• 學位論文

環狀高分子之結晶與熔融行為研究

Cyclic PCL with molecular weight of 7.5 kg/mol was studied by small-angle (SAXS) and wide-angle (WAXS) X-ray scattering, and differential scanning calorimetry (DSC). The cyclic and linear PCL crystallized to form identical crystallographic structure of PCL. The cyclic PCL can melt at a higher temperature than its linear analogue, which may be due to a lower entropy change of the cyclic chains upon melting. Investigations by SAXS have revealed that cyclic PCL displayed slightly larger lamellar thickness than that of linear PCL at a given T_c. As the Gibbs-Thomson and Hoffman-Weeks plots have also been frequently adopted to extrapolate the “equilibrium melting temperature” of cyclic polymer, we attempted to show here that the melting temperature from extrapolation is a characteristic temperature that depends upon the cyclization entropy of the polymer. We have obtained T^*=91.2℃, δ_e= 42.8 mJm^(-2) and 〖ΔS〗_cyc= -11.9 Jkg-1K-1 for cyclic PCL; T_mL^°=80.0℃ and δ_e= 30.3 mJm^(-2) for linear PCL. We also attempted to propose an alternative chain folding model for cyclic polymers.

• 學位論文

以桿狀病毒作為基因載體調控microRNA表現並抑制Mahlavu肝癌細胞株於小鼠體內之增生及轉移

MicroRNA (miRNA)透過造成基因之mRNA降解(mRNA cleavage)與阻擋蛋白質轉譯(translation)過程而影響基因表現。miR-122在肝癌細胞中，能抑制包括細胞增生、細胞週期及誘發細胞凋亡；而miR-151則透過瞄準RhoGDIA的途徑促使肝癌細胞的轉移。因此，在本研究中我們探討結合Sleeping Beauty (SB)長效系統與桿狀病毒載體分別或同時表現miR-122與miR-151 sponges，在小鼠體內實驗中抑制Mahlavu的增生和轉移。首先，我們使用四株重組桿狀病毒CdE(作為單純注射病毒的負對照組)、m122 (表現miR-122, m122組)、s151 (表現miR-151 sponge, s151組)及Dual (同時表現miR-122及miR-151 sponge, Dual組)或是磷酸鹽緩衝液(PBS組)注射至由Mahlavu細胞建立的腫瘤中，持續觀察並定期測量腫瘤大小。實驗結果發現在第30天，相對於PBS組的平均腫瘤大小，CdE組有46.9%的抑制效果；實驗組s151為70.6%，m122及Dual組的抑制效果分別為85%和86.2%。從免疫染色的實驗結果顯示，實驗組m122和Dual造成明顯的細胞凋亡並抑制細胞週期。此外，實驗組m122、s151、Dual中的腫瘤細胞轉移能力也明顯受到抑制。而肺臟轉移模型實驗的H&E染色結果顯示，實驗組m122組、s151組、Dual組則沒有看到明顯的腫瘤組織。這些結果顯示，以桿狀病毒載體在Mahlavu癌細胞內表現miR-122或/及抑制miR-151可以有效抑制腫瘤增長及轉移，也證實調控miR-122及miR-151在抑制肝癌的潛力。

• 學位論文

嵌段共聚物奈米薄膜之微結構取向與大範圍有序化及其應用

The fabrication of nanostructured thin films from the self-assembly of degradable block copolymers (BCPs) has attracted extensive attention in the past decade, and a variety of appealing applications in different research areas have been suggested by using the nanostructured thin films. To create useful BCP thin films for practical uses, controlling the orientation of self-assembled nanostructures is essential. In this study, we present a new method for forming well-ordered and oriented nanostructured thin films on Si wafer with a functionalized SiO2 surface, using homopolymers with hydroxyl group at the chain end to functionalize SiO2 surface, to give neutral substrate for the self-assembly of BCPs. To demonstrate the feasibility of suggested approaches, a series of degradable BCPs, polystyrene-b-poly(L-lactide) (PS-PLLA) with hexagonally packed cylinder and double gyroid phases, are used as model systems for creating nanostructured thin films with controlled orientation and long-range order of BCP nanostructures. In contrast to the use of random BCPs, a neutral substrate is formed by functionalizing a SiO2 substrate with hydroxyl-terminated PS (PS-OH) followed by hydroxyl-terminated PLLA (PLLA-OH). Accordingly, the surface properties can be fine-tuned by controlling the ratio of grafted PS-OH to PLLA-OH without the prerequisite of the synthesis of random BCPs. Subsequently, different methods such as thermal and solvent annealing are utilized to exploit the fabricated neutral substrate resulting from the grafting of mixed PS-OH and PLLA-OH brushes for creating expected nanostructured thin films. For cylinder-forming PS-PLLA thin film, well-ordered and perpendicular PLLA cylinders in PS-PLLA thin film can be formed by using the neutral substrate for thermal annealing. Surprisingly, the orientation that is driven by the neutral substrate is limited in that the effective length of orienting cylinders is less than twice the inter-domain spacing. By contrast, thermal annealing at high temperature can yield a neutral air surface, rendering perpendicular PLLA cylinders that stand sub-µm from the air surface. Consequently, the neutral substrate can be used to enable truly film-spanning perpendicular cylinders in films to be fabricated using the high-temperature thermal treatment. Most interestingly, the perpendicular cylinders can be laterally ordered by further increasing the annealing temperature to increase the mobility of the polymer chains for reoganization. By contrast, for gyroid-forming PS-PLLA thin film, the morphology remains as disorder-like texture after thermal annealing due to insufficient time for ordering. Note that degradation of PLLA will occur after long-time thermal annealing. Alternatively, long-range ordering of oriented gyroid thin films can be achieved by solvent annealing using appropriate solvents. With twice of integral gyroid lattice constant for sample thickness from swelling by solvent annealing to satisfy the criteria of commensuration, well-defined nanostructured thin films can be obtained. Interesting morphological evolution from disorder to gyroid and finally cylinder can be found while using a partially selective solvent for PS to anneal the PS-PLLA thin film. Moreover, during transition, characteristic crystallographic (211)G plane in the gyroid thin film parallel to the air surface can be observed, and will gradually transform into the (110)G plane due to the preferential segregation of one block to the surface that affects the relative amount of each component on the air surface. Similar morphological evolution can be found in the neutral substrate at which the PS chains on functionalized substrate will be stretched to preferentially reach the PS selective solvent while the PLLA chains will recoil from the solvent due to the effect of solvent selectivity. To acquire a thin-film sample with thermodynamically stable gyroid morphology, a non-preferential solvent should be used for solvent annealing to enable long-range ordering of gyroid thin film with the (211)G plane parallel to the air surface and also the substrate. The ability to achieve oriented PS-PLLA gyroid thin films with uniform surface opens up appealing applications in nanotechnology. For practical applications, by taking advantage of the degradable character of ester groups for PLLA blocks in PS-PLLA, nanoporous polymer thin films can be fabricated by hydrolyzing self-assembled PS-PLLA nanostructures, and then used as templates for the fabrication of nanohybrid materials with promising applications in electronic, optical, and magnetic devices. The fabrication of nanohybrids with different constituent components and structures can be achieved by using the templates for electroplating reaction. Consequently, nanostructured conductive polymers can be acquired by templated electrochemical polymerization through the combination of pulse electroplating method with the control of micro current. Similar approach can be exploited for the fabrication of PS/Au nanohybrid thin films by using Au precursors for templated electroplating.

• 學位論文

以狹縫式塗佈技術製備大面積小分子有機發光二極體

摘要 小分子有機發光二極體 (OLED) 為近年來廣受矚目的產品，可應用於 固態照明及顯示器。OLED 為多層結構元件，目前生產仍以高成本、高耗能 之真空蒸鍍製程為主，不僅產品製程成本高，同時也存在大面積量產及低良 率問題。自第一個OLED 元件發表以來，大部分小分子有機發光材料便是 為真空蒸鍍製程所設計，一般難溶於溶劑。近年來為降低製程成本，各界積 極開發可溶性小分子有機發光材料，期望能以溼式製程製備元件。溼式製程 為低設備成本、高材料利用率及高產率的量產方式，對於未來OLED 應用 於照明設備，在價格成本上有絕對優勢。 目前，學術研究OLED 溼式製程仍以旋轉塗佈 (spin coating) 為主，少 數以刮刀塗佈 (blade coating)或網版印刷 (screen printing) 方式製備，但以量產觀點而言，上述塗佈技非良好量產技術。本研究利用狹縫式塗佈技術製作有機層全溼式製程之OLED 元件，元件發光面積可達5 cm2，目前已克服 以溼式塗佈單一有機層膜厚30-50 nm 以及兩有機層間互溶問題。 關鍵字：狹縫式塗佈技術、有機發光二極體、OLED 照明

• 學位論文

人類胚胎幹細胞培養、分化及冷凍之研究

人類胚胎幹細胞由於其自我更新及多能性的細胞特性，使其成為再生醫學、細胞治療及臨床移植上一個重要的細胞來源。然而，在真正進入實際應用之前，它仍有許多亟需克服的障礙。在本研究中將分別針對：體外培養、誘導分化及冷凍保存三個方向著手進行改善。 首先，我們利用經合成胜肽-丙烯聚酯修飾的表面材質(Synthemax®)取代Matrigel於成分確定的培養基(mTeSR™1)內進行人類胚胎幹細胞的增殖，我們進一步確認細胞經過十次的繼代後仍表現多能性的標誌以及保有分化成三胚層細胞的能力，更重要的是其仍維持正常的染色體。接著，我們建立一不含血清的誘導分化培養基能使人類胚胎幹細胞有效率地分化成為定型內胚細胞(86%)，我們甚至可讓人類胚胎幹細胞經三階段共21天的誘導培養基中順利分化成為胰島素分泌細胞(25%)，且在免疫螢光染色及定量的基因分析結果中，我們發現細胞於Matrigel或Synthemax®表面上進行分化誘導所得之效率並無顯著差異。因此，Synthemax®不僅可以作為人類胚胎幹細胞的長期培養平台，亦可在其上進行胰島素分泌細胞的誘導分化以成為未來糖尿病患者的細胞治療來源。 最後，我們利用一結合動態磁場的程式降溫儀Cell Alive System (CAS)進行人類胚胎幹細胞的冷凍保存，以減少降溫過程中冰晶所造成之冷凍傷害。我們將人類胚胎幹細胞團塊回溶於冷凍培養基中分成三組：(1) 細胞於傳統的冷凍保存容器Mr. Frosty並置於-80度冰箱降溫(MF)；(2) 細胞利用CAS降溫至-32度後改置於-80度冰箱(CAS)；(3) 細胞利用CAS降溫至-32度後改放於預冷之Mr. Frosty並置於-80度冰箱降溫(CAS-MF)。隔夜，所有冷凍管皆保存於液態氮內，一周後將人類胚胎幹細胞解凍並培養於餵養細胞上7天。由鹼性磷酸酶的染色結果計算細胞凍後貼附率，經CAS或CAS-MF冷凍保存之貼附率分別為29.0%及44.0%，皆優於經MF冷凍保存之7.0%。我們更進一步確認細胞經CAS-MF冷凍保存後仍能持續繼代並表現多能性標誌，以及保有分化成三胚層細胞的能力並維持正常的染色體。由以上結果可知CAS-MF將可提供人類胚胎幹細胞庫一個更有效率的冷凍保存方式。

• 學位論文

Structural Evolution of Poly(9,9-di-n-octyl-2,7-fluorene) during Mesophase-modulated Crystallization

In a previous study of solution-cast poly(9,9-di-n-hexyl-2,7-fluorene) (PFH) [Polymer 2012, 53, 3928], transition from solvent-induced β mesomorph to crystalline α form had been identified: upon heating from 120 °C, growth/coalescence of 2D-ordered β nanograins effectively suppressed the formation of α nanograins below 189 °C, above which transformation from β nanograins to thermodynamically favored α crystals was activated by partial melting of the β mesomorph. Here we report results of our attempt to clarify if similar processes exist in its close homologue, poly(9,9-di-n-octyl-2,7-fluorene) (PFO), which is well-known to have a similar (yet less ordered) β phase. Structural evolution of β-rich PFO was monitored via simultaneous small/wide-angle X-ray scattering (SAXS/WAXS) and differential scanning calorimetry (DSC) during programmed heating of as-cast PFO specimen from 30 to 180 °C at 10 °C/min. After removal of background scattering from fractal-like matrix structure, SAXS profiles along with supporting WAXS observations can be interpreted with a similar sequence of events previously observed for as-cast PFH. Specifically, structural evolution of β-rich PFO above Tg involves four stages: (1) decreased lateral sixe of β nanograins with a minor change in ellipsoidal dimension (A, B) from (2.0 nm, 9.2 nm) to (2.1 nm, 8.2 nm) between 80 and 100 °C, (2) direct β-to-α transformation accompanied by emergence of α nuclei from the amorphous matrix, with a slight decrease in inter-particle distance from d = 28.4 to 26.0 nm, a concomitant change in ellipsoidal dimension changes from (A, B) = (2.1 nm, 8.2 nm) to (2.7 nm, 7.7 nm), and a significant increase in the SAXS invariant Qinv (signifying increased heterogeneity) from 100 to 110 °C, (3) growth of α nuclei resulting in increased ellipsoidal dimension from (A, B) = (2.7 nm, 8.5 nm) to (2.8 nm, 9.1 nm) with a concomitant DSC exotherm, and (4) partial melting/coalescence of α nanograins, leaving thick crystals of ellipsoidal dimension (A, B) = (3.9 nm, 14.5 nm) and wider inter-grain spacing d ≈ 40 nm before final melting near 145 °C. The distinct feature of the nanograin evolution process in β-rich PFO lies in Step 2, i.e., unlike the PFH case, the formation of α crystals in β-rich PFO is not limited to direct β-to-α transformation; nucleation and growth of α crystals from the amorphous matrix may also contribute significantly. This may probably be attributed to the less-ordered β mesomorphic structure in PFO as compared to the 2D-ordered β-packing in PFH.

• 學位論文

冷凍解凍法強迫二氧化矽漿料凝聚的應用研究

本研究主要為探討冷凍解凍(Freeze/Thaw)程序強迫二氧化矽漿料聚集的應用價值，吾人討論此法與傳統的量測漿料穩定性的方法比較，並探討pH和高分子保護劑聚乙烯吡咯烷酮(Polyvinylpyrrolidone, PVP)對二氧化矽聚集的影響。 實驗結果發現，若干二氧化矽漿料會於冷凍解凍後凝聚，使用雷射粒徑儀量測其直徑至少有二十倍的增加。除了肉眼可見漿料從透明轉成乳白色會沉澱的漿料，光學顯微鏡與電子顯微鏡也可看到聚集顆粒在漿料中產生。電子顯微鏡可看到聚集體多數呈圓形，推想這是從四面八方均勻受力擠壓的結果，因為在冷凍過程中，冰晶成長排擠二氧化矽顆粒，強制顆粒互相靠近而發生聚集。 二氧化矽漿料在高pH值和高PVP含量能抵抗因為冷凍解凍引發的聚集效果，pH=6時至少需添加0.075 (g/g Silica)的PVP能完全抵抗凝聚，隨著pH值增加，可以添加較少PVP就能抵抗凝聚，當pH=10時，僅需0.025就可以完全抵抗凝聚。然而在pH<4時，加入PVP反而會直接導致凝聚，不需要經過冷凍解凍程序。冷凍解凍所得的聚集體形狀是緊密的球形，但加入PVP而直接凝聚的聚集體結構鬆散不規則，因此猜測是PVP成二氧化矽之間的架橋，而導致凝聚。 二氧化矽與PVP的吸附平衡也被建立，初期結果發現有多層吸附現象，熱重分析(TGA)中有些仍維持原來的燃燒溫度(450℃)，而有些PVP燃燒溫度因為吸附而改變(350℃)。PVP以氫鍵吸附的強度必定大於外圍PVP的吸附強度，因此以水清洗多餘的PVP即可得到單層吸附曲線。 另外研究冷凍解凍法應用於造粒，溶膠的二氧化矽冷凍解凍造粒後震實密度(tap density) 比冷凍乾燥法大上五倍。燃燒法製造的粉末(fumed silica)經過冷凍造粒後，震實密度也提高至五倍。造粒成功的粉末在壓錠成型後並以高溫燒結，兩種樣品經可達一定的透明度，然而燒結效果除與堆積有關外，基本粒子的大小也有密切的關係，不過經由冷凍解凍程序強迫奈米粒子聚集成為自由流動的micron等級之粒子確為可行的簡易替代方法。

• 學位論文

立體規則高分子之掌性誘導與自組裝行為研究

Herein, we aim to systematically examine the ICD behavior of stereoregular vinyl polymers, poly(2-vinyl pyridine)s (P2VPs) with C-C single bond as the soft backbone through the association of a variety of chiral guest molecules. With increasing the molar ratio of [acid]/[2VP], the intensity of the ICD approximately increases linearly in the region of low molar ratio of [acid]/[2VP], and the increase in the intensity of ICD experiences a level off by further increasing the molar ratio of [acid]/[2VP], suggesting a saturation state for the association of the acid with the P2VP. As the induced helical conformation of iP2VP is highly dependent upon the concentration of the acid, the ICD will be affected by the chain length of P2VP. P2VPs with different molecular weight and controlled tacticity are synthesized to clarify the molecular weight dependence of optical activity. Our results indicate that the intensity of ICD is independent upon molecular weight while molecular weight is over 4500 g/mol due to a very low helical inversion barrier resulting in the reversal of handedness. To systematically investigative the isotacticity effect on the ICD of iP2VP associated with chiral acid, a series of iP2VP with different isotacticity ranging from 40mm% to 97mm% are synthesized. A nearly linear relationship between the ICD and isotacticity can be identified, indicating that the isotacticity of P2VP is the primary factor to determine the ICD of its complex. Also, an interesting phenomenon can be found at which, instead of splitting-type Cotton effect, the CD spectra of the iP2VP complex only show negative Cotton effect while the isotacticity of the P2VP used is low. According to the simulated results by using ChemDraw, the tacticity of stereoregular P2VP will significantly affect the intramolecular distance of 2-pyridine moieties in P2VP so that the formation of splitting-type Cotton effect will be justified by the stereoregularity of the P2VP. To quantitatively investigative the effect of bulkiness of chiral acid on the ICD of vinyl polymers, chiral acids with different molecular size are used to associate with the iP2VP. As found, while the bulkiness of chiral acid decreases, the steric hindrance will be too low to maintain helical conformation for the iP2VP associated with chiral acid. As iP2VP associated with chiral acids via hydrogen bonding, which is a secondary force (i.e., non-covalent bond interaction), the association will be highly dependent upon temperature. Moreover, the intensity in the ICD can be recovered after cooling, and the intensity variation in the ICD is almost identical with the results from heating, suggesting that the association/dissociation between stereoregular P2VP and chiral acid is a thermally reversible process. Because iP2VP serves as organic base, the ICDs of iP2VP associated with chiral acid can be determined by the equilibrium between the free acid (AH) and base (B) that can be determined by pKa. As found, adding organic base (n-Butylamine, nBA) in polymer solution will reduce the intensity of iP2VP and finally to cause the CD silence. These results suggest that the intensity in ICDs is reversible by changing pKa environment in solution, and one-handed helical conformation of the P2VPs induced by chiral acids might not be memorized after the chiral acids is neutralize by n-BA.

• 學位論文

三嵌段共聚物PI-PS-PLLA之相行為研究

Owing to the multiple interaction parameters resulting from the presence of a distinct third block, the phase behaviors of ABC triblock terpolymers are obviously much richer than that of AB diblock and ABA triblock copolymers. The diversity of self-assembled morphologies from ABC triblock terpolymers is appealing for practical applications, in particular by tuning the chemical and physical properties of three constituent blocks. In this study, we aim to systematically examine the phase behaviors of a dual degradable triblock terpolymer, polyisoprene -b-polystyrene-b-poly(L-lactide) (PI-PS-PLLA), at which the PI block can be ozonized and the PLLA can be hydrolyzed. Moreover, the chirality effect on the self-assembly of the PI-PS-PLLA due to the presence of the chiral PLLA is examined. The final goal is to search for network morphologies so as to use them for the fabrication of nanoporous polymers through degradation of the PI and/or the PLLA. For practical applications, network morphologies with PS or PLLA as a matrix will be acquired since the samples with PI-rich fraction is easy to be deformed due to its low Tg. A variety of nanostructured phases such as core-shell body centered cubic and core-shell double gyroid morphologies in the PI-PS-PLLA can be obtained with fPIv~0.3. With fPSv~0.35 and high amount of PLLA fraction, three-domain lamellar morphology can be found, indicating that the chirality effect of PLLA-rich samples on the self-assembly of the PI-PS-PLLA is trivial. As a result, the exploration of network phases is focused on the composition range with fPLLAv~0.35 and high amount of PS; an alternating gyroid can be found. Most interestingly, a novel network phase is discovered in a specific PI-PS-PLLA, ISL-38b (fIv=0.28; fSv=0.43; fLv=0.29), at which different projections including “knitting pattern” with sinusoidal waves and tetragonal dots combined with stacking lamellae can be observed. Nevertheless, the projections are much different from simulated images of any typical network phases acquired by Matlab and Meshlab. To truly examine the network morphologies, direct visualization of the network texture is carried out by using electron tomography. As observed in the 3D TEM results, dark contrast PI due to the staining of OsO4 appears as “wave-tube stacking” in the bright matrix. To visualize the texture of PLLA microdomains, hydrolysis is carried out. The SEM micrographs of the hydrolyzed samples demonstrate that the PLLA microdomain should be a network texture. By taking advantage of templated sol-gel process, the PLLA microdomains can be successfully replaced by SiO2, further evidencing the suggested network texture of PLLA. The corresponding SAXS results with the reflections at the relative q values of √2: √3: √4: √6: √8: √10, reflecting that the space group of this new network phase is a Pn-- type, similar to that of double diamond (Pn m), on the basis of systematic absence principle for the reflections. A hypothetic nanostructured phase is thus proposed.

• 學位論文

Nucleation and Growth of Silver Nanowires Synthesized via a Polyol Process

Previous studies have demonstrated that, upon addition of AgNO3 into a poly(vinyl pyrrolidone)/ethylene glycol (PVP/EG) solution, Ag nanoparticles are first produced, followed only significantly later by emergence and dominance of Ag nanowires. Mechanistic details in terms of nucleation and growth of Ag nanowires in competition with initially populated Ag nanoparticles remain unclear. Via in-situ small-angle X-ray scattering (SAXS) and scanning electron microscopy (SEM), here we show that, for a molar ratio of Ag/VP = 1, the first 5 min of reaction at 150 °C gave only Ag particles of radius up to RP ≈ 29 nm; after t = 6 min, Ag rods start to appear and become the dominant product after t ≥ 12 min. The rod radius was initially comparable (RR ≈ 26 nm) to coexisting nanoparticles before subsequent increases to RR ≈ 43 nm near the end of reaction at t = 19 min. More importantly, the apparent pH value was observed to decrease quickly from 3.7 to a minimum value of 1.8 at t = 5 min (which corresponds to the time that Ag rods start to appear) before gradually increasing to pH ≈ 3.2. Similar correlation between the change of pH and morphology of Ag nanocrystals was also observed for the case of Ag/VP = 2 with higher reaction rate and halved reaction period. We therefore conjectured that the change in polarizability of the reaction medium with the extent of reaction may affect the surface adsorption behavior of PVP onto different facets of Ag nanocrystals. In support of this conjecture, the pH-dependence of intrinsic viscosity of PVP in EG indeed indicated increased PVP coil size with decreasing pH, presumably due to intrachain ionic repulsion upon protonation of PVP. By adjusting the starting pH value to 1.5 for Ag/VP = 2, the rate of formation of Ag particles was decreased; nevertheless, once the population of Ag nanoparticles reached an adequate level, Ag rods/wires started to emerge as indicated by a rapid increase in UV-visible absorbance and the drastic change in color accompanied by an abrupt jump in apparent pH value within a short period of 1 min; this change in morphology of Ag nanocrystals was further confirmed by SEM and SAXS observations, from which evidences for coalescence of existing Ag nanoparticles were identified. Integrating all observations above, we conclude that the formation of Ag nanowires starts with nucleation from coalescence of Ag particles, followed by 1D growth with partial capping of the lateral (100) surfaces by protonated PVP chains.