I have investigated gap plasmon mode of an eccentric coaxial waveguide structure using effective index method. The results found good agreement with fully-vectorial numerical calculation. In the eccentric structure, a strong field localization has been noticed at and around the smallest gap. Analysis showed the increase of effective index of lowest-order waveguide mode to 3.7 in the structure considered with a 2 nm minimum gap for a wavelength of 4 micrometer. In the visible regime, the effective index increases to over 10 for the same structure. Nanohole arrays, both flowover and flow-through formats, have been fabricated using focused ion beam (FIB). A 2-color LED-based nanohole sensor has been presented. The objective of the sensing platform was to register mutually opposite intensity change of transmitted light when the dielectric medium of metal-dielectric interface of the nanohole sensor undergoes a change. A number of tests with microfluidics setup demonstrated the proof-of-concept.

Le projet vise à développer une nouvelle approche méthodologique dans le but d'améliorer l'utilisation combinée de plusieurs techniques de microscopies infrarouge et X lors de l'analyse de fragments de peintures. Historiquement et ordinairement, les fragments de peintures sont préparés en coupes épaisses polies et les analyses sont réalisées à la surface de ces dernières. Bien que cette préparation d'échantillon facilite sa manipulation ainsi que son orientation lors des analyses, elle limite aussi l'efficacité et la faisabilité de certaines techniques de microscopie. Par conséquent, ce travail propose d'explorer une nouvelle stratégie analytique : la préparation et l'analyse de coupes fines. Ces deux étapes ont été optimisées et validées dans le cadre d'analyses par µFTIR, µXRD, µXRF et µXANES. En parallèle, de nouvelles possibilités analytiques ont été testées dans le cadre de l'analyse des peintures, basées sur la technique XANES plein champ. Les échantillons de peintures se sont révélés être d'excellents candidats pour évaluer les avantages et inconvénients de cette technique pour les matériaux du Patrimoine Culturel en général. / This project aims at developing a new methodological approach, providing a more efficient and synergetic use of FTIR and X-ray microscopies, for the analysis of painting fragments. Usually, painting fragments are prepared as polished sections and analyses are carried out on the cross-section surface. This sample preparation is easy to handle, however ends into critical constraints regarding feasibility and efficiency of micro-analyses. We propose to explore a different strategy: preparation and analysis of thin sections. These preparation procedures were first optimized and validated with µFTIR, µXRF, µXRD and µXANES. Besides, new methodological capabilities based on full-field/µXANES were assessed. Paintings were ideal candidates for estimating pros and cons of this new strategy for CH materials in general.

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Metabolomics is the methodical scientific study of biochemical processes associated with the metabolome—which comprises the entire collection of metabolites in any biological entity. Metabolome changes occur as a result of modifications in the genome and proteome, and are, therefore, directly related to cellular phenotype. Thus, metabolomic analysis is capable of providing a snapshot of cellular physiology. Untargeted metabolomics is an impartial, all-inclusive approach for detecting as many metabolites as possible without a priori knowledge of their identity. Hence, it is a valuable exploratory tool capable of providing extensive chemical information for discovery and hypothesis-generation regarding biochemical processes. A history of metabolomics and advances in the field corresponding to improved analytical technologies are described in Chapter 1 of this dissertation. Additionally, Chapter 1 introduces the analytical workflows involved in untargeted metabolomics research to provide a foundation for Chapters 2 – 5. Part I of this dissertation which encompasses Chapters 2 – 3 describes the utilization of mass spectrometry (MS)-based untargeted metabolomic analysis to acquire new insight into cancer detection. There is a knowledge deficit regarding the biochemical processes of the origin and proliferative molecular mechanisms of many types of cancer which has also led to a shortage of sensitive and specific biomarkers. Chapter 2 describes the development of an in vitro diagnostic multivariate index assay (IVDMIA) for prostate cancer (PCa) prediction based on ultra performance liquid chromatography-mass spectrometry (UPLC-MS) metabolic profiling of blood serum samples from 64 PCa patients and 50 healthy individuals. A panel of 40 metabolic spectral features was found to be differential with 92.1% sensitivity, 94.3% specificity, and 93.0% accuracy. The performance of the IVDMIA was higher than the prevalent prostate-specific antigen blood test, thus, highlighting that a combination of multiple discriminant features yields higher predictive power for PCa detection than the univariate analysis of a single marker. Chapter 3 describes two approaches that were taken to investigate metabolic patterns for early detection of ovarian cancer (OC). First, Dicer-Pten double knockout (DKO) mice that phenocopy many of the features of metastatic high-grade serous carcinoma (HGSC) observed in women were studied. Using UPLC-MS, serum samples from 14 early-stage tumor DKO mice and 11 controls were analyzed. Iterative multivariate classification selected 18 metabolites that, when considered as a panel, yielded 100% accuracy, sensitivity, and specificity for early-stage HGSC detection. In the second approach, serum metabolic phenotypes of an early-stage OC pilot patient cohort were characterized. Serum samples were collected from 24 early-stage OC patients and 40 healthy women, and subsequently analyzed using UPLC-MS. Multivariate statistical analysis employing support vector machine learning methods and recursive feature elimination selected a panel of metabolites that differentiated between age-matched samples with 100% cross-validated accuracy, sensitivity, and specificity. This small pilot study demonstrated that metabolic phenotypes may be useful for detecting early-stage OC and, thus, supports conducting larger, more comprehensive studies. Many challenges exist in the field of untargeted metabolomics. Part II of this dissertation which encompasses Chapters 4 – 5 focuses on two specific challenges. While metabolomic data may be used to generate hypothesis concerning biological processes, determining causal relationships within metabolic networks with only metabolomic data is impractical. Proteins play major roles in these networks; therefore, pairing metabolomic information with that acquired from proteomics gives a more comprehensive snapshot of perturbations to metabolic pathways. Chapter 4 describes the integration of MS- and NMR-based metabolomics with proteomics analyses to investigate the role of chemically mediated ecological interactions between Karenia brevis and two diatom competitors, Asterionellopsis glacialis and Thalassiosira pseudonana. This integrated systems biology approach showed that K. brevis allelopathy distinctively perturbed the metabolisms of these two competitors. A. glacialis had a more robust metabolic response to K. brevis allelopathy which may be a result of its repeated exposure to K. brevis blooms in the Gulf of Mexico. However, K. brevis allelopathy disrupted energy metabolism and obstructed cellular protection mechanisms including altering cell membrane components, inhibiting osmoregulation, and increasing oxidative stress in T. pseudonana. This work represents the first instance of metabolites and proteins measured simultaneously to understand the effects of allelopathy or in fact any form of competition. Chromatography is traditionally coupled to MS for untargeted metabolomics studies. While coupling chromatography to MS greatly enhances metabolome analysis due to the orthogonality of the techniques, the lengthy analysis times pose challenges for large metabolomics studies. Consequently, there is still a need for developing higher throughput MS approaches. A rapid metabolic fingerprinting method that utilizes a new transmission mode direct analysis in real time (TM-DART) ambient sampling technique is presented in Chapter 5. The optimization of TM-DART parameters directly affecting metabolite desorption and ionization, such as sample position and ionizing gas desorption temperature, was critical in achieving high sensitivity and detecting a broad mass range of metabolites. In terms of reproducibility, TM-DART compared favorably with traditional probe mode DART analysis, with coefficients of variation as low as 16%. TM-DART MS proved to be a powerful analytical technique for rapid metabolome analysis of human blood sera and was adapted for exhaled breath condensate (EBC) analysis. To determine the feasibility of utilizing TM-DART for metabolomics investigations, TM-DART was interfaced with traveling wave ion mobility spectrometry (TWIMS) time-of-flight (TOF) MS for the analysis of EBC samples from cystic fibrosis patients and healthy controls. TM-DART-TWIMS-TOF MS was able to successfully detect cystic fibrosis in this small sample cohort, thereby, demonstrating it can be employed for probing metabolome changes. Finally, in Chapter 6, a perspective on the presented work is provided along with goals on which future studies may focus.