臺灣博碩士論文加值系統

伴隨著微、奈米製程技術的進步與發展，力學式生物感測器的尺寸已經可以達到奈米尺度，各式各樣因分子吸附造成之物理、化學訊號，皆可以經由微（奈）米等級之精密結構，轉換成力學上的撓曲變形。其兼具可量測性及高靈敏度的特性，使得奈米力學感測器於生物感測領域中具有相當的發展潛力。其中結合了微型化製程技術以及自組裝技術雙重優勢的微懸臂梁感測器，便是本研究中的重點。
本研究以微懸臂梁感測器搭配光學觀測系統，從光槓桿量測原理出發，以幾何轉換法建立一套量測方法，並引進誤差傳播定律，評估其量測之精度。而後以此基礎延伸至表面物理現象之量測與解析，對於不同碳鏈長度的自組裝分子吸附於金表面導致微懸臂梁受溫度撓曲變化而產生之表面應力差異進行量測，發現單位溫度造成之表面應力隨碳鏈長度之變化，有一趨勢上的轉變。最後，以本研究建立之光學式微懸臂梁感測平台，進行丙戊酸藥物分子感測實驗。
最後，本研究提出了一套完整且可以評估精度的量測方法及流程，並透過量測分析掌握了其中可控制誤差之因素。而自組裝分子碳鏈長度對金表面受溫度變化引發表面應力影響實驗的部分，配合分子動力學模擬之結果，我們得到了相同之趨勢，並由模擬進一步對其模型進行亂度計算，推論出不同碳鏈長度下造成微懸臂梁單位溫度之表面應力變化之差異應為熵、焓相互競爭下的結果。藥物感測實驗部分，雖然並未有顯著之發現及成果，但大致上完成以本研究建立之光學式微懸臂梁感測平台進行藥物感測實驗之原型，包含實驗方法及流程。

With the development of micro- and nanofabrication technique, a variety of chemical or physical responses of molecular adsorption can be translated into measurable deformation and detected by tiny devices, including doubly clamped beams, membrane, and cantilever, who has one of dimensions in micro- or nanoscale. These devices are referred to as nanomechanical biosensors. With the advantages of ease of measurement and high sensitivity, nanomechanical biosensors are expected to play a promising role in the field of biosensing.
In this thesis, we focus on development of the optical microcantilever sensor, including the calibration method, measurement analysis, and the application in the study of chain length effect of self-assembled monolayer (SAM) and drug detection. Firstly, based on the geometrical method, a calibration between signals of the position sensitive detector (PSD) and deflections of the microcantilever is obtained. By utilizing the concept of error propagation, the standard error of deflections calibrated from the PSD signals are defined. Secondly, experiments on the chain length effect of SAM under temperature change are conducted with the proposed calibrated method. Finally, the drug detection of valproic acid is performed with the optical microcantilever sensing platform proposed herein.
In this study, we successfully developed a calibration method of measurements, with the definition of accuracy, for the optical microcantilever sensor. The factors resulting in measurement error were found through the measurement analysis. In the experiments of the chain length effect of SAM, we found that the relationship between chain length of SAM and thermal-induced differential surface stress had a turning point when chain length was equal to six. A similar trend was identified when we conducted simulations using Molecular Dynamics simulation (MD). Further calculations of entropy and enthalpy were performed and we found that the change of thermal-induced differential surface stress with the change of chain length was governed by the competition of entropy and enthalpy. In the final part of this thesis, the detection of valproic acid by using the optical microcantilever sensor was performed. The response of molecular adsorption cannot be distinguished from the noise. However, the methods and the standard steps of conducting drug detection experiments were established.

口試委員會審定書 #
誌謝 i
中文摘要 iii
ABSTRACT iv
目錄 vi
圖目錄 viii
表目錄 xii
第1章 緒論 1
1.1 研究背景與動機 1
1.2 文獻回顧 2
1.2.1 微懸臂梁感測技術 2
1.2.2 光學式微懸臂梁之訊號轉換及校正 5
1.2.3 自組裝單層膜(Self-assembled monolayer, SAM) 7
1.2.4 生物感測器原理 9
1.3 研究目的 10
1.4 論文組織 10
第2章 實驗架構 12
2.1 微懸臂梁感測晶片製作 12
2.1.1 微懸臂梁之選用 12
2.1.2 微流道製作與晶片封裝 14
2.2 光學觀測系統 15
2.3 溫度控制系統 17
2.4 流體推進系統 18
第3章 量測訊號之轉換與誤差來源分析 19
3.1 PSD訊號轉換 19
3.2 誤差傳播(Error propagation) 22
3.3 量測誤差來源分析 24
第4章 自組裝分子碳鏈長度對金表面受溫度變化引發表面應力影響之實驗與模擬 27
4.1 實驗方法 28
4.1.1 實驗藥品 29
4.1.2 實驗器材架設 30
4.1.3 碳鏈長度影響溫度效應實驗 31
4.2 分子動力學模擬 33
4.2.1 模擬軟體與分析工具 34
4.2.2 模擬流程 35
4.2.3 表面應力計算理論 37
4.2.4 巨觀表面應力計算 40
4.2.5 亂度計算 43
4.3 結果與討論 44
4.3.1 不同碳鏈長度硫醇分子吸附的微懸臂梁受溫度效應之反應 44
4.3.2 熵(Entropy)和焓(Enthalpy)對表面能量之影響 48
第5章 丙戊酸藥物感測實驗 51
5.1 實驗藥品 52
5.2 實驗器材架設 54
5.3 熱效應轉換 54
5.4 感測層之製備 55
5.5 實驗結果討論 57
第6章 論文總結 62
6.1 結論 62
6.2 未來方向與建議 63
參考文獻 64

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