Bile acids are physiologically important metabolites, which are synthesized in liver as the end products of cholesterol metabolism and then secreted into the intestines. They play a critical role in the digestion and absorption of fats and fat-soluble vitamins through emulsifications. The amphipathic and chiral nature of bile acids makes their unique building blocks for assembling supramolecular structures including vesicles, fibers, ribbons and hollow tubes. Lithocholic acid (LCA) is a secondary bile acid. Our studies show LCA can selfassemble into helical tubes in aqueous solution by the linear aggregation and fusion of vesicles. The objective of this dissertation is to tune the structure of helical tubes and functionalize them by the co-assembly of ionic LCA and cationic cetyltrimethylammonium bromide (CTAB) and ionic LCA and cationic cyanine dye (CD), respectively. The first part of this dissertation focuses on the ionic-assembly of LCA and CTAB to synthesize the helical tubes with varied diameters and pitches. Our studies show that LCA and CTAB can self-assemble into helical tubes in NH4OH aqueous solution. The diameter of the helical tubes can be changed by adjusting the molar ratio of LCA and CTAB. The pitch of the helical tubes can be tuned by varying NH4OH concentrations. Differential scanning calorimetry studies indicate that there is a homogeneous composition distribution in the LCA/CTAB helical tubes. X-ray diffraction analysis studies show that the helical tubes have multibilayer walls with an average d-spacing of 4.11nm. We demonstrate that the helical tubes with varied diameters and pitches can be transformed into helical silica through the sol-gel transcription of tetraethoxysilane (TEOS). The second part of this dissertation is to use the ionic self-assembly of LCA and CD to design light-harvesting tubes iv by mimicking green sulfur bacteria that are known to be a highly efficient photosynthesizer. Xray diffraction and optical spectra show that LCA and CD can co-assemble into J- or Haggregate tubes, depending the condition under which the self-assembly occurs. We demonstrate the feasibility of using the J-aggregate nanotubes in the sensitive and selective detection of mercury (II) ions by the photoinduced electron transfer under sunlight. The presence of mercury (II) ions in aqueous solution could be detected for concentrations as low as 10 pM.

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.

<p>   Organic electronics has been a highly researched field owing to the low cost, biocompatibility, mechanical flexibility, and superior performance relative to their inorganic counterparts in some applications. Significant advancement has been achieved across various device platforms including organic light-emitting diodes (OLEDs), organic field effect transistors (OFETs), and organic solar cells, for instance. Recently, soft materials that can conduct both charge and ions simultaneously (i.e., organic mixed conductors) have been a major catalyst in the fields of biosensors and energy storage. Extensive research efforts in the organic electronics field are being invested to establish the relevant structure-property relationships to design and develop higher performing organic mixed conductors. Simultaneously, these materials are utilized in developing prototype biosensors with the aim of superior performance, lower cost, and better patient comfort and outcomes than currently available technologies. Following suit, this dissertation is dedicated to furthering organic electronics on both fundamental and applied fronts. Specifically, this work examines a novel class of redox-active macromolecules, radical polymers, as the organic electrochemical transistor (OECT) active layer. In addition, wearable ocular biosensors utilizing soft materials to realize design innovation are presented.</p> <p>   For the first part of the present dissertation, radical polymer-based blends are evaluated for mixed electron and ion conduction in OECTs. Traditional macromolecular design motifs for OECT active layer materials have been a closed-shell macromolecular backbone for electron conduction with charge-neutral hydrophilic side chains (e.g., triethylene glycol) for ion conduction. When poly(4-glycidyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl) (PTEO) is blended with poly(3-hexylthiophene) (P3HT), 2,2,6,6-tetramethylpiperidin-N-oxy (TEMPO) radicals in PTEO act as an independent voltage regulator that modulates the ionic and hence electronic transport of the OECT devices. Electrochemical analysis of the blend films reveals that the ionic transport and hence electrochemical doping of the P3HT phase occur when the applied bias matches the onset oxidation potential of TEMPO radicals in PTEO even though that of P3HT is lower than that of TEMPO oxidation. By optimizing the blend ratio, figure-of-merit (i.e., μC*) values over 150 F V–1 cm–1 s–1 at loadings as low as 5% PTEO (by weight) are achieved, placing the performance on the same order as top-performing conjugated polymers despite the mediocre performance of pristine P3HT (<10 F V–1 cm–1 s–1). These findings suggest that introduction of open-shell moieties in the OECT active layer as a secondary redox-active species may significantly improve OECT performance metrics and offer a new paradigm for future macromolecular designs.</p> <p>   In the second part of the dissertation, novel design strategies for wearable ocular electroretinography (ERG) sensors are presented. Typically, wearable sensors are custom-made contact lenses fabricated in a bottom-up fashion where the pre-fabricated sensor component is either embedded in the contact lens body or sandwiched between two. The present work instead utilizes commercially available contact lenses, and the corneal electrode is integrated via electropolymerization of poly(3,4-ethylenedioxythiophene):iron(III) p-toluenesulfonate (PEDOT:Tos) on the lens surface. Electrochemical analysis of the PEDOT:Tos reveals that the measured impedance is several orders of magnitude lower than that of noble metals (e.g., Au) used as the working electrode in commercial electrodes. The mechanical and chemical stability along with the soft form factor of the present design strategy enables high-fidelity recording of ERG signals in human subjects without the need for topical anesthesia.</p> <p>   Following the similar strategy, a new seamless wearable ocular sensor integration strategy utilizing polydopamine (PDA) conformal coating is demonstrated. In this work, we utilize its strong adhesive property originating from the van der Waals interactions between catechol moieties of PDA and various hydrophilic functional groups (e.g., hydroxy, ether, etc.) already present in commercial contact lens materials. The facile integration demonstrates high peeling strength (> 55 J m-2), chemical and mechanical stability. A series of <em>in vivo</em> assessments demonstrates high accuracy, reliability, and user comfort of the fabricated wearable sensor in both animal and human subjects. The findings suggest that the PDA-assisted integration strategy may be applied in designing various future-generation wearable ocular electrophysiological sensors.</p>

Although nucleic acid tests (NATs) for human immunodeficiency virus (HIV) exhibit many advantages, such as early detection and viral load quantification, over immunological assays, their widespread use is limited by their demand for high-level infrastructure, sophisticated equipment, and advanced staff competence. Furthermore, when quantifying viral loads of patients, it has been reported that these assays can underestimate viral quantities by 22- to 100-fold due to primer-template mismatches in more divergent HIV subtypes. Therefore, we have developed a cost-effective and sequence-independent assay for the detection and quantification of HIV utilizing a modified nucleic acid sequence-based amplification (NASBA) protocol coupled to an electrochemical DNA biosensor. The modified NASBA reaction involves the addition of a 22-nucleotide tag between the T7 RNA Polymerase Promoter and the hybridizing region of the reverse primer. As a result, this tag will be placed at the 5' end of each amplicon regardless of the target sequence. We then designed the DNA sensor to hybridize to this segment of the amplicon specifically. Therefore, hybridization, and subsequently, detection, is dependent only on the presence of this tag and not the viral RNA sequence itself. As a result, the issue of underestimating viral loads is eliminated as multiple primers can be used in one reaction without having to use multiple sensors. The use of an isothermal NASBA technique and a reusable gold-disc electrode for the sensor helps drive down the cost of the assay by eliminating the need for thermocyclers and fluorometers used by conventional NATs.

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京都大学 / 新制・課程博士 / 博士(農学) / 甲第23251号 / 農博第2458号 / 新制||農||1085(附属図書館) / 学位論文||R3||N5341(農学部図書室) / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 阪井 康能, 教授 小川 順, 教授 井上 善晴 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

<p>  </p> <p>As our ability to make more sensitive measurements increases, we begin to reach for the ultimate measurement sensitivity: a single entity. Mass spectrometry and fluorescence-based methods exist for single entity studies, and through these the intriguing effects of confinement begin to be observed. These mass spectrometry and fluorescence-based techniques are however, often destructive, which precludes measurements over time. The advent of nanoelectrochemical methods, however, allows for the creation of tools that can make measurements inside of confined volumes—a droplet, a cell, <em>etc</em>.—over extended periods of time. While most nanoelectrochemical methods are based on amperometry or voltammetry, potentiometry allows for minimal perturbation of the system’s homeostasis by passing negligible current.</p> <p>To overcome many of the issues involved in these other methods, we design potentiometric tools that can be easily miniaturized to fit within single entities, particularly within single cells. These tools include enzymatic biosensors designed to be minimally influenced by the cell’s O2 or NAD+ levels, as well as a novel reference electrode that can be made to be very low leakage or completely leakless to avoid contamination of the cell by the reference electrode’s internal filling solution. Both of these tools are designed such that they are easily modified to suit a number of different applications, including for use inside non-aqueous solutions.</p>

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