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研究生: Muhammad Faizul Zaki
Muhammad Faizul Zaki
論文名稱: 利用立體光刻技術3D列印和連續數位光罩製造單片式二維和三維紙基微流道晶片(2D/3D-µPADs),應用於多步驟化學分析和混合藥物之紙灑游離
Fabrication of Monolithic Two- and Three-Dimensional Paper-Based Microfluidic Devices (2D/3D-µPADs) using Stereolithography 3D Printing and Sequential Digital Masks for Multistep Chemical Assay and Paper-Spray Ionizations of Mixture Drugs
指導教授: 陳品銓
Pin-Chuan Chen
口試委員: 陳珮珊
Pai-Shan Chen
劉沂欣
Yi-Hsin Liu
葉怡均
Yi-Chun Yeh
林鼎晸
Ding-Zheng Lin
學位類別: 碩士
Master
系所名稱: 工程學院 - 機械工程系
Department of Mechanical Engineering
論文出版年: 2022
畢業學年度: 111
語文別: 英文
論文頁數: 97
中文關鍵詞: 立體光刻3D打印單片紙質微流控裝置多步驟多巴胺檢測紙質噴霧電離質譜
外文關鍵詞: Stereolithography 3D printing, monolithic paper-based microfluidic devices, multistep dopamine assay, paper-spray ionization mass spectrometry
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  • 這項研究描述了一種新的方法,利用立體光刻(SLA)數字光處理(DLP)3D打印和順序數字掩模來製造整體的二維和三維紙基微流控器件(μPADs)。極快的打印過程可以在<1s內進行,在10分鐘內完成二維或三維μPADs的製作,證明了所提方法的快速製造過程。為了了解通道的形成,研究了一些重要的參數,包括紫外光曝光時間的影響、紙張孔徑的影響、通道尺寸的限制以及連續數字掩膜的重要性,特別是為了創造一個整體的3D-µPADs。
    利用所提出的製造方法,獲得了一些新的方法,如:(1)成功創建了高分辨率的二維通道尺寸,寬度為100微米。 (2) 真正的3D-µPADs可以在單片紙基底內建立,不需要任何堆疊和折疊的方法,提高了流體運輸效率,減少了樣品體積。 (3)利用所提出的製造方法,引入了兩個功能,首先,通過通道深度的修改,能夠控制流體的流動速度,而不需要任何外部設備或其他材料;其次,在三維μPADs上開發了一種新的垂直混合,可以有效地混合兩種液體,其混合性能大於80%,而且樣品量最小。 (4) 通過整合可控流量和微混合,我們開發了高鹼性pH值下的多步驟多巴胺檢測,能夠在一個設備中首先進行pH濃度檢測,其次進行多巴胺檢測,成功檢測了生理範圍內多巴胺溶液的各種pH值,成功測量了0微米-50微米範圍內的多巴胺濃度,線性度很高(R2>0.9938和R2>0.991)。 (5) 最後,通過使用所提出的製造方法,我們創建了一個替代的環境電離平台,即基於紙張的微流控設備質譜(μPADs-MS)。 3D打印的μPAD證明了與空白紙相比,使用連續的溶劑可以將信號壽命延長到60分鐘,通過有限的溶劑(10微升)可以延長4倍,能夠重複使用和重新清洗,直到5次而沒有任何信號減少和交叉干擾,甚至進一步降低了成本。此外,混合藥物的色譜可以在採集過程中同時分離三種不同的藥物,產生清晰的峰值信號,並能減少每種藥物之間的競爭,從而使質譜分析具有較高的靈敏度和特異性,作為一個概念驗證,在血漿和水等兩种血漿中獲得了線性曲線和檢測限,從而獲得了很好的線性值(R2>0.99),檢測限降低到亞ng mL-1。


    This study described a novel approach to fabricating monolithic two-and three-dimensional paper-based microfluidic devices (µPADs) using stereolithography (SLA) Digital Light Processing (DLP) 3D printing and sequential digital mask. The extremely fast printing process can be proceeded within < 1s and the total time to create both 2D or 3D µPADs within 10 minutes demonstrated the rapid fabrication process of the proposed method. Some important parameters were studied to understand the channel formations including the influence of the UV light exposure time, the influence of the paper pore size, limiting channel dimension, and the importance of the sequential digital mask, especially to create a monolithic 3D-µPADs.
    Using the proposed fabrication approach some new approaches were obtained such as (1) a High-resolution 2D channel dimension successfully created with the size of 100 µm width. (2) Truly 3D-µPADs can be built using inside a monolithic paper substrate without any stacking and folding method which improved the fluid transportation efficiency and reduces the sample volume. (3) Two functionalities were introduced using the proposed fabrication approach, first, the controllable flow via channel depth modifications that be able to control the fluid velocity the flow without any external devices or other materials, and second, a new vertical mixing on 3D µPADs were developed which can efficiently mix two liquids using with the high mixing performance >80% and minimum sample volumes. (4) By integrating a controllable flow and the micromixing, we developed multistep dopamine detections at high alkaline pH values which be able to perform pH concentration assay firstly and the dopamine detections secondly in the one device, the various pH within dopamine solutions in physiological range successfully detected and the dopamine concentration ranged from 0 µm – 50 µm successfully measured with the great linearity value (R2 > 0.9938 and R2 > 0.991 respectively). (5) Lastly, by using the proposed fabrication approach, we created an alternative ambient ionizations platform namely paper-based microfluidic devices mass spectrometry (µPADs-MS). 3D printed µPAD demonstrated the ability to extend the signal lifetime up to 60 minutes spray using continuous solvent and four times longer via limited solvent (10 µl) compared to the blank paper, the ability to be reused and rewashed until five times without any signal reduction and cross-interferences even further decreased the cost. Furthermore, the chromatography of the mixture drugs can be obtained that can separate three different drugs simultaneously during the acquisitions, producing a clear peak signal, and be able to reduce the competitions between each drug that result in the high sensitivity and specificity of MS analysis, as a proof concept, the linear curve, and detections limit were obtained in two plasma such as plasma and water, resulting in the great linearity value (R2>0.99) and the detection limit lower to sub-ng mL-1.

    TABLE OF CONTENTS 摘要 i ABSTRACT ii ACKNOWLEDGEMENTS iv LIST OF TABLE vii LIST OF FIGURES viii CHAPTER 1: INTRODUCTION 1 1.1 Motivation for developing a three-dimensional paper-based microfluidic device using stereolithography 3D printing and sequential digital mask. 1 1.1.1 Introduction of paper-microfluidic devices 1 1.1.2 Two and Three-dimensional paper-based microfluidic devices: Fundamentals, Advantages, and Key Issues 3 1.1.3 Emergence of Applications Paper-Based Microfluidic Devices. 6 1.2 Objective and Significance of thesis 10 1.3. Structures of Thesis 14 CHAPTER 2: LITERATURE REVIEW 15 2.1 Current fabrication of three-dimensional paper-based microfluidic devices 15 2.1.1 The general fabrication process of µPADs 15 2.1.2 Three-dimensional µPADs fabrication process 16 2.2 3D printing Method 20 2.3 Current features and applications of paper-based microfluidic devices: POC via Multistep Assay and Mixing Mechanism on µPADs 22 2.3.1. Applications of µPADs for POC devices via Multistep Assay 22 2.3.2 Detection system via mixing mechanism in µPADs 24 2.4 Paper Spray Ionizations Mass-Spectrometry 26 CHAPTER 3: EXPERIMENT METHOD 30 3.1 Fabrication method of monolithic two-dimensional (2D) and three-dimensional (3D) paper-based microfluidic devices using 3D printing Stereolithography 30 3.1.1 3D Print System and General Printing Method 30 3.1.2 The Importance of Digital Mask for creating 2D and 3D channel via Stereolithography 3D printing 32 3.1.3 Channel Formation and Paper Influence Examinations 33 3.2. Transportation Efficiency Comparison 34 3.3 Controlling the Flow via Channel Depths Modification 36 3.4 Creating Vertical Mixing on 3D µPADs and Mixing Performance Evaluation 37 3.5 Application 1: 3D paper-based microfluidic devices for Multistep Dopamine Assay Design and Assessment 39 3.6 Applications 2: 3D Printed µPADs Integrated with the Mass-Spectrometry Analysis for Mixture Drugs Analysis 40 3.6.1 Fabrication of the 3D printed µPADs for paper spray using Stereolithography 3D printing and sequential digital mask. 40 3.6.2 3D printed Paper-Spray Ionization Mass-Spectrometry Setup (µPAD-MS) and Design Evaluation 41 3.6.3 µPADs-MS Chromatography Method. 43 3.6.4 Linear Curve and Detection Limit of Mixture Drugs on Plasma using 3D printed µPADs 44 CHAPTER 4: RESULTS AND DISCUSSION 45 4.1 Study of channel formations on paper using stereolithography 3D Printing 45 4.1.1. The response of exposure duration of the UV Light to the resin thickness 45 4.1.2 Influence of the paper pore size on the channel formation 47 4.1.3 High-resolution channel dimension 49 4.1.4 Three-dimensional (3D) structure in a monolithic paper substrate. 50 4.2 Liquid transportation efficiency monolithic and multiple layer 3D µPADs comparisons 51 4.3 Flow on Various Channel Depths Paper-Based Microfluidic Devices 52 4.4 Vertical Mixing on 3D Paper-based Microfluidic Devices Design and Characterization 54 4.5 Application 1: 3D paper-based microfluidic devices for Multistep Dopamine Assay 56 4.6 Applications 2: 3D Printed µPADs Integrated with the Mass-Spectrometry Analysis for Mixture Drugs Analysis 58 4.6.1 µPAD-MS printing parameters and surface characterizations 59 4.6.2 3D Printed Paper Chip Mass-Spectrometry Parameter Evaluations 60 4.6.3 3D Printed Paper Chip Design Evaluations to the Mass-Spectrometry Analysis Performance 62 4.6.4 Spray Performance of 3D printed Paper-Spray 64 4.6.5 Sample Extraction and Chromatography of the Mixture Drugs Sample using 3D Printed Paper-Spray during Acquisitions. 67 4.6.6 Calibration Curve and Detections Limit 69 CHAPTER 5: CONCLUSION, LIMITATIONS, AND RECOMMENDATIONS 71 REFERENCES 73 APPENDIX 78

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