京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第21113号 / 工博第4477号 / 新制||工||1696(附属図書館) / 京都大学大学院工学研究科材料化学専攻 / (主査)教授 田中 勝久, 教授 三浦 清貴, 教授 作花 哲夫 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

No description available.

表面プラズモン共鳴型超音波センサは高分解能な光音響顕微鏡用超音波受波器として期待されている．本研究では，サブナノ秒パルスレーザを利用したポンププローブシステムを構築してサブナノ秒域における表面プラズモン共鳴センサの熱・弾性的な過渡応答を光学的に評価した。特にプローブ光の反射率変化として観測される過渡応答の発生メカニズムについて，実験と理論の両方のアプローチから検討しており，観測される過渡応答は金属薄膜のプラズマ周波数の変化に起因することを明らかにした。 / Surface plasmon resonance (SPR) sensor has been expected as a ultrasonic sensor used in high resolution photoacoustic microscopy (PAM). In this thesis, thermoelastic transient responses in SPR sensor were evaluated by a pump probe system with a developed sub-nanosecond pulsed laser. Especially, the mechanism of the transient response to be observed as a reflectivity change of the probe light was studied by two approaches of the experiment and the theoretical estimation. As consequence of these approaches, it was revealed that the transient response was caused by the change of the plasma frequency in a thin metal film of SPR sensor. / 博士(工学) / Doctor of Philosophy in Engineering / 同志社大学 / Doshisha University

Localized surface plasmon resonance (LSPR) is induced in metal nanoparticles by resonance between incident photons and conduction electrons in nanoparticles. For noble metal nanoparticles, LSPR can lead to strong absorbance of ultraviolet-violet light. Although it is well known that LSPR depends on the size and shape of nanoparticles, the inter-particle spacing, the dielectric properties of metal and the surrounding medium, the temperature dependence of LSPR is not well understood. By thermally annealing gold nanoparticle arrays formed by nanosphere lithography, a shift of LSPR peak upon heating has been shown. The thermal characteristics of the plasmonic nanoparticles have been further used to detect chemicals such as explosive and mercury vapors, which allow direct visual observation of the presence of mercury vapor, as well as thermal desorption measurements

Current major demands in SPR sensor development are system miniaturization and throughput improvement. Structuring an array of integrated optical SPR sensor heads on a semiconductor based optoelectronic platform could be a promising solution for those issues, since integrated optical waveguides have highly miniaturized dimension and the optoelectronic platform enables on-chip optical-to-electrical signal conversion. Utilizing a semiconductor based platform to achieve optoelectronic functionality poses requirements to the senor head; the sensor head needs to have reasonably small size while it should have reasonable sensitivity and fabrication tolerance. This research proposes a novel type of SPR sensor head and demonstrates a fabricated device with an array of integrated optical SPR sensor heads endowed with optoelectronic functionality. The novel integrated optical SPR sensor head relies on mode conversion efficiency for its operational principle. The beauty of this type of sensor head is it can produce clear contrast in SPR spectrum with a highly miniaturized and simple structure, in contrast to several-millimeter-scale conventional absorption type or interferometer type sensor heads. The integrated optical SPR sensor with optoelectronic functionality has been realized by structuring a dielectric waveguide based SPR sensor head on a photodetector-integrated semiconductor substrate. A large number of unit sensors have been fabricated on a substrate with a batch fabrication process, which promises a high throughput SPR sensor system or low-priced disposable sensors.

This thesis successfully integrates laminate microfluidic devices with an analytic Surface Plasmon Resonance (SPR) instrument. Integration was accomplished at low-cost using materials such as polydimethylsiloxane (PDMS), Poly(methyl methacrylate) (PMMA), Tygon tubing, and a 3-way stopcock. The main components of this thesis are the design and fabrication of the low-cost, in-house fluidics that can integrate with upstream microfluidics and the validation of the in-house fluidics using the Biosensing Instruments BI-2000 SPR instrument. The low-cost fluidics was designed and fabricated “in-house” using a novel investment casting technique that required the use of laser cutting technology to make a master cast, and candle wax to make the fluidic flow gasket. Integration of upstream microfluidic devices is the next step towards fully integrated point-of-care (POC) diagnostics. Development of low-cost POC diagnostics will enable physicians to diagnosis patients outside of clinical settings, granting treatment access to a much wider population. Surface Plasmon Resonance is used for its detection abilities combined with its ability to perform real-time sample analysis. Validation of the in-house fluidics was accomplished by conducting (2) experiments: (1) to compare the angular shift elicited by ethanol solutions between in-house fluidics, factory fluidics, and the literature, and (2) to compare the angular shift between in-house fluidics and factory fluidics caused by the cleaving of fibroblasts from the SPR sensor chip. Successful comparisons made in both experiments proved successful development of low-cost fluidics that could integrate upstream microfluidic devices.

Protein disulfide isomerase (PDI) is an endoplasmic reticulum (ER)-resident chaperone with oxidoreductase and isomerase activity. Unique to its normal function, PDI also appears to disassemble the A1 subunits of cholera toxin (CT) and heat-labile enterotoxin (LT). It does so using an unfolding mechanism that knocks the catalytic A1 subunit away from the rest of the holotoxin. Release of the A1 subunit is linked to the diarrheal diseases caused by V. cholerae and enterotoxicogenic E. coli (ETEC). Due to the previously established difference in disease potency between CT and LT, we investigated and established a distinction between the two toxins in their efficacy of disassembly by PDI. We further identified four amino acid differences between the CTA2 and LTA2 linkers, which connect the A1 and cell-binding B subunits of both toxins, as the basis for this difference. We believe these four amino acids result in changes to holotoxin architecture that lead to antiparallel binding of PDI to LT as opposed to CT, which translates to a loss of momentum for the physical disassembly of LT. We have shown this through algorithmic simulations of the binding event between PDI and either CT or LT. We hypothesized the unfolding mechanism of PDI, which dislodges the A1 subunit of both CT and LT, can also break down neurotoxic aggregates of β-Amyloid (AB) and α-Synuclein (AS). PDI is known to inhibit the aggregation of the amyloid proteins. We demonstrated here that PDI could also reverse oligomeric and post-oligomeric aggregates of AB and AS, respectively. Our work sheds light on the specifics of PDI's novel physical mechanism as well as introduce it as a possible therapeutic for both Alzheimer's and Parkinson's disease due to its unique ability to disaggregate early fibrillar structures of AS and AB proteins.

The effects of taste masking are determined by interactions between drug and excipients as well as the microstructures of the particulate drug delivery systems (DDS). Cyclodextrin (CD) is a widely used taste masking agent, to which the relationship between kinetic parameters (Ka and Kd) of a drug and taste masking remains unexplored, which is investigated for the first time in this study. A data base of the kinetic parameters for drug-CD was established by Surface Plasmon Resonance Imaging (SPRi) and High Performance Affinity Chromatography (HPAC). Combined with the electronic tongue, Ka and Kd based models for the taste masking effect of HP-β-CD were successfully established and applied to the prediction of taste masking effects. Paracetamol was used as a model drug for taste masking formulation optimization. As well as drug release the microstructure of solid DDS has considerable influence on drug taste. The microstructure of lipid microspheres and the molecular distribution of drug and excipients in lipid microspheres were investigated by Synchrotron radiation-based micro-computed tomography (SR-μCT) and Synchrotron radiation-based Fourier-transform infrared spectromicroscopy (SR-FTIR), respectively. The results demonstrated that the polymeric formulation components as well as shape and particle size of the drug were the key factors to taste masking of paracetamol by inhibiting bust release thereby reducing the interaction intensity of the bitterness. The FTIR absorption spectra confirmed the deposition and formation of chitosan and gelatin films on the drug microsphere surface by layer-by-layer coating. In conclusion, this research demonstrates the molecular kinetic basis of CD taste-masking as well as microstructural basis of particle systems for bitter taste masking.

No description available.

No description available.