Dissertations / Theses on the topic 'Localised surface plasmon resonance (LSPR)'

La résonance de plasmon de surface localisée (LSPR) est définie comme l’oscillation collective du nuage d’électrons de conduction induite par un champ électrique externe. Dans le cas de nanoparticules composé de métaux nobles tels que l’or, l’argent, ou le cuivre,la résonance est localisée dans le visible ou le proche UV. La polarisabilité d’une nanoparticule est directement proportionnelle à quatre paramètres clefs : son volume, sa composition, sa forme et son milieu environnant. Ce sont ces propriétés qui font que la LSPR peut être utilisée à des fin de capteur. Dans le cas d’une particule isotrope, tel que la sphère, le spectre LSPR montre un seul pic d’absorption. Dans le cas d’une particule anisotrope, tel qu’une ellipsoïde, le spectre d’absorption a deux maxima distincts. Si on calcule la section efficace d’absorption en considérant une lumière non polarisée, on obtient deux maxima. Le point clef de ce type de système est la possibilité de découpler les deux résonances en utilisant une lumière polarisée. Dans cette description le système anisotrope est considéré comme microscopique, c’est à dire qu’il ne s’agit que d’une ou deux particules. Dans le cas d’un échantillon macroscopique, tel qu’une solution colloïdale d’ellipsoïdes ou nanotiges, le spectre d’absorption aura toujours deux maxima d’absorption, mais ceux-ci ne pourront pas être découplés car l’échantillon n’est pas globalement anisotrope. En revanche, si l’échantillon présente une anisotropie globale telle que des nanotiges alignés, ou des nanosphères organisées en ligne, il est possible d’avoir un spectre de plasmon dépendant de la polarisation de la lumière. Être capable de découpler les résonances d’un échantillon anisotrope permet de mesurer un spectre différentiel en prenant la différence des deux spectres d’absorption. Cela est expérimentalement possible en utilisant la spectroscopie de transmis- sion anisotrope qui permet la mesure de l’anisotropie optique. L’avantage est d’obtenir un spectre relative et différentiel donc plus stable et reproductible. De plus il est maintenant possible de suivre l’évolution de la réponse optique des particules plasmoniques, non plus en mesurant un déplacement spectral, mais en mesurant le changement d’intensité du signal à une longueur d’onde fixe. Cette méthode est utilisée pour deux cas d’études qui sont la mesure de l’interaction du dihydrogène avec des nanoparticules d’or, ainsi que la détection de faible pression partielle de dihydrogène dans un gaz porteur (argon, et air) à l’aide de palladium, pour des applications de capteur d’hydrogène
Localised surface plasmon resonance (LSPR) is defined as the collective oscillation of the conduction electron cloud induced by an external electric field. In the case of nanoparticles composed of noble metals such as gold, silver, or copper, the resonance is located in the visible or near UV range. The polarisability of a nanoparticle is directly proportional to four key parameters: its volume, its composition, its shape and its surrounding environment. It is these properties that make LSPR useful for sensor applications. In the case of isotropic particles, such as spheres, the LSPR spectrum shows only one absorption peak. In the case of an anisotropic particle, such as an ellipsoid, the absorption spectrum has two or more distinct peaks. If the absorption cross-section is measured with unpolarised light, multiple maxima are obtained. The key point for these type of systems is the possibility to decouple the resonances using polarised light. In this description the anisotropic system is considered microscopic, i.e. it is only made of one or two particles. In the case of a macroscopic sample, such as a colloidal solution of ellipsoids or nanorods, the absorption spectrum will always have multiple absorption maxima, and they cannot be decoupled because the sample is not globally anisotropic.On the other hand, if the sample has a global anisotropy such as aligned nanorods, or nanosphere organised in lines, it is possible to have a plasmon spectrum dependent on the light polarisation. Being able to decouple the resonances of an anisotropic sample makes it possible to measure a differential spectrum by taking the difference of the two absorption spectra. This is experimentally possible by using anisotropic transmission spectroscopy which measures the optical anisotropy. The advantage is to obtain a relative and differential spectrum more stable and reproducible. Moreover, it is now possible to follow the evolution of the optical response of the plasmonic particles no longer by measuring a spectral shift but by measuring the change in intensity of the signal at a fixed wavelength. This method is used on two case studies which are the measurement of the interaction of dihydrogen with gold nanoparticles, as well as the detection of low partial pressure of dihydrogen in a carrier gas (argon, and air) using palladium nanoparticles, for hydrogen sensing applications

This PhD thesis reports the use the emerging surface-sensitive optical technique of localized surface plasmon resonance (LSPR) to characterize the interaction of relevant classes of biomolecules, e.g. peptides, proteins, lipids and DNA strands, at solid-liquid interfaces, with an emphasis on deciphering kinetics and pathways of dynamic adsorption processes. LSPR-based biosensor exploits the high sensitivity of the plasmon frequency to refractive index changes confined to 5-30 nanometers around the metal nanoparticles deposited on the sensor surface to monitor in situ and in real time the interaction of unlabeled biological molecules skipping the misleading contribution from the bulk of solution affecting conventional optical technique, e.g. SPR and OWLS. In the present dissertation the advantages of applying this powerful technique are thoroughly demonstrated by investigating four case studies concerning relevant aspects for the biointerfaces science. The case of study 1 will involve the adsorption kinetics of single and binary solution of proteins onto model hydrophilic and hydrophobic surfaces. The analysis of the adsorption kinetics reveals that competitive adsorption occurs, at physiological pH 7.4 and relatively high ionic strength (NaCl 0.1 M), favoring the heavier protein (fibronectin, in our case), which is shown to adsorb faster and in larger amount than the lighter one (human serum albumin, in our case). The case of study 2 will discuss the DNA hybridization process for binary solutions of respectively perfectly matching (PM) and single base mismatching (MM) 93-mer ssDNA from KRAS codon 12, with a surface tethered probe complementary to the PM sequence. Sensitivity down to obtaining down to 10 nM and 13 nM, respectively for PM and MM were obtained, showing that the hybridization process occurs at a lower rate for MM with respect to PM target. The competitive hybridization was accounted for by an inhibition model, where the non-complementary sequences kinetically hinder the hybridization of the perfect matching sequences, owing to their above mentioned affinity constant differences for the same probe. The case of study 3 will cover the kinetics of phospholipid vesicle adsorption on silicon oxide surfaces as function of pH. Two different regimes have been observed for acidic and basic conditions. At low pH, vesicles adsorption showed one-step exponential kinetics. Moreover, no significantly variation of the adsorption rate was observed over the investigated pH range 3-6, suggesting the process is controlled by Van der Waals interactions and steric forces. At high pH, vesicles adsorb showing two-step kinetic. Furthermore, it was observed that the rate of the first step slows down linearly with the increasing of pH, suggesting that the process is primarily driven by vesicle-surface electrostatic repulsion. The case of study 4 will report preliminary results from the study of pH stimuli-responsive smart surfaces, formed by gold nanodisks array of an LSPR sensor chip decorated with Trichogin GA IV and two of its positively-charged analogs, i.e. Lipo-Lys and L20, in which four and eight Lysines positive charged residues have been introduced respectively. The surface-bound peptides exhibit reversible and rapid switching between conformations and can withstand several cycles of swelling and collapsing with no significant loss from the surfaces. Overall, the results here reported demonstrated the great potential of LSPR technique as a unique tool to monitor specific and non-specific biomolecular interactions at interfaces in application fields ranging from biosensing to materials science.

When exposed to light, metal nanoparticles exhibit a phenomenon known as LSPR, Localized Surface Plasmon Resonance. The wavelengths at which LSPR occurs is very dependent on the refractive index of the surrounding medium. Binding of biomolecules to the surface of gold nanoparticles result in a change in the refractive index that can be detected spectrophotometrically by monitoring the LSPR peak shift. When functionalized with the corresponding ligand(s), gold nanoparticles can be utilized in biosensors to detect the presence and concentration of a predetermined analyte. However, the system must exhibit high specificity and give rise to a detectable shift for analytes in the desired concentration range to be of commercial interest. The aim of the diploma project was to investigate and optimize the biofunctionalization and performance of a fiber optics based LSPR biosensor.  Three ligand systems were investigated for detection of antibodies (IgG), insulin and avidin. Binding of the analyte to the ligand caused a shift of a few nanometers when using spherical gold nanoparticles. The shifts were significantly larger when using gold nanorods. When using the IgG and insulin ligands, only minor unspecific binding was observed. The setup thus shows great potential for use in a wide range of sensing applications.

The study of interactions between plasmonic nanomaterials and dielectrics is a thriving field of research, which in recent years proved that such nanostructures can be applied in a wide range of applications, from sensing to catalysts. These are all based on the nanoscale surface interactions happening between the nanomaterials and their surrounding environment. In this thesis, the possible interaction between plasmonic nanoparticles and the V doping states in the Anatase (TiO_2) bandgap, rather than in their undoped counterpart, is studied. The aim is to better understand the dynamics of these phenomena, and obtaining insights on the V states position in the TiO_2 bandgap. The work done encompasses all the steps needed to achieve the experimental results: from the preparation and characterisation of the samples, to the simulations of the phenomena involved, until the actual measurements of their optical properties and the discussion of the results. The findings achieved are not decisive in explaining the dynamics involved, but preliminary interpretations could be formulated. Moreover, the specific investigations displayed in this thesis have never been done before in literature, and the work performed might be used in the future as a starting point for more thorough and deep studies of these phenomena.

Anisotropic plasmonic noble metallic nanoparticles (APMNs) have received enormous attention due to their distinct geometric features and fascinating physicochemical properties. Owing in large part to their tailored localized surface plasmon resonance (LSPR) and the intensive electromagnetic field at the sharp corners and edges, APMNs are exceptionally well suited for biomedical applications such as biosensing, bioimaging, diagnostics and therapeutics. Although a rich variety of surfactant-assisted colloidal routes have been developed to prepare well-defined APMNs, biomedical applications necessitate tedious and rigorous purification processes for the complete removal of toxic surfactants. In this dissertation, we aim to develop generic bioenabled green synthetic methodologies towards APMNs. By applying a series of thermodynamic, kinetic and seed quality control, a series of APMNs with varied morphologies such as branched nanostars and triangular nanoprisms have been successfully prepared. We first presented the preparation of gold nanostars (Au NSTs) through a two-step approach utilizing a common Good's buffer, HEPES, as a weak reducing agent. Single crystalline Au NSTs with tunable branches up to 30 nm in length were produced and the halide ions rather than the ionic strength played a significant roles on the length of the branches of Au NSTs. Then consensus sequence tetratricopetide repeat (CTPR) proteins with increasing number of repeats were used as model proteins to probe the effects of concentration as well as the protein shape on the morphology and resulting physicochemical properties of plasmonic gold nanoparticles. Since the underlying growth mechanism for the biomimetic synthesis of APMNs remains elusive and controversial, the other objective is to elucidate the molecular interactions between inorganic species and biopolymers during the course of NP evolution. Fluorescent quenching and 2D NMR experiments have confirmed the moderate binding affinity of CTPR to the Au(0) and Au(III). We observed that the initial complexation step between gold ions and CTPR3 is ionic strength dependent. Furthermore, we also found that NPs preferentially interact with the negatively charged face of CTPR3 as observed in 2D NMR. Knowledge of binding behavior between biospecies and metal ions/NPs will facilitate rational deign of proteins for biomimetic synthesis of metallic NPs. A modified seed-mediated synthetic strategy was also developed for the growth of silver nanoprisms with low shape polydispersity, narrow size distribution and tailored plasmonic absorbance. During the seed nucleation step, CTPR proteins are utilized as potent stabilizers to facilitate the formation of planar-twinned Ag seeds. Ag nanoprisms were produced in high yield in a growth solution containing ascorbic acid and CTPR-stabilized Ag seeds. From the time-course UV-Vis and transmission electron microscopy (TEM) studies, we postulate that the growth mechanism is the combination of facet selective lateral growth and thermodynamically driven Ostwald ripening. By incorporation of seeded growth and biomimetic synthesis, gold nanotriangles (Au NTs) with tunable edge length were synthesized via a green chemical route in the presence of the designed CTPR protein, halide anions (Br⁻) and CTPR-stabilized Ag seeds. The well-defined morphologies, tailored plasmonic absorbance from visible-light to the near infrared (NIR) region, colloidal stability and biocompatibility are attributed to the synergistic action of CTPR, halide ions, and CTPR-stabilized Ag seeds. We also ascertained that a vast array of biosustainable materials including negatively charged lignin and cellulose derivatives can serve as both a potent stabilizers and an efficient nanocrystal modifiers to regulate the growth of well-defined Ag nanoprisms using a one-pot or seeded growth strategy. The influential effects of reactants and additives including the concentration of sodium lignosulfonate, H2O2 and NaBH4 were studied in great detail. It implies that appropriate physicochemical properties rather than the specific binding sequence of biomaterials are critical for the shaped-controlled growth of Ag NTs and new synthetic paradigms could be proposed based on these findings. Last but not the least, we have demonstrated the resulting APMNs, particularly, Au NSTs and Ag NTs exhibit remarkable colloidal stability, enhanced SERS performance, making them promising materials for biosensing and photothermal therapy. Since the Ag nanoprisms are susceptible to morphological deformation in the presence of strong oxidant, they also hold great potential for the colorimetric sensing of oxidative metal cation species such as Fe3+, Cr3+, etc.
Ph. D.

Cette thèse considère de nouvelles architectures prometteuses des métamatériaux plasmoniques pour biosensing, comprenant: (I) des réseaux périodiques 2D de nanoparticules d'Au, qui peuvent supporter des résonances des réseaux de surface couplées de manière diffractive; (II) Reseaux 3D à base de cristaux plasmoniques du type d'assemblage de bois. Une étude systématique des conditions d'excitation plasmonique, des propriétés et de la sensibilité à l'environnement local dans ces géométries métamatérielles est présentée. On montre que de tels réseaux peuvent combiner une très haute sensibilité spectrale (400 nm / RIU et 2600 nm / RIU, ensemble respectivement) et une sensibilité de phase exceptionnellement élevée (> 105 deg./RIU) et peuvent être utilisés pour améliorer l'état actuel de la technologie de biosensing the-art. Enfin, on propose une méthode de sondage du champ électrique excité par des nanostructures plasmoniques (nanoparticules uniques, dimères). On suppose que cette méthode aidera à concevoir des structures pour SERS (La spectroscopie du type Raman à surface renforcée), qui peut être utilisée comme une chaîne d'information supplémentaire à un biocapteur de transduction optique
This thesis consideres novel promissing architechtures of plasmonic metamaterial for biosensing, including: (I) 2D periodic arrays of Au nanoparticles, which can support diffractively coupled surface lattice resonances; (II) 3D periodic arrays based on woodpile-assembly plasmonic crystals, which can support novel delocalized plasmonic modes over 3D structure. A systematic study of conditions of plasmon excitation, properties and sensitivity to local environment is presented. It is shown that such arrays can combine very high spectral sensitivity (400nm/RIU and 2600 nm/RIU, respectively) and exceptionally high phase sensitivity (> 105 deg./RIU) and can be used for the improvement of current state-of-the-art biosensing technology. Finally, a method for probing electric field excited by plasmonic nanostructures (single nanoparticles, dimers) is proposed. It is implied that this method will help to design structures for SERS, which will later be used as an additional informational channel for biosensing

Les matériaux composites peuvent présenter des propriétés qu'aucun des composants individuels ne présente. En outre, à l'échelle du nanomètre les nanocomposites peuvent présenter de nouvelles propriétés par rapport à l'état massif ou à des macrocomposites des mêmes composants en raison d’effets de confinement et d’effets quantiques liés à la taille. Les nanocomposites semi-conducteur/métal sont très intéressants en raison de leurs uniques propriétés catalytiques et opto-électroniques et la possibilité de les ajuster facilement. Ce travail de thèse étudie les interactions spécifiques et les propriétés physiques qui se manifestent dans les films minces de ZnO et nanocomposites ZnO-Au synthétisés par pulvérisation magnétron réactive continue. Premièrement, il est observé qu’il est possible d'ajuster les propriétés microstructurales et optiques des couches de ZnO en réglant les paramètres expérimentaux. La croissance épitaxiale de ZnO sur saphir a été réalisée pour la première fois dans des conditions riches en oxygène sans assistance thermique. En outre, une étude des propriétés optiques met en évidence la relation étroite entre les propriétés optiques et de la chimie des défauts dans les couches minces de ZnO. Un modèle a été proposé pour expliquer la grande dispersion des valeurs de gap rencontrées dans la littérature. Deuxièmement, il a été possible de révéler l'influence profonde de l'incorporation de l'or dans la matrice de ZnO sur des propriétés importantes dans des films nanocomposites. En outre, la présence de défauts donneurs (accepteurs) au sein de la matrice ZnO se permet de réduire (oxyder) les nanoparticules d’or. Ce travail de recherche contribue à une meilleure compréhension des nanocomposites semi-conducteurs/métal et révèle le rôle important de l'état de la matrice semi-conductrice et de la surface des particules pour les propriétés finales du matériau
Composite materials can exhibit properties that none of the individual components show. Moreover, composites at the nanoscale can present new properties compared to the bulk state or to macro-composites due to confinement and quantum size effects. The semiconductor/metal nanocomposites are highly interesting due to their unique catalytic and optoelectronic properties and the possibility to tune them easily. This PhD work gives insight into the specific interactions and resulting physical properties occurring in ZnO and ZnO-Au nanocomposite films grown by reactive DC magnetron sputtering. The results can be summarized in two points: First, it was possible to tune the microstructural and optical properties of ZnO. Epitaxial growth of ZnO onto sapphire was achieved for the first time in O2-rich conditions without thermal assistance. Also, a study of the optical properties highlights the close relationship between the bandgap energy (E_g ) and the defect chemistry in ZnO films. A model was proposed to explain the large scatter of the E_g values reported in the literature. Second, the deep influence of the incorporation of gold into the ZnO matrix on important material properties was revealed. Moreover, the presence of donor (acceptor) defects in the matrix is found to give rise to the reduction (oxidation) of the Au nanoparticles. This research work contributes to a better understanding of semiconductor/metal nanocomposites revealing the key role of the state of the semiconductor matrix

Metal nanoparticles have recently gained popularity in many research areas due to their nanosize-related properties. Depending on the size of the metal nanoparticle, their mode of interaction with electromagnetic radiation and the outcome of this interaction vary; in turn the effect exerted on a protein which is conjugated to a nanoparticle varies, because different sized nanoparticles demonstrate different modes of energy transfer with electromagnetic radiation and molecules conjugated to them. Very small cluster with sizes around 1 – 1.2 nm tend to get excited by incident light and emit fluorescence, whereas larger nanoparticles absorb the incoming light very strongly due to their LSPR. In this study we observed the outcomes of the interaction between two types of nanoparticles, namely gold and gold/silver alloyed nanoparticles with the fluorescence emission of two fluorophores, namely eGFP and rPhiYFP; and demonstrated a bioassay where the fluorescence modulation by gold nanoparticles can be used as the sensing strategy. Lastly, we demonstrated the potential of autofluorescent gold nanoparticles as intracellular reporters.

Le développement de méthodes rapides, précises et ultra-sensibles pour la détection d'analytes cibles en solution est crucial pour la recherche et les applications potentielles en médecine ou biologie moléculaire. Une approche très prometteuse consiste à développer des nano-capteurs à partir de nano-objets métalliques (NOM) qui présentent une résonance d'extinction dans leur réponse optique. Cette résonance nommée résonance de plasmon de surface localisée (RPSL) peut être ajustée spectralement en jouant sur la nature, la morphologie et l'environnement du NOM. Mesurer des modifications sur la RPSL de nano-objets individuels en présence d'analytes cibles doit permettre de s'affranchir des effets de moyennes dans les mesures d'ensemble. De plus, cela ouvre la voie vers le développement d'échantillons micrométriques pour des tests multicibles sans étiquette (« label-free »).Dans ce travail on a développé un nouveau dispositif expérimental basé sur la technique de spectroscopie à modulation spatiale (SMS) permettant de sonder la réponse optique de NOM individuels en milieu liquide. En parallèle des méthodes de synthèse ont été mises au point pour obtenir des échantillons sondes stables permettant des mesures sur NOM unique, en particulier sur des bipyramides d'or qui présentent de nombreuses qualités intrinsèques faisant d'elles de bonnes candidates pour le « bio-sensing ».Des mesures ont été réalisées dans des environnements d'indice variable et les changements détectés sont en bon accord avec les simulations théoriques. De plus, de nombreuses études ont été réalisées pour comprendre l'influence des nombreux paramètres agissant sur la réponse optique des systèmes étudiés
Advances in the development of rapid, accurate and highly sensitive methods for detecting target analytes in solution will provide crucial tools for research and applications in medicine and molecular biology. One of the currently most promising approaches is the development of nanosensors based on the localized surface plasmon resonance (LSPR) of noble metal nano-objects (MNOs), which is an optical response that depends on their size, shape, composition and local environment. The ability to measure the modification of the reponse of a single MNO in the presence of a target analyte would allow each object to act as an independent probe with increased sensitivity as the signal would be isolated from the averaging effects of ensemble measurements. Furthermore it would allow the development of micrometric, functionalized multiprobe samples for multitarget label-free assays.In this work, a novel experimental setup based on the spatial modulation spectroscopy (SMS) technique has been developed to measure the optical response of individual nano-objects in a liquid environment. In parallel, a new technique has also been developed to elaborate stable probes for measurements with the new setup, with a focus on gold bipyramids due to numerous qualities that make them excellent candidates for biosensing probes. The setup has been used to measure the response of individual objects in environments of different real refractive indices and the detected changes have been shown to be in good agreement with theoretical calculations. Numerical studies have also been performed to investigate the influence on the optical response of numerous factors encountered in the studied systems

Les polymères à empreintes moléculaires (MIP), également appelés "anticorps en plastique", sont des récepteurs biomimétiques synthétiques qui sont capables de reconnaître et lier une molécule cible avec une affinité et une spécificité comparables à celles des récepteurs naturels tels que des enzymes ou des anticorps. En effet, les MIP sont utilisés comme éléments de reconnaissance synthétiques dans les biocapteurs et biopuces pour la détection de petits analytes et les protéines. La technique d'impression moléculaire est basée sur la formation de cavités de reconnaissance spécifiques dans des matrices polymères par un procédé de moulage à l'échelle moléculaire. Pour la conception de capteurs et biopuces, une cinétique d'adsorption et une réponse du capteur rapide, l'intégration des polymères avec des transducteurs, et une haute sensibilité de détection sont parmi les principaux défis. Dans cette thèse, ces problèmes ont été abordés par le développement de nanocomposites MIP / d'or via le greffage du MIP sur les surfaces en utilisant des techniques de polymérisation dédiées comme l'ATRP qui est une technique de polymérisation radicalaire contrôlée (CRP). Ces techniques CRP sophistiquées sont en mesure d'améliorer considérablement les matériaux polymères. L'utilisation de l'ATRP dans le domaine de MIP a été limitée jusqu'à présent en raison de son incompatibilité inhérente avec des monomères acides comme l'acide méthacrylique (MAA), qui est de loin le monomère fonctionnel le plus largement utilisé dans les MIP. Ici, un nouveau procédé est décrit pour la synthèse de MIP par ATRP photo-initiée utilisant fac-[Ir(Ppy)3] comme catalyseur. La synthèse est possible à température ambiante et est compatible avec des monomères acides. Cette étude élargit considérablement la gamme de monomères fonctionnels et de molécules empreintes qui peuvent être utilisés lors de la synthèse de MIP par ATRP. La méthode proposée a été utilisée pour la fabrication de nanocomposites hiérarchiquement organisés sur des surfaces métalliques nanostructurés avec des nano-trous et nano-ilots, présentant des effets plasmoniques pour l'amplification du signal. La synthèse de films de MIP à l'échelle du nanomètre localisés sur la surface d'or a été démontrée. Des méthodes de transduction optiques, à savoir la résonance de plasmons de surface localisée (LSPR) et la spectroscopie Raman exaltée par effet de surface (SERS) ont été exploitées. Ces techniques se sont montrées prometteuses pour l'amélioration de la limite de détection dans la détection d'analytes biologiquement pertinents, y compris les protéines et le médicament propranolol
Molecularly imprinted polymers (MIPs), also referred to as plastic antibodies, are synthetic biomimetic receptors that are able to bind target molecules with similar affinity and specificity as natural receptors such as enzymes or antibodies. Indeed, MIPs are used as synthetic recognition elements in biosensors and biochips for the detection of small analytes and proteins. The molecular imprinting technique is based on the formation of specific recognition cavities in polymer matrices by a templating process at the molecular level. For sensor and biochip development, fast binding kinetics of the MIP for a rapid sensor response, the integration of the polymers with transducers, and a high sensitivity of detection are among the main challenges. In this thesis, the above issues are addressed by developing MIP/gold nanocomposites by grafting MIPs on surfaces, using dedicated techniques like atom transfer radical polymerization (ATRP) which is a versatile controlled radical polymerization (CRP) technique. Theses ophisticated CRP techniques, are able to greatly improve the polymeric materials. The use of ATRP in the MIP field has been limited so far due to its inherent incompatibility with acidic monomers like methacrylic acid (MAA), which is by far the most widely used functional monomer. Herein, a new method is described for the MIP synthesis through photo-initiated ATRP using fac-[Ir(ppy)3] as ATRP catalyst. The synthesis is possible at room temperature and is compatible with acidic monomers. This study considerably widens the range of functional monomers and thus molecular templates that can be used when MIPs are synthesized by ATRP. The proposed method was used for fabrication of hierarchically organised nanocomposites based on MIPs and nanostructured metal surfaces containing nanoholes or nanoislands, exhibiting plasmonic effects for signal amplification. The fabrication of nanometer scale MIP coatings localized on gold surface was demonstrated. Optical transduction methods, namely Localized Surface Plasmon Resonance (LSPR) and Surface Enhanced Raman Spectroscopy (SERS) were exploited and shown that they hold great promise for enhancing the limit of detection in sensing of biologically relevant analytes including proteins and the drug propranolol

In this dissertation, I have verified that the striking purple color of the intermetallic compound AuAl2, also known as purple gold, originates from surface plasmons (SPs). This contrasts to a previous assumption that this color is due to an interband absorption transition. The existence of SPs was demonstrated by launching them in thin AuAl2 films in the Kretschmann configuration, which enables us to measure the SP dispersion relation. I observed that the SP energy in thin films of purple gold is around 2.1 eV, comparable to previous work on the dielectric function of this material. Furthermore, SP sensing using AuAl2 also shows the ability to measure the change in the refractive index of standard sucrose solution. AuAl2 in nanoparticle form is also discussed in terms of plasmonic applications, where Mie scattering theory predicts that the particle bears nearly uniform absorption over the entire visible spectrum with an order magnitude higher than a lightabsorbing carbonaceous particle. The second topic of this dissertation focuses on plasmon enhanced fluorescence in gold nanoparticles (Au NPs). Here, I investigated the distance-dependent fluorescence emission of rhodamine green 110 fluorophores from Au NPs with tunable spacers. These spacers consist of polyelectrolyte multilayers (PEMs) consisting of poly(allylamine hydrochloride) and poly(styrene sulfonate) assembled at pH 8.4. The distance between Au NPs and fluorophores was varied by changing the ambient pH from 3 to 10 and back, which causes the swelling and deswelling of PEM spacer. Maximum fluorescence intensity with 4.0-fold enhancement was observed with 7-layer coated Au NPs at ambient pH 10 referenced to pH 3. The last topic of this dissertation examines a novel approach to assemble nanoparticles, in particular, dimers of gold nanospheres (NSs). 16 nm and 60 nm diameter NSs were connected using photocleavable molecules as linkers. I showed that the orientation of the dimers can be controlled with the polarization of UV illumination that cleaves the linkers, making dipolar patches. This type of assembly provides a simple method with potential applications in multiple contexts, such as biomedicine and nanorobotics.
PHD

Dans ce travail de thèse, la synthèse de nanoparticules d'argent (Ag) est réalisée par une méthode simple, efficace et rapide basée sur la réduction du nitrate d'argent (AgNO3) dans un milieu organique (éthanol) sous chauffage par irradiation micro-ondes (MW) pendant quelques secondes en présence d'une émulsion aqueuse de copolymère latex. Les expériences ont été effectuées soit de manière séquentielle en faisant varier les paramètres expérimentaux les uns après les autres (approche classique) ou bien en moyennant la méthodologie des plans d'expérience qui sert à varier simultanément ces conditions expérimentales dans le but à la fois d'optimiser et d'évaluer l'impact de ces facteurs sur les propriétés physico-chimiques des particules produites. L'objectif est d'arriver à préparer un maximum de concentration en nanoparticules d'argent avec un minimum de concentration en copolymère latex et en AgNO3. Les nanoparticules préparées sont trouvées extrêmement stables en solution colloïdale avec des distributions de taille très étroites, ce qui confirme la qualité élevée et le diamètre uniforme des nanoparticules obtenues par l'approche de synthèse micro-ondes. Ceci pourrait être probablement dû à l'effet de stabilisation produit par les molécules du latex, qui est un bon environnement pour contrôler efficacement la croissance de nanoparticules métalliques d'argent. En tant que principal objectif d'une telle réalisation de la synthèse de nanoparticules d'argent par la méthode MW ouvre la voie à l'exploitation d'effets plasmoniques de surface dans des réactions photocatalytiques en utilisant des structures semi-conductrices bien définies (Bi2O3, In2O3, TiO2...)
In this thesis work, the synthesis of silver nanoparticles (Ag) is carried out by a simple, efficient and fast method based on the reduction of silver nitrate (AgNO3) in an organic medium (ethanol) under heating by micro irradiation (MW) for a few seconds in the presence of an aqueous emulsion of latex copolymer. The experiments were performed either by varying the experimental parameters one after the other (classical approach) or by means of the experimental design methodology which serves to vary simultaneously these experimental conditions in order to both optimize and evaluate the impact of these factors on the physicochemical properties of the nanoparticles. The main goal is to prepare a maximum concentration of silver nanoparticles with a minimum concentration of latex copolymer and AgNO3. The prepared nanoparticles were found to be extremely stable in colloidal solution with very narrow size distributions, which confirms the high quality and the uniform diameter of the nanoparticles obtained by the microwave synthesis approach. This could possibly be due to the stabilizing effect produced by the latex molecules, which is a good environment for effectively controlling the growth of metallic silver nanoparticles. As the main objective of such realization of the silver nanoparticle synthesis by the MW method opens the way to the exploration of surface plasmonic effects in photocatalytic reactions using well-defined semiconducting structures (Bi2O3 , In2O3, TiO2 ...)

Die Raman-Spektroskopie ist eine der nützlichsten optischen Methoden zur Untersuchung der Phononen organischer und anorganischer Materialien. Mit der fortschreitenden Miniaturisierung von elektronischen Bauelementen und der damit einhergehenden Verkleinerung der Strukturen von der Mikrometer- zur Nanometerskala nehmen das Streuvolumen und somit auch das Raman-Signal drastisch ab. Daher werden neue Herangehensweisen benötigt um sie mit optischer Spektroskopie zu untersuchen. Ein häufig genutzter Ansatz um die Signalintensität zu erhöhen ist die Verwendung von Resonanz-Raman-Streuung, das heißt dass die Anregungsenergie an die Energie eines optischen Überganges in der Struktur angepasst wird. In dieser Arbeit wurden InAs/Al(Ga)As-basierte Multilagen mit einer Periodizität unterhalb des Beugungslimits mittels Resonanz-Mikro-Raman-Spektroskopie und Raster-Kraft-Mikroskopie (AFM) den jeweiligen Schichten zugeordnet. Ein effizienterer Weg um die Raman-Sensitivität zu erhöhen ist die Verwendung der oberflächenverstärkten Raman-Streuung (SERS). Sie beruht hauptsächlich auf der Verstärkung der elektromagnetischen Strahlung aufgrund von lokalisierten Oberflächenplasmonenresonanzen in Metallnanostrukturen. Beide oben genannten Signalverstärkungsmethoden wurden in dieser Arbeit zur oberflächenverstärkten Resonanz-Raman-Streuung kombiniert um geringe Mengen organischer und anorganischer Materialien (ultradünne Cobalt-Phthalocyanin-Schichten (CoPc), CuS und CdSe Nanokristalle) zu untersuchen. Damit wurden in beiden Fällen Verstärkungsfaktoren in der Größenordnung 103 bis 104 erreicht, wobei bewiesen werden konnte, dass der dominante Verstärkungsmechanismus die elektromagnetische Verstärkung ist. Spitzenverstärkte Raman-Spektroskopie (TERS) ist ein Spezialfall von SERS, bei dem das Auflösungsvermögen von Licht unterschritten werden kann, was zu einer drastischen Verbesserung der lateralen Auflösung gegenüber der konventionellen Mikro-Raman-Spektroskopie führt. Dies konnte mit Hilfe einer Spitze erreicht werden, die als einzelner plasmonischer Streuer wirkt. Dabei wird die Spitze in einer kontrollierten Weise gegenüber der Probe bewegt. Die Anwendung von TERS erforderte zunächst die Entwicklung und Optimierung eines AFM-basierten TERS-Aufbaus und TERS-aktiver Spitzen, welche Gegenstand dieser Arbeit war. TERS-Bilder mit Auflösungen unter 15 nm konnten auf einer Testprobe mit kohlenstoffhaltigen Verbindungen realisiert werden. Die TERS-Verstärkung und ihre Abhängigkeit vom Substratmaterial, der Substratmorphologie sowie der AFM-Betriebsart wurden anhand der CoPc-Schichten, die auf nanostrukturierten Goldsubstraten abgeschieden wurden, evaluiert. Weiterhin konnte gezeigt werden, dass die hohe örtliche Auflösung der TERS-Verstärkung die selektive Detektion des Signals weniger CdSe-Nanokristalle möglich macht.

This thesis is a comprehensive study of plasmonic gold photocatalysts for organic conversions. It presents the advantages of plasmonic gold photocatalysts in the selective oxidation, reduction, and acetalisation. It is discovered that plasmonic gold photocatalysts exhibit better catalytic performance (higher selectivity or activity) in these organic conversions. The study in this thesis highlights the capacity of plasmonic gold photocatalysts in harvesting solar energy for converting organic raw materials to value-added chemicals, and the great potential of gold photocatalysts in chemical production.

This thesis presents spectroscopic studies of metallic nanoparticle localized surface plasmons and plasmon enhanced fluorescence. We investigated the dielectric sensitivity of silver nanoprisms to an external electric field and gold nanorods to the formation of a self-assembled surface monolayer. Dark field microscopy was used to image plasmonic scattering from single nanoparticles, and a liquid crystal tunable filter was used to construct corresponding spectra. The plasmon resonances of silver nanoprisms displayed both reversible red shifts and irreversible blue shifts along with drastic intensity changes upon exposure to an applied bias. The plasmon resonances of gold nanorods showed sensitivity to the presence of alkanethiol molecules adhered to the particle surface by a moderate red shift. An increase in the effective external dielectric caused a shift toward longer wavelengths. We imaged plasmon enhanced fluorescence in order to optimize experimental parameters for a developing project that can characterize nanoparticle structure on sub-wavelength dimensions. Preliminary controls were performed to account for the effect of O₂ plasma treatment, solvent and alkanethiol monolayer formation on surface plasmon resonances. We found that O₂ plasma treatment for different time intervals did not result in a plasmon shift compared to untreated nanoparticles exposed to N₂; however when exposed to solvent the surface plasmons of the treated particles shifted five times as far toward the red. Interestingly, the solvent effect only resulted in a plasmon shift when the particles were N₂ dried after solvent incubation. Gold nanorods incubated in ethanol showed no wavelength maximum shift in pure solvent over time, but shifted moderately to the red after incubation in a solution of alkanethiol molecules. Conditions for the plasmon enhanced fluorescence study were optimized using a dye conjugate of the same alkanethiol molecule used previously by formation from solution in a monolayer on the gold nanorod surface. The appropriate synthesis for dye functionalization, molecular concentrations, solvents and optical settings were determined.
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碩士
國立成功大學
生物醫學工程學系
102
Localized surface plasmon resonance (LSPR) biosensors have attracted many attentions. Scientists want to develop this kind of biosensors into point-of-care diagnostics. The optical setups of localized surface plasmon resonance biosensor are simpler and compact in comparison with surface plasmon resonance biosensor. Because of the short evanescent depth, the resonance shift which result from changing refractive index on the surface is often smaller than 1 nm. Using LSPR biosensor to detect small molecules and targets which are low concentration is difficult. So, many enhance mechanisms have applied on these biosensors. In our thesis, we use DNA-conjugated nanorod to enhance the resonance shift of LSPR biosensor. The aptamer and DNA which conjugate on the gold nanorod has been designed. When these two strands of DNA hybridize, the gold nanorod will be very close to the metal surface which is fabricated on LSPR biosensor. Thus, the significantly resonance shift will appear. Gold nanorod can increase plasmon coupling and change the refractive index drastically. Furthermore, we can measure different concentration ranges of analyte by adjusting the amount of gold nanorod. In this study, we use LSPR biosensor to measure interferon-gamma. Interferon-gamma is a cytokine that can be detect in cultured white blood cells of latent tunerculosis patients. We have gained calibration curves in pure buffer and serum containing buffer, respectively.

碩士
國立陽明大學
生醫光電研究所
105
In recent year, localize surface plasma resonance (LSPR) biosensor develops rapidly. In our experiment, using disposable gold nanostructures chips and enzymatic reaction for Matrix metallopeptidase 9 (MMP-9) detection. It is detected by simple optic setup. Disposable LSPR chips can cut costs, mass manufacture and low consume. And then using enzymatic reaction to produce precipitation for the change of surface refractive index. The change signal is positive correlation to MMP-9 concentration. In our experiment, it can be detect 1 femtomolar.

This dissertation comprises experimental studies on the synthesis and applications of metallic nanoshells. These are a class of nanoparticles composed of a dielectric core and a thin metallic shell. Metallic nanoshells play an important role in nanotechnology, particularly in nanomedicine, due to their peculiar optical properties. The overall objectives of the dissertation were to improve the fabrication of these nanoparticles, and to demonstrate new applications of these materials in cancer research and spectroscopy. The fabrication of nanoshells is a multi-step process. Previously to our work, the procedures for the synthesis of nanoshells reported in the literature lacked systematic characterization of the various steps. The procedure was extremely time-consuming and the results demonstrated a high degree of size variation. In Chapter 3, we have developed characterization tools that provide checkpoints for each step of the synthesis. We demonstrated that it is possible to control the degree of coverage on the shell for a fixed amount of reagents, and also showed important differences on the shell growth phase for gold and silver. The synthetic optimization presented in Chapter 3 led to an overall faster protocol than those previously reported. Although the improvements presented in Chapter 3 led to a higher degree of control on the synthesis of nanoshells, the variations in the resulting particle population were still too large for applications in single particle spectroscopy and imaging. In Chapter 4, the synthesis was completely reformulated, aiming to narrow the size distribution of the nanoshell colloids. Through the use of a reverse microemulsion, we were able to fabricate ultramonodisperse silica (SiO2) cores, which translate into nanoshell colloids with narrow extinction bands that are comparable to those of a single nanoshell. We then fabricate a library of colloids with different core sizes, shell thicknesses and composition (gold or silver). The localized surface plasmon resonance (LSPR) of these colloids span across the visible range. From this library, two nanoshells (18nm silver on a 50nm SiO2 core, and 18nm gold on a 72nm SiO2 core) were selected for a proof of principle cell imaging experiment. The silver nanoshells were coated with a nuclear localization signal, allowing it to target the nuclear membrane. The gold nanoshells were coated with an antibody that binds to a receptor on the plasma membrane of MCF-7 human breast cancer cells. The nanoshells were easily distinguishable by eye in a dark field microscope and successful targeting was demonstrated by hyperspectral dark field microscopy. A comparison was made between fluorescent phalloidin and nanoshells, showing the superior photostability of the nanoparticles for long-term cell imaging. The results from Chapter 4 suggest that the nanoshells obtained by our new synthetic route present acceptable particle-to-particle variations in their optical properties that enables single particle extinction spectroscopy for cell imaging. In Chapter 5 we explored the use of these nanoshells for single-particle Surface-enhanced Raman spectroscopy (SERS). Notice that particle-to-particle variations in SERS are expected to be more significant than in extinction spectroscopy. This is because particle-to-particle SERS variabilities are driven by subtle changes in geometric parameters (particle size, shape, roughness). Two types of gold nanoshells were prepared and different excitation wavelengths (λex) were evaluated, respective to the LSPR of the nanoshells. Individual scattering spectra were acquired for each particle, for a total of 163 nanoshells, at two laser excitation wavelengths (632.8 nm and 785 nm). The particle-to-particle variations in SERS intensity were evaluated and correlated to the efficiency of the scattering at the LSPR peak. Chapter 6 finally shows the application of gold nanoshells as a platform for the direct visualization of circulating tumor cells (CTCs). 4T1 breast cancer cells were transduced with a non-native target protein (Thy1.1) and an anti-Thy1.1 antibody was conjugated to gold nanoshells. The use of a transduced target creates the ideal scenario for the assessment of nonspecific binding. On the in vitro phase of the study, non-transduced cells were used as a negative control. In this phase, parameters such as incubation times and nanoshell concentration were established. A murine model was then developed with the transduced 4T1 cells for the ex vivo portion of the work. Non-transduced cells were implanted in a control group. Blood was drawn from mice in both groups over the course of 29 days. Antibody-conjugated nanoshells were incubated with the blood samples and detection of single CTCs was achieved in a dark field microscope. Low levels of nonspecific binding were observed in the control group for non-transduced cells and across different cell types normally found in peripheral blood (e.g. lymphocytes). All positive and negative subjects were successfully identified. Chapter 7 provides an outlook of the work presented here and elaborates on possible directions to further develop the use of nanoshells in bioapplications and spectroscopy.
Graduate
2019-05-03

Tese de doutoramento em Engenharia Mecânica, no ramo de Engenharia de Superfícies, apresentada ao Departamento de Engenharia Mecânica da Faculdade de Ciências e Tecnologia da Universidade de Coimbra
Nowadays, nanoparticles are considered as novel materials; a reduction in size down to a few nanometers often leads to size- or material- specific peculiarities, which are not present in bulk, and that can be used in new applications of the materials. Nanocomposite coatings containing metal nanoparticles have been receiving exponential interest from both the applied researchers and industry. One of the main properties of the metal nanoparticles that is sustaining this increasing interest is their ability to support Localized Surface Plasmon Resonances (LSPRs), optically induced oscillations of free electrons at the surface of the metal nanoparticles. The excitation of LSPRs by incoming light results in strong light extinction effects that are heavily dependent on the nanoparticle’s dielectric constant, size, shape and concentration and also on the dielectric constant of the surrounding medium. Since for each application a specific LSPR signal is needed, it becomes of paramount importance to be able to produce nanocomposites with good control over the nanoparticle’s morphology and its distribution in the matrix material. Among the various production methods available for obtaining nanostructured coatings exhibiting LSPR, the sputtering technique has become widely used due to its low cost, simplicity in the process and flexibility with the materials. In this work Au nanoparticles were incorporated into four different matrixes: Al2O3, WO3, TiO2 and AlN. Beyond their extensive utilization in various applications, these matrixes have different refractive indexes, which allow varying the LSPR throughout the visible region. The LSPR-exhibiting nanocomposites were obtained using three different sputtering techniques, in order to test their capabilities and limitations: (i) cosputtering followed by thermal annealing treatments up to 500°C, (ii) alternatingsputtering using both conventional and high power impulse magnetron sputtering (HiPIMS) source and (iii) alternating-sputtering using a plasma gas condensation (PGC) nanoparticle source. The first method of deposition allowed achieving nanocomposites with a relatively homogeneous dispersion of spherical Au nanoparticles within the matrixes, after some optimization of the deposition conditions. The Au integration in the matrix was found to be highly dependent on the chemistry of the matrix and also on the concentration of noble metal. The application of thermal annealing treatments allowed increasing the Au nanoparticles sizes (up to 8 nm) and also affected the dielectric properties of the matrix. The main drawback of this procedure is that the precipitation process is dependent on the nature of the nanoparticle/matrix system and that the range of achievable nanoparticles sizes is limited. The second method allowed a more effective and independent control over the nanoparticles morphologies than with the co-sputtering case, without the application of any thermal annealing. With the Au content the mean nanoparticle size increased progressively (up to 15 nm) whereas the shape of the nanoparticles evolved from rather spherical to spheroidal with decreasing aspect ratios. The decreased aspect ratios strongly red-shifted the SPR peaks and allowed more intense absorption peaks. The main drawback of this method was that the size, shape and separation distance of the nanoparticles cannot be controlled separately, they evolved together according to the different growth modes, which are dependent on the surface mobility of Au on the oxide surface. The third method allowed the production of large amounts of nanoparticles with a high level of control over its mean size. Au nanoparticles were produced by PGC method and studied in great detail for the first time. Au spherical nanoparticles with sizes between 5-65 nm were deposited with varying deposition rates and size dispersions. Nanocomposites were obtained with good control over the nanoparticle size, demonstrating the very high potential of this technique for LSRP-based applications.
Hoje em dia as nanopartículas (NPs) metálicas são consideradas como novos materiais, uma vez que apresentam propriedades significativamente diferentes das do material maciço. Filmes nanocompósitos consistindo em NPs metálicas dispersas em matrizes dielétricas têm ganho um interesse exponencial por parte da investigação aplicada e da indústria. Um dos principais motivos deste interesse prende-se com o facto de estas NPs apresentarem o efeito LSPR (ressonância localizada dos plasmões de superfície), que são oscilações coletivas das cargas elétricas nas NPs metálicas, capazes de serem excitadas pela luz. As LSPRs são extremamente sensíveis à forma e ao tamanho das NPs, e também a variações na função dielétrica do meio circundante. Uma vez que cada aplicação específica requer um certo sinal de LSPR, torna-se importante haver métodos de deposição que permitam ter controlo sobre o tamanho, a forma e a dispersão de NPs no interior ou à superfície de uma matriz. De entre os vários métodos de produção disponíveis para a obtenção de filmes nanocompósitos exibindo LSPR, a técnica de pulverização catódica tornou-se numa das mais usadas, devido ao seu baixo custo, simplicidade no processo e flexibilidade com os materiais. Neste trabalho, NPs de Au foram incorporadas em quatro matrizes diferentes: Al2O3, WO3, TiO2 e AlN. Estas matrizes possuem um leque alargado de aplicações e têm índices de refração distintos permitindo variar o pico de LSPR ao longo do espectro de luz visível. Os filmes nanocompósitos exibindo LSPR foram obtidos através de três métodos de pulverização catódica diferentes, com o intuito de estudar as suas vantagens e limitações: (i) co-pulverização catódica seguida de tratamentos térmicos até 500°C; (ii) pulverização catódica alternada usando fontes convencionais e HiPIMS (high power impulse magnetron sputtering); (iii) pulverização catódica alternada usando um canhão de NPs baseado em PGC (plasma gas condensation). O primeiro método permitiu a obtenção de nanocompósitos com uma distribuição aproximadamente homogénea de NPs esféricas na matriz, após alguma otimização das condições de deposição. Verificou-se que a integração de Au na matriz foi dependente dos elementos da matriz e também da concentração de metal. A aplicação de tratamentos térmicos promoveu a precipitação e crescimento das NPs (até um tamanho de 8 nm) e também influenciou as propriedades dielétricas da matriz. As principais desvantagens desta técnica são que o processo de precipitação é dependente do binómio Au/matriz e que a gama de tamanhos de NPs alcançados é limitada. O segundo método permitiu um controlo mais eficaz e independente da morfologia e tamanho das NPs, sem a aplicação de qualquer tratamento térmico. O tamanho médio das NPs aumentou com o teor em Au enquanto a sua forma evoluiu de esférica para esferoide com a sua razão de aspeto a diminuir progressivamente. A principal desvantagem desta técnica é que o tamanho, a forma e a distância de separação das NPs não podem ser controlados separadamente, eles evoluem em conjunto e de acordo com os vários modos de crescimento, que são dependentes da mobilidade do Au à superfície dos óxidos. O terceiro método permitiu a produção de grandes quantidades de NPs com controlo sobre o seu tamanho médio. NPs de Au foram produzidas por PGC e estudadas em grande extensão pela primeira vez. NPs esféricas de Au com tamanhos entre 5-65 nm foram depositadas com diferentes taxas de deposição. De seguida foram obtidos nanocompósitos contendo NPs com tamanho controlável, demonstrando o elevado potencial que esta técnica tem para a produção de filmes em aplicações LSPR.

碩士
國立臺灣大學
生醫電子與資訊學研究所
107
Cytokine detection allows the immune system to be monitored, providing useful information related to infectious diseases, cancer, autoimmune diseases, allergy transplantation, and drug discovery. However, conventional methods of cytokine measurement usually require multiple labor-intensive labeling procedures as well as long processing time (8-24 hours). Besides, the requirement of labeling process lead to only end-point readout measurements, which makes the monitoring of dynamic cytokine concentration variation impossible. Moreover, the long processing time hinders diagnosis and precludes timely treatments. In this thesis, a localized surface plasmon resonance (LSPR) platform is proposed to address these problems. The LSPR platform consists of three components: (1) a dual-mode microchannel which can switch into the synchronized or independent mode based on different assay steps; (2) an automatic microfluidic system which can control all reagent flow; and (3) a spectroscopy setup which performs label-free and real-time biomolecular detection. Our study first optimized the microchannel design through simulations. Then, the performance of the immunoassay protocol, the spectroscopy setup, the sensor, and automatic microfluidic system are validated in succession. Finally, an automated, label-free, real-time, and multi-parallel cytokine detection is performed by our LSPR platform in under 4.5 hours, which is 2-6 times faster than conventional methods. We believe our LSPR platform have the potential to overcome the limitations of conventional cytokine measurements and perform rapid cytokine detection for punctual diagnosis and timely treatments.

Le méthotrexate (MTX), un agent anti-cancéreux fréquemment utilisé en chimiothérapie, requiert généralement un suivi thérapeutique de la médication (Therapeutic Drug Monitoring, TDM) pour surveiller son niveau sanguin chez le patient afin de maximiser son efficacité tout en limitant ses effets secondaires. Malgré la fenêtre thérapeutique étroite entre l’efficacité et la toxicité, le MTX reste, à ce jour, un des agents anti-cancéreux les plus utilisés au monde. Les techniques analytiques existantes pour le TDM du MTX sont coûteuses, requièrent temps et efforts, sans nécessairement fournir promptement les résultats dans le délai requis. Afin d’accélérer le processus de dosage du MTX en TDM, une stratégie a été proposée basée sur un essai compétitif caractérisé principalement par le couplage plasmonique d’une surface métallique et de nanoparticules d’or. Plus précisément, l’essai quantitatif exploite la réaction de compétition entre le MTX et une nanoparticule d’or fonctionnalisée avec l’acide folique (FA-AuNP) ayant une affinité pour un récepteur moléculaire, la réductase humaine de dihydrofolate (hDHFR), une enzyme associée aux maladies prolifératives. Le MTX libre mixé avec les FA-AuNP, entre en compétition pour les sites de liaison de hDHFR immobilisés sur une surface active en SPR ou libres en solution. Par la suite, les FA-AuNP liées au hDHFR fournissent une amplification du signal qui est inversement proportionnelle à la concentration de MTX. La résonance des plasmons de surface (SPR) est généralement utilisée comme une technique spectroscopique pour l’interrogation des interactions biomoléculaires. Les instruments SPR commerciaux sont généralement retrouvés dans les grands laboratoires d’analyse. Ils sont également encombrants, coûteux et manquent de sélectivité dans les analyses en matrice complexe. De plus, ceux-ci n’ont pas encore démontré de l’adaptabilité en milieu clinique. Par ailleurs, les analyses SPR des petites molécules comme les médicaments n’ont pas été explorés de manière intensive dû au défi posé par le manque de la sensibilité de la technique pour cette classe de molécules. Les développements récents en science des matériaux et chimie de surfaces exploitant l’intégration des nanoparticules d’or pour l’amplification de la réponse SPR et la chimie de surface peptidique ont démontré le potentiel de franchir les limites posées par le manque de sensibilité et l’adsorption non-spécifique pour les analyses directes dans les milieux biologiques. Ces nouveaux concepts de la technologie SPR seront incorporés à un système SPR miniaturisé et compact pour exécuter des analyses rapides, fiables et sensibles pour le suivi du niveau du MTX dans le sérum de patients durant les traitements de chimiothérapie. L’objectif de cette thèse est d’explorer différentes stratégies pour améliorer l’analyse des médicaments dans les milieux complexes par les biocapteurs SPR et de mettre en perspective le potentiel des biocapteurs SPR comme un outil utile pour le TDM dans le laboratoire clinique ou au chevet du patient. Pour atteindre ces objectifs, un essai compétitif colorimétrique basé sur la résonance des plasmons de surface localisée (LSPR) pour le MTX fut établi avec des nanoparticules d’or marquées avec du FA. Ensuite, cet essai compétitif colorimétrique en solution fut adapté à une plateforme SPR. Pour les deux essais développés, la sensibilité, sélectivité, limite de détection, l’optimisation de la gamme dynamique et l’analyse du MTX dans les milieux complexes ont été inspectés. De plus, le prototype de la plateforme SPR miniaturisée fut validé par sa performance équivalente aux systèmes SPR existants ainsi que son utilité pour analyser les échantillons cliniques des patients sous chimiothérapie du MTX. Les concentrations de MTX obtenues par le prototype furent comparées avec des techniques standards, soit un essai immunologique basé sur la polarisation en fluorescence (FPIA) et la chromatographie liquide couplée avec de la spectrométrie de masse en tandem (LC-MS/MS) pour valider l’utilité du prototype comme un outil clinique pour les tests rapides de quantification du MTX. En dernier lieu, le déploiement du prototype à un laboratoire de biochimie dans un hôpital démontre l’énorme potentiel des biocapteurs SPR pour utilisation en milieux clinique.
Methotrexate (MTX) cancer therapy requires therapeutic drug monitoring (TDM) for following its levels in a patient during the course of treatment in order to maximize efficacy while minimizing side effects. Despite its narrow therapeutic window, MTX remains until this date, one of the most employed chemotherapy agents. Existing TDM analytical techniques for MTX are costly, time-consuming and labor intensive which are not suitable to promptly generate results within the therapy timeframe. To provide rapid MTX quantification for TDM, a strategy is proposed based on a competitive assay featuring gold nanoparticles and surface plasmonic coupling. More specifically, the inhibition of MTX with its molecular receptor, human dihydrofolate reductase (hDHFR), an enzyme associated with proliferative diseases, is explored. Free MTX mixed with folic acid-functionalized gold nanoparticles (FA-AuNP) are in competition for hDHFR binding sites immobilized on a SPR active surface or free in solution. FA-AuNP binding to hDHFR provides signal amplification which is inversely proportional to the concentration of MTX. Surface plasmon resonance (SPR) is commonly used as a spectroscopic technique for the interrogation of biomolecular interactions. Current commercial SPR instruments are laboratory-based, bulky, expensive, lack sensitivity in complex matrix and have not shown adaptability in clinical settings. In addition, SPR analysis of small molecules such as drugs has not been extensively explored due to lack of sensitivity. The recent advances in materials science and surface chemistry exploiting gold nanoparticle integration for SPR response enhancement and peptide surface chemistry have shown potential in overcoming the poor sensitivity and surface-fouling limitations for crude biofluids analysis. These novel concepts of SPR technology are incorporated with a miniaturized fully integrated SPR prototype to conduct fast, reliable and sensitive analysis to monitor MTX levels of a patient undergoing chemotherapy. The objective of the thesis is to explore different strategies in improving drug analysis in a complex matrix using SPR biosensors and to put in perspective of the potential of SPR biosensors as a useful TDM tool in clinical laboratories or at a point-of-care situation. To achieve these objectives, a colorimetric solution-based MTX competitive assay is first established with FA-AuNP. Then, the solution-based MTX competitive assay is translated onto a SPR platform. For both developed assays, sensitivity, selectivity, detection limit, dynamic range optimization as well as analysis of methotrexate in complex matrix are inspected. Furthermore, the SPR prototype is validated by its equivalent performance to existing SPR systems and by its utility in executing MTX analysis in actual serum samples from patients undergoing chemotherapy. The concentrations of MTX obtained by SPR biosensing are compared to standard techniques: fluorescence polarization immunoassay (FPIA) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in order to confirm the feasibility of SPR biosensors as a useful clinical tool for performing rapid MTX concentration evaluation. Finally, the successful deployment of the prototype to a hospital laboratory demonstrates enormous prospective of SPR biosensors in clinical use.

Strong light matter interactions in metallic nanoparticles (NPs), especially those made of noble metals such as Gold and Silver is at the heart of much ongoing research in nanoplasmonics. Individual NPs can support collective excitations (Plasmon’s) of the electron plasma at certain wavelengths, known as the localized surface Plasmon resonance (LSPR) which provides a powerful platform for various sensing, imaging and therapeutic applications. For a collection of NPs their optical properties can be signify cannily different from isolated particles, an effect which originates in the electromagnetic interactions between the localised Plasmon modes. An interesting aspect of such interactions is their strong dependence on the geometry of NP collection and accordingly new optical properties can arise. While this problem has been well considered in one and two dimensions with periodic as well as with random arrays of NPs, three dimensional systems are yet to be fully explored. In particular, there are challenges in the successful de-sign and fabrication of three dimensional (3D) plasmonic metamaterials at optical frequencies. In the work presented in this thesis we present a detail investigation of the theoretical and experimental aspects of plasmonic interactions in two geometrically different three dimensional plasmonic nanostructured systems - a chiral system consisting of achiral plasmonic nanoparticles arranged in a helical geometry and an achiral system consisting of achiral plasmonic nanoparticle arrays stacked vertically into three dimensional geometry. The helical arrangement of achiral plasmonic nanoparticles were realised using a wafer scale technique known as Glancing Angle Deposition (GLAD). The measured chiro-optical response which arises solely from the interactions of the individual achiral plasmonic NPs was found to be one of the largest reported value in the visible. Semi analytical calculation based on couple dipole approximation was able to model the experimental chiro-optical response including all the variabilities present in the experimental system. Various strategies based on antiparticle spacing, oriented elliptical nanoparticles, dielectric constant value of the dielectric template were explored such as to engineer a strong and tunable chiro-optical response. A key point of the experimental system despite the presence of variabilities, was that the measured chiro-optical response showed less than 10 % variability along the sample surface. Additionally we could exploit the strong near held interactions of the plasmonic nanoparticles to achieve a strongly nonlinear circular differential response of two photon photoluminescent from the helically arranged nanoparticles. In addition to these plasmonic chiral systems, our study also includes investigation of light matter interactions in purely dielectric chiral systems of solid and core shell helical geometry. The chiro-optical response was found to be similar for both the systems and depend strongly on their helical geometry. A core-shell helical geometry provides an easy route for tuning the chiro-optical response over the entire visible and near IR range by simply changing the shell thickness as well as shell material. The measured response of the samples was found to be very large and very uniform over the sample surface. Since the material system is based entirely on dielectrics, losses are minimal and hence could possibly serve as an alternative to conventional plasmonic chiro-optical materials. Finally we demonstrated the used of an achiral three dimensional plasmonic nanostructure as a SERS (surface enhance Raman spectroscopy) substrate. The structure consisted of porous 3D metallic NP arrays that are held in place by dielectric rods. For practically important applications, the enhancement factor, as well as the spatial density of the metallic NPs within the laser illumination volume, arranged in a porous 3D array needs to be large, such that any molecule in the vicinity of the metal NP gives rise to an enhanced Raman signal. Having a large number of metallic NPs within the laser illumination volume, increases the probability of a target molecule to come in the vicinity of the metal NPs. This has been achieved in the structures reported here, where high enhancement factor (EF) in conjunction with large surface area available in a three dimensional structure, makes the 3D NP arrays attractive candidates as SERS substrates.

Strong light matter interactions in metallic nanoparticles (NPs), especially those made of noble metals such as Gold and Silver is at the heart of much ongoing research in nanoplasmonics. Individual NPs can support collective excitations (Plasmon’s) of the electron plasma at certain wavelengths, known as the localized surface Plasmon resonance (LSPR) which provides a powerful platform for various sensing, imaging and therapeutic applications. For a collection of NPs their optical properties can be signify cannily different from isolated particles, an effect which originates in the electromagnetic interactions between the localised Plasmon modes. An interesting aspect of such interactions is their strong dependence on the geometry of NP collection and accordingly new optical properties can arise. While this problem has been well considered in one and two dimensions with periodic as well as with random arrays of NPs, three dimensional systems are yet to be fully explored. In particular, there are challenges in the successful de-sign and fabrication of three dimensional (3D) plasmonic metamaterials at optical frequencies. In the work presented in this thesis we present a detail investigation of the theoretical and experimental aspects of plasmonic interactions in two geometrically different three dimensional plasmonic nanostructured systems - a chiral system consisting of achiral plasmonic nanoparticles arranged in a helical geometry and an achiral system consisting of achiral plasmonic nanoparticle arrays stacked vertically into three dimensional geometry. The helical arrangement of achiral plasmonic nanoparticles were realised using a wafer scale technique known as Glancing Angle Deposition (GLAD). The measured chiro-optical response which arises solely from the interactions of the individual achiral plasmonic NPs was found to be one of the largest reported value in the visible. Semi analytical calculation based on couple dipole approximation was able to model the experimental chiro-optical response including all the variabilities present in the experimental system. Various strategies based on antiparticle spacing, oriented elliptical nanoparticles, dielectric constant value of the dielectric template were explored such as to engineer a strong and tunable chiro-optical response. A key point of the experimental system despite the presence of variabilities, was that the measured chiro-optical response showed less than 10 % variability along the sample surface. Additionally we could exploit the strong near held interactions of the plasmonic nanoparticles to achieve a strongly nonlinear circular differential response of two photon photoluminescent from the helically arranged nanoparticles. In addition to these plasmonic chiral systems, our study also includes investigation of light matter interactions in purely dielectric chiral systems of solid and core shell helical geometry. The chiro-optical response was found to be similar for both the systems and depend strongly on their helical geometry. A core-shell helical geometry provides an easy route for tuning the chiro-optical response over the entire visible and near IR range by simply changing the shell thickness as well as shell material. The measured response of the samples was found to be very large and very uniform over the sample surface. Since the material system is based entirely on dielectrics, losses are minimal and hence could possibly serve as an alternative to conventional plasmonic chiro-optical materials. Finally we demonstrated the used of an achiral three dimensional plasmonic nanostructure as a SERS (surface enhance Raman spectroscopy) substrate. The structure consisted of porous 3D metallic NP arrays that are held in place by dielectric rods. For practically important applications, the enhancement factor, as well as the spatial density of the metallic NPs within the laser illumination volume, arranged in a porous 3D array needs to be large, such that any molecule in the vicinity of the metal NP gives rise to an enhanced Raman signal. Having a large number of metallic NPs within the laser illumination volume, increases the probability of a target molecule to come in the vicinity of the metal NPs. This has been achieved in the structures reported here, where high enhancement factor (EF) in conjunction with large surface area available in a three dimensional structure, makes the 3D NP arrays attractive candidates as SERS substrates.

Plasmonic properties and the related novel applications are studied on various types of metallic nano-structures in one, two, or three dimensions. For 1D nanostructure, the motion of free electrons in a metal-film with nanoscale thickness is confined in its normal dimension and free in the other two. Describing the free-electron motion at metal-dielectric surfaces, surface plasmon polariton (SPP) is an elementary excitation of such motions and is well known. When further perforated with periodic array of holes, periodicity will introduce degeneracy, incur energy-level splitting, and facilitate the coupling between free-space photon and SPP. We applied this concept to achieve a plasmonic perfect absorber. The experimentally observed reflection dip splitting is qualitatively explained by a perturbation theory based on the above concept. If confined in 2D, the nanostructures become nanowires that intrigue a broad range of research interests. We performed various studies on the resonance and propagation of metal nanowires with different materials, cross-sectional shapes and form factors, in passive or active medium, in support of corresponding experimental works. Finite- Difference Time-Domain (FDTD) simulations show that simulated results agrees well with experiments and makes fundamental mode analysis possible. Confined in 3D, the electron motions in a single metal nanoparticle (NP) leads to localized surface plasmon resonance (LSPR) that enables another novel and important application: plasmon-heating. By exciting the LSPR of a gold particle embedded in liquid, the excited plasmon will decay into heat in the particle and will heat up the surrounding liquid eventually. With sufficient exciting optical intensity, the heat transfer from NP to liquid will undergo an explosive process and make a vapor envelop: nanobubble. We characterized the size, pressure and temperature of the nanobubble by a simple model relying on Mie calculations and continuous medium assumption. A novel effective medium method is also developed to replace the role of Mie calculations. The characterized temperature is in excellent agreement with that by Raman scattering. If fabricated in an ordered cluster, NPs exhibit double-resonance features and the double Fano-resonant structure is demonstrated to most enhance the four-wave mixing efficiency.

Structures composed of two gold disks with different diameters and separated by a thin alumina layer were studied for protein biodetection. The small top disk will be used as the biosensing element since it has a shorter decay length (and thus, it has a higher sensitivity) whereas the big bottom one will give a high signal due to its bigger interaction with light. The interaction between both disks will happen through plasmon hybridisation. The samples were prepared using colloidal lithography and material deposition was made through an electron beam assisted evaporation system. A fabrication method was developed to spatially isolate the bottom disk from the sensing medium to fully exploit the small disk’s higher sensitivity. Sample’s characterisation consisted in a morphologic analysis by scanning electronic microscopy (SEM), the optical response was studied experimentally and by finite-domain time-difference (FDTD) simulations and also the electric field distribution was analysed in three types of structures. Structures with the upper disk centred relative to the lower disk and at the edge of it. The oxide’s thickness effect was studied (3 and 6 nm). The low energy peak is mainly given by a plasmonic gap dipole mode, whereas as the high energy peak is given by a contribution from a gap mode and the structure’s overall net dipole. The structure with a smaller separation and the top disk centre regarding the bottom disk was found to have a higher electric field enhancement around it and should be the one to be used as a biosensor.

Cette thèse caractérise les propriétés optiques des matériaux plasmoniques microstructurés et procède à l’évaluation des paramètres analytiques afin de les employer comme plateforme de biodétection en spectroscopie de résonance des plasmons de surface (SPR). Aux dimensions micrométriques, les matériaux plasmoniques présentent des caractéristiques optiques propres aux nano- et macromatériaux. La cartographie physicooptiques en SPR de matériaux méso- et microscopiques s’est effectuée à l’aide de films structurés de motifs périodiques triangulaires et circulaires fabriqués par une technique modifiée de lithographie par nanosphères (nanosphere lithography, NSL). À partir de cette vue d’ensemble, quelques films structurés ont été sélectionné en fonction d’aspects analytiques tels que la sensibilité et la résolution face aux variations d’indice de réfraction (RI) pour déterminer le potentiel de ces matériaux comme plateforme de biodetection. Les propriétés optiques distinctes des films microstructurés proviennent d’interactions résonantes entre les modes de plasmons de surface (SP) localisé et délocalisé identifiés par la relation de dispersion en SPR ainsi que l’imagerie Raman. Les conditions de résonance des modes SP dépendant de paramètres expérimentaux (λ, θ, η) tel qu’observés numériquement par rigorous coupled wave analysis (RCWA) et empiriquement. Ces travaux démontrent la nature plasmonique distincte des micro-matériaux et leur potentiel d’intégration aux techniques analytiques SPR existantes. Les matériaux plasmoniques micrométriques furent également étudiés pour l’implémentation de la SPR à une pointe de microscopie à force atomique (atomic force microscopy, AFM) combinant ainsi la spectroscopie à l’imagerie topographique. Des travaux préliminaires se sont concentrés sur la signature spectroscopique de leviers en silicium (Si) et en nitrure de silicium (Si3N4), l’impact d’un revêtement d’or sur les pointes et l’influence de milieu environnant. Une image d’origine plasmonique a été obtenue avec des leviers en Si3N4 revêtus d’or en transmission dans un environnement aqueux, indiquant ainsi le potentiel de ces pointes comme micro-biocapteur SPR. Ces résultats préliminaires servent de fondement pour orienter les prochaines investigations dans ce projet.
This thesis characterizes the optical properties of microstructured plasmonic materials and evaluates analytical parameters to use them as biosensing platforms in surface plasmon resonance (SPR) spectroscopy. At microscopic dimensions, plasmonic materials present optical characteristics unique to nano- and macromaterials. A SPR physico-optic mapping of meso- and microscopic materials was performed using structured films with triangular and circular periodic patterns fabricate by modified nanosphere lithography (NSL) technique. From this overview, a few structured films were selected based on analytical aspects such as sensitivity and resolution with respect to the refractive index (RI) to determine the potential of these materials as biosensing platforms. The distinct plasmonic properties of microstructured films emerge from resonant interactions between localized and propagating surface plasmons (SP) modes identified by the SPR dispersion relation and by Raman imaging. The conditions of SP modes resonant interactions depend on experimental parameters (λ, θ, η) as observed numerically in rigorous coupled wave analysis (RCWA) and empirically. These works show the distinct plasmonic nature of micromaterials and their potential integration to existing SPR techniques. Plasmonic micromaterials were also studied for the implementation of SPR to an atomic force microscopy (AFM) cantilever, hence combining spectroscopy to topographic imaging. Preliminanry works were focused on the spectroscopic response of silicon (Si) and silicon nitride (Si3N4) cantilever, the impact of gold coating on the cantilever is tip, and the influence of the adjacent environment. An image of plasmonic nature was obtained in transmission spectroscopy with gold coated Si3N4 cantilever in water environment, thus indicating the potential of these cantilevers as micro-SPR sensing probes. These preliminary results provide a basis to guide future investigations in this project.