho, J. U. Bu, C. J. Kim, and E. Yoon, “A surface-tension

driven micropump for low-voltage and low-power operations,” Journal of Microelectromechanical Systems, vol. 11, no. 5, pp. 454-461, 2002.