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作者(中文):林彥碩
作者(外文):Lin, Yen-Shuo
論文名稱(中文):太赫茲結合超材料技術之微流體晶片的靈敏度強化與Troponin抗原檢測
論文名稱(外文):Sensitivity Enhancement and Troponin Antigen Detection of Microfluidic Chips Based on Terahertz Combined with Metamaterial Technology
指導教授(中文):饒達仁
指導教授(外文):Yao, Da-Jeng
口試委員(中文):嚴大任
徐文祥
口試委員(外文):Yen, Ta-Jen
Hsu, Wen-Syang
學位類別:碩士
校院名稱:國立清華大學
系所名稱:奈米工程與微系統研究所
學號:108035512
出版年(民國):111
畢業學年度:110
語文別:中文
論文頁數:148
中文關鍵詞:太赫茲波超材料靈敏度提升益生菌實驗抗原檢測
外文關鍵詞:TerahertzMetamaterialSensitivity improvementProbiotic experimentAntigen detection
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此篇論文根據太赫茲的物理特性,結合超材料以及微流體晶片,進行一系列的實驗。實驗方面,有溶液樣本、乾式益生菌樣本以及生物抗原鍵結之實驗;而在模擬方面,透過調整超材料圖形設計,一步步提升晶片感測能力。
在基板材料方面,將晶片的基板從介電常數較大 (ɛ=11.4) 的矽基板與介電常數較小(ɛ=3.8)石英基板進行比較,矽基板之最大偏移量僅為21GHz,而石英基板之最大偏移量可高達68GHz。在超材料幾何大小的分析,比較Type A、B、C的共振電場與偏移。在共振電場方面,模擬與實驗結果顯示,Type A具有最微弱的共振電場,而Type C具有最明顯的共振電場,其最大偏移量可提升至89 GHz。
模擬方面,為了進一步提升晶片的靈敏度,透過軟體模擬不同夾角的XPS與十字形圖形,模擬結果顯示十字形具有最佳的靈敏度。並且透過調整超材料的比例、週期長度與寬度,將十字形超材料晶片共振位置設計在VDI System頻段內。而後透過益生菌薄膜的實驗,量測不同介電常數的乳酸菌(ɛ=3.7)、糞腸球菌(ɛ=2.7)與酵母菌(ɛ=5.6)。證實十字形在辨識不同益生菌種類的能力比Type C優異。
在Troponin抗原的檢測,以生化鍵結方式進行表面修飾。首先透過螢光抗體的觀察,單位十字形超材料平均螢光亮點數目為25.60個,而後透過參數調整鍵結溫度與浸泡時間,單位十字形超材料平均螢光亮點數目可增加為181.02個。透過螢光抗體的觀察,確認抗原可成功穩固在超材料上。因此透過抗體抓取目標抗原,晶片可檢測之最小濃度為0.05μg/100μL ~ 0.1μg/100μL之間,濃度與ΔY呈現R2 =0.9909正相關,成功透過太赫茲結合超材料微流體晶片進行低濃度檢測結果。
Based on the physical properties of terahertz, combining metamaterials and microfluidic chips, this paper conducts a series of experiments. In terms of experiments, there are solution samples, dry probiotic samples, and biological antigen binding experiments; in terms of simulation, by adjusting the metamaterial pattern design, the chip's sensing ability is improved step by step.
In terms of substrate materials, comparing the substrate of the chip from a silicon substrate with a large dielectric constant (ɛ=11.4) to a quartz substrate with a small dielectric constant (ɛ=3.8), the maximum shift of the silicon substrate is only 21GHz. The maximum shift of the quartz substrate can be as high as 68 GHz. In the analysis of metamaterial geometry, compare the resonance electric field and shift of Type A, B, and C. In terms of resonance electric field, simulation and experimental results show that Type A has the weakest resonance electric field, while Type C has the most obvious resonance electric field, and its maximum shift can be increased to 89 GHz.
In terms of simulation, in order to further improve the sensitivity of the chip, XPS with different angles and cruciform patterns are simulated through software. The simulation results show that the cruciform has the best sensitivity. And by adjusting the ratio, periodicity and width of the metamaterial, the resonance position of the cruciform metamaterial chip is designed within the VDI System regime. Through the experiment of probiotic film, the Lactobacillus (ɛ=3.7), Faecalis (ɛ=2.7) and Yeast (ɛ=5.6) with different dielectric constants were measured. It is proved that the Cruciform is better than Type C in identifying different types of probiotics.
In the detection of Troponin antigen, the surface is modified by biochemical binding. First, through the observation of fluorescent antibodies, the average number of fluorescent bright spots per unit cruciform metamaterial is 25.60, and then by adjusting the binding temperature and immersion time, the average number of fluorescent bright points per unit cruciform metamaterial can be increased to 181.02. Through the observation of fluorescent antibodies, it is confirmed that the antigen can be successfully stabilized on the metamaterial. Therefore, the target antigen can be captured by the antibody, and the minimum concentration that the chip can detect is between 0.05μg/100μL ~ 0.1μg/100μL, and the concentration is positively correlated with ΔY (R2 = 0.9909). The low concentration is successfully achieved through the terahertz-combined metamaterial microfluidic chip.
第一章 緒論 1
1.1 前言與研究背景 1
1.2 研究動機 3
1.3 太赫茲技術 6
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 8
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 太赫茲波於偵查郵件毒品的應用 14
1.3.7 太赫茲時域光譜技術 17
1.4 微流體生醫晶片 20
1.4.1 微陣列型晶片 20
1.4.2 微流體生醫晶片之應用 21
第二章 文獻回顧 23
2.1 超材料的Split Ring Resonator設計 24
2.2 使用太赫茲超材料測量液體實驗 26
2.3 使用太赫茲超材料測量微生物實驗 28
2.4 超材料幾何改變之影響 34
2.4.1 超材料SRR與Fano幾何圖案 34
2.4.2 超材料週期長度的變化 37
2.4.3 超材料間隙寬度的變化 39
2.5 基板介電常數對共振結果之影響 42
第三章 實驗用設備 45
3.1 Polyscanner-FL7 45
3.2 TeraPulse 4000 45
3.3 VDI system 46
第四章 晶片的設計與製程 49
4.1 實驗室晶片設計 49
4.1.1 微流道結構設計 49
4.1.2 超材料幾何設計 50
4.2 實驗室晶片製程 51
4.2.1 微流道結構製程 51
4.2.2 超材料幾何製程 53
4.2.3 氧電漿接合技術 55
4.3 錸德晶片設計 57
第五章 基板比較(矽與石英) 59
5.1 太赫茲系統架構 59
5.2 實驗方式 60
5.3矽與石英基板的共振電場 61
5.3.1 模擬 61
5.3.2 實驗 61
5.3.3 結果討論 62
5.4矽與石英基板的偏移 64
5.4.1 模擬 64
5.4.2 實驗 66
5.4.3 結果討論 68
第六章 超材料幾何大小比較 70
6.1 Type A、B、C超材料幾何設計 71
6.2 Type A、B、C的共振電場 72
6.2.1 模擬 72
6.2.2 實驗 72
6.2.3 結果討論 73
6.3 Type A、B、C的偏移 75
6.3.1 模擬 75
6.3.2 實驗 77
6.3.3 結果討論 80
第七章 模擬結果: 提升晶片靈敏度 81
7.1 以十字形幾何圖形提升晶片靈敏度 82
7.2 調整單位十字形超材料的比例、週期長度與寬度 86
7.2.1 共振位置的調整 86
7.2.2 靈敏度的提升 90
7.3統整 & 設計實驗室製成的改良式晶片(檢驗十字形具有較好靈敏度) 92
7.4 介電常數、吸收係數對於X、Y軸位置之影響 93
第八章 益生菌薄膜實驗 96
8.1 以乾式乳酸菌樣本測定Type C與十字形超材料晶片之效能 96
8.2 以乾式糞腸球菌&酵母菌樣本測定晶片之效能 101
8.3 統整 105
第九章 小濃度混合溶液與相異溶劑實驗 107
9.1 小濃度差混合溶液 107
9.1.1 異丙醇(IPA)+乙醇(Ethanol) 混合溶液 108
9.1.2 甲醇(Methanol)+丙酮(Acetone)混合溶液 111
9.2 相異溶劑實驗 115
9.2.1 PEG(溶質) +異丙醇(溶劑) 116
9.2.2 PEG(溶質) +乙醇(溶劑) 118
9.2.3 結果討論 120
第十章 晶片表面修飾設計與結果討論 124
10.1 銀表面修飾實驗方法 124
10.2 螢光抗體檢視表面修飾流程 125
10.2.1 螢光抗體實驗流程 125
10.2.2 螢光抗體實驗結果 126
10.3 實驗參數優化與調整 127
10.3.1 抗體參數調整 127
10.3.2 EDC/NHS參數調整 128
10.4 太赫茲檢測Troponin抗原之結果 130
10.4.1 Troponin實驗流程 130
10.4.2 Troponin實驗結果 (TeraPulse量測) 131
10.4.3 Troponin實驗結果 (VDI System量測) 134
第十一章 結論 137
第十二章 未來計畫 139
10.1 超材料結構的設計改良 139
10.2 減少液體吸收之影響 142
參考文獻 145
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