臺灣博碩士論文加值系統

電容式生物感測器的製造多採用微機電或半導體製程，儘管其具有良好的感測性能及穩定性，但高昂的成本卻限制著實際應用上的發展。本研究以10 μm聚對苯二甲酸乙二酯（PET）絕緣薄膜貼合於單面覆銅的印刷電路板（PCB）上，做為工作電極。透過胺解反應將PET表面功能化，再以戊二醛作為交聯劑，固定5’端修飾胺基之核酸適體。完成核酸適體固定化之電極，與另一作為輔助電極的裸銅PCB，以5 mm的間隔，面對面平行放置在自製電容量測配件中。注入PBS(+)緩衝溶液後，使用LCR測試儀測得兩電極間的電容動態響相當穩定，30 分鐘內電容變化皆小於0.5%（N=3）。以凝血酶核酸適體感測器對標準品進行偵測，所得電容變化與10^-6~10^-10 M凝血酶濃度呈線性關係（R2>0.99）。然而，對AFB1的感測效果並未如預期，受限於分子尺寸相較於絕緣層厚度過小，僅對10~1000 ppb的AFB1達到半定量的結果。

Most of the capacitive biosensor was manufactured by the MEMS or semiconductor process. Although these sensors possess good performance and stability, high cost limited their practical applications. In this study, the 10 μm PET insulating film was attached onto the single-sided copper-clad of PCB as working electrode. The functionalization of PET surface was achieved by aminolysis reaction, then the 5’-amino-terminated aptamer was immobilized through the crosslinker, glutaraldehyde. The aptamer-immobilized electrode was paralleled face-to-face with another bare PCB as the counter electrode and separated by a distance of 5 mm in a home-made capacitive sensing chamber. The dynamic capacitance response measured in PBS(+) buffer by LCR meter was very stable, where the capacitance change was less than 0.5% within 30 min. With introducing the analyte into the thrombin recognized aptasensor, the measured capacitance change was linearly related to thrombin concentration from 10^-10 up to 10^-6 M (R2>0.99). Besides, the sensing performance of the other AFB1 recognized aptasensor was not as good as expected due to the unmatched size between sensing target and insulation film, only semi-quantitative agreement was achieved for AFB1 concentration from 10 to 1000 ppb.

口試委員審定書 i
誌謝 ii
摘要 iii
Abstract iv
目錄 v
圖目錄 ix
表目錄 xi
第一章　前言及研究目的 1
第二章　文獻探討 3
2.1　電容式感測原理 3
2.2　電容測器之電極配置 4
2.2.1　指叉電極 4
2.2.2　電極-溶液界面電容器 6
2.3　絕緣層製程 8
2.3.1　半導體材料 8
2.3.2　金屬/氧化層 8
2.3.3　SAM絕緣層 9
2.3.4　PET薄膜 11
2.3.4.1　PET特性介紹 11
2.3.4.2　PET表面胺解改質 12
2.4　電容量測方法 14
2.4.1　EIS法電容量測 14
2.4.2　步階偏壓量測 14
2.4.3　以電荷分配（Charge sharing）原理量測 15
2.4.4　交換式電容（Switched capacitor）量測 16
2.5　核酸適體（Aptamer） 18
2.5.1　核酸適體簡介 18
2.5.2　核酸適體之篩選與合成 18
2.5.3　核酸適體的化學修飾與固定化 19
2.6　待測物介紹 22
2.6.1　凝血酶 22
2.6.1.1 凝血酶簡介 22
2.6.1.2 凝血酶檢測於臨床上應用 23
2.6.1.3 凝血酶生物感測器 24
2.6.2　AFB1 25
2.6.2.1　AFB1簡介 25
2.6.2.2　食品中黃麴毒素限量標準 28
2.6.2.3　AFB1檢驗方法 29
第三章　研究方法 31
3.1　實驗藥品與材料 31
3.2　實驗設備 32
3.3　於金電極表面以分子自組裝技術製備絕緣層 33
3.3.1　金電極前處理 33
3.3.2　以十二烷基硫醇分子於金電極表面分子自組裝 33
3.3.3　自製對極式/三極式-電容/電化學量測流穿槽（Flow cell） 33
3.3.4　金電極電容量測系統架設 34
3.3.5　金電極表面特性分析 35
3.3.6　分子自組裝過程絕緣性變化 36
3.3.7　Au/SAM電極電容動態響量測 36
3.4　經濟型電容式感測電極片製備及電容量測 37
3.4.1　PCB前處理與電化學蝕刻 37
3.4.2　以胺解反應進行PET表面改質 38
3.4.3　核酸適體固定化 39
3.4.4　PET絕緣膜封裝 40
3.4.5　電容量測系統架構 40
3.5　感測電極片製程有效性驗證 41
3.5.1　PET薄膜做為絕緣層之可行性評估 41
3.5.2　以FITC染色結果評估PET胺化效果 41
3.5.3　以DAPI染色結果評估核酸適體交聯效果 41
3.5.4　以電容動態響應評估核酸適體交聯效果 41
3.5.5　絕緣層封裝失效模型分析 42
3.5.6　薄膜-分子親和模型分析 42
3.6　凝血酶與AFB1感測 44
3.6.1　背景值電容動態響應量測 44
3.6.2　凝血酶標準品製備 44
3.6.3　AFB1標準品製備 44
3.6.4　標準品電容量測 44
第四章　結果與討論 46
4.1　Au/SAM電極表面之電化學特性分析 46
4.2　SAM應用於電容式感測器絕緣膜可行性評估 49
4.3　PET薄膜應用於電容式感測器絕緣層可行性評估 52
4.4　PET薄膜表面胺解改質結果 54
4.5　核酸適體固定化結果 55
4.6　絕緣層缺陷模擬與界面親和情形模擬 57
4.7　電容動態響應背景值分析 59
4.8　凝血酶感測結果 62
4.9　AFB1感測結果 64
第五章　結論 66
參考文獻 67

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