本論文研究利用自行開發的新式三維列印系統將石蠟塗佈於濾紙上，形成微流道圖案，完成紙基底微流道裝置，並且固定生物辨識分子於微流道內，做成生物分子感測器，並透過比色分析法進行亞硝酸根離子以及血紅素感測，論文中將分成兩部份，討論紙基底微流道感測器在亞硝酸根離子以及血紅素檢測的設計與感測表現。
論文的第一部分為利用紙基底微流道感測器，對唾液中亞硝酸根離子進行感測，口腔中的亞硝酸根離子被牙醫師視為牙周病的指標，透過格里斯氏試劑 (Griess reagent) 進行化學反應，可將亞硝酸根離子消耗並轉換具有顏色的偶氮化合物，並呈現於紙基底微流道感測器。實驗中藉由改變感測器的物理與化學保存環境，測試感測器在不同保存天數後的表現，本論文亦使用不同的微流道圖樣並製作成品，因此透過改變微流道的設計，可觀察改變流道長短、試劑量以及滴入樣品多寡對於亞硝酸根離子感測的影響，並使用不同黏度的亞硝酸鈉溶液與人體唾液樣品進行裝置測試，完成無須對唾液樣品進行前處理步驟的紙基底感測器，亞硝酸根離子的感測結果經過數據迴歸後，得到最佳線性範圍為7.8 - 500 uM ( R2 = 0.99 )，檢測極限為 38.3 uM，靈敏度為0.08 a.u/uM，針對未知濃度樣品與真實口水樣品，比較紙基底微流道感測器與微孔盤分光光度計的感測結果，未知濃度樣品平均恢復率 (recovery) 達到91.5 %，而真實唾液樣品的恢復率則達到85.2 %。
論文的第二部分是利用新式三維列印技術，製作紙基底微流體感測器，此感測器檢驗糞便潛血為目的，於微流道中固定對去氧核醣核酸適體 (DNA aptamer)，藉此捕捉樣品中的血紅素，再透過將微流道設計成可折疊結構，利用毛細現象完成過濾、洗脫與濃縮等多步驟程序，紙基底感測器可藉由血紅素的催化性質，將四甲基聯苯胺 ( TMB) 反應成藍色化學物質，達到不須標記 (label-free) 且定量的感測結果。為固定適體作為生物辨識元件，此裝置利用3-氨基丙基三乙氧基矽烷 (APTES ) 與戊二醛 (GA) 產生的席夫鹼 (schiff base) 反應，將胺基修飾的適體 (NH2 aptamer) 固定於纖維素上，由於長鏈的適體較為昂貴，為提升適體的利用效率，此論文研究化學修飾的時間與氧氣電漿處理對基材表面官能基密度與適體固定效率的影響。完成的紙基底感測器則透過場發射掃描式電子顯微鏡 (FE-SEM)、全反射傅立葉紅外線光譜儀 (ATR-FTIR)、甲基橙吸附、茚三酮反應、與超微量分光光度計分析材料的表面型態、定量官能基密度與固定的適體重量，最終計算適體固定的效率。使用10 uM適體進行修飾時，依照化學修飾時間得到的是固定效率約為14 % 至 94 %，使用50 uM適體進行修飾時，固定效率約為4 % 至 91 %，而經過氧氣電漿前處理的裝置，則適體固定效率提升，使用10 uM適體進行修飾時，固定效率約為84 % 至 91 %，使用50 uM適體進行修時時，固定效率約為57至85 %，結果顯示透過氧氣電漿對基材進行處理可以縮短化學修飾時間，並提升適體固定效率。

In this thesis, the novel three dimensional wax printing method was utilized to develop micropattern on filter paper to fabricate microfluidic paper-based analytical devices (uPADs). By immobilizing bimolecular recognition element on the prepared uPADs, on-site nitrite and hemoglobin detection would be facilitated. The detection method was based on colorimetry through analyzing the color intensity on uPADs. The thesis is composed by two parts: detection of nitrite in aqueous solution and saliva, and uPAD for blood detection.
For the first part of this thesis, the prepared uPAD aimed to be applied for salivary nitrite detection because the nitrite molecule was considered as an inflammation biomarker for periodontist. When uPAD was modified with Griess reagent, this device can detect nitrite though azo coupling that generates pink color. In order to evaluate and prolong the shelf life of uPAD, the device was selected to undergo different conditions of storage by changing the composition of ambient gas and the time period of light exposure. The validity of uPAD was checked by means of sensing performance every day. To enable uPAD to be used for viscous saliva sample, the design of micropattern, the volume of Griess reagent, and the volume of sample were optimized, followed by further detecting two samples with different viscosity including sodium nitrite solution and saliva. The results revealed a good sensing performance on both samples. Moreover, this design of uPAD can detect raw saliva without any pretreatment. The linear range is 7.8 - 500 uM (R2 = 0.99) with the sensitivity of 0.08 a.u/uM. For the sodium nitrite solution and the raw saliva sensing, the recovery achieved 91.5 % and 85.2 %, respectively.
The second part of this thesis focused on applying uPAD for the detection of hemoglobin for fecal occult blood test. To achieve this purpose, the structure of uPAD was designed as a foldable form and the anti-hemoglobin aptamer was immobilized on the microchannel to capture the suspended hemoglobin in solution. The foldable structure could offer specific function as filtering, capturing, enrichment and washing. Due to the catalytic property of hemoglobin, the 3,3’,5,5’-tetramethylbenzidine substrate can be converted into dye in the presence of hydrogen peroxide to achieve label-free detection. In order to anchor aptamer, the device was modified with (3-aminopropyl) triethoxysilane and glutaraldehyde to generate the imine bond with amino-terminated aptamer. The chemically modified PAD was characterized by SEM, ATR-FTIR, spectrophotometer, methyl orange absorption test, and ninhydrin test. To maximize the efficiency of aptamer immobilization, the time of chemical treatment was varied and oxygen plasma was utilized as pretreatment. Without plasma treatment, the immobilization efficiency was 14 % for GA (10)-APTES (10)-cellulose. With plasma treatment, the immobilization efficiency increased to 84 % for GA (10)-APTES (10)-O2-cellulose. The result suggests that oxygen plasma treatment provides the potential for aptamer immobilization.

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