飛行時間二次離子質譜術TOF-SIMS(Time of Flight-Secondary Ion Mass Spectrometry)，具有同時分析微量有機分子與無機元素的能力，質量分析範圍可從氫原子到分子量上萬的合成高分子與天然物分子，質量解析能力(M/□M)可達10000以上，具高靈敏度(一般元素在ppma~ppba範圍)，可藉由調整一次離子強度分析固態樣品表面單一層原子或分子，以Ga+液態金屬離子槍可做化學離子影像分析，解析可達100nm以下，具縱深分析與次微米微區分析能力，其研究範圍涵蓋微電子技術、奈米科技、合成高分子、生命科技材料、環境分析、醫藥技術與臨床分析等，是具有同時提供樣品多項資訊的多功能分析儀器。
在第二章中，利用新竹科學園區五部SIMS分析銅膜中佈植的碳、硫及氯之標準品，並進行實驗室間的比對實驗，結果得到相近的最高濃度位置，但不同SIMS機台所測得定量所需的相對感應因(RSF)值，隨不同機台有相當大的差異，扇行磁場式較四極柱式有較低的偵測極限。在第三章中，以飛行時間式二次離子質譜儀快速分析血袋中的DEHP — bis(2-ethylhexyl) phthalate和擴散到儲存的血液中的現象。從質譜圖中可測得DEHP的分子離子及碎片離子。第四章中，利用電化學鍍膜的方法將Biotin 生化分子固定到導電高分子(Polypyrrole)中，由螢光顯微鏡所得結果看到Biotin 分子可被固化入導電高分子(polypyrrole)中，由飛行時間式二次離子質譜儀所得表面影像，可觀察到Biotin 分子及其碎裂離子。由Biotin裂解實驗中，在4oC下 Biotin 可穩定存在於(Polypyrrole)中持續14天以上。在第五章中，利用合成的4種陽離子型高分子做為基因傳遞的載體，在細胞實驗中呈現很好的基因傳遞作用，高於市售Lipofactamin 2000。在低的高分子載體的使用量下，對細胞的毒性在可接收範圍內。在第六章中，我們利用TOF-SIMS 分析導電高分子(Polypyrrole)分析在電化學鍍膜時進入的陽離子鈉與陰離子DBS(dodecylbenzene sulfonate)的含量，探討其與導電度的關係，並以電子顯微鏡(FE-SEM)觀察表面形貌與導電度的關係。

Abstract
Time-of-flight secondary ion mass spectrometer (TOF-SIMS) is capable of simultaneously analyzing trace organic molecules and inorganic elements in mass ranging from hydrogen atom to synthetic and natural polymers with molecular weight up to ten thousands and more. TOF-SIMS could distinguish analytes with mass resolution different by 10000 at ppma to ppba sensitivity. Top monolayer atomic or molecular information could be determined by adjusting primary ion current density. Chemical images with lateral resolution 100 nm or less can be obtained by using Ga+ ion gun. The nm-scale depth profile and sub-□m area analysis capabilities inherent in TOF-SIMS extend its applicability to broad fields such as microelectronics, nano-technology, polymer science, life science technology, environmental analysis, \medical technology and clinical diagnostics. TOF-SIMS could simultaneously provide critical chemical information and is a multi functional state-of-the-art instrument.
In chapter 2, the round robin study of reference standards of Cl, S and C implanted into Cu films with known energy and dosage using five SIMS instruments was attempted in this work. Quantifying these impurities and comparing the results in terms of relative sensitivity factor (RSF) was the objective to check the discrepancy in results. Significant differences in RSFs but similarity in maximum peak concentration among different instruments was observed. Each sample was tested for the background level of C, O, S and Cl before being ion-implanted. The extent of uncertainty due to sample inhomogeneities was estimated using analytical results from a single instrument run by an operator. Relative standard deviations (RSDs) of maximum peak concentration 5.5 % and of peak position for Cl (1x1015 ions/cm2) were obtained, respectively. The detection limit and dynamic range were estimated from the depth profiles.
In chapter 3, use of TOF-SIMS to analyze plasticiser like bis(2-ethylhexyl) phthalate (DEHP) from the inner surface of the blood bags and their migration into the blood is discussed. Food packing materials were also analyzed for DEHP. The simplicity of using TOF-SIMS with improved mass resolution as an aid in the identification and analysis are discussed. The TOF-SIMS results, the fragmentation pattern and the ratio of ions were comparable to those obtain from traditional GC-MS analysis, indicates that TOF-SIMS could be a promising technique for direct analysis of DEHP, and phthalates in general, in blood bags and food packagings made of polymeric materials
In chapter 4, an easy and rapid method to doped biotin into polypyrrole thin film by electro-polymerization was demonstrated. The results of fluorescence and TOF-SIMS image have an agreement with each other. Modification of Ppy/Biotin surface could be made for further application. Degradation study shows biotin doped polypyrrole was stable in the PBS solution. No significant decay was found after two week. Applying 0.5 mA constant current for 5 min for electro-polymerization could form approximately 4 μm thick polypyrrole thin film on gold electrode. Electro-polymerization at 25 oC showed higher ion intensity than 4 oC of m/z 227(532:444). It might be due to the increasing of the diffusion coefficient of biotin toward the electrode surface.
In chapter 5, four different polymers for DNA delivery and three polymers for siRNA delivery into cells were synthesized. All these four polymers for DNA delivery showed promising result compared with C32 polymer from previous screening. They also show good transfection efficiency in the presence of serum in vitro. They might have great potential to delivery gene in vivo also. siRNA delivery showed better efficiency compared with commercial transfection reagent Lipofatamine 2000. Cytotoxicity of these polymers at low concentration is acceptable. For DNA delivery, compared with viral vector, non-viral cationic polymer vectors provide a lot of advantages; most significant is safe and easy to produce. These polymers might further conjugate with functional peptides and PEG to increase their tranfection efficiency and specific cell targeting.
In chapter 6, Polypyrrole(dodecylbenzene sulfonate) (PPy(DBS)) was electro-polymerized on indium tin oxide (ITO) glass using different concentration of sodium dodecylbenzene sulfonate (NaDBS) ranging from 0.002M to 0.2M in aqueous solution. The PPy(DBS) films were studied using time of flight secondary ion mass spectrometry (TOF-SIMS) in which the cation and anion doping concentrations were monitored on surface and along the thickness of the film. TOF-SIMS depth profiles showed interesting variations of sodium concentration along the thickness of electro-polymerized PPy(DBS) films. The morphology of the PPy(DBS) films was characterized using field emission scanning electron microscope (FE-SEM) and correlate with conductivity study.

Chpater 1
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Chapter 2
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Chpater 3
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Chpater 4
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Chapter 5
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Chapter 6
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