簡易檢索 / 詳目顯示

研究生: 周世彥
Chou, Shih-Yen
論文名稱: 以多維結構之微流體元件於糖尿病檢測之應用
Study of Multi-Dimensional Structure-based Microfluidic Device for Diabetes Detection
指導教授: 張天立
Chang, Tien-Li
學位類別: 碩士
Master
系所名稱: 機電工程學系
Department of Mechatronic Engineering
論文出版年: 2017
畢業學年度: 105
語文別: 中文
論文頁數: 100
中文關鍵詞: 皮秒脈衝雷射靜電紡絲製程微流體元件奈米線糖尿病
英文關鍵詞: Picosecond pulse laser, Microfluidic device, Nanowire, Diabetes
DOI URL: https://doi.org/10.6345/NTNU202202921
論文種類: 學術論文
相關次數: 點閱:211下載:0
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 奈微米製程技術發展不斷創新,進而可使元件的體積微小化、降低重量,同時提升單位面積的結構密度於產品的應用。目前微流體元件具有輕薄、價格低廉、即時檢測、可攜、樣本微量化和定量分析檢測的優點,將可有效獲得身體的資訊,在疾病初期獲得有效治療,也能有治療及疾病追縱的功能。本研究結合兩種奈微米製程製造微流體元件,以波長(Wavelength)為355 nm皮秒脈衝雷射(Picosecond pulse laser)製程,藉由探討不同雷射能量密度(Fluence)對玻璃基板寬度(Width)和深度(Depth)的影響,直寫長2 cm、寬2 mm、深度300 m的流道,並在流道上製作直徑400 m的微圓柱(Pillar)結構。另一方面,以靜電紡絲製程(Electrospinning process)在微圓柱上製作線徑為285 nm聚丙烯腈(PAN, Polyacrylonitrile)的奈米線,PAN奈米線會因微圓柱結構而形成三維奈米線支架,在微流體元件周圍塗UV固化膠,以蓋玻片封裝,並進一步進行細胞攔截測試。以肺腺癌細胞(A549)作為多種微流體元件攔截率測試之檢體,在細胞濃度為1.35×107 cell/mL下,以流量5 mL/hr流入0.2 mL,於僅有流道的微流體元件攔截率為41.54%,於同時具有流道和一維奈米線結構於微流體元件的攔截率為53.93%,於同時具有流道和三維奈米線結構在微流體元件的攔截率為100%,利用微流體元件捕捉細胞之功能捕捉紅血球(Red blood cell, RBC),具血液純化的作用,以能增加糖化血色素檢測的準確性,有效應用於糖尿病(Diabetes)檢測。

    Since the innovation of the micro-nanotechnology, the volume of device can be miniaturization, reduced weight, and enhanced the density of structure per unit area. Because the advantages of microfluidic device are light thin, low cost, real-time detection, portable, sample miniaturization, quantitative analysis, people can obtain the information about their bodies from these. Hence, the patients can get effectively treatment early and also follow the recover from the illness. In this study, the picosecond pulse laser and electrospinning processes were used to formed the microfluidic device and nanowires, respectively. Due to the effects of the different fluence on glass substrate, it can fabricate the structure device with the different width and depth, laser ablated channel (length 2 cm, width 2 mm, depth 300 m) and micro-pillar (diameter 400 m). And then, the formed Polyacrylonitrile (PAN) nanowires scaffold can be on micro-pillar by electrospinning. Here, microfluidic device was engaged by UV glue and driving by syringe pump. Finally, microfluidic device can test based on intercept rate by adenocarcinomic human alveolar basal epithelial cells (A549). When the A549 concentration was 1.35×107 cell/mL, the microfluidic device indicated that only channel intercept rate was 41.54% and the channel with one-dimensional nanowire structure microfluidic device intercept rate was 53.93%. Additionally, the channel with three-dimensional nanowire structure microfluidic device intercept rate was 100%. Therefore, the design of microfluidic device was able to capture the red blood cells (RBC) in order to purify blood and increase glycosylated hemoglobin sensing for diabetes detection.

    摘要 ii Abstract ii 總目錄 iii 圖目錄 vi 表目錄 xii 第一章 緒論 1 1.1研究背景與目的 1 1.2生醫晶片簡介 2 1.3雷射簡介 2 1.4靜電紡絲製程簡介 3 第二章 文獻回顧 9 2.1微流體元件 9   2.1.1微影製程 9   2.1.2微細製程 9   2.1.3雷射製程 10 2.2靜電紡絲製程 11 2.3 生醫晶片應用 13   2.3.1細胞培養 13   2.3.2疾病檢測 13 第三章 研究設計與實驗規畫 47 3.1 研究設計 47 3.2 雷射製程 47   3.2.1 雷射加工 48   3.2.2 移除能量閥值 49   3.2.3 雷射掃描間距和探討介面關係 50 3.3 靜電紡絲製程 50   3.3.1 聚乙烯醇奈米線 50   3.3.2聚丙烯腈奈米線 51   3.3.3 孔隙率計算 51 3.4 封裝 52 3.5 細胞來源 53 3.6 細胞觀察 53   3.6.1 螢光顯微鏡 53   3.6.2 掃描式電子顯微鏡 54 3.7 微流體元件攔截率 54 3.8 血糖量測 55 3.9 實驗設備 55 第四章 研究結果與討論 67 4.1 玻璃基板之雷射能量測試 67   4.1.1 雷射能量密度和寬度關係 67   4.1.2 雷射能量密度和深度關係 67   4.1.3 親疏水性 68 4.2 流道製作結果 68 4.3 奈米線測試 69   4.3.1 PVA奈米線 69   4.3.2 PAN奈米線 70 4.4 PAN奈米線支架 70 4.5 封裝 71 4.6 細胞來源 71 4.7 攔截率測試 72 4.8 細胞投入微流體元件 72 4.9 血糖量測 73 第五章 結論與未來展望 93 5.1結論 93 5.2未來展望 94 參考文獻 95

    [1] 健康雜誌187期, 20140601
    [2] 臺灣醫界, Vol 54,No.3 2011
    [3] Lab on a Chip.gene-quantification.info
    [4] Microfluidic device market and forecast from 2011 to 2018, Yole Développement report (2011).
    [5] L. Mercante, V. Scagion, F. Migliorini, L. Mattoso, D. Correa, “Electrospinning-based (bio)sensors for food and agricultural applications: A review”, TrAC Trends in Analytical Chemistry, Vol. 91, pp. 91-103 (2017).
    [6] A. Babace, D. Pérez, D.J. Hansford, S. Arana, E. Lorenzob, M. Mujika, “Single-cell trapping and selective treatment via co-flow within a microfluidic platform”, Biosensors and Bioelectronics, Vol. 61, pp. 298-305 (2014).
    [7] S. Ameri, P. Singh, S. Sonkusale, “Utilization of graphene electrode in transparent microwell arrays for high throughput cell trapping and lysis”, Biosensors and Bioelectronics, Vol. 61, pp. 625-630 (2014).
    [8] S. Lee, K. Hyun, S. Kim, J. Kang, H. Jung, “Continuous enrichment of
    circulating tumor cells using a microfluidiclateral flow filtration chip”, Journal of Chromatography A , Vol 1377, pp. 100-105 (2015).
    [9] D. H. Kuan, I. S. Wang, J. R. Lin, C. H. Yang, C. H. Huang, Y. H. Lin, C. T. Lin, N. T. Huang, “A microfluidic device integrating dual CMOS polysilicon nanowire sensors for on-chip whole blood processing and simultaneous detection of multiple analytes”, Lab on a chip, Vol. 16, pp. 3015-3113 (2016).
    [10] Y. Liao, J. Song, E. Li, Y. Luo, Y. Shen, D. Chen, Y. Cheng, Z. Xu, K. Sugiokad, K. Midorikawa, “Rapid prototyping of three-dimensional microfluidic mixers in glass by femtosecond laser direct writing”, Lab on a Chip, Vol. 12, pp.746-749 (2012).
    [11] S. Darvishi,T. Cubaud, J. Longtin, “Ultrafast laser machining of tapered microchannels in glass and PDMS”, Optics and Lasers in Engineering, Vol. 50, pp.210-214 (2012).
    [12] E. Bulushev, V. Bessmeltsev, A. Dostovalov, N. Goloshevsky, A. Wolf, “High-speed and crack-free direct-writing of microchannels on glass by an IR femtosecond laser”, Optics and Lasers in Engineering, Vol. 79, pp.39-47 (2016).
    [13] C. Pana, K. Chena, B. Liu, L. Rena, J. Wang, Q. Hua, L. Liang, J. Zhou, L. Jiang, “Fabrication of micro-texture channel on glass by laser-induced plasma-assisted ablation and chemical corrosion for microfluidic devices”, Journal of Materials Processing Technology, Vol. 240, pp. 314-323 (2017).
    [14] Y. Liu, G. Ma, D. Fang, J. Xu, H. Zhang, J. Nie, “Effects of solution properties and electric field on the electrospinning of hyaluronic acid”, Carbohydrate Polymers, Vol. 83, pp. 1011-1015 (2011).
    [15] K. Matsubara, S. Huang, M. Iwamoto, W. Pan, “Enhanced conductivity and gating effect of p-type Li-doped NiO nanowires”, Macromolecules, Nanoscale, Vol. 6, pp. 688-692 (2013).
    [16] X. Jiang, T. Herricks, Y. Xia, “CuO nanowires can be synthesized by heating copper substrates in air”, Nano Letters, Vol. 2, pp. 1333-1338 (2002).
    [17] L. Peng, Q. Ying, Z. Lili, Y. Dahu, S. Haixiang, H. Yingfei, L. Shuo, L. Qi, “Electrospun PS/PAN fibers with improved mechanical property for removal of oil from water”, Marine Pollution Bulletin, Vol. 93, pp. 75-80 (2015).
    [18] H. Abiri, M. Abdolahad , M. Gharooni, S. A. Hosseini, M. Janmaleki, S. Azimi, M. Hosseini, S. Mohajerzadeh, “Monitoring the spreading stage of lung cells by silicon nanowire electrical cell impedance sensor for cancer detection purposes”, Biosensors and Bioelectronics, Vol. 68, pp. 577-585 (2015)
    [19] W. Zhao, B. Yalcin, M. Cakmak, “Dynamic assembly of electrically conductive PEDOT:PSS nanofibers in electrospinning process studied by high speed video,” Synthetic Metals, Vol. 203, pp. 107-116 (2015).
    [20] D. Nguyen, Y. Hwang, W. Moon, “Electrospinning of well-aligned fiber bundles using an End-point Control Assembly method,” European Polymer Journal, Vol. 77, pp. 54-64 (2016).
    [21] D. Kang, H. Kang. D. Dandy, T. Chen, “Surface energy characteristics of zeolite embedded PVDF nanofiber films with electrospinning process,” Applied Surface Science, Vol. 387, pp. 82-88 (2016).
    [22] C. Huang, K. Hu, Z. Wei, “Comparison of cell behavior on pva/pva-gelatin electrospun nanofibers with random and aligned configuration,” Scientific Reports, Vol. 6 (2016).
    [23] C. Zhu, D. Du, Y. Lin, “A simple method for fabricating highly electrically conductive cotton fabric without metals or nanoparticles, using PEDOT:PSS,” Journal of Alloys and Compounds, Vol. 702, pp.266-273 (2017).
    [24] S. Gautam, A. Dinda, N. Mishra, “Fabrication and characterization of PCL/gelatin composite nanofibrous scaffold for tissue engineering applications by electrospinning method,” Materials Science and Engineering C, Vol. 33, pp. 1228-1235 (2013).
    [25] D. Lia, W. Chen, B. Sun, H. Li, T. Wu, Q. Ke., C. Huang, H. E. Hamshary, S. S. A. Deyab, X. Mo, “A comparison of nanoscale and multiscale PCL/gelatin scaffoldsprepared by disc-electrospinning,” Colloids and Surfaces B: Biointerfaces, Vol. 146, pp. 632-641 (2016).
    [26] H. Lee, S. Nam, K. Son, W. Koh, “Micropatterned fibrous scaffolds fabricated using electrospinning and hydrogel lithography: new platforms to create cellular micropatterns”, Sensors and Actuators B: Chemical, Vol. 148 (2010).
    [27] A. Weltin, K. Slotwinski, J. Kieninger, I. Moser, G. Jobst, M. Wego, R. Ehret, G. A. Urban, “Cell culture monitoring for drug screening and cancer research: A transparent, microfluidic multi-sensor microsystem”, Lab on a Chip, Vol. 14, pp. 138-146 (2014).
    [28] E. Sollier, D. E. Go, J. Che, D. R. Gossett, S. O'Byrne, W. M. Weaver, N. Kummer, M. Rettig, J. Goldman, N. Nickols, S. McCloskey, R. P. Kulkarni, D. Di Carlo, “Size-selective collection of circulating tumor cells using vortex technology”, Lab on a Chip, Vol. 14, pp. 63-77 (2014).
    [29] Y. Wu, P. Xuea, K. M. Huib, Y. Kang, “A paper-based microfluidic electrochemical immunodevice integrated with amplification-by-polymerization for the ultrasensitive multiplexed detection of cancer biomarkers”, Biosensors and Bioelectronics, Vol. 52, pp. 180-187 (2014).
    [30] S. Steinhauer, E. Brunet, T. Maier, G. C. Mutinati, A. Köck, O. Freudenberg, C. Gspan, W. Grogger, A. Neuhold, R. Resel, “Gas sensing properties of novel CuO nanowire devices”, Sensors and Actuators B, Vol. 187, pp. 50-57 (2013).
    [31] S. K. Ameri, P. K. Singh, M. R. Dokmeci, A. Khademhosseini, Q. Xu, S. R. Sonkusale, “All electronic approach for high-throughput cell trapping and lysis with electrical impedance monitoring”, Biosensors and Bioelectronics, Vol. 54, pp. 462-467 (2014).
    [32] X. Fan, C. Jia, J. Yang, G. Li, H. Mao, Q. Jin,J. Zhao, “A microfluidic chip integrated with a high-density PDMS-based microfiltration membrane for rapid isolation and detection of circulating tumor cells”, Lab on a Chip, Vol. 71, pp. 380-386 (2015).
    [33] W. Chao, Y. Min, C. Liang, L. Rui, Z. Wenwen, S. Zhen, F. Chunhai, H. Jinkang, L. Jian, L. Zhuang “Simultaneous isolation and detection of circulating tumor cells with a microfluidic silicon-nanowire-array integrated with magnetic upconversion nanoprobes”, Biomaterials, Vol. 54, pp. 55-62 (2015).
    [34] B. Xu, Y. Du, J. Lin, M. Qi, B. Shu, X. Wen, G. Liang, B. Chen, D. Liu, “Simultaneous identification and antimicrobial susceptibility testing of multiple uropathogens on a microfluidic chip with paper-supported cell culture arrays”, American Chemical Society, Vol. 88, pp.11593-1160 (2016).
    [35] D. H. Kuan, I. S. Wang, J. R. Lin, C. H. Yang, C. H. Huang, Y. H. Lin, C. T. Lin, N. T. Huang, “A microfluidic device integrating dual CMOS polysilicon nanowire sensors for on-chip whole blood processing and simultaneous detection of multiple analytes”, Lab on a chip, Vol. 16, pp. 3015-3113 (2016).
    [36] S. Jin, M. Kim, Y. Jeong, Y. Yoon, W. Park, “Effect of alkaline hydrolysis on cyclization reaction of PAN nanofibers”, Materials and Design, Vol. 124, pp. 69-77 (2017).
    [37] Tien-Li Chang, Chi-Huang Huang, Shih-Yen Chou, Shih-Feng Tseng, Ya-Wei Lee, “Direct Fabrication of Nanofiber Scaffolds in Pillar-Based Microfluidic Device by Using Electrospinning and Picosecond Laser Pulses,” Microelectronic Engineering, Vol. 177, 52-58. (2017)
    [38] Shih-Yen Chou, Chi-Huang Huang, Tien-Li Chang, Zhao-Chi Chen, Ching-Hao Li, “Investigation on Picosecond Laser-Ablated Microfluidic Micropillar Arrays with Electrospun Nanofibers for Trapping Structures,” 42nd International Micro- and Nano- Engineering Conference (MNE2016), Vienna, Austria, D4-278.

    無法下載圖示 本全文未授權公開
    QR CODE