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研究生： 郝旭昶
Hao, Hsu-Chang
論文名稱： 氣相與液相表面聲波感測器元件與系統之研究、製作及開發
Investigation, Fabrication and Development of Surface Acoustic Wave Sensor Chip and System in gas and liquid
指導教授： 饒達仁
Yao, Da-Jeng
口試委員: 許宗雄
鄭桂忠
詹宇鈞
李承龍
劉奕汶
學位類別： 博士
Doctor
系所名稱： 工學院 - 奈米工程與微系統研究所
Institute of NanoEngineering and MicroSystems
論文出版年： 2012
畢業學年度： 100
語文別： 中文
論文頁數： 118
中文關鍵詞： 表面聲波 、高分子聚合物 、抗體 、蛋白質 、階層式群集分析法
外文關鍵詞： Surface Acoustic Wave, Polymer, antibody, protein, Hierarchical Clustering Analysis
相關次數： 點閱：3  下載：0 
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    • 本研究致力於開發陣列式表面聲波(Surface Acoustic Wave, SAW)氣相與液相量測系統，晶片材料的選擇上，本文選用高K2值之128º YX-LiNbO3 與YX-LiNbO3壓電基板，在其上製作指叉換能器（Interdigital Transducer, IDT），並將多種高分子聚合物或抗體固定修飾於感測區之上。將做好之晶片配合製作出之震盪電路，在以主動式之量測機制下，再結合感測環境系統以量測特定溶劑之揮發性氣體與特定生物檢體，經固定之薄膜捕捉標的物造成重量變化，導致表面聲波傳遞速度改變，由此觀察頻率飄移的下降量。
    氣體感測器方面：利用1L四頸瓶系統以七種高分子薄膜對甲醇、乙醇、氨、三甲基胺、丙酮之量測，確定了陣列化的可行性，以長條圖、雷達圖做分析，可得知每種膜在不同測試條件下之反應特性，建立簡單的資料庫，利用異丙醇氣體模擬一未知氣體，進入感測系統，經過2-way階層式群集分析法(Hierarchical Clustering Analysis)及樹狀圖分析後，可正確地將異丙醇氣體與已知醇類歸為同一群集，並與胺類氣體分開為兩大群集，丙酮則被歸類為較靠近醇類之群集。
    液體感測器方面：利用矽烷化的方式修飾SiO2表面，成功抗固定體於3 -aminopropyl triethoxy lsilane （ATPES）表面。連續式注入偵測蛋白質濃度由250~3μg/ml。捕捉標定細胞方面，在藉由光學與螢光影像，瞭解抗體固定後具有活性且在特定細胞濃度（K562、106 cell/ml; Jurkat、103 cell/ml） 1000:1下，成功的捕捉到標的細胞導致SH-SAW細胞感測器的頻率下降。

    This thesis gives a historical account of the development, and the theory of piezoelectric phenomenon, Rayleigh wave, shear horizontal plate wave, interdigital transducer (IDT), surface acoustic wave (SAW), performance criteria and device for application in sensor. The detection results for organic vapors by different polymer deposited on 128° YX-LiNbO3 surface acoustic wave (SAW) delay lines are studied in this work. The gas sensor array is based on 2×2 non-continuously working oscillators equipped with differently polymer-coated surface acoustic wave sensors.The SAW detection system which is employed to detect various organic molecules and bio-sample was prepared using two-port SAW resonators and a computer for signal acquisition and data process.
    This gas sensor array system consists of SAW sensors, polymers with different polarity and function groups, and signal readout electronics. The appropriate coating materials on to the SAW crystal would be used for gas detection. The gas sensing properties of polymer film, deposited onto 1280YX-LiNbO3 substrate, have been monitored shift in frequency by SAW delay lines and analysis the properties of the gas sensor. The good result of tree-view from the two-way hierarchical clustering analysis is studied in this work after comparing the correlation between the coating materials and organic vapors. Furthermore, the SAW detection system can distinguish unknown gas or mixed gas by the database of pattern recognition in the future.
    The Rayleigh-wave presents the very high decay and the SH-SAW presents a less energy decay when operating in liquid phase. For this reason, the SH-SAW device is selected to be used in gaseous and liquid phase application and The Y360-X LiTaO3 was selected as the substrate of the SH-SAW sensor chip. we developed an SH-SAW sensor to detect ipaB molecules by means of the antibody–antigen binding mechanism. The sensor showed stable relationship between its the oscillation frequency and the ipaB concentration in a protein solution. A SiO2 layer was on both the IDTs and the sensing area. The SiO2 waveguide used in these devices can be easily functionalized with 3-aminopropyltriethoxysilane (APTES) and to detect protein concentrations as low as 3 μg / ml. To replace the sensor surface antibody, the cell isolation and purification studied targeted cells (Jurkate), as a model for low abundance cells (1 ∶1,000), with more dilute cells as the ultimate goal. T cells were successfully separated on-chip from the mixed cell medium (Jurkate cells/ K562 cells, 1/1000). The results are quite promising and the developed SH-SAW sensor can be applied to the detection of various protein molecules with different antibody immobilization layers while maintaining all the beauties of general SAW sensors.

    目錄 摘要 i Abstract ii 致謝 iii 表目錄 vii 圖目錄 viii 第1章 緒論 1 1.1 前言: 1 1.1.1 微陣列氣體感測器研究動機 2 1.1.2 微陣列液體生化感測器研究動機 5 1.2 研究目標： 6 第2章 文獻回顧 8 2.1 氣體生化感測器（電子鼻）簡介: 12 2.1.1 傳導性感測器 12 2.1.2 金氧半場效電晶體（Metal Oxide Field Transistors, MOSFET）感測器 15 2.1.3 光感測器（Fluorescent Odor Sensors） 16 2.1.4 石英晶體微量天平 （Quartz-Crystal Microbalance, QCM）與表面聲波感測器 （Surface Acoustic Wave , SAW） 18 2.1.5 離子機動性測譜儀（Ion Mobility Spectrometry, IMS） 21 2.1.6 各種電子鼻之比較 21 2.2 陣列式表面聲波感測器 24 2.3 液體生化感測器簡介: 26 2.4 蛋白質與細胞晶片簡介 29 2.5 晶片固定化蛋白質動態擷取技術之發展 31 2.6 固定化蛋白質 34 第3章 表面聲波基本理論及參數 38 3.1 表面聲波（Surface Acoustic Wave, SAW）簡介 38 3.2 表面聲波感測器之分類 40 3.2.1 Thickness shear mode,TSM 40 3.2.2 Surface acoustic wave, SAW 41 3.2.3 Shear horizontal Surface acoustic wave, SH-SAW 42 3.2.4 Flexural plate wave, FPW 43 3.3 壓電理論 43 3.3.1 壓電材料的種類 44 3.3.2 壓電效應 45 3.4 指叉式電極換能器（IDT） 47 3.5 表面聲波元件感測原理 51 3.6 頻率飄移效應 52 3.7 質量負載效應 53 3.8 相關參數 54 3.8.1 傳遞波速 55 3.8.2 機電耦合係數（electromechanical coupling coefficient K2） 55 3.8.3 延遲溫度係數（Temperature coefficient of delay，TCD） 56 3.9 壓電基材之傳遞損失 56 3.10 Scattering parameter 57 第4章 表面聲波感測元件系統設計 60 4.1 表面聲波感測晶片 60 4.1.1 氣體與液體感測器基材選擇 60 4.1.2 黃光製程 62 4.2 感測薄膜製作 66 4.3 液體SH-SAW感測元件表面矽烷化 69 4.4 液體SH-SAW感測元件表面分子固定 70 4.5 液體SH-SAW感測元組裝 70 4.6 表面聲波震盪電路製作 71 4.7 表面聲波陣列化電路 75 4.8 實驗儀器及環境架設 77 4.8.1 被動式量測 77 4.8.2 主動式量測 77 4.8.3 氣體量測系統 78 4.8.4 液體量測系統 80 第5章 實驗結果 82 5.1 表面聲波感測晶片 82 5.2 表面聲波感測器與震盪電路結合 84 5.2.1 被動式量測 84 5.2.2 主動式量測 85 5.2.3 穩定性測試 86 5.3 氣體測試 87 5.3.1 四頸瓶量測系統 87 5.3.2 穩定性測試 88 5.4 統計分析 89 5.5 氣體分類與辨識 91 5.5.1 建立氣體資料庫 91 5.5.2 Two-way階層式集群分析（Hierarchical Clustering Analysis） 92 5.5.3 探討高分子膜與氣體間的物理性吸附 94 5.6 液相穩定性測試 98 5.7 ATPES表面修飾與抗體固定 99 5.8 SH-SAW 蛋白質晶片 101 5.9 SH-SAW細胞晶片 105 5.9.1 SH-SAW細胞晶片測試 106 5.9.2 抗體捕捉細胞專一性測試 107 5.9.3 SH-SAW細胞晶片 109 第6章 結論與展望 110 第7章 參考文獻 112

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