本論文根據太赫茲的物理特性，結合超材料微流體晶片的應用，目標對於心肌梗塞疾病(AMI)進行檢測。先以模擬與量測做測試實驗，前者包含介電損耗與環境變化靈敏度，後者除了流體樣本也嘗試將乾式生物樣本沉積於超材料晶片表面，以觀察晶片實際的感測效果。
超材料的結構設計為X型幾何形狀，可根據不同的尺寸設計產生不同頻率下的共振響應，模擬頻率分別在0.30、0.39和0.46 THz，命名為設計A、B、C，實際結果顯示共振頻率分別為0.2831、0.3685和0.4393 THz，且在以石英為基板的超材料相較矽基板能更準確指出共振響應之頻率值。
於流體樣本的結果中，證實太赫茲成功於超材料微流體晶片辨識出乙醇與異丙醇(IPA)兩相似的化學結構，此根據共振頻率響應的紅移量，前者為28.1 GHz，後者為19.5 GHz。然而於不同濃度甘油水溶液的結果中，所有液體樣本之紅移量為21.9 GHz，且隨甘油濃度下降，共振響應隨之減弱，再藉由頻域圖與吸收率圖便更進一步確定水於太赫茲波的吸收程度已大幅影響超材料之共振響應。
故在進行本論文的檢測目標前，先嘗試對乾式乳酸菌樣本的部分進行量測，五種濃度變化為每微升0.005 mg、0.01 mg、0.025 mg、0.05 mg、0.1 mg，於C設計的晶片所得到的平均偏移量分別為0.96 GHz、1.92 GHz、3.36 GHz、6.82 GHz和11.92 GHz，其結果顯示超材料晶片的共振響應可成功觀察到不同低濃度樣本間的微量變化。
最後，針對超材料微流體晶片的組成材料，做表面修飾的設計，使得AMI的對應抗原(Troponin I, cTnI)能透過免疫反應穩固在超材料金屬表面上。經過螢光抗體的確認後，成功在晶片中完成表面修飾流程，並且以抗體專一性抓取cTnI後進行太赫茲波檢測，於各設計均顯示在3.33μg/mL的濃度下，平均共振紅移量1.708、2.196、2.440 GHz，此為成功透過太赫茲結合超材料微流體晶片做到超快速且低濃度檢測結果。

According to the physical properties of Terahertz (THz), this research performs a series of measurement on microfluidic device integrated with metamaterials, and Acute myocardial infarction(AMI) detection is the object of the thesis. To accomplish it, there are several trials including sensitivity simulation and experiment. The former involves in dielectric loss and environmental change; the latter, except of liquid sample measurement, the dry sample which is deposited on the surface of metamaterial shows the sensitivity of it as well.
The type of metamaterial called X-shaped plasmonic sensor (XPS) may perform different position of resonant dip, and it depends on the scale of the design. For simulation on quartz substrate, the resonant dips are located at 0.30, 0.39, 0.46 THz according to three designs named A, B and C, respectively. However, the experiment results show at 0.2831, 0.3685, 0.4393 THz, and indicate the effect of quartz based metamaterial precedes that of the silicon based.
For the results of the liquid sample measurement, it proves that THz is able to differentiate similar structure such as ethanol and IPA sample, which is according to red shift of frequency resonance, and the shift is 28.1 GHz and 19.5 GHz respectively. However, in the measurement on variation of glycerin concentration, all of the red shifts of liquid samples are 21.9 GHz, and the effect of frequency resonance becomes weak as the concentration decreases, while it makes sure that the absorption of water in THz regime is strong enough to influence the effect of metamaterial by observing the phenomenon in frequency domain and absorption rate.
Therefore, before the final project, there is a trial for dry Lactobacillus sample on metamaterial sensors, the concentration varies from 0.005 mg, 0.01 mg, 0.025 mg, 0.05 mg and 0.1 mg per μ L, and the average of red shifts perform 0.48 GHz, 1.46 GHz, 2.92 GHz, 4.39 GHz and 6.59 GHz, respectively. It reveals the sensitivity is available for extreme low concentration detection.
Eventually, the surface modification design is made for the material of the metamaterial microfluidic device, so that the related antigen of AMI (Troponin I, cTnI) can be stabilized on the metamaterial metal surface through the immune reaction. After the confirmation by fluorescent inspection, the surface modification process was successfully completed in the device, and the cTnI was specifically captured by the antibody. In the results of measurement, each design showed an average resonance red shift at a concentration of 3.33 μg/mL, which are 1.708, 2.196, 2.440 GHz, respectively. Therefore, it successfully proves the ability to application on terahertz combined with metamaterial microfluidic device, which is ultra-fast and low-concentration detection

第一章 緒論 1
1.1 前言與研究背景 1
1.2 研究動機 2
1.3 太赫茲技術 5
1.3.1 太赫茲波的特性 6
1.3.2 以光學方法產生太赫茲波輻射源 9
1.3.3 利用電子學方法產生太赫茲波輻射源 11
1.3.4 太赫茲波於生醫領域的應用 12
1.3.5 太赫茲波於食安檢測與國防安全的應用 14
1.3.6 透過太赫茲光譜學進行分析 15
1.4 微流體技術 18
1.4.1 微流體晶片的優勢 19
1.4.2 微流體晶片相關應用實例 19
第二章 文獻回顧 22
2.1 超材料的原理與設計 22
2.2 超材料靈敏度 25
2.3 超材料生醫感測器 27
2.4 超材料結合微流道的應用 34
2.5 提升超材料靈敏度之設計 45
第三章 實驗材料與設備 50
3.1 實驗用流體 50
3.1.1 TWEEN 20®溶液 50
3.1.2 F-127溶液 50
3.1.3 乳酸菌溶液 50
3.1.4 細胞培養溶液 51
3.2 心肌梗塞抗原表面修飾之藥品 51
3.2 實驗設備 52
第四章 超材料微流體晶片之設計與製程方法 57
4.1 晶片設計 57
4.2 晶片製程 62
第五章 超材料晶片之靈敏度模擬 71
5.1 超材料晶片材料的影響 72
5.2 待測物折射率變化靈敏度分析 74
5.3 介電損耗於超材料共振響應之影響 76
第六章 超材料微流體晶片之研究方法 77
6.1 系統架構 77
6.2 XPS於實際量測之共振頻率響應 79
6.3 矽基板超材料晶片靈敏度測試 79
6.3.1 以液體樣本測定XPS超材料微流體晶片之效能 79
6.3.2 以乾式癌症細胞樣本測定XPS超材料之效能 81
6.4 以石英基板提升超材料晶片靈敏度 82
6.4.1 以液體樣本測定改良後超材料微流體晶片之效能 82
6.4.2 以乾式乳酸菌樣本測定改良後超材料晶片之效能 84
第七章 超材料微流體晶片實驗結果與討論 86
7.1 XPS於實際量測之共振頻率響應測試結果 86
7.2 矽基板超材料晶片靈敏度測試結果 88
7.2.1 XPS超材料微流體晶片於液體樣本之測定結果 88
7.2.2 XPS超材料晶片於乾式乳酸菌樣本之測定結果 90
7.3 以石英基板提升超材料晶片靈敏度量測結果 92
7.3.1 改良後超材料微流體晶片於液體樣本之測定結果 92
7.3.2 改良後超材料晶片於乾式乳酸菌樣本之測定結果 95
7.4 綜合結果統整 100
第八章 晶片表面修飾設計與結果討論 102
8.1 金薄膜表面的清潔處理 102
8.2 末端為羧基的自組性單層膜(Self-Assembled Monolayer, SAM)表面處理 103
8.3 抗體修飾與免疫反應 103
8.4 表面修飾實驗步驟流程 105
8.4.1 以螢光抗體檢視表面修飾流程 106
8.4.2 於微流體晶片中的表面修飾流程 107
8.5 以螢光抗體檢視表面修飾效果 108
8.6 於超材料微流體晶片中檢測心肌梗塞抗原之結果 109
第九章 結論 112
第十章 未來計畫 114
10.1 超材料結構的設計改良 114
10.1.1 超材料幾何設計 114
10.1.2 以MIM結構提升晶片靈敏度 116
10.2 批量製程生醫晶片 117
參考文獻 118

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