設計與製作微流體螺旋結構元件應用於細胞顆粒捕捉之研究

Design and Fabrication of Microfluidic Spiral Structure Devices for Cell Particle Trap

潘昱辰(Pan Yu-Chen)

指導教授 ： 張天立

國立臺灣師範大學/科技與工程學院/機電工程學系/碩士(2017年)

https://doi.org/10.6345/NTNU202202102

摘要

本研究主要設計與製作微流體螺旋結構元件(Microfluidic spiral structure device)於細胞顆粒(Cell particles)行為之探討，以有限元素法(Finite element method, FEM)分析不同設計的微流體幾何結構元件，包括分散(Separation)、聚集(Aggregation)與渦流溢放(Vortex shedding)流場行為及特性。本研究於微流體元件結構分析重點分為三部份：在第一部份單螺旋式微流體結構中，該微流道設計寬度300 μm、環(Loop)間距450 μm與深寬比(h/w) 0.167條件下，產生迪安流(Dean flow)之擺甩運動，並進行相異尺寸細胞顆粒相對位置之研究，其顆粒分散的位置距離微流道內壁面(Inner)分別為55 ± 25 μm (粒徑: 18 μm) 及155 ± 55 μm (粒徑: 5 μm)。第二部份為非對稱式三道分叉流道，為導引分離後不同大小之細胞顆粒至指定微流道元件中，該設計顯示在設計寬度分別為95 μm及120 μm下，針對大/小細胞顆粒導引效率分別為90±1.84%及93±0.79%，以達到分離後即時篩選之效果。第三部份為設計I型柱狀、圓形柱狀以及混合柱狀之微流體結構，為了降低細胞顆粒在微流體系統中之流速，以增加碰撞柱狀結構的機率及聚集調控，達到即時偵測和原位捕捉的能力。本實驗結果顯示以相同流速 1.83 × 10-5 m/s下，細胞顆粒環繞在混合柱狀微流體結構旁之時間達19 sec，相較於I型柱狀與圓形柱狀結構其停留時間提升44%。進一步，本實驗亦以軟微影技術(Soft lithography)製作微流體元件，並投入聚甲基丙烯酸甲酯(Poly methyl methacrylate, PMMA)之微米尺度顆粒，結果顯示實際與模擬顆粒數據於分散效果可達到82%，其聚集效果與模擬數據提升20%。本研究證實了單螺旋式及柱狀結構設計，會有助於提升不同大小之細胞顆粒分散與聚集效果，亦能應用於生物晶片細胞捕抓設計，將能在生醫微流體檢測研究給予重要參考。

關鍵字

螺旋結構 ； 微流體元件 ； 柱狀結構 ； 細胞顆粒 ； 有限元素法

並列摘要

This study mainly presents the design and fabrication of microfluidic spiral structure-based devices for the flow behavior of cell particles. Based on the finite element method (FEM) for the design of microfluidic geometry devices, the characteristics of flow field, including separation, aggregation and vortex shedding can be obtained. In this study the analysis of microfluidic device structures can be divided into three parts. In the first part of a single spiral microfluidic structure device, the design of its channel where the width, loop pitch and aspect ratio (h/w) are 300 μm, 450 μm, and 0.167, respectively. The indicates Dean flow with a pendulum swing to separate the different sizes of cells (particles). The particle diameters in the microfluidic device are 18 and 5 μm, in which the particle distributed locations from the inner wall surface are 55 ± 25 μm and 155 ± 55 μm, respectively. The second part is to use the asymmetric microfluidic channel device with three bifurcated flow channels. To induce the cell particle to the specific channel position (the capacity of cell trap) after the mechanism of separation in microfluidic device, the design widths of the channel are 95 μm and 120 μm where the granules guide efficiency of cell particle can be 90 ± 1.84% and 93 ± 0.79%, respectively. The third part is to design the mixing pillar shape structures (I-based and circular-based pillars) in microfluidic channel device. On the ground that the microfluidic design to reduce the velocity of the cell particles and increase the probability of collision and aggregation control, the real-time detection and capture of cells in microfluidic device can be performed. Under the same velocity of 1.83 × 10-5 m/s, the experimental results show that the cell particles are around the pillar structure about 19 sec in microfluidic device. Compared the I-based and circular-based pillar structures, it can be seen the residence time increases the efficiency of 44%. Finally, the experiment for fabricating the microfluidic devices is employed by soft lithography process. The results show that the both practical experiment and simulation for particle dispersion can reach the efficiency of 82% where the simulation of aggregation increases the efficiency of 20%. This study demonstrates the design of microfluidic spiral structure-based devices that can be useful to enhance the control of dispersion and aggregation at the different cell-particle sizes. Additionally, the study can be used in the design of cell-trapping device for the biomedical detection that will give the significant reference for medical applications of microfluidics.

並列關鍵字

Spiral structure ； Microfluidic devices ； Pillar structures ； Cell particles ； Finite element method

參考文獻

[1] N. L. Huang, L. Ye, W. D. Du, G. E. Schneider, Y. X. Du, Y. H. Xu, L. B. Fan, Development of a novel protein biochip enabling validation of immunological assays and detection of serum IgG and IgM antibodies against Treponema pallidum pathogens in the patients with syphilis, Biosensors and Bioelectronics, Vol. 75, pp. 465-471 (2016)

[2] R. M. Guijt, Future technology for characterizing biotechnology products, Reference Module in Life Sciences, pp. 753-764 (2017)

[3] K. Hashimoto, K. Ito, N. Nakamura, Rapid highly sensitive and highly specific gene detection by combining enzymatic amplification and DNA chip detection simultaneously, Sensing and Bio-Sensing Research, Vol. 8, pp. 27-30 (2016)

[4] L. Bai, S. Guo, W. Wang, H. Cui, L. Li, L. Wei, L. Deng, J. Li, X. Ren, Lab-on-a-chip technologies for genodermatoses: Recent progress and future perspectives, Journal of Dermatological Science, Vol 85, pp. 71-76 (2017)

[5] M. B. Mood, M. Moshiri, L. Etemad, Bio Warfare and Terrorism: Toxins and