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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 謝之真 | zh_TW |
dc.contributor.advisor | Chih-Chen Hsieh | en |
dc.contributor.author | 林志穎 | zh_TW |
dc.contributor.author | Chih-Ying Lin | en |
dc.date.accessioned | 2023-10-03T17:33:50Z | - |
dc.date.available | 2023-11-10 | - |
dc.date.copyright | 2023-10-03 | - |
dc.date.issued | 2023 | - |
dc.date.submitted | 2023-08-09 | - |
dc.identifier.citation | Ehrenhofer-Murray, A.E. DNA | Structure and Function. 2006.
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Dorfman, Tilted hexagonal post arrays: DNA electrophoresis in anisotropic media. Electrophoresis, 2014. 35(2-3): p. 405-411. Thomas, J.D.P. and K.D. Dorfman, Tilted post arrays for separating long DNA. Biomicrofluidics, 2014. 8(3). 陳致安, 以布朗動態法模擬DNA於圓柱陣列微流道中之電泳分離, in 化學工程學研究所. 2015, 國立臺灣大學. p. 1-112. Trahan, D.W. and P.S. Doyle, DNA Collisions with a Large, Conducting Post. Macromolecules, 2010. 43(12): p. 5424-5432. Yasui, T., et al., Arrangement of a Nanostructure Array To Control Equilibrium and Nonequilibrium Transports of Macromolecules. Nano Letters, 2015. 15(5): p. 3445-3451. Wunsch, B.H., et al., Gel-on-a-chip: continuous, velocity-dependent DNA separation using nanoscale lateral displacement. Lab on a Chip, 2019. 19(9): p. 1567-1578. Strom, O.E., J.P. Beech, and J.O. Tegenfeldt, High-Throughput Separation of Long DNA in Deterministic Lateral Displacement Arrays. Micromachines, 2022. 13(10). Han, J., S.W. Turner, and H.G. Craighead, Entropic trapping and escape of long DNA molecules at submicron size constriction. Physical Review Letters, 1999. 83(8): p. 1688-1691. Han, J. and H.G. Craighead, Separation of long DNA molecules in a microfabricated entropic trap array. Science, 2000. 288(5468): p. 1026-1029. Duan, L., Z. Cao, and L. Yobas, Continuous-Flow Electrophoresis of DNA and Proteins in a Two Dimensional Capillary-Well Sieve. Analytical Chemistry, 2017. 89(18): p. 10022-10028. Agrawal, P., Z. Bognar, and K.D. Dorfman, Entropic trap purification of long DNA. Lab on a Chip, 2018. 18(6): p. 955-964. Liu, X., M.M. Skanata, and D. Stein, Entropic cages for trapping DNA near a nanopore. Nature Communications, 2015. 6. Azuma, N., et al., Separation of large DNA molecules by size exclusion chromatography-based microchip with on-chip concentration structure. Japanese Journal of Applied Physics, 2016. 55(6). Heidari, M., M. Mikani, and N. Nikoofard, Mechanism of rectification of polymer motion in an asymmetric nano-channel. Journal of Nanostructure in Chemistry, 2020. 10(2): p. 131-142. Dorfman, K.D., et al., Beyond Gel Electrophoresis: Microfluidic Separations, Fluorescence Burst Analysis, and DNA Stretching. Chemical Reviews, 2013. 113(4): p. 2584-2667. Olson, D.W., et al., Continuous-time random walk models of DNA electrophoresis in a post array: Part II. Mobility and sources of band broadening. Electrophoresis, 2011. 32(5): p. 581-587. Minc, N., et al., Quantitative microfluidic separation of DNA in self-assembled magnetic matrixes. Analytical Chemistry, 2004. 76(13): p. 3770-3776. Larson, R.G., The rheology of dilute solutions of flexible polymers: Progress and problems. Journal of Rheology, 2005. 49(1): p. 1-70. 陳冠綸, 以布朗動態法模擬線形與環形DNA於微流道中之電泳分離, in 化學工程學研究所. 2021, 國立臺灣大學. p. 1-137. Kim, J.M. and P.S. Doyle, A Brownian dynamics-finite element method for simulating DNA electrophoresis in nonhomogeneous electric fields. Journal of Chemical Physics, 2006. 125(7). Toda, M., et al., Statistical Physics II: Nonequilibrium Statistical Mechanics. 2012: Springer Berlin Heidelberg. Grassia, P. and E.J. Hinch, Computer simulations of polymer chain relaxation via Brownian motion. Journal of Fluid Mechanics, 1996. 308: p. 255-288. Marko, J.F. and E.D. Siggia, Stretching DNA. Macromolecules, 1995. 28(26): p. 8759-8770. Jendrejack, R.M., J.J. de Pablo, and M.D. Graham, Stochastic simulations of DNA in flow: Dynamics and the effects of hydrodynamic interactions. Journal of Chemical Physics, 2002. 116(17): p. 7752-7759. Jendrejack, R.M., et al., Effect of confinement on DNA dynamics in microfluidic devices. Journal of Chemical Physics, 2003. 119(2): p. 1165-1173. Heyes, D.M. and J.R. Melrose, Brownian dynamics simulations of model hard-sphere suspensions. 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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/90775 | - |
dc.description.abstract | 近年來,微流道分離DNA的相關技術因其快速、便利且成本低廉的優勢,顯著改善了傳統技術的限制。先前本實驗室曾透過模擬,在微流道中使用高導電性的六角圓柱障礙物陣列,期望藉由電力線會在流體中彎曲並集中穿透障礙物的特性,以改良DNA在高電場下的分離成效。雖然此設計確實提升DNA對障礙物的碰撞頻率,並且DNA也會因長度不同而出現滑行或跳躍行為,但由於長DNA無法在通過障礙物之間的有限時間內改變其拉伸型態,導致每次的撞擊僅是擦過而無法勾住障礙物,所以無法成功的分離DNA。因此在本研究中,我們使用布朗動態法(Brownian Dynamics)模擬DNA於微流道的電泳情形,並在成功重現文獻的模擬結果後,藉由延續高導電性障礙物的效應與多種分離機制的結合,探討改良圓柱陣列幾何以達成快速且妥善分離DNA的方法。
在首次的嘗試中,我們於圓柱陣列移除部分障礙物以創造週期性間隙,期望藉由改變DNA撞擊圓柱前的型態,進而提升DNA撞擊的有效性並改善分離效果。然而,在電場提升的過程中,儘管越大的間隙越能夠提升DNA的有效撞擊分率,但即使在間隙最大的微流道中,長DNA在撞擊障礙物前的鬆弛程度仍會因電場的增強而降低,進而造成有效撞擊次數減少,這不僅導致障礙物未能增進對長DNA的延滯效果,也無法顯著改善分離解析度。 在第二個嘗試裡,我們透過長短DNA滑行與跳躍的行為做為發想,並藉由高導電性圓柱陣列旋轉後所提供之傾斜電泳路線,預期不同長度的DNA會與電場方向產生不同程度的偏移,進而導致DNA的分離。我們預期較長的DNA以斜向滑動收穫較大的偏移角度,較短的DNA則容易跳離傾斜路徑而縮減偏移角度。然而,由模擬的結果發現,除了DNA最突出的鏈段單體是影響其移動方向最主要的因素外,它的折疊行為也會導致電泳路徑的偏離,在兩個因素交互作用下,導致長短DNA之間的偏移角度差異不夠顯著,我們發現無法透過此方法快速分離長短DNA。 在最後的嘗試中,我們借鏡亂度井(entropic trap)的分離機制,在高導電性圓柱障礙物幾何設計一淺缺口,以產生局部位能井限制DNA的行為。由於較大的DNA鏈段較長,接觸陷阱出口的機會較大而逃出的速度較快,進而提供此障礙物應用於DNA分離技術的潛能,我們同時也旋轉障礙物以探討其是否影響DNA之逃脫速度。由DNA與單一障礙物碰撞的延滯時間差異來看,模擬的結果的確印證了我們的預期,但未來仍需藉由優化障礙物之幾何與其於微流道中之排列,再結合先進的製程技術,才能實現於高電場下快速分離DNA之技術。 | zh_TW |
dc.description.abstract | In recent years, microchannel-based DNA separation techniques have overcome the limitations of traditional methods, offering advantages in terms of speed and convenience. In our previous study, we explored the use of highly conductive hexagonal obstacle arrays in a microchannel to enhance DNA separation under high electric fields. While this innovative design did increase the collision frequency between DNA with the obstacles and prompted novel sliding and jumping behaviors in DNA with different lengths, we found longer DNA strands were incapable of adjusting their stretched conformation within the confined time frame available before encountering the obstacles. This led to grazing collisions rather than effective hooking, rendering the DNA separation process inefficient. In this study, we again employ Brownian Dynamics simulations to model DNA's electrophoretic behavior within microchannels with highly conductive obstacles. We aim to achieving swift and efficient DNA separation by refine the geometric attributes of obstacle arrays and by introducing different separation mechanisms.
As the first attempt, we introduced periodic gaps by selectively removing obstacles from the obstacle arrays. The intent was to manipulate the DNA conformation prior to collision with the cylinders, envisioning an enhancement in the efficacy of DNA collisions and consequently, leading to better separation. However, despite the fact that larger gaps indeed increased the effective collision of DNA, longer DNA strands were still unable to adapt their configuration promptly enough before engaging with the obstacles, particularly under stronger electric fields. This resulted in reduced effective collision frequency, a setback that not only thwarted the anticipated augmentation of obstacle hindrance for longer DNA strands but also failed to enhance separation. At the second attempt, drawing inspiration from the novel sliding and jumping behaviors of DNA strands found in our previous study, we conceived an approach involving tilted conductive obstacle arrays, thus creating an inclined electrophoretic pathway. The objective was to induce varying degrees of offset from the electric field direction for DNA of differing lengths, ultimately leading to their separation. We postulated that longer DNA strands would exhibit more pronounced offset angles through sliding while shorter DNA would exhibit less pronounced offset angles through jumping. However, simulation results unveiled a more complex reality. In addition to the influential impact of DNA's most prominent monomer segment on its trajectory, we discerned that DNA folding behaviors also introduced deviations in the electrophoresis path. The intricate interplay between these factors led to insignificant differences in offset angles between short and long DNA strands, resulting in inefficient separation. Finally, we sought inspiration from the separation mechanism of DNA by an entropic trap. To this end, we introduced a cavity on the cylindrical obstacle, creating a localized potential well to restrict DNA behavior. We found that longer DNA segments were more likely to escaping the trap due to their extended length. Furthermore, we explored the impact of obstacle rotation on DNA escape rate. Examination of the temporal discrepancy in DNA delay times upon collision with individual obstacles corroborated our initial expectations. Although this innovative concept held promise for advancing DNA separation technology, realizing DNA separation technology under high electric fields will necessitate further optimization of obstacle geometry and arrangement within microchannels, coupled with the integration of cutting-edge fabrication techniques. | en |
dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-10-03T17:33:50Z No. of bitstreams: 0 | en |
dc.description.provenance | Made available in DSpace on 2023-10-03T17:33:50Z (GMT). No. of bitstreams: 0 | en |
dc.description.tableofcontents | 致謝 I
摘要 II Abstract IV 目錄 VI 圖目錄 X 表目錄 XVIII 第1章 緒論 1 1.1 前言 1 1.2 研究動機與目的 1 第2章 文獻回顧 2 2.1 DNA的性質 2 2.1.1 去氧核糖核苷酸( DNA ) 2 2.1.2 輪廓長度(Contour length) 3 2.1.3 堅韌長度( Persistence Length ) 3 2.1.4 鬆弛時間(Relaxation time) 3 2.2 以高分子模型模擬DNA力學行為 5 2.2.1 理想鏈(Ideal Chain) 5 2.2.2 真實鏈(Real Chain) 7 2.3 線形DNA模型 9 2.3.1 Bead-Stick Model 9 2.3.2 Bead-Spring Model 10 2.4 DNA受到電場之效應 11 2.4.1 電泳(Electrophoresis) 11 2.4.2 DNA 於高電場下之自纏繞現象(Self-Entaglement) 11 2.5 分離DNA之文獻回顧 14 2.5.1 傳統凝膠法(Gel Electrophoresis)[8] 14 2.5.2 脈衝式凝膠電泳(Pulsed Field Gel Electrophoresis, PFGE) 15 2.5.3 圓柱障礙物陣列(Post Array) 16 2.5.4 亂度井(Entropic Trap) 31 2.5.5 快拍法(Snapshot Mode)與終點線法(Finish-line Mode)[37] 35 2.5.6 DNA於微流道電泳之相關參數 37 2.5.6.1 電泳遷移率(Electricphoretic mobility) 37 2.5.6.2 離散係數(Dispersion coefficient) 38 2.5.6.3 分離解析度(Separation resolution) 39 2.5.6.4 匹列數(Péclet number) 41 2.6 微流道設計之改良策略 42 2.6.1 驗證DNA於導電性六角圓柱障礙物微流道的分離結果(Case 1) 42 2.6.2 以週期性間隙結合高導電性圓柱提升撞擊之有效性(Case 2) 43 2.6.3 旋轉高導電性六角圓柱陣列以產生垂直距離的偏移(Case 3) 44 2.6.4 於高導電性圓柱障礙物中創造位能井以侷限DNA (Case 4) 45 第3章 模擬方法 47 3.1 布朗動態法(Brownian Dynamics, BD) 47 3.1.1 布朗力(Brownian Force) 48 3.1.2 彈簧力[40, 45] 49 3.1.3 體積排斥力[40, 46] 50 3.1.4 通道牆壁之體積排斥力[46-48] 51 3.1.5 無因次化 52 3.2 有限元素法(Finite Element Method, FEM) 53 3.2.1 通道中的電場計算[42, 49] 53 3.3 有限元素法結合布朗動態法 57 3.4 本研究之流程 59 3.5 模擬參數設定 60 3.5.1 時間步階 60 3.5.2 參數設定 60 3.6 DNA結果分析 63 3.6.1 DNA移動行為之分析 63 3.6.2 以短距離電泳長度擬合長距離微流道之分離解析度 64 3.6.3 以垂直於流動方向之位置差異分離 64 3.6.4 判定DNA對圓柱障礙物的有效撞擊次數 65 3.6.5 位能井對DNA之延滯時間統計 65 第4章 結果與討論 66 4.1 DNA於不同導電性之六角圓柱障礙物陣列微流道的電泳分離 66 4.1.1 Case 1之電場與電力線分布 66 4.1.2 DNA於Case 1之分離結果 67 4.2 DNA於結合週期性間隙與高導電性圓柱陣列微流道的電泳分離 75 4.2.1 Case 2之電場及電力線分布 75 4.2.2 DNA於Case 2之分離結果 76 4.3 DNA於不同旋轉角之高導電性六角圓柱陣列微流道的電泳分離 86 4.3.1 Case 3之電場及電力線分布 86 4.3.2 DNA於Case 3之分離結果 88 4.4 含位能井之高導電性柱狀障礙物對DNA之侷限行為 95 4.4.1 Case 4之電位及電力線分布 95 4.4.2 DNA於Case 4-1之侷限效果 97 4.4.3 探討Case 4-2對DNA造成之影響 104 第5章 結論與未來展望 110 第6章 參考文獻 114 | - |
dc.language.iso | zh_TW | - |
dc.title | 以布朗動態法模擬DNA於高導電性柱狀障礙物微流道中之電泳分離 | zh_TW |
dc.title | Brownian Dynamics Simulation of Electrophoretic DNA Separation in Highly Conductive Post Array | en |
dc.type | Thesis | - |
dc.date.schoolyear | 111-2 | - |
dc.description.degree | 碩士 | - |
dc.contributor.oralexamcommittee | 童世煌;趙玲;莊怡哲 | zh_TW |
dc.contributor.oralexamcommittee | Shih-Huang Tung;Ling Chao;Yi-Je Juang | en |
dc.subject.keyword | 布朗動態法,DNA,電泳分離,微流道,高導電性,柱狀障礙物,位能井, | zh_TW |
dc.subject.keyword | Brownian Dynamics simulations,DNA,Electrophoresis separation,Microchannel,Highly conductive,Cylindrical obstacle,Potential well, | en |
dc.relation.page | 118 | - |
dc.identifier.doi | 10.6342/NTU202303270 | - |
dc.rights.note | 未授權 | - |
dc.date.accepted | 2023-08-11 | - |
dc.contributor.author-college | 工學院 | - |
dc.contributor.author-dept | 化學工程學系 | - |
顯示於系所單位: | 化學工程學系 |
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