以布朗動態法模擬DNA在微流道中受流場拉伸之研究

Abstract

我們使用布朗動態法( Brownian dynamics ) 連結有限元素法( Finite element method )模擬DNA於微流道裝置中受流場拉伸之行為，並與實驗結果作比較。這是第一個在複雜流場下模擬DNA之行為並與實驗做比較的研究。由於模擬複雜流場下流體動力作用(Hydrodynamic interaction，HI)的成本太高，我們的模擬忽略HI，也希望藉由本研究評估HI對DNA在複雜微流場中的行為影響有多大，以期在未來裝置設計上作為參考。 本研究使用的三種通道分別為只有漸縮通道的case I、在漸縮通道上游加上漸擴通道之case II以及將case II沿中心線切一半的case III，其中case II與case III為case I 改良後的通道。以DNA的平均伸長量而言，我們的模擬結果雖然定量上與實驗結果有偏差，但整體趨勢與實驗一致。仔細比較個別DNA分子在實驗與模擬中的行為，我們發現：(a)在case II 和case III中，實驗與模擬中皆觀察到DNA在漸縮通道之上游出現「拉伸-旋轉」的預拉伸行為，並在漸縮通道達到較佳的拉伸率。(b) 在case I的實驗中，DNA在漸縮通道中有時會因觸碰通道側壁而發生頭尾位置互換的「翻轉」情形；在模擬中則因側壁上排斥能過於簡化而沒有出現 (c) case III的模擬結果低估DNA的拉伸率，主要成因是因為忽略HI，以致於模擬中沒有出現如實驗觀察中的DNA遷移(migration)。由我們比較結果發現，雖然我們的模擬忽略HI，但只要小心考慮HI造成的效果，模擬仍可以相當準確地用來預測實驗的趨勢，並作為實驗設計的輔助工具。

We used Brownian dynamics-finite element method (BD-FEM) to simulate DNA stretching by pressure-driven flow through a microcontraction, and compared our results with the experimental data. This was the first time that simulations involving DNA in a complex flow field were compared head-to-head against the experimental results. Since including the hydrodynamic interaction (HI) in complex field is prohibitively expensive, we have neglected hydrodynamic interaction in our simulations. Thus, our study shall also give us an evaluation of how important the hydrodynamic interaction is in such a micro-environment. The result can be used to guild the device design in the future. Three devices were used in this study: Case I is a microfluidic device with a simple contraction, case II is different from case I by having an expansion between the inlet of the device and the contraction and case III is derived from case II by cutting case II along its center axis. The simulated average DNA extension was found qualitatively very similar to experimental observation. From the detailed comparison of single DNA behavior, we found: (a) In both simulations and experiments, DNA in case II and case III experienced “rotation-extension” motion in the upstream of the contraction. This “rotation-extension” can facilitate DNA stretch in the contraction as expected. (b) In the experiments of case I, DNA sometimes flipped its head with its tail as a result of the collision with the side wall of the contraction. This phenomenon, however, has not been observed in our simulations due to the oversimplified boundary condition used to exclude DNA from the wall. (c) The simulated average DNA extension in case III was lower than the experimental value. The cause of this deviation was found to be the neglect of HI that in reality will make DNA migrate from the wall and therefore reduce DNA population in the low-extension regime. We conclude that our simulations, even though not including HI effect, can be used as an auxiliary tool for device design as long as the HI effect is carefully evaluated.