以布朗動態法模擬DNA於圓柱陣列微流道中之電泳分離

Abstract

本研究利用電腦模擬，以布朗動態法(Brownian Dynamics)和有限元素法做結合，測試DNA在六角排列之圓柱陣列微流道中的電泳分離。在直流電場下DNA會與圓柱障礙物有碰撞、上鉤與脫鉤的行為，而不同分子量的DNA經歷此一連串的行為所需的時間也不同，因而能達到分離的效果。此研究從參考文獻開始，一步步從發現前次設計的問題再做改良，共模擬了四種不同的設備與電場模式。 首先我們參考文獻中，使用絕緣圓柱障礙物於微流道中以六角陣列排列，利用連續恆定的直流電場作為電泳驅動的結果，發現在高電場下DNA以直線型態於圓柱之間前進，大幅減少了碰撞機率，因此也嚴重影響到分離的效率。因此為了增加高電場下碰撞的頻率，我們將障礙物改為具高導電性的物質，電力線會向障礙物內縮，也就是電場驅使流道中的物質朝向障礙物進行碰撞，但如此的改良僅讓DNA擦過所有接近的障礙物，並沒有上鉤與脫鉤的過程，仍無法加大不同DNA間的距離，且DNA仍是以直線型態於圓柱之間前進。因此我們將目標轉移為改變DNA在碰撞前的型態，將連續性直流電場改變為間歇性電場，當電場關閉時DNA能鬆弛成線圈狀，提升垂直電場方向的投影長度，如此一來電場再啟時DNA就能造成有效碰撞，提升上鉤與脫鉤的頻率進而增加分離效率，但從DNA的鬆弛過程中我們發現，六角陣列排列的障礙物限制了DNA鬆弛的空間，使得DNA常只是縮短，仍為直線狀，因此我們再將障礙物的排列加入週期性的空隙，增加DNA鬆弛的空間，使DNA在電場關閉時增加鬆弛成線圈狀的機率，進而提升上鉤的機率而增加分離解析度。

Electrophoretic separation of DNA through a post array has been heavily investigated in both experiments and simulations. However, the efficiency of the post array for separating long DNA has been found decreased rapidly with increasing Peclet number (or electric field). The loss of resolution power is largely due to the onset of channeling phenomenon that DNA move through the hypothetical “channel” between posts without collisions with the posts. To improve the efficiency of separation at high Peclet number, we propose to use several revised devices. The first is to substitute insulated post with conductive post, in order to increase colliding frequency. But most of the collision is not efficient hooking. Then we introduce intermittent electric field to replace the traditionally adopted constant electric field. When the electric field is turned off, DNA relax and diffuse, resulting in higher probability of collision with posts as the field is turned on. Furthermore, we create periodic spacing in post array, in order to increase spacing for DNA to relax. To test our idea, we have used Brownian dynamics simulations and computational fluid dynamics to simulate lambda-DNA(48.5 kbp) and T4GT7-DNA (166 kbp) under intermittent electric field through a hexagonal post array.