我們使用布朗動態法(Brownian dynamics)連結有限元素法(finite element method)來設計能夠更有效率地拉伸DNA的微流道裝置。我們希望能將這種新設計應用於基因圖譜技術。我們的設計以Kim 和 Doyle[1] 的漸縮通道裝置為基礎,以電場梯度來拉伸DNA。為了提高DNA的拉伸效率,我們提出兩種在DNA進入漸縮通道前的預處理策略。第一種為先使用漸擴通道來對DNA做漸縮通道對稱軸垂直方向的預拉伸,然後將已經部分拉伸的DNA往漸縮通道對稱軸旋轉,則此DNA能夠於漸縮通道中經歷第二次拉伸。就結果而言,DNA能在進入漸縮通道前就具有較高的拉伸狀態,因此能夠達到較高的拉伸效率。第二種策略為先將DNA做震盪拉伸的預處理,這種預處理在理想情況下能夠有效率地減低DNA的摺疊率,然而這種預處理模式無法明顯地提升DNA之拉伸效率,我們發現原本的預測會錯誤是由於選擇不正確的流場。 我們接著測試我們的設計是否能夠有效地拉伸更大分子量的DNA。發現新設計的拉伸效率會隨分子量增大而逐漸遞減。藉由分析DNA在裝置中的拉伸分布,我們提出另一種新設計。這種新設計主要是利用裝置邊界對DNA的體積排斥力,以降低DNA摺疊的機率。由我們的模擬結果發現即使在更低電場梯度下,這種新設計也能大幅提高大分子量DNA的拉伸效率與拉伸均勻度。
We use Brownian dynamics-finite element method (BD-FEM) to design microfluidic devices that are capable to efficiently and uniformly stretch DNA for the application of gene mapping. Our design is based on the devices proposed by Kim and Doyle[1] that stretches DNA electrophoretically with the electric field gradient generated in a hyperbolic contraction. To enhance DNA stretching, we propose two strategies that pre-condition DNA before they enter the contraction. For the first approach, we pre-stretch DNA in the direction perpendicular to the funnel axis with a expansion geometry. The partially stretched chains are then turned to align with the axial of the funnel, and experience the second stretching. As a result, DNA chains adapt more extended configurations before going into the funnel, and therefore achieve a higher degree of extension. For the second approach, we pre-condition DNA conformation using an oscillating extensional electric field that has been shown to effectively reducing the population of folded DNA at an ideal condition. However, this approach shows negligible effect in our design, and we find that the original prediction was actually wrong due to the erroneous choice of flow filed. We further examine the efficiency of our design for stretching longer DNA. It is found the performance of the pre-conditioning strategy deteriorates with increasing DNA molecular weight. By analyzing the probability distribution of DNA extension in the device, we propose a new design that utilizes the excluded volume effect of the device boundary to prevent the formation of folded DNA. Our simulation results indeed show that the design with both tricks can provide very uniform, highly stretched DNA even under relatively low field gradient.