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研究生: 林俊毅
Chun-Yi Lin
論文名稱: 開發一智慧型手機結合紙基晶片檢測系統用於檢測酪氨酸羥化酶缺乏症
Developing a smartphone combined with a paper-based chip detection system to detect Tyrosine Hydroxylase Deficiency
指導教授: 陳品銓
Pin-Chuan Chen
口試委員: 葉怡均
Yi-Chun Yeh
林鼎晸
Ding-Zheng Lin
劉沂欣
Yi-Hsin Liu
陳珮珊
PAI-SHAN CHEN
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: 2021
畢業學年度: 109
語文別: 中文
論文頁數: 121
中文關鍵詞: 酪胺酸羥化酶缺乏症左旋多巴肌酐酪氨酸紙基微流體晶片3D列印智慧型手機
外文關鍵詞: Tyrosine hydroxylase deficiency, L-DOPA, Creatinine, Tyrosine, Paper-based microfluidic chip, 3D printing, Smartphone
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  • 酪氨酸羥化酶是一種關鍵酶,參與人體內酪氨酸向左旋多巴的轉化。它是一種罕見的常染色體隱性遺傳病,導致腦兒茶酚胺的缺乏,進而造成抑鬱、運動障礙和發育受損的症狀。左旋多巴是兒茶酚胺神經遞質的常見前體,因此如何快速、準確、同時測定生物基質中左旋多巴與酪氨酸的比例,對臨床診斷疾病具有重要意義。
    本研究利用易於取得且成本低廉的纖維素紙張,配合使用簡易的微影製程設備、材料、方法及平台,製作出一種低成本、精確、易於使用和便攜式的即時檢測系統。此系統包括一個光固化3D列印紙基微流體晶片作為反應平台,用高碘酸鈉進行表面改性以提高檢測性能、一個透過積層製造封閉外殼的檢測環境及一個 iOS APP 來驅動智慧型手機的成像以同時量化左旋多巴、肌酐和酪氨酸。
    本研究透過四個實驗以測試此系統之性能:(1)為了找出替代蠟的疏水性材料,本實驗測試三種光固化樹脂,透過光固化列印圖案在紙張上,觀察樹脂在紙基晶片上的結構強度是否足夠,以及滴定化學藥品在紙基上的呈色效果是否明顯,藉此來選用最適合本研究的疏水性材料;(2)利用一次一因子實驗法,透過設定曝光時間、後固化時間和後固化溫度參數列印紙基晶片,再透過滴定化學物質顯色進行RGB分析後,建立顏色量化強度後的校正曲線,以找出製程中最佳參數;(3)在本研究設計的模具平台內建立光源環境作為系統的量測基準;(4)為了證明本研究開發系統的測量精度和準確性,與其他APP做比較。實驗結果表明,左旋多巴、肌酐和酪氨酸可通過已建立的系統快速地定量,且具有高可靠性和可重複性,展示了一種有效常規檢查酪氨酸羟化酶缺陷患者的新工具。


    Tyrosine hydroxylase (TH) is a critical enzyme and involved in the conversion of tyrosine to L-DOPA in the human body. It is a rare auto-somal recessive disorder resulting in cerebral catecholamine deficiency causing symptoms of depression, movement disorders, and impaired development. L-DOPA is the common precursor of catecholamine neu-rotransmitters, therefore how to rapidly, precisely, and simultaneously determine the ratio of L-DOPA and tyrosine in the bio-matrix is important to the clinical diagnosis of disorder.
    In this study, we used a cellulose paper, combined with the simple lithography process equipment, materials, methods and platforms to cre-ate a low-cost, accurate, easy-to-use and portable real-time detection system.This system includes a light-cured 3D printing paper microflu-idics as reaction platform, surface modification with sodium periodate for improving detection performance, an additive manufactured enclosed case for maintaining detection environment, and an iOS APP to drive wisdom imaging of a mobile phone to quantify L-DOPA, Tyrosine and creatinine at the same time.
    Four experiments wew conducted in this study, including: (1) In order to find out the hydrophobic material that replaces wax, this ex-periment tested three light-curing resins, printed patterns on paper through light-curing, and observed the resin on the paper-based wafer whether the structural strength above is sufficient, and whether the color rendering effect of the titration chemicals on the paper base is obvious, to choose the most suitable hydrophobic material for this study; (2) Using the One-Factor-at-a-Time experiment method by setting the exposure time, the post-curing time and post-curing temperature to print the pa-per-based, and then RGB analysis is performed by dropping chemical substances. After color quantification intensity, a calibration curve is es-tablished to find the best parameters in the process; (3) The light source environment is established in the platform as the measurement benchmark of the system; (4) In order to verify the measurement accuracy of the system by comparing with other APPs. The experimental show that L-DOPA, creatinine and tyrosine can be quickly quantified through the established system, with high reliability and repeatability, and demon-strate a new tool for effective routine examination of patients with TH deficiency.

    摘要 Abstract 致謝 目錄 圖目錄 表目錄 第一章 緒論 1.1 研究背景 1.1.1 微流體生醫晶片 1.1.2 紙基微流體晶片 1.1.3 比色法 1.2 研究動機與目的 1.3 研究方法 1.4 論文架構 第二章 文獻回顧 2.1 紙基微流體平台製作相關文獻 2.1.1 蠟列印式 2.1.2 繪製 2.1.3 噴墨蝕刻式 2.1.4 雷射處理 2.1.5 油墨沖壓式 2.1.6 剪切式 2.1.7 噴漆式 2.1.8 絲網印刷式 2.1.9 光刻微影法 2.1.10 等離子處理 2.1.11 噴墨列印 2.1.12 化學氣相沉積式 2.1.13 濕蝕刻式 2.2 紙基微流體平台應用於化學比色測定之相關文獻 2.2.1 結合智慧型手機針對金屬離子進行比色檢測 2.2.2 基於奈米顆粒的傳感器用於比色檢測 2.2.3 基於紙張的比色法 2.3 用於檢測神經傳導遞質與肌酐之相關文獻 2.3.1 L-DOPA左旋多巴 2.3.2 Creatinine肌酐 2.3.1 Tyrosine酪氨酸 第三章 紙基微流體晶片檢測系統 3.1 光固化列印技術在積層製造上的應用 3.1.1 光聚合固化技術(Vat Photopolymerization, VP) 3.1.2 粉床熔化成型技術(Powder Bed Fusion, PBF) 3.1.3 材料擠製成型(Material Extrusion, ME) 3.2 模具平台及iOS APP手機介面 3.2.1 模具平台製作 3.2.2 iOS APP簡介 3.3 紙基微流體晶片系統製程 3.3.1 紙基微流體平台製作 3.3.2 酵素和待測物質在紙基上之表現 3.3.3 基於智慧型手機定量神經傳導物質 第四章 研究設備介紹 4.1 製程設備與軟體 4.2 檢測設備與軟體 4.3 化學材料 第五章 實驗方法 5.1 紙基微流體晶片之疏水性材料選用 5.1.1 實驗設計概念 5.1.2 實驗操作方式 5.2 基於一次一因子實驗法之紙基晶片製程參數 5.2.1 實驗設計概念 5.2.2 實驗操作方式 5.3 建立模具平台內的光源環境 5.3.1 實驗設計概念 5.3.2 實驗操作方式 5.4 探討iOS APP與ColorPicker應用比色分析的線性比較 5.4.1 實驗設計概念 5.4.2 實驗操作方式 第六章 實驗結果與討論 6.1 紙基微流體晶片之疏水性材料選用 6.1.1 Durable 0.4 光固化樹脂 6.1.2 Rigid 3157 光固化樹脂 6.1.3 Model 3158 光固化樹脂 6.2 基於一次一因子實驗法之紙基晶片製程參數 6.2.1 L-DOPA校正曲線(R12) 6.2.2 Creatinine校正曲線(R22) 6.2.3 Tyrosine校正曲線(R32) 6.3 建立模具平台內的光源環境 6.4 探討iOS APP與ColorPicker應用比色分析的線性比較 第七章 結論與未來展望 7.1 結論 7.2 未來展望 參考文獻 附錄A RGB轉換CMYK

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