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This thesis describes methods for improving sensitivity in rapid singleplex and multiplex microarray assays. The assays utilize the optical characteristics of colloidal gold nanoparticles for the colorimetric detection of proteins. Multiplexed detection in sandwich immunoassays is limited by cross-reactivity between different detection antibodies. The cross-reactivity between antibodies can contribute to increased background noise - decreasing the Limit-of-Detection of the assay - or generate false positive signals. Paper I shows improved assay sensitivity in a multiplexed vertical flow assay by the application of ultrasonic energy to the gold nanoparticles functionalized with detection antibodies. The ultrasonication of the antibody conjugated gold nanoparticles resulted in a 10 000 fold increase in sensitivity in a 3-plex assay. COMSOL Multiphysics was used to simulate the acoustical energy of the probe used in Paper I for obtaining an indication of the size and direction of the forces acting upon the functionalized gold nanoparticles. In Paper II, it was studied if different gold nanoparticle conjugation methods and colorimetric signal enhancement of the gold nanoparticle conjugates could influence the sensitivity of a paper-based lateral flow microarray assay, targeting cardiac troponin T for the rapid diagnostics of acute myocardial infarction. Ultrasonication and signal enhancement of the detection gold nanoparticles has the potential of improving the sensitivity of paper based assays and expanding their potential future applications. / <p>QC 20170911</p>

The increase in the magnitude of local electric fields through resonances of plasmonic excitations in metallic nanoparticles is a major area of current optical research. This dissertation is focused on plasmon-enhanced second harmonic generation of organic ionic self-assembled films via localized surface plasmon resonance of gold nanorods. By matching the plasmon resonance of the gold nanorods to the wavelength of the fundamental light, it is possible to greatly enhance the SHG efficiency. To demonstrate this, the surface of the gold nanorods was functionalized with a nonlinear-optical (NLO) polymer, PCBS, via the layer-by-layer method and deposited on a polymer thin film created on a glass substrate using the ionic self-assembled multilayer (ISAM) method. The sample fabrication is divided into two parts: gold nanorod synthesis and functionalization. The gold nanorods were synthesized by the seed-mediated method with varying amounts of silver ions to control their LSPR wavelengths. The functionalization started by replacing the original thick CTAB bilayer on the surface of the gold nanorods by a thin PAH-DTC layer via dialysis. The nanorods were then alternately coated with PAH (polycation) and PCBS (NLO polyanion) up to three bilayers of PAH/PCBS. The number of polymer layers on the nanorods was chosen in consideration of the LSPR decay length (a few nm). The functionalized gold nanorods were then deposited on either PAH/PCBS or PAH/PSS ISAM films. Characterization was performed via optical spectral measurement, zeta potential measurement, and field-emission scanning electron microscopy (FESEM). The LSPR wavelength shifted when the surrounding medium changed. It was red-shifted for each added polymer layer on the nanorod surface. However, when the functionalized nanorods were deposited on the ISAM film, the resonance peak blue-shifted. The zeta potential confirmed the proper electric charge of each polymer layer coated on the nanorods. Finally, FESEM was performed on the samples for visual inspection of the nanorod deposition and distribution after the SHG measurement was complete. The SHG from the functionalized gold nanorods was measured using a Maker-like fringe method. In this method, second harmonic waves generated from the front and rear sides of the substrate interfere constructively and destructively when the sample is rotated with respect to the incoming pump wave. Electrical noise reduction techniques were implemented to improve the SHG signal readings. Signal processing was implemented using LabVIEW software in order to read a reliable SHG signal from the setup. The maximum tolerable fluence of the gold nanorods was determined in order to prevent optical damage. The interference fringe pattern was observed from the functionalized gold nanorods and compared with that from the conventional ISAM film. The enhancement from the gold nanorods was as high as 600 times compared to the bare films. Polarization dependent SHG measurements were conducted to ascertain the effect of coupling between p- or s-polarized fundamental incident light to the SH light. To further improve the SHG enhancement, the self-assembly method herein can be extended from a monolayer to multilayers of functionalized gold nanorods. / Ph. D.

Metallic nanoparticles (MetNPs) with unique nanoscale properties, including novel optical behavior and superparamagnetism, are continually being developed for biomedical and industrial applications. In certain biomedical applications where extended blood half-lives are required, MetNPs are surface-functionalized using polymers, proteins, and other stabilizing agents to facilitate their resistance to salt-induced aggregation. Given their colloidal stability in high ionic-strength matrices, functionalized MetNPs are anticipated to be persistent aquatic contaminants. Despite their potential environmental significance, the persistence of surface- functionalized MetNPs as individually-stabilized nanoparticles in aquatic environments is largely unknown. Further, few studies have investigated the fundamental factors that influence MetNP uptake and fate/transport processes in ecologically susceptible aquatic biota, such as filter- feeding bivalves, which ingest and accumulate a broad range of dissolved- and particulate-phase contaminants. The present study describes a comprehensive approach to prepare and rigorously characterize MetNP test suspensions to facilitate fundamental examinations of nanoparticle uptake and fate/transport processes in freshwater and marine bivalves. We demonstrate the importance of accurately characterizing test suspensions in order to better understand MetNP persistence as individually-stabilized nanoparticles within aquatic test media, and define an optical-activity metric suitable for quantifying and comparing the persistence of variable MetNP formulations as National Nanotechnology Initiative (NNI) definable nanoscale materials. We also show that individually-stabilized MetNPs of variable elemental composition, particle diameter, and surface coating are accessible to bivalves in both freshwater and marine environments. Clearance rates for MetNPs are positively related to the diameter and initial concentration of MetNP suspensions. The observed size-dependence of particle filtration rates facilitates ‘size-selective biopurification' of particle suspensions with nanoscale resolution, and may have applicability in future sustainable nanomanufacturing processes. Filtered MetNPs are retained for extended periods post-exposure primarily within the bivalve digestive tract and digestive gland, but migration to other organ systems was not observed. Clusters of MetNPs were recovered in concentrated form from excreted feces, suggesting that biotransformation and biodeposition processes will play an important role in transferring MetNPs from the water column to benthic environments. / Ph. D.

Surface enhanced Raman spectroscopy (SERS) is highly promising analytical technique for trace detection of analytes. It is particularly well suited for environmental analyses due to its high sensitivity, specificity, ease of operation and rapidity. The detection and characterization of environmental contaminants, using SERS is highly related to the uniformity, activity and reproducibility of the SERS substrate. In this thesis, SERS substrates were produced by gold nanoparticle formation on wax patterned chromatography paper. In situ reduction of hydrogen tetrachloroaurate (gold precursor) by trisodium citrate dihydrate (reducing agent) was used to produce gold nanoparticles within a paper matrix. These gold nanoparticle based SERS substrates were analyzed by FE-SEM, UV-Vis and Raman spectroscopy. This work discusses the SERS signal enhancements for Raman active MGITC dye for a series of substrates prepared by in situ reduction of gold salt and pre-produced gold nanoparticles. UV-Vis analysis was performed to understand the effect of different molar ratio (reducing agent to gold precursor) and reaction time on the size and shape of the localized surface plasmon resonance (LSPR) band that dictates the SERS enhancements. It was concluded that lower molar ratio (1:1 and 2:1) of citrate-to gold produced better SERS signal enhancements and broader LSPR band. Therefore, use of lower molar ratio (MR) was recommended for paper-based substrates using in situ-based reduction approach. / Master of Science

Si la microscopie de fluorescence est la plus couramment utilisée pour détecter des nano-objets individuels, les méthodes d’absorption permettent de s’affranchir de la photostabilité imparfaite des objets luminescents et d’accéder à d’autres objets en ne se limitant pas aux espèces luminescentes. Au cours de ce travail de thèse, nous avons cherché à pousser les limites des méthodes basées sur l’absorption existantes en termes de sensibilité et de caractère quantitatif. La microscopie photothermique hétérodyne permet de détecter une grande variété de nano-objets absorbants sur fond noir. Nous présentons une nouvelle implémentation de cette technique permettant d’exalter la réponse photothermique de nanoparticules d’or individuelles autour de la transition de phase du milieu les entourant. Un gain d’un facteur 10 a été obtenu par rapport à un milieu classique. Afin de déterminer l’absorption de petits nano-objets à fort rapport d’aspect, comme les nanotubes de carbone, la détection directe est en revanche plus quantitative. En développant une méthode d’absorption à modulation spatiale optimisée, nous avons déterminé pour la première fois la valeur de la section efficace d’absorption de nanotubes de carbone (6,5) de manière absolue. Finalement, nous avons mis au point un protocole de préparation et de tri en longueur de nanotubes de carbone ultracourts. Les longueurs obtenues ont été caractérisées par spectroscopie, microscopies optique et à force atomique. Dans le futur, ces nanotubes pourront être utilisés comme sondes biologiques détectées par le dispositif photothermique. Les nanotubes possèdent en effet des résonances optiques dans le proche infrarouge correspondant à la plage de transparence des tissus biologiques. / Absorption methods can overcome the limited photostability of luminescent nano-objects and allow for detection of non-luminescent ones, making it a desirable alternative to commonly used fluorescence microscopy for single particle detection. During this project, we optimized the sensitivity of existing absorption based methods and developed their use for quantitative applications. Photothermal heterodyne microscopy is a highly sensitive, “background-free” detection method that can be applied to a large variety of individual absorbing nano-objects. We implement a new version of this technique that enhances the photothermal response of single gold nanoparticles by using a phase transition in their surrounding environment. Compared to a standard medium, we demonstrate a 10 fold enhancement of the signal to noise ratio. On the other hand, for measurement of the absorption cross section of small, and high aspect ratio nano-objects, such as carbon nanotubes, direct detection is more quantitative. In pursuit of this goal, we developed an optimized modulated absorption method and used it to directly measure the absolute absorption cross section of (6,5) carbon nanotubes for the first time. Finally, we set up a protocol to prepare ultrashort carbon nanotubes and sort them by length. As they exhibit strong optical resonances in the near infrared corresponding to a transparency window in biological tissues, they will be useful as photothermally detected biological probes. These nanotubes were characterized spectroscopically, and by optical and atomic force microscopy.

L’Optique non linéaire est un outil très puissant pour étudier les propriétés des matériaux. Dans cette thèse, nous avons utilisé deux techniques d’optique non linéaire pour l’étude des non linéarités moléculaires: la génération de seconde harmonique induite sous champ électrique (EFISH) et la diffusion harmonique de la lumière (DHL). Tout d'abord, nous avons mis en évidence la conjugaison des groupements donneurs pi- dans les complexes d’iridium cyclométallés. Nous avons également exploré une série de molécules trinucléaires organométalliques (triaryle-1, 3, 5-triazinane-2, 4, 6-triones) fonctionnalisées par des acétylures métalliques avec des complexes des métaux de transition à leur périphérie- l’hyperpolarisabilité est beaucoup plus élevée que celles des dérivés purement organiques équivalents. D'autre part une série de complexes métalliques dipolaires et octupolaires contenant des ligands 2, 2-bipyridine photochromes à base de dithiényléthène (DTE) ont été synthétisés et caractérisés. L'étude révèle une forte augmentation de Les hyperpolarisabilités après irradiation UV correspondant à la fermeture de cycle associée au DTE. Cette forte exaltation reflète bien la délocalisation du système d’électrons pi- et la formation de chromophores push-pull dans les formes fermées. Troisièmement, nous avons étudié les propriétés optiques non linéaires de complexes de bis (phtalocyaninato) lanthanide (III) en sandwich, avec 2 phthalocyanines substituées en ABAB (alternance de donneurs d'électrons et d’accepteurs d'électrons), AB3 (3 groupes de donneurs), A4 (4 groupes d’accepteurs) et B4 (aucun groupe de donneur). L’hyperpolarisabilité du 1er ordre beta- mesurées sont les plus élevées jamais enregistrées pour des molécules octupolaires. La contribution directe d’électrons f dans les ions lanthanides complexés est également observée sur l'activité non linéaire du second ordre. Enfin, des nanosphères (AuNSs) et des nanotubes d'or (AuNRs) avec différents rapports d'aspect (AR) allant de 1,7 à 3,2 nm ont été synthétisés par la méthode de radiolyse. Le signal de deuxième harmonique émis par des AuNRs est nettement supérieur à celui des nanosphères et révèle leur dépendance à l'AR. Nous avons également mélangé un dérivé du chromophore 4-diméthylamino-N-méthyl-4-stilbazolium tosylate (DAST) avec les AuNRs et observé une influence des AuNRs sur l'amélioration des propriétés ONL du DAST. Une nette augmentation de l’hyperpolarisabilité (par un facteur 8) du derive de DAST en est la preuve. / Nonlinear optics is well known to be a highly powerful tool to investigate the properties of the materials. In this thesis we used two important nonlinear optical techniques known as Electric Field Induced Second Harmonic Generation (EFISH) and Harmonic Light Scattering (HLS) to study the first hyperpolarizability of various molecular objects. Firstly, we evidenced the pi donor conjugation in cyclometallated Ir complexes. We have also explored the series of trinuclear organometallic triaryl-1, 3, 5-triazinane-2, 4, 6-triones functionalized by d6-transition metal acetylides complexes at their periphery- large hyperpolarizabilities, far higher than those of related purely organic derivatives are reported. Secondly, a series of dipolar and octupolar dithienylethene (DTE)-containing 2, 2-bipyridine ligands with different metal ions featuring two, four and six photochromic dithienylethene units have been synthesized and fully characterized. The study reveals a large increase in the hyperpolarizability after UV irradiation and subsequent formation of ring-closed isomers. This efficient enhancement clearly reflects the delocalization of the pi-electron system and the formation of strong push&pull chromophores in the closed forms. Thirdly, we have investigated NLO properties of bis (phthalocyaninato) lanthanide-(III) double-decker complexes with crosswise ABAB (phthalocyanine bearing alternating electron-donor and electron-acceptor groups), AB3 (3 donor groups), A4 (4 donor groups) and B4 (no donor groups) ligands. First-order hyperpolarizability is measured and displays the highest quadratic hyperpolarizability ever reported for an octupolar molecule. The direct contribution of f-electrons in coordinated lanthanides ions is also observed on second order nonlinear activity. Finally, gold nanospheres (AuNSs) and gold nanorods (AuNRs) with different aspect ratios (AR) ranging from 1.7 to 3.2 nm have been synthesized by Radiolysis method. Second harmonic intensity collected from AuNRs is clearly higher than that of the nanospheres and reveals their dependence on the AR. We have also mixed the chromophore 4-dimethylamino-N-methyl-4-stilbazolium tosylate (DAST) derivative with AuNRs and observed the enhancement of DAST NLO properties in the presence of AuNRs. A clear increase in the hyperpolarizability (by a factor of 8) of DAST derivatives has been evidence.

Cette thèse concerne le développement et l'évaluation des nanoparticules pour le traitement du cancer et plus particulièrement pour le cancer de la prostate.Le manuscrit comprend une revue de la littérature sur l'application de la nano médecine pour le traitement du cancer de la prostate. Dans la première partie expérimentale, des nanoparticules d'or fonctionnalisées ont été caractérisées et chargées avec le docétaxel par adsorption non covalente.Ces nanoparticules d'or ont montré un effet cytotoxique in vitro prolongé contre les cellules cancéreuses de la prostate. La deuxième partie expérimentale de cette thèse décrit une étude de synthèse et une nano-précipitation de polyesters pour la co-délivrance de deux médicaments chimio-thérapeutiques, le docétaxel (DOC) et la mitoxantrone (MIT). Les polycaprolactone, poly(acide lactique) et poly(lactide-co-glycolide) ont été synthétisés par polymérisation par ouverture de cycle avec des poids moléculaires différents de polyéthylène glycol. Des nanoparticules monodisperses d’un diamètre d’environ 80 nm ont été obtenues et se sont avérées être efficaces contre les cellules cancéreuses de la prostate quand cela est chargé en MIT et DOC. De plus, un effet synergique a été observé en utilisant des combinaisons de ces nanoparticules. Par conséquent, ces nanoparticules, à base de polyester, ont de potentielles applications cliniques. / This thesis concerns the development and evaluation of nanoparticles for cancer treatment, and in particular to prostate cancer. The manuscript includes a literature review on the application of nanomedicine to the treatment of prostate cancer. In the first experimental part, functionalized gold nanoparticles were characterized and loaded with docetaxel by non covalent adsorption. These gold nanoparticles showed a sustained cytotoxic effect in vitro against prostate cancer cells. The second experimental part of this thesis describes a study of synthesis and nanoprecipitation of polyesters for the co-delivery of two chemotherapeutic drugs, docetaxel (DOC) and mitoxantrone (MIT). Polycaprolactone, poly(lactic acid) and poly (lactide-co-glycolide) were synthesized by ring-opening polymerization with different molecular weights of polyethylene glycol. Monodisperse nanoparticles with diameters of less than 80 nm were produced and were shown to be effective against prostate cancer cells when loaded with MIT and DOC. Moreover, a synergistic effect was observed using combinations of these nanoparticles. Therefore, these polyester based nanoparticles have potential clinical applications.

L’obtention de nanoparticules d’or nécessite le contrôle de nombreux paramètres et la compréhension du mode d’interaction entre l’or et le support. Pour cela, le choix du support est très important. Le premier volet de la thèse concerne la préparation contrôlée des catalyseurs à base d’or supporté sur les oxydes mésoporeux réductibles TiO₂, CeO₂ et Fe₂O₃ synthétisés via deux stratégies Soft et hard template en utilisant respectivement comme agents structurants le tribloc copolymère (Pluronic 123) et la silice mésoporeuse SBA-15. Les différentes techniques de caractérisation mettent bien en évidence que le taux de dépôt de l’or dépend de la concentration initiale de HAuCl₄, de la méthode de préparation (DPU, DP NaOH), de la teneur en or visée et de la nature du support ; Ces résultats sont à relier à la spéciation des espèces or en solution en fonction du pH final de la solution. Les taux de dépôt de l’or sont plus importants sur CeO₂ et ceci quelle que soit la teneur en or visée dans ce travail. Une dispersion très élevée est obtenue (la taille moyenne des particules d’or est de 2nm) sur les catalyseurs à 1% et 2%Au/CeO₂ préparés par la méthode DPU et calcinés à 400°C. Le deuxième volet de cette étude concerne l’oxydation en phase gaz d’une molécule organique modèle le toluène et l’oxydation en phase liquide d’une molécule organique modèle le phénol par des réactions de type Fenton et photo Fenton. Dans l’oxydation du toluène en phase gazeuse, les catalyseurs à base d’or supportés sur oxydes mésoporeux sont totalement sélectifs en CO₂ et H₂O. Les performances catalytiques dépendent des conditions de synthèse des catalyseurs et de la nature de l’oxyde utilisé ; le catalyseur 1%Au/CeO₂ est très actif et très stable au cours de quatre cycles successifs et au cours du temps. L’oxydation en phase liquide d’une molécule organique modèle le phénol par des réactions de type Fenton et photo Fenton a été effectuée sur les catalyseurs FeSBA-15 synthétisés via différentes stratégies : introduction du fer par voie postsynthétique et par voie hydrothermale en milieu faiblement et fortement acide respectivement à pH=6 et pH=3. Les performances catalytiques dépendent du rapport Si/Fe et de la taille des particules des espèces de fer, la taille des particules étant directement liée à la stratégie de synthèse des catalyseurs. Le catalyseur FeSBA-15(Si/Fe=60) synthétisé à pH=6 est un candidat potentiel dans la dégradation de polluants organiques par procédé Fenton et photo-Fenton en milieu neutre. / Well dispersed gold nanoparticles are the key to obtain an active gold catalyst. Obtaining gold nanoparticles requires control of many parameters and understanding of the interaction mode between gold and the support. For this reason the choice of the support is very important. The first part of this thesis concerns the controlled preparation of gold catalysts supported on reducible mesoporous oxides TiO₂, CeO₂ and Fe₂O₃ synthesized via two strategies Soft and Hard template using respectively. triblock copolymer (Pluronic 123) and mesoporous silica SBA-15 as template. This study clearly shows that the gold loading depends on the initial concentration of HAuCl₄, the method of preparation (DPU DP NaOH), theoretical gold content and the nature of the support. These results are to relate to the gold speciation which is a function of pH of the solution. The gold loading is higher on CeO₂ than on TiO₂ and Fe₂O₃ whatever the theoretical gold content. Very high gold dispersion is obtained (the gold particle size is 2 nm) on 1wt% and 2wt% Au/CeO₂ prepared by DPU and calcined at 400°C. The second part of this study concerns the toluene oxidation in the gas phase on Au/mesoporous oxide catalysts and the Fenton and photo-Fenton degradation of phenolic aqueous solutions by H₂O₂ on FeSBA-15 catalysts prepared following different synthesis routes, direct synthesis by adjusting pH at 3 and 6 and with post synthesis procedure. In the toluene oxidation in the gas phase Au/mesoporous oxide catalysts are totally selective for CO₂ and H₂O. The catalytic performances depend on the synthesis conditions of catalysts and the support; the 1wt% Au/CeO₂ catalyst is very active and exhibits a long-term stability. In the Fenton and photo-Fenton degradation of phenolic aqueous solutions the catalytic performances depend on the Si/Fe ratio and the particle size of the iron species, the particle size being directly related to the synthesis strategy of the catalysts. The catalyst FeSBA-15 (Si/Fe = 60) synthesized at pH = 6 is a potential candidate in the degradation of organic pollutants by Fenton and photo-Fenton process in neutral medium. / م لخصمسقني لمعلا يف هذه ةحورطألا ىلإ نيئزج:OiT 2ب وا سطة OeC 2و , Fe2O ي خ تص الاول ال ق سم ب تح ض يرمح فزات من ال ذهبن وع من م يزوب ري ة ب مواد مدعم 3ان واع مخ ت لف ال تح ض ير. ت شخ يص ف ي ال م س ت عم لة ال ت ق ن يات مخ ت لفت ب ين ال مح ضرة ل مح فزات انال دعم ط ب ي عة ك ذا و ال مح فز ت ح ض ير وطري قة HAuCl ت ر سب معدل ي ت ع لق ل ذه با ت رك يز ع لى 4ي ع ضو جزيء و سطغازي enèuloT أك سدة ف ي ال مواد هذه ب تط ب يق ي ت ع لق ال ثان ي ال ق سم ف يال مح فز ت ح ض ير Ò طرق ك ذا و ل ت فاعل هذا ع لى ال مؤث رة ل عوامل ب درا سة ق م نا سال فا ال مذك ورة ل لمح فزات ال ف عال ية ع لان واع مخ ت لف ب وا سطة FeSBA- ي ع ضو جزيء lonehP ت فاعل ب وا سطة notneF سائ ل و سط ف ي وعمن 51 ن مح فزات ع لىوHp ال و سط Si/Fe قلعتي ةبسنب FeSBA- ريضحتلا.ادأء 1515FeSBA-15, Fenton, Phenol, Toluène, TiO و 2 CeO2, Fe2O3, SBA- ال ك لمات ال م ف تاح ية ׃م يزوب وري ة ,